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The Clinical Outcomes Regarding to Tumor-Infıltrating Lymphocytes in the Breast Cancer Patients Treated with Neoadjuvant Chemotherapy- Juniper Publishers

In breast cancer great endeavors are going on to find new markers in determining the prognosis. In addition to well-known prognostic factors such as tumour size, grade, nodal status, molecular subtype, proliferation index, gene-expression based recurrence score, recently there is increasing evidence that tumor-infiltrating lymphocytes (TILs) are of important role as an immune biomarker in breast carcinoma [1-3]. TILs might be a reflection of host immune response which plays an important role in cancer control and patient’s clinical outcome. TILs are mononuclear immune cells that infiltrate tumour tissue and mainly comprised of cytotoxic (CD8+) T cells as well as macrophages, helper (CD4+) T cells, B cells, and NK cells [4,5]. There are two types of TILs: Stromal TILs (sTILs) are defined as the percentage of tumour stromal field in which lymphocytes are located without direct connection to tumour cells. In contrast, intratumoural TILs reflect immune cells within the tumour cells. Stromal TILs are commonly detected in H&E stained sections by light microscopy, and consist the majority of TILs in breast cancer [1]. Its assessment is the most reproducible parameter by pathologists. Moreover, lymphocytes-predominant breast cancer (LPBC) is defined as those cancer with TILs occupies at least 50 % to 60 % of the stroma [4].

The clinical importance and amount of TILs appear to vary significantly among different subtypes of breast cancer [2,6]. TILs are more common in triple-negative breast cancer (TNBC) and HER2-overexpressing breast cancer, with LPBC frequency of 15-25 % in these groups. Contrary, luminal tumour is the least immune infiltrated breast cancer subtype [3,6,7]. Large series suggest that tumour with higher TILs levels are associated with improvement of prognosis by longer survival rates and with reduction of locoregional recurrences [8,9]. This positive prognostic effect is especially striking on TNBC and HER2 positive patient populations [6,10]. In addition to prognostic value of TILs, trials also indicate the predictive role of TILs in response to neoadjuvant chemotherapy [11,12]. The aim of this study was to determine the association between TILs level and other clinicopathological parameters and to explore the prognostic and predictive roles of TILs in our breast cancer patients treated with neoadjuvant therapy.

Materials and Methods

The study was conducted to determine the association of TILs value with the clinical outcomes at neoadjuvant settings. Breast cancer patients treated after neoadjuvant chemotherapy at Bakırköy Sadi Konuk Training and Research Hospital from July 2011 to January 2016 were included in this study. All were followed up in our hospital. Patient’s demographic information, characteristics, outcomes and follow-up were obtained from hospital records. The study protocol was approved by the ethics committee of our institute (No:2017/09-20). Neoadjuvant therapy were taxane and anthracycline-based protocol, adding transtuzumab in the HER2 positive subtypes. Surgical treatment was decided as to treatment response. Radiotherapy and endocrine therapy were given in accordance with institutinal guidelines. Inoperable patients following neoadjuvant therapy were excluded of this study. The patients were categorized according to molecular subtypes as triple negative (TN), HER2 positive and luminal type. All patients in each subtypes were distributed into two groups according to TILs, with 10 % of cut-off value. In order to determine TILs value all patients’ paraffin sections stained hematoxilyn and eosin (H&E) from core biopsies were retrospectively assessed by an experienced pathologist (S.A.), blinded of clinical information. Briefly, all mononuclear cells (including lymphocytes and plasma cells) in the stromal compartment within the borders of invasive tumour were evaluated and reported as a percentage value. pCR was defined as ypT0/Tis ypN0.

We analysed associations of TILs with other clinicopathological factors such as menopausal status, tumour molecular type, ypTNM classification, histology, grade, lymphovascular and perineural invasion. In order to evaluate the predictive role of TILs, we investigated pathological responses to neoadjuvant therapy in high and low TILs groups of each subpopulation. To determine the prognostic role of TILs we recorded the patients’ locoregional recurrence and systemic metastasis in all groups and detected overall survival and disease free survivals. Statistical analysis was carried out using NCSS 11 package program. For categorical variables the frequency and percentage values were calculated and for continuous variables, average and standard derivation values were calculated. Standard distribution sort of variables was made with Kolmogorov-Smirnov test. Student t test was used in the comparison of two groups and single direction variance analysis was used in the comparison of more than two groups for variables exhibiting standard distribution. Disease-free survival (DFS) and overall survival (OS) were obtained using Kaplan-Meier survival analysis. The relations between categorical variables were examined with Chi square test, Fisher exact probability test and Fisher-Freeman-Halton test. P<0,05 was accepted as statistically significant.

Results

The study consisted of 89 breast cancer patients who underwent neoadjuvant chemotherapy. The mean follow-up duration of all patients was 33,8 (15-84) months. According to molecular subtypes, 39 patients had luminal tumour, and 25 patients each triple negative and HER2 positive.

TILs values in all groups and its relation with other clinicopathological factors

The mean TILs values were 10.8%, 15.4%, 6% in TN, HER2 positive and luminal groups, respectively. Among the patients of high TILs levels, HER 2 positive group was the most frequent molecular subtype (50 %), followed by triple negatives (32%) (Table 1). Sixty percent of patients with TILs less than 10 % had luminal tumour. There was statistically significant relationship between TILs value and both molecular type of tumour (p=0.0001) and presence of lymphovascular invasion (p=0.048). No association was detected between TILs and other variables such as menopausal status, ypTNM classification, histology, grade, and perineural invasion (Table 2).

TILs and prognosis

No association was seen in any subtypes between TILs levels and presence of either locoregional recurrence or systemic metastasis (Table 3). Neither OS nor DFS were significantly different between high and low TILs groups in both TN and HER2 positive groups. Because there was no death in luminal group, we could not detected survival analyses in this subtype.

Predictive role of TILs

In the neoadjuvant setting, no interaction was found between TILs level and complete pathological response according to each subtypes (Table 4). But, there was non-significantly better pathological response rates in high TILs group of HER2 (+) population.

Discussion

The constant interaction between tumour and host immunity influences patient’s outcome. Innate and adaptive immune response in the tumour milieu require functional cytotoxic T-cells in order to achieve efficent tumour elimination [1]. The impact of TILs on the prognosis and treatment prediction suggests its importance on the reflection of individual immunity [13]. Various studies of TN and HER2 (+) breast cancer have pointed consistent results that the increased TILs value the patients have, the better OS and DFS in the adjuvant setting [6,14]. Moreover, the highest TILs also show the highest expression of T-cell checkpoint receptors which found on T cells [1]. Antitumour immunity is enhanced by monoclonal antibodies against checkpoint inhibitors. In addition to standard therapeutic options, immunotherapy in breast cancer is a new and promising implication especially in selected patient population. Therefore, TILs evaluation may be accepted as a biomarker for immunotherapeutics in patients with breast cancer at near future.

In the light of these rapidly evolving field, in 2014 international TILs working group has recommended TILs evaluation as a immune parameter along with standard histopathological practise to facilitate its use in research setting and clinical trials [4]. They reported TILs measurement as a percentage of stromal TILs on a continuous scale by visual assessment of H&E-stained sections of primary tumour specimens similar to any other quantitative histological biomarker. Several studies have evaluated lymphocyte subtypes by using immunohistochemical analysis, yet added value of immunohistochemistry on to TILs evaluation remains to be demonstrated [4,15]. Moreover, digital image analysis of TILs can provide more exact measurement and eliminate inter-pathologists differences in TILs assessment [13]. Visual measurement of TILs is prefered at many trials like our study [4,6]. Because this route is stated as rapid, easly available, less expensive and adequate tool in TILs assessment. There is no established threshold for high TILs. Various studies used different cut-off values [7,9,16,17]. Moreover, 50-60 % of TILs value for lymphocytes-predominant breast cancer had been arbitrarly chosen [17]. In this study, ROC Curve was applied for the estimation of pathological response of TILs values, but a significant breakpoint could not be found (unreported data). Therefore, we accepted 10 % of TILs level as a cut-off value similar to many studies [6,18].

In our study, we investigated the relation of TILs value with other clinicopathological parameters and its impact on patients with all molecular subtypes of breast carcinoma who were operable following neoadjuvant treatment. The positive relation of higher quantities of TILs and both negative steroid receptor status and presence of HER2 positivity is striking in the literature like in our study [6]. Also LPBC is commonly found in HER2 positive and triple negative subtypes [4,19]. Similarly, in our study HER2 positive group was the main molecular subtype (50%) that harbours the high percentage of TILs. But, interestingly unique patient with LPBC was seen in our series. In this study, patients with luminal type breast cancer had lower TILs value, with the median of 6%. Similar to litreture, no significant prognostic role of TILs was found in patients of our luminal group [1]. According to the trial by Huszno [7] higher grades of TILs were present more frequently in younger patients than older women (47% vs. 24%). Moreover, higher TILs levels was appeared to be associated with higher histological grades. On the other hand, TILs value also was significantly correlated with lymphovascular invasion in our study.

The positive association between TILs levels and favourable clinical outcomes was based on Sistrunk’s cohort trial at 1922 [20]. Eastern Cooperative Oncology Group’s phase III trials showed that each 10 % increase in TILs levels significantly predicted better DFS and OS in TNBC with a median follow-up of over 10 years [21]. A recent meta-analysis of twenty-five trials including more than twenty thousands patients confirmed the survival benefit of TILs in TN and HER2 positive breast cancer patients [18]. Moreover, according to secondary analysis of the NeoALTTO trial reported by Salgado [17] patients with high TILs levels at baseline had better outcomes for event free survival independent of whether they achieved pCR in the neoadjuvant phase. The association between higher levels of TILs and decreased distant recurrence rates in TN breast cancer was found in FinHER trial [22].

Contrary to obvious results as to prognostic impact of higher TILs levels on the adjuvant and neoadjuvant settings, we could not detected any significant relationship between TILs and survival analysis. Another issue related to TILs is its utility in prediction of adjuvant and neoadjuvant therapy response [6]. At the adjuvant setting, the association between higher levels of TILs and increased transtuzumab benefit in HER2 (+) subtype was detected in phase III trial including 1010 early stage BC patients [22]. Positive correlation between TILs levels and pCR rates was prominent in HER2 (+) tumours. According to the study of Carbognin [12] pCR rates were increased by nearly 30 % in the presence of TILs reported as LPBC. Another trial has also indicated that the level of TILs greater than 5% was associated with higher pCR rates [17]. Although we could not detected significant correlation between TILs value and pCR in our study, there were non-significantly higher pCR rates in HER2 (+) group. The minority of our patient population explains the limited power of the statistical analysis.

Conclusion

Host immunity controls cancer and influences patient’s outcome. How can a host enhance anti-tumor immune response and which biomarker provides better treatment approach are the main questions. Although which level of TILs should be used to determine optimal treatment strategy for breast cancer patients has not been certain yet, many trials indicate that TILs is of prognostic effect in long-term disease control and predictive effect of a better local response to treatment. But, further resaerchs are warrented before the utility of TILs as an immune biomarker for routine clinical practise of breast cancer patients.

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juniperpublishersoa · 2 years

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A Rare Cause of Gastrointestinal Bleeding: A Jejunal Dieulafoy’s Lesion- Juniper Publishers

One in a thousand people have an acute gastrointestinal (GI) hemorrhage per year [1]. There are around 300,000 hospitalizations for GI bleeds, costing an estimated $2 billion per year [2-4]. Compared to lower gastrointestinal bleeding (LGIB), upper gastrointestinal bleeding (UGIB) is associated with a much higher mortality rate, with some studies suggesting a 30-day mortality rate of up to 14% [2,3]. A majority of these UGIB (67 - 80%) are attributed to gastric erosions/ulcers 6,17,18. However, of this morbid group of bleeds, a rare (1% or less), yet more serious cause is a Dieulafoy’s lesion (DFL). DFL, is an obscure type of bleeding that can cause life threatening hemorrhages with a mortality rate ranging from 28-67% [5,6].

DFL was first described by MT Gallard [7] in 1884 as a type of aneurysm and later clarified by P. G. Dieulafoy in 1898 who believed this was an early stage of ulceration [7-9]. DFL’s are a collection of large tortuous arterioles of the gastrointestinal vessels. These are often compared to aneurysms, however, DFL’s are caused by genetic malformations rather than degeneration. While the exact mechanism of rupture and subsequent hemorrhage is still poorly understood, several studies have suggested mucosal erosion and ischemic injury, related to aging and/or cardiovascular disease, as possible causes [10]. DFLs are predominantly seen in elderly patients (mean age 69.7 years) though they can be seen in younger patients as well. A vast majority of patients also will have underlying comorbidities such as renal failure, diabetes, or coronary artery disease. Additionally, there have been a few isolated cases associated with chronic immunosuppression whether from underlying malignancies or medication induced [11].

More than 70% of these rare lesions are found in the stomach, usually near the lesser curvature. The discovery of extragastric DFL’s are infrequent, with the duodenum (14%) and colon (5%) being the most common locations [12-14]. The most unusual site is the jejunum, which accounts for 1% of all DFL’s [12-14]. Historically, there have been a few case reports worldwide of jejunal DFL’s, however, of these reported cases, the lesions were found by advanced imaging (CT angiogram or Bleeding scan). We present a case of a jejunal DFL that was unable to be found by advanced imaging but was diagnosed on push enteroscopy.

Assessment

The patient was a 79-year-old African American female with a known history of end stage renal disease and large granular lymphocytic leukemia. Over the course of 8 months, the patient had 3 admissions for gastrointestinal bleeds. She received a total of 16 units of blood with 4 EGDs, 2 colonoscopies, 1 bleeding scan and 1 CT angiogram. Of the listed procedures performed, all were negative for active bleeding and there was no solid evidence of a bleeding source. She was presumed to have bled twice from erosive gastritis and the most recent admission was from an unknown etiology. An outpatient small bowel capsule study was done after these admissions showing no findings.

She subsequently presented to the ER 24 days after her most recent admission for melena and orthostasis, where she was found to have a hemoglobin of 4.4 g/dL (previous hemoglobin was 10.2 g/dL). EGD and colonoscopy did not show any findings or source of bleeding. The patient continued to have melena and required 8 units of blood. A CT angiogram and bleeding scan were again inconclusive. A push enteroscopy was performed on day 6 of admission, showing an actively oozing area in the jejunum with no surrounding ulceration or malformations (Figure 1). Bipolar cauterization and 2 hemoclips were placed ceasing the actively bleeding Dieulafoy’s lesion. The patient’s hemoglobin stabilized, and the melena resolved 1 day after the enteroscopy.

Management

Our patient had a history of large granulocytic lymphocytic leukemia (LGL) and end stage renal disease. Though the usual course of LGL presents with neutropenia and anemia, thrombocytopenia can be seen in up to 20% of cases [15]. Thrombocytopenia combined with immunosuppression from underlying malignancy and ESRD put this patient at an increased risk of developing hemorrhagic complications such as DFLs. On multiple admissions, our patient was found to pancytopenia, likely as a result of her bleeding and immunosuppression. To date, there have been a few case reports citing immunosuppression, immunotherapy, and thrombocytopenia all being associated with GI bleeds due to a DFL [16,17]. While the mechanism is not yet established, it is thought to be related to impaired tissue remodeling and repair.

The current endoscopic modalities to manage a DFL include mechanical treatment (with endoclips or band ligators), injection therapy (with diluted epinephrine), thermal coagulation therapy, or in some cases, a combination of different modalities. Two controlled trials suggested that mechanical hemostasis with endoclips can control acute bleeding and may reduce recurrent bleeds compared to injection therapy alone [18]. There have been no studies comparing the efficacy of thermal coagulation alone or in combination with other methods. A second trial comparing endoclips to injection therapy with epinephrine showed equal rates of initial hemostasis but significantly lower rates of rebreeding in the endoclip arm (0%) vs epinephrine arm (35%) [19].

Post endoscopic management depends on whether the patient is at high risk or low risk for rebleeding. One method used to calculate risk of recurrence is the Glasgow - Blatchford bleeding score (GBS score). A GBS score of 0-1 is considered low risk for rebleeding, and in this case the patient may be discharged from inpatient care with plans for outpatient endoscopic intervention. Inpatient treatment is recommended for patients with GBS scores of 2 or greater [20]. The rate of recurrence of bleed for a Dieulafoy’s lesion ranges from 9-40% [21]. There is a higher rate of recurrence with endoscopic monotherapy compared to combined endoscopic interventions [22]. The rate of rebleeding is not associated with gender or location of DFL or past medical history [23]. Inpatient treatment recommendation is to treat with IV pantoprazole for 72 hours in order to keep gastric pH above 6 in order to maintain intact coagulation process, followed by oral pantoprazole therapy. While mortality is lowest in patients with no significant medical history or comorbidities, overall longterm prognosis of a DFL is favorable once primary hemostasis is achieved [24]. Following push enteroscopy our patient did well without any further complications or signs of rebleeding [25-30].

Conflict of Interest

All authors have read and approved the submission of this manuscript. The manuscript has not been published and is not being considered for publication elsewhere, in whole or in part. The authors declare that there is no conflict of interests regarding the publication of this paper

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A Rare Cause of Gastrointestinal Bleeding: A Jejunal Dieulafoy’s Lesion- Juniper Publishers

Assessment

Management

Conflict of Interest

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Pheochromocytoma Associated with Renal Agenesis:A Case Report and Review of Literature- Juniper Publishers

Pheochromocytomas are neuroendocrine tumors developed at the expense of cells derived from the neural crest. They occur sporadically in 50-55% of cases, but they can be familial in 5 to 10% of cases and then be isolated or integrated into an inherited syndrome of multiple neuroendocrinopathy. The properly operated pheochromocytoma is radically and definitively cured as long as it is benign and sporadic. Renal anomalies have been reported rarely in this disease. Here we report a rare case of pheochromocytoma associated with renal agenesis. Patient was a female presented with headache and hypertension. In radiologic examinations, an adrenal mass was detected in the right side, with no renal tissue on that side. It was reported an adrenal pheochromocytoma in histopathology. Renal agenesis confirmed during surgery. All of the patient’s symptoms alleviated after the resection of tumor. Considering association of renal abnormalities with pheochromocytoma, it is recommended to perform genetic analysis and kidney evaluation in cases with MEN type 2 or each of its components.

Keywords:Pheochromocytoma; Renal agenesis; RET gene mutation

Introduction

Pheochromocytoma and unilateral renal agenesis/hypoplasia are well-reported conditions. Their combination, however, is rare with few cases reported [1-3]. Rearranged in Transfection (RET) gene mutations are proven to cause both of these conditions. RET mutation as a possible common mechanism of the both conditions is discussed briefly along with literature review and possible clinical implications of the association.

Observation

Pheochromocytoma and renal agenesis are commonly reported conditions. Their coexistence, however, is rare, with few cases reported. The case of 31-year-old female was admitted for headache and occasional night sweating. Family history was negative for any significant disease. Physical examination was normal except for hypertension (BP= 160/90). Laboratory examinations consisted of complete blood count (CBC), serum and urine biochemistry, serum renin and aldosterone level were all-normal. Abdominal MRI and abdominal CT scan detected in the right side an adrenal gland (60-80-40 mm ) with calcifications and necrosis area driving back the liver and the vena cava right renal agenesis. Therefore, urine VMA and NMN checked which both were higher than normal. MIBG scan showed increased radiotracer uptake in adrenal mass (Figure 1).

Surgery

Right adrenalectomy

Steps of surgery:

a) Laparotomy (Figure 2).

b) Installation: The patient is installed in an intermediate position between the dorsal and lateral decubitus.

Procedure: Vascular access, from the inferior vena cava (Figures 3 and 4).

Resection of the tumor mass (Figure 5).

Follow up: Favorable and patient discharge 6 days later.

Anatomopathological study: In favor of a pheochromocytoma (Figure 5).

On follow-up, patient is normotensive and asymptomatic.

Discussion

This coexistence of paraganglioma / pheochromocytoma and renal agenesis may have a common genetic mechanism in the form of Rearranged in Transfection (RET) gene mutation. This is a well-characterized gene, mutations of which are known to be associated with both conditions. Current knowledge of the role of RET gene in both conditions is reviewed to put forth RET mutation as the possible common underlying genetic mechanism along with possible clinical implications of the combination. With a mutated common gene, it is logical to expect association of congenital renal abnormalities and chromaffin tumors (those due to RET mutations). However, we noted one case of renal agenesis associated with chromaffin tumors in literature [1-4]. To our best knowledge, we are reporting a case of pheochromocytoma associated with renal agenesis. The following discussion is an endeavor to explain this association in the light of role of RET gene uncovered in embryology and cancer biology.

Rearranged in Transfection gene is located on chromosome 10 and gene product is a cell membrane receptor of tyrosine kinase family. Ligand (molecule which attaches to receptor) of glial cell line-derived neurotrophic factor (GDNF) family binds to RET receptor resulting in activation of multiple downstream pathways that promote cellular proliferation, survival and/or differentiation. Gain of function mutations cause persistently activated receptor in the absence of ligand promoting malignant transformation. RET mutations are well-established cause of multiple endocrine neoplasia type 2 (MEN2) syndromes (medullary carcinoma thyroid, adrenal pheochromocytoma, ganglioneuromas) [5,6]. Incidence of RET mutation in paraganglioma is variably reported but estimated to be 5% in a recent review article [5,7].

How can loss of function phenotype (renal agenesis) possibly coexist with a gain of function phenotype (pheochromocytoma)? Different RET mutations in different cases are described [2,8]. A subset of RET mutation (called Janus mutation) may have a negative role in neural and/or renal development but promote cellular proliferation. Experimental evidence for such mutation was found when a particular type of RET mutation was found to promote cellular proliferation but which impaired GDNF action on RET on cellular migration and differentiation in vitro [9] about our case of renal agenesis with pheochromocytoma described previously [2]. Further, same gene mutation may manifest with only loss of function phenotype in one generation but with loss and gain of function mutation in a different generation, for example, familial renal agenesis with medullary carcinoma thyroid in a mother and with Hirschsprung disease in son [8]. Similarly, “carriers” of MEN2 patients having renal agenesis have been described, who possibly show only one manifestation of the full spectrum of RET mutation effects [10]. Precise molecular mechanisms in such cases remain to be to be elucidated completely

However, we do realize potential problems in conjuncture of RET mutation being an underlying common link for renal agenesis and paraganglioma. It is well known that unilateral renal agenesis is a common condition (1 in 1000 live births) and so association with paraganglioma may be incidental. Also, reported RET mutation incidence in renal agenesis is variable, quoted as 7–20% in stillborn fetuses [7,11]. However, this may explain as a common final pathway of RET gene being influenced by mutation in other modulating genes. It can also be due to low penetration of RET gene to cause renal agenesis as compared to high penetration for malignant transformation [10]. In our case, we could not carry out testing for RET gene due to financial constraints of the patient.

Conclusion

There are a few reports of renal abnormalities in patients with pheochromocytoma. Genetically, the significance of RET protooncogene gene and its encoding protein related to tyrosin kinase family has been documented in the induction of metanephric blastema and ureteric bud during kidney morphogenesis . Mutation of this gene is known to be responsible for developing MEN type 2A, renal agenesis or severe dysplasia. The association of renal abnormalities with pheochromocytoma, it is recommended to perform genetic analysis and kidney evaluation in cases with MEN type 2 or each of its components.

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juniperpublishersoa · 3 years

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Juniper Publishers| A Review of Indication and Complications of Extracorporeal Membrane Oxygenation

Journal of Surgery

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Abstract

Mechanical circulatory support may be the last life-saving resort in certain circumstances such as life-threatening pulmonary failure, cardiac failure, or both. ECMO has been shown to provide adequate cardiopulmonary support and can be initiated rapidly in an emergent setting by either percutaneous or surgical implantation. It allows bridging of patients with cardio-pulmonary collapse to recovery or long-term mechanical support. Veno-arterial ECMO (VA-ECMO) is used as bridge-to-decision and/or bridge-to-recovery in patients with cardiogenic shock. Long-term mechanical circulatory support devices such as left ventricular assist devices (LVADs) are widely available and play a central role in bridge-to-transplantation in those eligible for heart transplantation (HTX) and as destination therapy (DT) in those not eligible for HTX. LVAD-implantation or HTX in patients with acute cardiogenic shock is associated with dismal outcomes; this illustrates the importance and necessity for short-term support like ECMO. This manuscript provides an overview of indications, outcome, and complications of ECMO.

Keywords: Acute cardiogenic shock; Mechanical circulatory assist device; Extracorporeal membrane oxygenation; Bridging to transplantation; Left ventricular assist device

Abbreviations: VA-ECMO: Veno-Arterial ECMO; LVADs: Left Ventricular Assist Devices; HTX: Heart Transplantation; DT: Destination Therapy; CPB: Cardiopulmonary Bypass; VV: Venovenous; VA: Venoarterial; PCI: Percutaneous Coronary Intervention; VAD: Ventricular Assist Device; IABP: Intra-Aortic Balloon Pump; AFM: Acute Fulminant Myocarditis; AKI: Acute Kidney Injury; CRRT: Continuous Renal Replacement Therapy; ELSO: International Extracorporeal Life Support Organization; APACHE: Acute Physiology and Chronic Health Evaluation

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Historic Background

It is controversial to refer to ECMO as a cardiopulmonary bypass (CPB); however, ECMO is based on the same principle -- in other words, ECMO is a variation of CPB and may be viewed as prolonged cardiopulmonary bypass, allowing for a prolonged cardiopulmonary support [1,2]. The history of ECMO is date back to invention of CPB. Gibbon attempted to create a heart-lung machine and designed an oxygenator, where the anticoagulated blood was exposed directly to oxygen (bubble oxygenators). However, this approach caused severe hemolysis, thrombocytopenia, hemorrhage and multiorgan failure [3]. In 1956, Clowes et al. [4] introduced the membrane oxygenator that separated blood from oxygen by a membrane, securing efficient and safe blood oxygenation and fewer complications compared to film or bubble oxygenators. In 1983, Larm et al. [5] introduced a new ECMO system in which heparin molecules are covalently bonded to the synthetic surfaces of the ECMO circuit. The heparin coating of the ECMO circuit comes into contact with the blood, reducing complications significantly [6]. In a prospective randomized controlled study, Knoch et al. [7] reported that the use of heparin-coated circuits and oxygenators reduces blood loss and the need for blood transfusion. Introduction of heparin-coated ECMO circuit revitalized this technology.

Indication

Fundamentally, ECMO is used as a bridge to an eventual recovery in patients with cardiogenic shock [8-10]. The indication for ECMO has been divided into three major categories: cardiogenic, respiratory, or cardiopulmonary failure. There are two primary forms of ECMO, based on the indication and the type of access: venovenous (VV) and venoarterial (VA). Table 1 demonstrates some of the characteristics of VV- and VA-ECMOs [1]. ECMO management (i.e., how ECMO should be utilized once initiated) is based on consensus guidelines and institutional experience; however, there are not established guidelines regarding the indication and timing for the initiation of ECMO support and the approach should be individualized to each patient’s condition [2,11]. ECMO can also be used as temporary hemodynamic support in order to perform an invasive cardiac treatment (percutaneous coronary intervention (PCI)), or to assess the eligibility of the patient for LVAD placement [1,2].

A. Cardiogenic shock

ECMO is indicated for the management of refractory cardiac or cardiopulmonary failure. While it is used in a variety of clinical scenarios, the outcome often depends on the primary indication [15,19,20]. Postcardiotomy shock, the main indication for ECMO in adult populations (occurs in 0.5% to 1.5% of cases), is defined as the inability to wean the patient from extracorporeal circulation using inotropic and vasoactive drugs as well as an intra-aortic balloon pump (IABP) [20-22]. ECMO may allow the affected organ to recover (bridge to recovery) or provide enough time for the decision (bridge to decision) and prepare the patient for a long-lasting organ substitution either by a ventricular assist device (bridge to bridge, or destination LVAD) or transplantation [23]. ECMO can be used to bridge patients with end-stage heart failure to heart transplant [12,24]. Earlier initiation of ECMO may prevent complications and improve outcomes [25]. It provides temporary assisted circulation, (partial) off-loading of LV, and respiratory support to prevent multisystem organ failure and death [10,21,26].

B. Acute fulminant myocarditis

Acute fulminant myocarditis (AFM) carries high mortality and those affected are candidates for short-term mechanical support. Though highly morbid, most patients with AFM recover and are weaned from ECMO [27]. In a retrospective review of Extracorporeal Life Support Organization Registry database (n=19,348 patients), 260 ECMO patients (1.3%) had AFM. Survival to discharge from the hospital was 61%. The female gender, arrhythmia while on ECMO, and acute renal failure requiring dialysis were predictors of worse outcomes in patients with AFM who received ECMO [28]. In a different series of 75 patients with AFM, the survival to discharge was 64% (n = 48). Pre-ECMO resuscitation did not have a negative impact on survival [27]. In a larger series of patients with acute cardiogenic shock, 11 patients had fulminant myocarditis. Eight patients recovered and one was successfully transplanted. All three deaths were due to neurologic complications [29].

Furthermore, using ECMO during pregnancy was discouraged in the past, with the assumption of increased risk of bleeding as well as increased fetal and maternal mortality. However, a recent metaanaylsis demonstrated the safety of ECMO for severe cardiopulmonary failure during pregnancy. The overall maternal and fetal survival on ECMO has been reported to be about 80% and 70%, respectively. Meticulous anticoagulation at lower therapeutic levels may be required [30].

C. Septic shock

ECMO is a valuable therapeutic option for adults in severe septic shock with refractory cardiac and hemodynamic failure. Brechot et al. [28] reported using ECMO for hemodynamic support of patients with severe septic shock refractory to medical management. All patients had severe myocardial dysfunction (EF10%-30%). Twelve patients (86%) could be weaned off ECMO after 5.5 days of support and 10 patients (71%) recovered to be discharged from hospital and remained alive at a mean follow up of 13 months [28]. However, Huang et al. [31] reported a series of 52 adult patients in refractory septic shock, who received VA-ECMO, with only 15% (n=8) survival. The authors reported that using ECMO in adult patients with refractory septic shock is associated with unsatisfactory outcome [31]. ECMO has also been utilized to stabilize adult trauma patients in the presence of coagulopathy and/or brain injury. The benefits include rapid re-warming, acid base correction, oxygenation, and circulatory support [28].

D. ECMO after Heart Transplant, Acute Graft Failure

Acute graft failure following heart transplant is a serious complication and ECMO support might be beneficial. A retrospective review of 385 consecutive heart transplants revealed that 46 patients suffered acute graft failure requiring ECMO support. The overall success rate, defined as removal of ECMO, was 47.9%; 51.4% for early graft failures and 50% for late graft failure, while the long-term outcome remained similar. Any graft failure requiring mechanical support is associated with high mortality and unfavorable short- and long-term outcome [32].

E. TAVR

Considering the evolving field of enodvascular procedures, and the complexity of procedure performed in multimorbid ever aging patient population, ECMO may provide adequate short term cardiopulmonary support during TAVR on emergency or prophylactic bases. High Euro-score might be an indication for using prophylactic VA-ECMO support during complex endovascular procedures. Life-threatening complications during TAVR can be managed using emergency VA-ECMO but mortality remains high [33].

F. Hypothermia

ECMO has been used to resuscitate patients with severe accidental hypothermia with or without cardiac arrest (n=26). Sawamoto et al. [34] reported a survival rate of 38.5% in a series of 26 patients. While neurological outcome was generally acceptable at discharge; a cardiac rhythm other than asystole, nonasphyxial hypothermia, higher pH, and lower serum lactate were associated with more favorable neurological outcome [34]. Considering these patients’ condition prior to initiation of ECMO, the neurologic injury may not be an immediate complication of ECMO, rather a feature of their condition on presentation.

G. Technical aspects

The cannulation can be done either peripherally or centrally. After gas exchange in vitro, the blood is returned either peripherally or centrally into the patient’s venous or arterial system, depending on type of ECMO [35]. Components utilized for conduction of ECMO include: a pump, an oxygenator, and a circuit. The oxygenation of blood occurs via a membrane, which is a cylindrical rotor comprised of a strong textile support coated by a plastic microporous film [36]. Currently, the most efficient systems utilize a small centrifugal pump and a low-resistance polymethylpentene-oxygenator. Models such as the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and CentriMag (Levitronix LCC, Waltham, MA, USA) are used for this propose [37]. ECMO flow depends on the available volume in the heart chambers, the speed of the pump, and the vascular resistance. Attention should be paid to avoid hypovolemia, cannula malposition, pneumothorax, and pericardial tamponade.

H. Central vs peripheral cannulation

ECMO can be placed either centrally (Figure 1) through a sternotomy or peripherally, percutaneous (Figure 2), frequently using the femoral artery and vein [38]. Central ECMO cannulationis achieved with direct cannulation of the aorta and provides antegrade flow to the arch vessels, coronaries, and the rest of the body. In contrast, the retrograde aortic flow by peripheral ECMO leads to mixing of the blood in the arch or descending aorta and may not adequately supply the arch vessels with oxygenated blood. In certain patients with cardiac or respiratory failure who have recently undergone cardiac surgery, transthoracic cannulation of the right atrial appendage and the ascending aorta is performed. A disadvantage of central cannulation is that the chest must be left open which is associated with increased risk of infection and bleeding. Newer cannulae are designed to be tunneled percuatneously through the subcostal margin and abdominal wall, allowing the chest to be closed. Transthoracic cannulation may allow better left heart decompression and oxygenation of vital organs.

On the other hand, percutaneous cannulation is less invasive and can be performed at the bed side with the guidance of transthoracic echocardiogram [39]. The major disadvantages of the transthoracic approach are vascular injury during cannulation and ischemia of ipsilateral lower extremity distal to the cannulation site. ECMO through peripheral vessels is associated with early [40] and late vascular complications at the femoral access site [41]. However, some authors advocate peripheral cannulation in selected patients. Using femoral vessels is an established access route for peripherally-inserted ECMO. However, in some patients, alternative cannulation sites should be considered [42]. However, in a retrospective series of 50 ECMO cases, the cannulation was performed either by central or peripheral cannulation. The authors did not report any difference in the incidence of ischemia or compartment syndrome in the lower extremities, while central cannulation was associated with a higher risk of bleeding, need for transfusion, and greater utilization of resources. There was no difference in 30-day mortality [38]. Difficulty during ECMO placement or removal and a history of peripheral vascular disease are predictors of long-term vascular complications [26,41]. Symmetrical peripheral gangrene is an unusual complication of ECMO that may arise in the setting of DIC, sepsis, or other hemostatic and/ or hemodynamic imbalance [40]. Minor vascular complications after ECMO support are not associated with higher mortality rates [43].

I. ECMO via axillary artery

ECMO via axillary cannulation, though still considered peripheral, allows for antegrade perfusion and supplies the aortic arch vessels with adequately oxygenated blood. Axillary artery cannulation is commonly performed through a Dacron graft sutured in an end-to-side fashion to the axillary artery. Direct cannulation of the axillary artery is a reliable option with an acceptable complication rate [44-47]. Exposure of the artery is achieved via the deltoid-pectoral approach. Advantages of axillary artery cannulation are the nearly central cannulation with antegrade perfusion and excellent upper body oxygenation. It also allows for chest closure after postcardiotomy shock or avoids the sterntomy in the first place [45]. Axillary cannulation is a viable option, especially in patients with significant peripheral vascular disease, [45,48] and may avoid many complications inherent to transfemoral ECMO. However, hematoma formation has been reported which may cause injury to the nearby brachial plexus [48].

In a series of 308 adult ECMO patients, axillary artery cannulation was performed in 81 patients (26.3%), 166 patients (53.9%) received femoral arterial cannulation, and 61 (19.8%) underwent ascending aortic cannulation. The most common complication following axillary cannulation was hyperperfusion syndrome of the ipsilateral upper extremity (up to 25%), followed by bleeding from the arterial outflow graft. Lower extremity ischemia and fasciotomy were the most frequent complications after femoral arterial cannulation [49]. Wada et al. [50] compared the efficacy of transfemoral with transaxillary ECMO in a canine model. Percutaneous cardiopulmonary support was initiated via the left femoral artery and then switched to the right axillary artery. Cerebral tissue oxygen saturation was 54.2±3.4% with femoral artery cannulation verses 82.3±4.6% during axillary artery cannulation. LV dP/dt max as a sign of myocardial contractility increased significantly after switching to the axillary perfusion [50].

Comparing central (n=65; 53.7%) vs peripheral (n=55; 46.2%) cannulation for ECMO, Loforte et al. [37] reported overall survival of 64.7% (n=77), weaning from mechanical support (n=51; 42.8%) and bridge to heart transplantation (n=26; 21.8%). Regardless of cannulation site, the overall mortality was 35% (n=42). Serum lactate levels, creatine kinase-MB relative index at 72h after ECMO initiation and number of packed red blood cells (PRBCs) transfused on ECMO were predictors of mortality. The central ECMO cannulation group had a higher rate of bleeding events compared with the peripheral cannulation group [37]. Saeed et al. [51] compared peripheral access (n=25) with the central approach (n=12) in 37 patients. While, 11(44%) of the pECMO patients required exploration for bleeding compared to 100% of patients with cECMO. The same study reported a 30-day mortality in patients with pECMO and cECMO of 60% versus 67%, respectively [51].

J. Complications of ECMO

ECMO complications include those associated with cannulation (pneumothorax, vascular disruptions, bleeding, infection, emboli), systemic anticoagulation (GI bleeding, intracranial bleeding, etc), and exsanguination resulting from circuit disruptions. The majority of complications fall into one of three major categories: bleeding, sepsis with multisystem organ failure, or neurologic sequelae. Bleeding and hemolysis, which are out of proportion to the severity of coagulopathy, may occur while on ECMO support; [25,26,52-54] cardiac tamponade and acute renal insufficiency may also occur [21]. Some of the major complications and contraindications are shown in (Table 2) [9,18,22,27,55-63].

In a meta analysis which included 12 studies (n=1763 patients), the most common complications associated with ECMO were renal failure/dialysis (occurring in 52%), bacterial pneumonia (33%), bleeding (33%), oxygenator dysfunction requiring replacement (29%), and sepsis (26%). Pneumonia, sepsis, arrhythmia, and multisystem organ failure comprise additional complications of prolonged ECMO support [54-57]. In a series of 117 postcardiotomy ECMO patients, the most common complications were re- exploration for bleeding (n = 24), alimentary tract hemorrhage (n = 14), renal failure requiring renal replacement therapy (n = 29), infection (n = 32), limb ischemia (n = 5), oxygenators malfunction (n = 29), and hemolysis (n = 7). Overall, 87 patients (74.4%) were successfully weaned from ECMO and 69 patients survived to discharge [25]. In another series of 129 patients undergoing VA-ECMO 59 patients (38%) were weaned, 7 (5.4%) were bridged to a LVAD, and 6 (5.2%) were listed for heart transplantation [64]. Overall mortality was reported as 54%, with 45% of events during ECMO support and 13% after weaning.

Finally, In a metaanalysis by Cheng et al. [65] including 1,866 patients, major complications were: lower extremity ischemia (16.9%), fasciotomy or compartment syndrome (10.3%), lower extremity amputation (4.7%), stroke (5.9%), neurologic complications (13.3%), acute kidney injury (55.6%), need for hemodialysis (46.0%), major or significant bleeding 40.8%, rethoracotomy for bleeding or tamponade in postcardiotomy patients (41.9%), liver dysfunction, and infection (30.4%). Survival to hospital discharge ranged from 20.8% to 65.4% [65]. Device-related complications include tubing rupture, pump malfunction, oxygenator failure, heat exchanger malfunction, and cannula-related problems [66]. Lewandowski et al. [67] reported a total of 27 device related complications during 27,137 hours of ECMO support. The documented complications included pump malfunction (n=6), tubing rupture (n=6), and cannula placement or removal problems (n=5) [67].

a) Bleeding

Continuous activation of fibrinolytic systems by the circuit and consumption and dilution of coagulation factors may occur. Platelets may adhere to the circuit surface and become activated, resulting in platelet aggregation, clumping, and subsequent thrombocytopenia [68]. A plasma free hemoglobin > 10 mg% may indicate hemolysis [69]. Bleeding seems partly related to intravenous heparinization, [25,26,53,54,70,71] and can be managed in any standard situation by decreasing or stopping heparin and infusing platelets and blood products. However, increased red blood cell transfusion is associated with adverse outcomes in ECMO patients [70]. Smith et al. [70] reported in 484 ECMO runs with a median duration of ECMO support of 4.6 days that patients with post cardiotomy cardiogenic shock required increased RBC transfusion compared to other patients with cardiogenic shock. A higher RBC transfusion rate carried higher in-hospital mortality. A lower baseline hematocrit and increasing duration of ECMO support were risk factors for increased RBC transfusion [71]. Regular monitoring of coagulation profile, platelet count, hemoglobin, and creatinine are the routine, while an early replacement of clotting factors and electrolytes may prevent complications [69]. In addition to bleeding at the surgical site, other bleeding related complications include intracerebral bleeds [9,18,22,27,55-63].

b) AKI

Acute kidney injury (AKI) is a major complication and is associated with high mortality in adult ECMO patients. Oliguria followed by acute tubular necrosis occurs with AKI, which may require hemofiltration and dialysis [56-58]. The impact of fluid status, while on ECMO, was evaluated in 115 patients with acute cardiogenic shock and 57 patients with refractory respiratory failure. Fifty-seven per cent of patients had acute kidney injury (AKI) after ECMO initiation, and 60% (n = 103) of patients received hemodialysis/continuous renal replacement therapy (CRRT) during ECMO course. Overall 90-day mortality was 24%. Acute Physiology and Chronic Health Evaluation (APACHE) III, CRRT during the first 3 days, major bleeding, and positive FB was independent predictors of 90-day mortality [72]. ECMO may alter serum concentration of drugs due to increased volume of distribution, which makes dose adjustments necessary [56,57].

K. Neurologic Complications

Neurologic adverse events range from gross motor delay to spastic quadriparesis and seizures. Intracranial bleeds, and hemorrhagic as well as embolic stroke, remain the main culprits for neurologic adverse events. Intracranial hematoma, while on ECMO, is a serious complication. Neurologic adverse events occur in approximately 7-15% patients [25,73,74]; while, systemic heparinization, thrombocytopenia, coagulopathies, and systolic hypertension are the major risk factors [73]. Although the risk is substantial, surgical evacuation of hemorrhage might be indicated in some patients [73]. Management of intraparenchymal hemorrhage while on ECMO has limited success and carries high rates of re-bleeding and in-hospital mortality (75%). Krenzlin et al. [75] reported such complications in 12 patients; 11 LVAD, and one ECMO. Surgical hematoma evacuation was performed in 11 patients; one patient received decompressive hemicraniectomy [75]. Reversing the anticoagulation may be lifesaving in those patients. Acidosis, renal failure, and cardiopulmonary resuscitation increase the risk of neurologic complications [76].

The survivors of prolonged ECMO may suffer from longterm neurologic sequelae, regardless of manifested neurologic complications during the time of ECMO support as noted [77,78]. Indeed, The intelligence quotient (IQ) scores of patients who received ECMO have been reported to be lower [74]. Moreover, ECMO is associated with an increased prevalence of long-term psychiatric disorders and distress [76,79]. While neurologic complications occur with prolonged ECMO support, in some patients, ECMO can prevent cerebral hypoperfusion and actually improve neurologic outcome after cardiac arrest.

L. Vascular complications

Peripheral vascular complications occur in less than 20% of patients and are more common with peripheral cannulation [80]. Among those patients who develop vascular complications, the most common indication for ECMO is cardiogenic shock [80]. In a series of 100 VA-ECMO patients, the majority of ischemic episodes were resolved or prevented with the insertion of a distal perfusion catheter [81]. An adequate distal limb perfusion via a 6-8 Fr cannula, placed in distal femoral artery, may reduce the risk. In a series of 83 ECMO patients; 45 received peripheral VA-ECMO. Distal limb perfusion was achieved with an introducer sheath (6-8 Fr) in 13 cases and with a distal-perfusion cannula (10-12 Fr) in 32 cases. Nine (20%) patients developed signs of ischemia; five (11.2%) were treated conservatively, while four (8.8%) required surgical intervention. The incidences of limb ischemia and limb ischemia requiring surgical intervention were significantly lower using the introducer sheath compared with the cannula [82]. In 101 patients receiving ECMO, vascular complications were observed more frequently in male patients (78%), in those receiving prolonged ECMO support, and in patients with chronic CHF (72%). Overall mortality was 42% (n=42) [80].

M. Infection on ECMO

Prolonged ECMO support is associated with higher infection rate [83]. In a series of 139 patients undergoing ECMO, 36 patients had a total 30 infectious episodes per 1,000 days of ECMO. Enterobacteriaceae and Candida were the most frequent pathogens. Infection did not significantly increase the risk of mortality, but the length of stay in the ICU and in hospital were prolonged following infection [83].

N. Risk Factors for Adverse Outcome

Wang et al. [84] reported 59% of patients (n=87) were successfully weaned from VA-ECMO and 49% were discharged. Older age (>65 years), postoperative hemodialysis, a peak lactate level (> 12 mmol), LVEF <40%, and prolonged ECMO support (>60 hours) were independent predictors of in-hospital mortality. IABP placement had a favorable impact on survival [84]. Prolonged ECMO support (48 hours) and incomplete sternal closure were significant risk factors for mortality [59]. Slottosch et al. [39] reported an overall 30-d mortality rate of 70% in 77 patients who required ECMO following cardiotomy. Age at ECMO implantation, high lactate levels, prolonged ECMO support, and gastrointestinal complications were independent predictors for 30-day mortality [39].

ECMO-assisted PCI for patients with AMI complicated by profound CS was shown to improve the 30-day and 1-year survival rates [85]. The 6-h pH value at the time of ECMO was an independent risk factor of 30-day mortality. Neither CPR nor implantation under ongoing CPR results in significant differences in outcome [86]. In a series of 129 patients undergoing VAECMO, myocardial function improved significantly. Lower dose of inotropes before ECMO was a positive predictor of weaning from ECMO. Longer ECMO support, transfusion rate, and central cannulation were predictor of unfavorable outcome, even after successful weaning from ECMO; 15 (31%) patients died following weaning from ECMO. Central ECMO, persistent RV failure, need for dialysis, higher inotropic score, lower systolic pressure, or higher leukocyte count at weaning correlated with mortality [64]. In a metaanalysis (12 studies, n=1763 patients), mostly VA-ECMO, for various pathology, the 30 day mortality was 54%; 45% while on ECMO and 13% after weaning. Almost 50% of patients receiving ECMO survived to be discharged.

O. ECMO and IABP

One important pitfall of ECMO is the inappropriate offloading of the LV, leading to pulmonary stasis and inadequate myocardial recovery. Off-loading the LV is crucial for possible myocardial recovery. Barbone et al. [87] used a 7F pigtail to offload the LV. The pigtail catheter was placed in LV through the aortic valve. The authors reported that this approach provided a better off-loading of LV and prevented distension as well as lung congestion [87]. Simultaneous IABP or a left ventricular vent may improve the LV off-loading [88]. Ma et al. [88] reported the benefits of IABP in 54 ECMO patients; 31 patients received IABP followed by ECMO, and the remaining patients had ECMO placement first prompted by LV distention and minimal opening of the aortic valve. The authors reported favorable outcome combining ECMO and IABP [88]. We recommend using a simultaneous IABP to offload the LV and improve the outcome.

P. Age

Survival to hospital discharge is lower in elderly patients (>65 years) who received ECMO support compared to younger adult patients (28.7% vs. 40.0%). In one study, a total of 212 patients received ECMO for cardiac (n = 126) or respiratory (n = 86) failure. The overall survival to discharge was 33%; older age, chronic cardiac related issues, and transfusions were predictors of unfavorable outcome. In another study, age was a significant risk factor in cardiac patients [89]. However, advanced age should not be an absolute contraindication for ECMO. The International Extracorporeal Life Support Organization (ELSO) registry database was used to investigate ECMO support among 99 elderly patients (>65 years of age, median age of 70 years). For survivors, the median time spent on ECMO was 69 hours, and the median time to discharge spent off ECMO was 587 hours. Overall, survival at hospital discharge was 22.2% (22/99). The presence of acute renal failure, which preceded ECMO placement, was found to be the most significant risk factor for mortality [90].

Q. Comment

Despite substantial mortality, ECMO implantation in selected patients might be a life preserving measure that otherwise would not survive. ECMO may result in recovery in 40%-60% of the patients with cardiogenic shock; this survival rate has remained stable over the past decade [9,18,22,27,55-63]. The favorable long-term outcomes of ECMO survivors may justify itsuse; however, the decision to utilize ECMO should be made on case by case bases depending on patient’s individual risk profile [84]. Patients with chronic heart failure may have structural remodeling in the myocardium and increased interstitial fibrosis, which results in a combined systolic and diastolic dysfunction [91]. These patients may not recover on ECMO and a long-term plan should be in place before placement of ECMO in this patient population. A preoperative poor left- ventricular ejection fraction, [92] systolic blood pressure <90 mmHg, poor myocardial systolic function, and severe refractory metabolic acidosis are associated with poor outcomes [93].

Although ECMO is associated with adverse events, the patients underlying condition may contribute significantly to this adverse event profile. Therefore, the terminology “ECMO mortality” most likely reflects the combined mortality of the patient’s already poor condition as well as ECMO itself, not ECMO alone. The efficacy of ECMO would be better evaluated in a prospective randomized clinical trial; however, given the end point of such a study would be death, a study of this kind cannot be ethically justified. Furthermore, only a small number of adult patient populations receive ECMO support, which makes it difficult to study the outcome and management of ECMO [94].

Once patients survive the acute phase of ECMO implementation, they have a reasonable long-term survival, [59] depending on the etiology of their underlying disease. Survival on ECMO depends on multiple factors such as patient’s age and etiology of the disease [55,64]. In a diverse group of 45 patients with cardiogenic shock who required temporary ECMO support, 27 patients could be successfully weaned from support (60%); additionally, five were bridged to heart transplantation. The in-hospital mortality was 42% (19/45). The main cause of death remained multisystem organ failure [26]. In a series of 108 patients with postcardiotomy cardiogenic shock [55], pediatric patients had the best survival (65.7%), followed by patients who suffered primary graft failure following cardiac transplantation (42.9%). The worst survival rates were observed with postcardiotomy shock (15.2%). Older age, high body weight, increased AST/GOT levels, thrombocytopenia, and higher serum creatinine were predictors of mortality [55]. These findings have been confirmed by other authors [60]. In addition, greater lactate levels after 24 h of ECMO therapy, lactate level during ECMO support, urine output, postoperative need for dialysis, serum total bilirubin >6 mg/dL, mean arterial pressure (MAP), duration of ECMO, low serum albumin level, low oxygen pressure of the venous tube of the ECMO, and pre-ECMO EF < 30% seem to be significant predictors of hospital mortality [22,60,62,63,78,93].

In a larger series of 137 ECMO patients, 39% of patients survived to be discharged home. Male gender, a longer duration of mechanical ventilation before initiation of ECMO, and renal or hepatic failure while on ECMO were risk factors for higher mortality [95]. Zangrillo et al. [96] did a meta-analysis including 12 studies (1763 patients) and reported a 30-days mortality of 54%; of which 45% occurred while on ECMO and 13% after weaning and explantation of ECMO [96]. Acute Physiology and Chronic Health Evaluation (APACHE) IV scores have been reported to have a prognostic value in patients who required postcardiotomy ECMO [60].

Patient selection, based on preoperative parameters and underlying condition of patients, though difficult, may be a major determining factor for a favorable outcome [97]. ECMO placement in a report of 517 postcardiotomy cardiogenic shock patients showed high weaning rate of 63%, while 24.8% were discharged from the hospital. Neurologic complications occurred in 17%. Age greater than 70 years, DM, preoperative renal insufficiency, EuroSCORE greater than 20%, and a lactate level greater than 4 mmol/L were significant risk factors of mortality. Isolated coronary artery bypass grafting had a positive impact on outcome [22]. Lan et al. [61] reported in a larger series of 607 adult patients that age, stroke, the need for dialysis during ECMO, pre-ECMO infection/bactermia, hypoglycemia, and alkalosis were independent predictors of mortality [61]. Wang et al. [59] reported a series of 62 patients who required temporary postcardiotomy ECMO support: 40 patients (64.5%) were successfully weaned from ECMO and 34 patients (54.8%) were discharged from hospital. With an in-hospital mortality of 45%, the main cause of death was multisystem organ failure [78]. Early ECMO placement may improve the outcome, i.e. successful weaning as well as shorter hospital stay [98] while, prolonged use of ECMO with refractory cardiac failure, respiratory failure, or both is associated with reduced survival [60].

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Summary

For some patients with acute cardiogenic shock or pulmonary failure, ECMO is the last life preserving option. It may provide partial biventricular off-loading as well as respiratory support. A recovery without the need for long-term extracorporeal circulation may be achieved in selected patients. Early implementation, control of complications, and meticulous management during ECMO and explantation of ECMO in a timely fashion can improve the patient outcome. Early placement may improve outcomes and give clinicians the necessary time for further work-up and bridge the patients to decision.

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JuniperPublishers Juniper Publishers. is established with the aim of spreading quality scientific information to the research community throughout the universe. Juniper Publishers as Open Access publishers, strive to offer the best in class online science publications. Juniper Publishers as an open Access process eliminates the barriers associated with the older publication models, thus matching up with the rapidity of the twenty-first century. Juniper Publishers Inc main areas of interest lie in the fields of science, engineering and other related areas. Juniper Publishers is a platform for professors and researchers who aspire to give out quality information based on their research and expertise, in an attempt to aid scholars/researchers in their field of interest with the latest information. For More Open Access Journals in Juniper Publishers Click on: https://juniperpublishers.com/journals.php https://www.scienceopen.com/user/9f93b14f-c289-4e21-b3c8-8f448ea424ab

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Juniper Publishers| Does Conservative Surgical Management of Early Stage Cervical Cancer Represent a Persistent Dilemma in Young Patients?

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Nowadays, cervical cancer (CC) is the most common malignancy of the female reproductive system and the fourth most common cancer in general female population [1,2]. The disease is more prevalent among young women and related directly with persistent HPV infection [1,2]. Especially in developing countries CC represents almost 12% of all malignancies in women [1,2]. Additionally, the mortality rate from CC is almost 10-14 times higher in poor and less developed countries (Melanesia, Middle and Eastern Africa), when compared with developed ones (Western Asia, Western Europe, Australia and New Zealand) [1,2].

Based on recently published recommendations and guidelines, the primary management of CC depends mainly on disease stage and could be either surgical or non-surgical (radiotherapy, chemoradiotherapy) [3-5]. Nevertheless, the type and extend of surgical procedure and the type of non-surgical approach should be thoroughly individualized according to disease stage, histologic subtype, fertility issues and patient’s general performance status [3,5-7]. According to the abovementioned, conservative management could be offered in well selected young patients with early stage CC and intense desire for future fertility, after extensive and detailed counseling regarding disease recurrence, future fertility, pregnancy complications and perinatal issues [3,5-9]. In contrast, conservative therapeutic approach should be avoided in CC patients having rare histologic subtypes with aggressive or possibly aggressive clinical behavior (small cell neuroendocrine carcinoma, minimal deviation adenocarcinoma and gastric type adenocarcinoma) [3,10,11].

Patients with FIGO stage IA1 disease without lymphovascular space invasion (LVSI), could be treated with cervical cone excision only [3,5-7,12-14]. This is based on the fact that in this patients’ subgroup, the risk of lymphatic metastasis or recurrent disease is very low (0.8% and 0.6% respectively) [15-18]. The procedure could be performed with cold knife or loop and both ectocervix and endocervical canal should be removed in a single specimen having at least 3 mm clear margins for pre-invasive or invasive disease [3,5,7]. In most cases, cold knife conization (CKC) provides many advantages compared to loop electrosurgical excision procedure (LEEP), regarding accurate evaluation of marginal status in conization specimens [7,19,20]. However in case of cone margin involvement, cervical conization should be repeated or radical trachelectomy should be offered and discussed with the patient [3,7].

Patients with FIGO stage IA1 disease and LVSI, could be treated with cervical conization or radical trachelectomy, with additional pelvic lymph node dissection and sampling of paraaortic lymph nodes [3,5-7,13,14,21-23]. In this patient subgroup, the risk of lymphatic metastasis or recurrent disease is significantly higher (8.2% and 3.1% respectively) [7,16-18]. Particularly in cases with marginal involvement, conization should be repeated or radical trachelectomy should be offered and discussed with the patient [3,7,22,23].

Likewise, patients with FIGO stage IA2 disease, could be treated with radical trachelectomy, pelvic lymph node dissection and sampling of paraaortic lymph nodes [3,5-7,9,22,24,25]. This is based on the fact that the risk of lymphatic metastasis is almost 8% in this stage, while the risk of recurrent disease is essentially greater in the LVSI subgroup (15.7% and 1.7% respectively) [7,15,16,18,26]. In addition, cervical conization with pelvic lymphadenectomy and paraaortic lymph node sampling is an alternative therapeutic approach for patients with FIGO stage IA2 disease and no cone margins or lymph node involvement [3,5-7,14,21,22].

Patients with FIGO stage IB1 disease, are in even higher risk for lymphatic metastasis (14.9%) and disease recurrence [15,27]. Tumor size more than 2 cm, depth of stromal invasion greater than 50% and presence of LVSI, represent some dismal prognostic factors [24,25]. Consequently, only in patients with FIGO stage IB1 disease and tumor size up to 2 cm, should be offered fertility sparing approach with radical trachelectomy, pelvic lymph node dissection and sampling of paraaortic lymph nodes [3,5-7,9,22,24,25,28]. The procedure of radical trachelectomy could be performed via vaginal or abdominal approach, as there are no important differences regarding oncologic outcome [7,29]. Moreover, some studies evaluating the role of abdominal radical trachelectomy in FIGO stage IB1 CC with tumor size more than 2 cm, are very promising [30,31].

In conclusion, the conservative management of early stage CC is possible in well selected young patients with intense desire for future fertility [3,5-7]. However, all of them should have a thorough preoperative assessment and a detailed counseling regarding disease recurrence, impaired cervical function, fertility issues, miscarriages and preterm labor [7,9].

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Juniper Publishers| The Use & Risk of endoscopy in the GI Tract Disease

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Endoscopy is a nonsurgical procedure used to examine a person’s digestive tract. The primary aim of endoscopy in the management of patients with UGI symptoms is to detect organic disease. Using an endoscope, a flexible tube with a light and camera attached to it, your doctor can view pictures of your digestive tract on a color TV monitor. During an upper endoscopy, an endoscope is easily passed through the mouth and throat and into the esophagus, allowing the doctor to view the esophagus, stomach, and upper part of the small intestine.

Endoscopy is a team activity, requiring the collaborative talents of many people of different backgrounds and training. It is difficult to overstate the importance of an appropriate environment and professional support staff, in order to maintain patient comfort and safety, and to optimize clinical outcomes. Procedures are performed by many different types of doctor, including gastroenterologists, surgeons, and some radiologists. Specially trained endoscopy nurses are essential for endoscopic procedure. Because they have many important functions, including, prepare patients for their procedures, physically and mentally, set up all of the necessary equipment, assist the endoscopist during procedures, monitor patients’ safety, sedation and recovery, clean, disinfect and process equipment, and also maintain quality control.

Typically, endoscopy is employed via an endoscope in a variety of medical procedures for both diagnostic and therapeutic purposes. An upper gastrointestinal (GI) endoscopy is where the doctor uses an instrument called an endoscope to look at the inside lining of your oesophagus (food pipe), stomach and duodenum (first part of the small intestine). This is done to look at reasons as to why you may have swallowing problems, nausea, vomiting, reflux, bleeding, indigestion, abdominal pain or chest pain [1]. Endoscopic procedure is done in the expert opinion for the disease such as dyspepsia, in the event of isolated nausea or vomiting persisting for more than 48 hours, acute digestive bleeding which is assumed to originate in the upper gastrointestinal tract (haematemesis or melaena), upper gastrointestinal endoscopy should be repeated when bleeding persists or when a first investigation including upper gastrointestinal endoscopy and colonoscopy has been inconclusive and for peptic ulcer. Peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD) and cancers affect millions of people worldwide [2]. Upper Gastrointestinal (UGI) symptoms are among the commonest complaints for which patients seek medical attention, with the annual prevalence of dyspepsia approximating 25% [1].

Upper gastrointestinal endoscopy is recommended if there are symptoms of gastrooesophageal reflux combined with warning signs (weight loss, dysphagia, bleeding, anaemia), or if the patient is aged over 50 years, or if there is a recurrence on withdrawal of treatment or resistance to medical treatment. Endoscopy gives a better diagnostic yield over radiology particularly in the investigation of upper gastrointestinal bleeding, inflammatory conditions of the upper gastro-intestinal track like esophagitis, gastritis and duodenitis [3]. Upper gastrointestinal endoscopy for diagnostic purposes is recommended if portal hypertension is suspected, and particularly when cirrhosis is diagnosed, to look for any oesophageal or gastric varices. Biopsy during upper gastrointestinal endoscopy is indicated in the following situations such as esophageal and duodenal tumor and ulcer for the diagnosis of cancerous growth.

Risks of an upper gastrointestinal endoscopy

There are risks and complications with this procedure include some common risks and complications are, nausea and vomiting, Faintness or dizziness, especially when you start to move around, headache, pain, muscle aches and pains, allergy to medications given at time of the procedure. Some uncommon risks and complications include, about one person in every 1,000 will experience bleeding from the oesophagus (food pipe), stomach and duodenum where a lesion or polyp was removed.This is usually minor and can usually be stopped through the endoscope. Rarely, surgery is needed to stop bleeding. Heart and lung problems such as heart attack or vomit in the lungs causing pneumonia. Adverse events are inherent in performing the UGI endoscopic procedures. Because endoscopy assumes a more therapeutic role in the management of GI disorders, the potential for adverse events will likely increase.

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Juniper Publishers| Helicobacter in Biliary Calculus Disease: Histopathological and Serological Association in a Rural Population of Southern India

Journal of Surgery

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Abstract

Introduction: Biliary calculus disease is one of the most common disorders and is an important cause of morbidity world over. In USA and Europe, the prevalence of biliary calculus disease ranges from 7% to 33% among general population. Though accurate estimates are not available, gall stones disease forms an important cause of suffering in India. In recent years, Helicobacter pylori has been detected in the human bile and gall bladder tissues. This has evoked considerable interest in the possibilities of colonization and causation of biliary calculus disease by this organism.Here is the study for investigating the evidence of Helicobacter infection by histopathological and serological methods at R.L. Jalappa hospital, Kolar, Karnataka which caters mainly for rural population.

Materials and methods: During the period November 2011 to August 2013, 65 patients with clinical features of biliary calculus disease admitted at R.L.Jalappa hospital, Kolar were included in the study. After performing cholecystectomy on the patients selected as above, gall bladder tissues were fixed in 10% formaldehyde and were subjected to histopathological examination. Patients who were treated for Helicobacter pylori infections in the past 4 weeks and those with clinical features of gastritis were excluded from the study. A 5 ml blood sample was collected prior to surgery from all the above patients, serum was separated and tested for IgM antibodies to Helicobacter pylori using a commercially available ELISA kit.

Results: Sixty five patients of calculus cholecystitis were included in the study. Among them, 27(41.5%) were males and 38 (58.5%) were females. The mean age of overall study population was 41.78± 8.8 years. The youngest patient was 14 years old and the oldest patient was 77 years old. Among the patients studied, all patients had pain in the right hypochondrium, in addition, 20 (30.7%) had dyspepsia and 9(13.8%) had fever. There were no patients with jaundice or mass per abdomen.

Coclusion: In the study reported here from southern India, we found that Helicobacter species in gall bladder tissue could be detected in 3(4.6%) of 65 patients with Biliary calculus disease. These findings suggest that Helicobacter pylori infection in biliary calculus disease is less common among the rural population from southern India. IgM antibody against Helicobacter pylori could act as a serological marker for associating Helicobacter species with biliary calculus disease.

Keywords: Helicobacter pylori; Biliary Calculus Disease; Rural setup

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Introduction

Biliary calculus disease is one of the most common disorders and is an important cause of morbidity world over. In USA and Europe, the prevalence of biliary calculus disease ranges from 7% to 33% among general population. Though accurate estimates are not available, gall stones disease forms an important cause of suffering in India. It is thought to be more common in northern than the southern parts of the country [1-3]. In recent years, Helicobacter pylori has been detected in the human bile and gall bladder tissues. This has evoked considerable interest in the possibilities of colonization and causation of biliary calculus disease by this organism [4]. In addition to Helicobacter pylori, other Helicobacter species such H.bilis, H.pullorum and others have been isolated from the bile specimens of humans and animals [5-7]. There are very few studies which have investigated the role of Helicobacter species in gall bladder disease from India. We investigated the patients with gall stone disease for evidence of Helicobacter infection by histopathological and serological methods at R.L.Jalappa hospital, Kolar, Karnataka which caters mainly for rural population.

After primary repair, rates of recurrence range from 24 percent to 54 percent. Repairs that include the use of mesh to close the defect have better but still high recurrence rates, up to 34 percent. After repair of recurrent incisional hernias, recurrence rates of up to 48 percent have been reported [4,5]. In this study, we wanted to report the place of mesh use in our clinic in the treatment of incisional hernia, examining the demographic information of elective and emergency cases operated with the diagnosis of incisional hernia in our clinic, clinicopathologic findings, mesh use and its related results.

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Materials and Methods

Subjects

During the period November 2011 to August 2013, 65 patients with clinical features of biliary calculus disease admitted at R.L.Jalappa hospital, Kolar were included in the study. A diagnosis of calculus cholecystitis was made in these patients based on detailed clinical examination and relevant laboratory and radiological investigations. Patients who were treated for Helicobacter pylori infections in the past 4 weeks and those with clinical features of gastritis were excluded from the study.

Histopathology

After performing cholecystectomy on the patients selected as above, gall bladder tissues were fixed in 10% formaldehyde and were subjected to histopathological examination. Sections from the sample were stained by Haematoxylin and Eosin (H & E) stain and Giemsa stains and examined under microscope for evidence of organisms morphologically resembling Helicobacter.

Serological testing

A 5 ml blood sample was collected prior to surgery from all the above patients, serum was separated and tested for IgM antibodies to Helicobacter pylori using a commercially available ELISA kit (calbiotech, California. USA). The kit detects Cag-A antibodies against an 128 kd antigen. The results were expressed in antibody units by dividing the optical density value (OD value) of the sample by the cut-off value as per the instructions from the manufacturer. Samples that showed an antibody index of more than 1.1 were considered to be positive for IgM antibodies for Helicobacter.

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Results

Sixty five patients of calculus cholecystitis were included in the study. Among them, 27(41.5%) were males and 38 (58.5%) were females. The mean age of overall study population was 41.78± 8.8 years. The youngest patient was 14 years old and the oldest patient was 77 years old. Among the patients studied, allpatients had pain in the right hypochondrium, in addition, 20 (30.7%) had dyspepsia and 9 (13.8%) had fever. There were no patients with jaundice or mass per abdomen (Table 1) (Figure 1). Among the above 65 patients, 42 patients underwent open cholecystectomy and 23 underwent laparoscopic cholecystectomy. 2 patients of laparoscopic cholecystectomy had to be converted to open cholecystectomy due to dense adhesions (Figure 2).

On histopathological examination, 61 (94%) of the cholecystectomy specimens showed features of calculus cholecystitis and 4 (6%) patients showed features of acalculus chronic cholecystitis. H & E stained sections showed diffuse infiltration of gall bladder wall by lymphocytes, plasma cells, histiocytes and perimyceal fibrosis. In three cases H & E and Giemsa stain showed organisms morphologically resembling H.pylori (Figures 3 & 4). The IgM antibodies against Helicobacter Cag-A antigen could be demonstrated in the five (7.6%) of 65 patients. The antibody index varied between 1.10 to 4.27. The serological findings along with histopathological observations are presented in Table 2. It was observed that organisms resembling Helicobacter pylori were detected in the gall bladder tissues of all the 3 patients who showed an antibody index of 4.02 and above.

*The antibody index was calculated by dividing OD value of the sample by the cut off value.

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Discussion

In the study described here, we could detect organisms resembling Helicobacter pylori in gall bladder tissues in 3 (4.6%) of 65 patients subjected to histopathological examination. We could demonstrate IgM class of antibodies among 5 (7.6%) of the patients studied. However, those patients with IgM antibody index of 4 and above only (high titres), were associated with histopathological evidence of Helicobacter like organisms in gall bladder tissues. Helicobacter species have been associated with gall stone disease in 1.05% to 55% of patients from different parts of the world. Mexico, Greece, Germany and Korea have reported an association of less than 10% [8-11]. In contrast, Turkey and Pakistan have reported an association of Helicobacter 22% and 55% respectively in gall stone disease [12,13].

There are a few studies from India which have explored the possibility of HelicobacterM infection in gall bladder disease. The study by Bansal et al. [14] conducted on patients at Delhi showed that Helicobacter DNA could be detected in 32.6% of 49 gall bladder tissues with gall stone disease. The study at Varanasi by Shukla et al. [5] demonstrated Helicobacter in 28% of 54 patients with gall stone disease by histopathology, serology and molecular biological methods. Deeba et al. [15] demonstrated IgG class of antibodies against Helicobacter in 80% of 75 patients with gall stone disease studied at Aligarh. To our knowledge there are no studies examining the role of Helicobacter in gall stone disease, to date, from Southern India.

Our study conducted among a rural population with biliary calculus disease shows that 4.6% of patients can be associated with Helicobacter infection both by histology and serology. This detection rate is lower compared to that from Northern India. Further investigations are required to confirm the disparity in the association of Helicobacter in gall bladder disease from different parts of the country. Detection of IgM class of antibodies against Helicobacter pylori with higher antibody index in ELISA in the very same patients who had histopathological evidence of presence of organism in the gall bladder tissue suggests that IgM antibodies against Helicobacter pylori can be used as serological a marker to detect the presence of Helicobacter pylori in gall bladder disease.

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Similar Studies

Association of the Presence of Helicobacter in Gallbladder Tissue with Cholelithiasis and Cholecystitis. According to this study, results support the hypothesis that Helicobacter is associated with the pathogenesis of human cholelithiasis and cholecystitis but it is less significant and further studies on larger group of population are required to confirm the observations.

Helicobacter pylori DNA in gallbladder tissue of patients with cholelithiasis and cholecystitis. According to this study results, although H. pylori DNA was detected by PCR in gallbladder tissue of patients with cholecystitis, a clinical correlation with biliary disease could not be established but further studies are required to confirm the results.

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Conclusion

In the study reported here from southern India, we found that Helicobacter species in gall bladder tissue could be detected in 3(4.6%) of 65 patients with Biliary calculus disease. All the 3 patients with histopathological evidence of Helicobacter in gall bladder tissue had higher antibody index(>4.02) for IgM class of antibodies to Helicobacter pylori in ELISA test.

In similarity to the findings of other studies on this subject, we were unable to isolate the bacterium by culture; that may have been due to the fact that the DNA we detected was from nonviable organisms. Conversely, there are different ways to explain our inability to isolate viable bacteria. Firstly, most (85.9%) patients had received antimicrobial therapy before surgery. In addition, the samples were maintained frozen without any protective solution, which may have compromised bacterial viability. Finally, as discussed above, it is possible that the number of bacterium is very few and that they may have been partially inhibited by adverse conditions in the biliary milieu. In addition, we can speculate that these strains might have had some distinct requirements that are as yet unknown. These facts highlight the need to improve the conditions for the growth of Helicobacter species from the biliary tree to better characterize the microorganism and to allow the development of experimental models for studying the role of Helicobacter in the genesis of biliary diseases.

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Juniper Publishers| The Place of Mesh Use in the Treatment of Incisonal Hernia; Emergent and Elective Cases

Journal of Surgery

JuniperPublishers

Abstract

Aim: In this study, we wanted to report the place of mesh use in our clinic in the treatment of incisional hernia in elective and emergency cases.

Methods: Patients who operated for incisional hernia under urgent and elective conditions were evaluated in the General Surgery Clinic of Göztepe Training and Research Hospital of the Istanbul Medeniyet University between January 2014 and September 2015. Patient files, surgical notes and patient reports were screened retrospectively. IBM SPSS Statistics Version 23 was used for statistical analysis of data and findings.

Results: A total of 149 patients examining the demographic information of elective and emergency cases operated with the diagnosis of incisional hernia in our clinic. Between January 2014 –September 2015, 149 cases with incisional hernia, 125 of them were elective and 24 were emergency conditions, were operated in our clinic.

Coclusion: We concluded that mesh repair of incisional hernias elective and emergent cases associated with simultaneous colonic operations was possible, allowing abdominal wall anatomy reestablishment. There is no reason to believe that abdominal wall prostheses must be avoided in contaminated operations when an adequate surgical technique is used.

Keywords: Incisional hernia; Mesh repair

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Introduction

Incisional hernias represent one of the most frequent complications of abdominal surgery. The incidence is probably underestimated. The pathogenesis is complex and not fully understood, implying patient-related factors (i.e., collagen biochemistry, obesity, age) as well as technical factors, including, among others, wound infection, suture material, and types of incisions and closures [1,2]. Incisional hernias (IH) are one of the most common complications of abdominal surgery, with an overall estimated incidence ranging from 2 to 11% after abdominal operations [3]. Such hernias can cause serious morbidity, such as incarceration (in 6 to 15 percent of cases) and strangulation (in 2 percent). Although many techniques of repair have been described, the results are often disappointing.

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Material and Method

A total of 149 cases operated with an incisional hernia under urgent and elective conditions were evaluated in the General Surgery Clinic of Göztepe Training and Research Hospital of the Istanbul Medeniyet University between January 2014 and September 2015. Patient files, surgical notes and patient reports were screened retrospectively. The cases of all the general surgery specialists working at the hospital were included in the study and one-on-one interviews were conducted in terms of surgical techniques and mesh use to the accompaniment of surgical techniques such as primary repair, mesh repair and laparoscopic repair. As an exclusion criterion, cases operated for other abdominal wall hernias, cases with incisional hernia repair in addition to the main surgical indications and patients under the age of 18 were excluded from the study. IBM SPSS Statistics Version 23 was used for statistical analysis of data and findings.

Findings

Between January 2014 -September 2015, 149 cases with incisional hernia, 125 of them were elective and 24 were emergency conditions, were operated in our clinic. While 82 of the cases that were operated under elective conditions were women (65.6%), 43 were men (34.4%), the average duration of hospital stay was 4.2 days and the mean age was 56,in 106 cases, mesh procedure was applied (84.8%) and in 19 cases (15.2%) mesh was not applied. In the cases that were operated under emergency conditions, it was determined that the number of women was 18 (75%) and the number of males was 6 (25%), while the average duration of hospital stay was 10.4 days and the mean age was 71 of them. While mesh method was used in 10 (41.7%) of emergency cases, it was not used in 14 (58.3%) cases.

When surgical techniques were evaluated, it was observed that 3 subjects (2.4%) in elective cases underwent laparoscopic surgical procedure, and that no laparoscopic procedure was performed for any subject in emergency cases. It was found that bowel resection was performed in 5 cases in post-operative follow-up of elective cases, and surgical mesh procedure was applied for 3 of them. It was determined mesh extirpation was required in 2 cases, abscess/hematoma drainage was yet performed in 2 cases and mesh was used in these 2 cases. No mortality was observed in any case in follow-ups. When emergency cases were examined, bowel resection was performed in 4 cases and meshes were used in 1 case. Abscess/hematoma drainage was administered in 2 cases and mesh method was used in 1 of 2 cases.

In emergency cases, it was found that the mortality rate was 16.6% (4 cases). When the cases with mortality were examined in itself, it was determined that 2 patients had mesh, while 3 patients had bowel resection. When the causes of exitus state were examined in 2 cases intestinal leakage, and in 2 cases mortality due to cardiopulmonary causes were observed. When the average hospital stays were compared, it was observed that emergency cases had longer hospitalization stays than elective cases. (p<0.05) When the cases were distributed in emergency and elective forms and then the average age of the patients was examined, it was determined that the age average in the emergency group was higher (p <0.05) and the preference of mesh method use in the elective cases was significantly higher than that in the emergency cases (p <0.05).

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Discussion

The principles of incisional hernia repair in the setting of surgical field contamination involve the removal of the source of contamination and the reconstruction of the abdominal wall. These operations are challenging and often result in complications that lead to both surgeon and patient frustration. Colonic operations are classified as contaminated and infected (class 3-4) procedures according to Altemeier classification. For this reason the use of mesh in potentially contaminated procedures has been strongly discouraged [5]. Morris et al. [6] suggest abandonment of the use of mesh for repairs in which open bowel is encountered. A trend of increased pain and more severe wound infections after mesh repair were the basis for discontinuation of randomized control trial by Korenkov et al. highlighting the risk of using a foreign body in a hernia repair.

Temudom et al. [7] in a series of 50 complex prosthetic giant ventral hernia repairs reported that the two patients with simultaneous bowel surgery subsequently required mesh removal. Others recommend that intestinal resection be done first and hernia repair should be postponed for a second time. The overall 28.3% infection rate in this study is significantly higher compared to the previous studies. Kelly et al. [8] reported 21% infection rate in a series of emergency and elective incisional hernia repairs. Infection rates were 21% and 4% as reported by Alaedeen et al. and Ahmed et al. [9] in a similar patient casemix. We concluded that mesh repair of incisional hernias elective and an emergent case associated with simultaneous colonic operations was possible, allowing abdominal wall anatomy reestablishment. There is no reason to believe that abdominal wall prostheses must be avoided in contaminated operations when an adequate surgical technique is used.

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