Akash Agarwal

Video Endoscopic Inguinal Lymphadenectomy (VEIL) -a prospective critical perioperative assessment of feasibility and morbidity with points of technique in penile carcinoma

BackgroundInguinal lymph node involvement is an important prognostic factor in penile cancer. Inguinal lymph node dissection allows staging and treatment of inguinal nodal disease. However, it causes morbidity and is associated with complications, such as lymphocele, skin loss and infection. Video Endoscopic Inguinal Lymphadenectomy (VEIL) is an endoscopic procedure, and it seems to be a new and attractive approach duplicating the standard open procedure with less morbidity. We present here a critical perioperative assessment with points of technique.MethodsTen patients with moderate to high grade penile carcinoma with clinically negative inguinal lymph nodes were subjected to elective VEIL. VEIL was done in standard surgical steps. Perioperative parameters were assessed that is - duration of the surgery, lymph-related complications, time until drain removal, lymph node yield, surgical emphysema and histopathological positivity of lymph nodes.ResultsOperative time for VEIL was 120 to180 minutes. Lymph node yield was 7 to 12 lymph nodes. No skin related complications were seen with VEIL. Lymph related complications, that is, lymphocele, were seen in only two patients. The suction drain was removed after four to eight days (mean 5.1). Overall morbidity was 20% with VEIL.ConclusionIn our early experience, VEIL was a safe and feasible technique in patients with penile carcinoma with non palpable inguinal lymph nodes. It allows the removal of inguinal lymph nodes within the same limits as in conventional surgical dissection and potentially reduces surgical morbidity.

Association of genetic variants of xenobiotic and estrogen metabolism pathway (CYP1A1 and CYP1B1) with gallbladder cancer susceptibility

Gallbladder carcinoma is a highly aggressive cancer with female predominance. Interindividual differences in the effectiveness of the activation/detoxification of environmental carcinogens and endogenous estrogens may play a crucial role in cancer susceptibility. The present study included 410 patients with carcinoma of the gallbladder (GBC) and 230 healthy subjects. This study examined association of CYP1A1-MspI, CYP1A1-Ile462Val, and CYP1B1-Val432Leu with GBC susceptibility. CYP1A1-MspI [CC] and CYP1A1-Ile462Val [iso/val] genotypes were found to be significantly associated with GBC (p = 0.006 and p = 0.03, respectively), as compared to healthy controls, while CYP1B1-Val432Leu was not associated with GBC. The CYP1A1 haplotype [C-val] showed a significant association with GBC (p = 0.006). On stratification based on gender, the CYP1A1-MspI [CC] genotype showed an increased risk of GBC in females (p = 0.018). In case-only analysis, tobacco users with CYP1A1-MspI [CT] genotypes were at a higher risk of GBC (p = 0.008). Subdividing the GBC patients on the basis of gallstone status, the CYP1A1 haplotype [C-val] imparted a higher risk in patients without stones when compared to controls (p = 0.001). The results remained significant even after applying Bonferroni correction. Multivariate analysis revealed an increased risk of CYP1A1 iso/val and val/val genotypes in GBC patients having BMI >25 (p = 0.021). The CYP1A1 polymorphisms may confer increased risk of GBC, probably due to impaired xenobiotic or hormone metabolism through a gallstone-independent pathway.

EpCAM-based Flow Cytometric Detection of Circulating Tumor Cells in Gallbladder Carcinoma Cases

Purpose: Liquid biopsy has entered the arena of cancer diagnostics in the past decade and detection of circulating tumor cells (CTC) is one diagnostic component. CTCs in gallbladder cancer (GBC) have hitherto not been comprehensively analysed. Methods and Results: The current study focused on the diagnostic role of CTCs in 27 cases of treatment-naive GBC and 6 normal controls as well as 6 cases of cholecystitis. An EasySep kit featuring negative immunomagnetic bead separation and flow cytometric detection of EpCAM positive and CD45 negative cells revealed CTCs in 25 of the 27 cases. At a cut-off point of ≥1, the CTC count discriminated GBC from controls with a sensitivity, specificity and diagnostic accuracy of 92.6%, 91.7% and 92.3%, respectively. CTC levels in turn correlated significantly with clinico-pathological parameters of cases in terms of known prognostic indicators, with significant diagnostic potential at a cut-off point of >4, to discriminate disease stage I and II vs. III and IV GBC. With a cut-off of >3, the CTC count discriminated tumor stages I and II vs. III and IV and at >6 CTCs could discriminate metastatic vs. non metastatic GBCs with a sensitivity, specificity and diagnostic accuracy of 55. 6%, 100.0% and 85.2, respectively. A review of CTC in pancreatico-biliary malignancies is included. Conclusion: Detection and quantification of CTCs may serve as a non-invasive biomarker for GBC diagnosis in correlation with radiological studies.

Carcinoma Gallbladder- an Indian Problem.

Gallbladder cancer is an uncommon cancer worldwide, but one of the commonest cancer in North India. Apart from India, it is common in South America and Japan. The disease is characterized by late onset of symptoms, advanced stage at presentations and a rapidly progressive disease with a median survival of 6 months in advanced disease [1]. Epidemiological studies have been few and it is difficult to draw much meaningful conclusions from these studies. The etiological factors contributing to the development of this disease still remains to be elucidated. Numerous risk factorsfemale sex, high BMI, multiparity, lifestyle risk factors like smoking have been found to be associated with GBC. However, the strength of these associations remaining variable in different studies and all are not modifiable. The pathogenesis of GBC remains to be understood. The presence of gallstones in majority of patients with GBC raises questions whether the calculi are merely associated or do they have a role in the pathogenesis of GBC. Both, the adenomacarcinoma pathway, as well as the inflammation driven dysplasia-carcinoma pathway, has been proposed. However, there is lack of clarity as to which pathway is involved in the pathogenesis of GBC [2]. Numerous studies have been done to study the molecular alterations which lead to increased susceptibility to GBC. Molecular studies have failed to find clinically relevant biomarkers which would help in the early detection and treatment of GBC [3]. Lack of a recognizable premalignant state precludes screening. Studies for early diagnosis in high risk populations are necessary. The role of prophylactic cholecystectomy in high risk individuals is debatable. Prospective cohorts need to be identified in these high risk populations to determine the natural history of disease and development of cancer. There is, at times, a failure to detect early gallbladder cancer. Number of patients have GBC incidentally detected at the time of cholecystectomy for gallstone disease, or at the time of histopathological examination of the gallbladder specimen [4]. Similarly, despite looking operable on conventional imaging, many patients of GBC have metastatic disease on laparotomy/diagnostic laparoscopy. Improved imaging techniques and use of functional imaging may help in both these circumstances. The extent of surgery varies by centre and surgeon. Data suggests that a large number of patients are still treated with cholecystectomy alone and not by the full procedure. The extent of lymphadenectomy is still debatable as so is the role of extended lymphadenectomy. Only well designed trails can help define the optimal extent of lymphadenectomy. Over the past few decades, the role of neoadjuvant treatment for most gastrointestinal cancers has evolved. Most of these cancers are now treated with preoperative chemotherapy/chemoradiation in order to make surgery less extensive along with increased overall survival. However, there has not been much positive clinical data generated for this strategy for GBC and at present, neoadjuvant treatment protocols are restricted to clinical trials only. Similarly, most of data for adjuvant treatment comes from studies which pool * Sanjeev Misra misralko@gmail.com

Cancer surgery: an Indian-Asian perspective

www.thelancet.com/oncology Vol 16 September 2015 1189 Cancer surgery is an integral part of the multimodal management of solid cancers and has a central role in the treatment of several common cancers in Asian countries. As stressed in The Lancet Oncology Commission on global cancer surgery, there is a need for surgery—curative or palliative—in over 80% of patients with cancer. Providing safe, aff ordable, and timely surgery for cancer is a complex task. It involves health-care policy, training and education, management and delivery of health care, fi nance, social, and economic issues. Many of the general principles for providing safe surgery—described in The Lancet Commission on global surgery—apply also to cancer surgery. The diffi culty for economically constrained low-income and middle-income countries (LMICs) in Asia is to fi nd resources to fund and manage the infrastructure and manpower needed to achieve this task. Some of the unique diffi culties faced in countries such as India and China are the many alternative and traditional systems of medicine available. In India, a large proportion of the population is illiterate and not knowledgeable about health care and tends to opt for easy (eg, non-invasive treatments requiring no investigations or waiting, with minimum side-eff ects and few functional and cosmetic problems) and less expensive methods of treatment. These unproven methods of treatment result in delays and disease progression, and the potential curative role of surgery may be lost. The government policy of promoting alternative and traditional systems of medicine only worsens this situation. Myths and prejudice against surgery and surgical interventions for cancer also exist, which drives patients to seek inappropriate non-surgical treatments. Finally, when these patients reach the cancer surgeon, they have advanced unresectable disease and surgical interventions are doomed to fail. In India, the National Cancer Control Programme has been in place for almost four decades. However, this programme ignores the need for cancer surgery and places strong emphasis on providing infrastructure for radiotherapy alone. No concerted eff ort has been made to develop surgical oncology as a specialty, and there is a major shortage of trained cancer surgeons. Few surgical oncology training opportunities are available at present. In the absence of formal guidelines, general surgeons, who might have a limited understanding and ability of cancer surgery, perform most of the surgery for patients with cancer. Incomplete and inadequate primary surgery further complicates the management of these patients. Finances for cancer surgery, in the absence of health insurance, remain an out-of-pocket expenditure by patients. In India, to some extent, government hospitals provide cancer surgery at a subsidised cost or fund the management of patients who are below the poverty line. However, these facilities are not available in all places, and a large inequality exists in the aff ordability and quality of cancer care, including cancer surgery, in India. Major infrastructure defi ciencies also exist. Highquality pathology, imaging, safe anaesthesia, and ancillary specialties (eg, reconstructive surgery) are scarce. Quality cancer care is available in only a handful of government institutions and a rapidly expanding group of private or corporate hospitals. Most patients with cancer cannot aff ord treatment in these exclusive hospitals. The absence of a standardised referral system Cancer surgery: an Indian-Asian perspective timely, and safe interventions with the aim of achieving cost-eff ective global technological advances. Laproscopes and robots do not operate, surgeons do.