Tushar K. Chattopadhyay

Hepatobiliary and pancreatic tuberculosis: A two decade experience

BackgroundIsolated hepatobiliary or pancreatic tuberculosis (TB) is rare and preoperative diagnosis is difficult. We reviewed our experience over a period two decades with this rare site of abdominal tuberculosis.MethodsThe records of 18 patients with proven histological diagnosis of hepatobiliary and pancreatic tuberculosis were reviewed retrospectively. The demographic features, sign and symptoms, imaging, cytology/histopathology, procedures performed, outcome and follow up data were obtained from the departmental records. The diagnosis of tuberculosis was based on granuloma with caseation necrosis on histopathology or presence of acid fast bacilli.ResultsOf 18 patients (11 men), 11 had hepatobiliary TB while 7 had pancreatic TB. Two-thirds of the patients were < 40 years (mean: 42 yrs; range 19–70 yrs). The duration of the symptoms varied between 2 weeks to 104 weeks (mean: 20 weeks). The most common symptom was pain in the abdomen (n = 13), followed by jaundice (n = 10), fever, anorexia and weight loss (n = 9). Five patients (28%) had associated extra-abdominal TB which helped in preoperative diagnosis in 3 patients. Imaging demonstrated extrahepatic bile duct obstruction in the patients with jaundice and in addition picked up liver, gallbladder and pancreatic masses with or without lymphadenopathy (peripancreatic/periportal). Preoperative diagnosis was made in 4 patients and the other 14 were diagnosed after surgery. Two patients developed significant postoperative complications (pancreaticojejunostomy leak [1] intraabdominal abscess [1]) and 3 developed ATT induced hepatotoxicity. No patient died. The median follow up period was 12 months (9 – 96 months).ConclusionTuberculosis should be considered as a differential diagnosis, particularly in young patients, with atypical signs and symptoms coming from areas where tuberculosis is endemic and preoperative tissue and/or cytological diagnosis should be attempted before labeling them as hepatobiliary and pancreatic malignancy.

Endoscopic or percutaneous biliary drainage for gallbladder cancer: a randomized trial and quality of life assessment.

BACKGROUND & AIMS Patients with carcinoma of the gallbladder (GBC) and obstructive jaundice are usually not amenable to curative resection. Effective palliation by biliary decompression is the goal of treatment. Endoscopic stenting (ES) and percutaneous transhepatic biliary drainage (PTBD) can provide biliary decompression. We compared unilateral PTBD and ES in patients with a hilar block caused by GBC and assessed their quality of life (QOL). METHODS Consecutive patients with GBC not suitable for curative resection with Bismuth type 2 or 3 block were randomized to either PTBD or ES with a 10F plastic stent. Technical success, successful drainage, early cholangitis, complications, procedure-related mortality, 30-day mortality, survival, and QOL before and 1 and 3 months after stenting were compared between the 2 groups. All patients were followed up until death. RESULTS Fifty-four patients were randomized to PTBD or ES (27 each). Successful drainage was better in the PTBD group (89% vs 41%; P < .001). Early cholangitis was significantly higher in the ES group (48% vs 11%; P = .002). Procedure-related (4% vs 8%) and 30-day mortality (4% vs 8%) and median survival were similar (60 days in both; P = .71). Although the World Health Organization-Quality of Life 1- and 3-month physical and psychological scores were better after PTBD, the difference was not significant. The European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire 30 global health status at 3 months was significantly better after PTBD (75 vs 30.5, P = .02). The EORTC symptom scores improved in both groups, but only fatigue was significantly better after PTBD. CONCLUSIONS PTBD provides better biliary drainage and has lower complication rates in patients with GBC and hilar block.

Circulating p53 antibodies, p53 gene mutational profile and product accumulation in esophageal squamous-cell carcinoma in India†

Esophageal cancer (EC) in the Indian population presents in advanced stages with poor prognosis and warrants the identification of a non‐invasive marker for early detection and better prognostic assessment. We have previously reported high prevalence of p53 protein accumulation in esophageal squamous‐cell carcinomas (ESCCs). The present study was designed to determine (i) if esophageal cancer patients elicit a humoral immune response to intra‐tumoral p53 protein accumulation and (ii) their relationship with p53 gene mutations. The goal was to compare the cellular events, p53 protein accumulation and gene mutations with the presence of serum anti‐p53 antibodies (p53‐Abs) and to assess the utility of serological p53‐Ab analysis as a surrogate marker for p53 alterations in esophageal cancer. A high prevalence of circulating p53‐Abs was observed in 36 of 60 (60%) ESCC patients. In a subset of 44 ESCCs, exons 5–9 of the p53 gene were examined for mutations by PCR and direct sequencing of PCR products. Mutational data have been correlated with p53‐Abs and p53 protein accumulation in ESCCs. Circulating p53‐Abs in ESCC patients were significantly associated with intra‐tumoral p53 protein accumulation (p=0.0005). A strong correlation observed between humoral immune response against p53 protein, missense gene mutations and protein accumulation warrants the application of serological p53‐Abs as a non‐invasive surrogate marker in screening high‐risk populations for early detection of malignancy. Int. J. Cancer 85:791–795, 2000.

Palliative stenting for relief of dysphagia in patients with inoperable esophageal cancer: impact on quality of life

The aim of palliation in patients with inoperable esophageal cancer is to relieve dysphagia with minimal morbidity and mortality, and thus improve quality of life (QOL). The use of a self-expanding metal stent (SEMS) is a well-established modality for palliation of dysphagia in such patients. We assessed the QOL after palliative stenting in patients with inoperable esophageal cancer. Thirty-three patients with dysphagia due to inoperable esophageal cancer underwent SEMS insertion between October 2004 and December 2006. All patients had grade III/IV dysphagia and locally advanced unresectable cancer (n = 13), distant metastasis (n = 14), or comorbid conditions/poor general health status precluding a major surgical procedure (n = 6). Patients with grade I/II dysphagia and those with carcinoma of the cervical esophagus were excluded. The QOL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 (version 3) and EORTC QLQ-Esophagus (OES) 18 questionnaire (a QOL scale specifically designed for esophageal diseases) before and at 1, 4, and 8 weeks after placement of the stent. The mean age of the patients was 56 (range 34-78) years, and 22 were men. A covered SEMS was used in all patients. The most common site of malignancy was the lower third of the esophagus (n = 18, 55%). In 23 (77%) patients, the stent crossed the gastroesophageal junction. Seven patients required a reintervention for stent block (n = 5) and stent migration (n = 2). Dysphagia improved significantly immediately after stenting, and this improvement persisted until 8 weeks (16.5 vs. 90.6; P < 0.01). The global health status (5.8 vs. 71.7; P < 0.01) and all functional scores improved significantly after stenting from baseline until 8 weeks. Except pain (14.1 vs. 17.7; P = 0.67), there was significant improvement in deglutition (22.7 vs. 2.0; P < 0.01), eating (48 vs. 12.6; P < 0.01), and other symptom scales (19.7 vs. 12.1; P = 0.04) following stenting. The median survival was 4 months (3-7 months). Palliative stenting using SEMS resulted in significant improvement in all scales of QOL without any mortality and acceptable morbidity.

En bloc resection of right-sided colonic adenocarcinoma with adjacent organ invasion

BackgroundRight-sided colon cancers that invade the adjacent organs are often missed on preoperative imaging. These patients are often considered unresectable at laparotomy as the surgeon is not prepared for en bloc resections. A few centers have reported extended survival after en bloc resection in such tumors. We therefore decided to evaluate the outcome of our patients after en bloc right hemicolectomy.Patients and methodsThe records of all patients who underwent en bloc resection of adjacent organs for right colon cancers were analyzed.ResultsBetween 1992 and 2004, 11 patients had an en bloc right hemicolectomy for right-sided colon cancer. There were ten males and one female with a mean age of 44 years (35–80 years). All patients had anaemia at presentation and most had weight loss and a fixed palpable lump. Preoperative CT scan was able to detect adjacent organ infiltration in nine patients. Six patients had an en bloc pancreaticoduodenectomy, three patients had en bloc local excision of duodenal wall, one patient had en bloc resection of segments 5 and 6 of the liver and one patient had en bloc distal gastrectomy. There was one operative mortality after an en bloc pancreaticoduodenectomy. The median disease-free survival was 54 months.ConclusionRight-sided colon cancers that invade adjacent organs in the absence of distant spread may be a subset of tumors that behave in a locally aggressive manner without causing hematogenous spread. En bloc resection of these tumors is possible, in select centers, with low mortality and morbidity and extended survival.

Giant Haemangioma of the Liver: Is Enucleation Better than Resection?

INTRODUCTION Haemangioma is the most common liver tumour. Treatment is indicated for symptomatic tumours, rapid increase in size, rupture or doubt in diagnosis. There is continuing debate regarding the ideal method of surgical treatment for liver haemangiomas, with some surgeons favouring enucleation over liver resection. PATIENTS AND METHODS Retrospective analysis of prospectively compiled database of patients who were surgically treated for liver haemangioma. RESULTS Between 1987 and 2003, we operated on 21 patients with liver haemangioma. Pre-operative diagnosis on imaging was made in 16 patients (13 symptomatic, 3 had progressive increase in size). In five patients, the indication of surgery was uncertain diagnosis. Enucleation was performed in 9 patients and liver resection in 12. The size of the haemangioma was similar in the enucleation and resection groups (8.9 cm versus 10 cm; P = 0.85). The mean intra-operatiive blood loss was significantly less in the enucleation group (400 ml versus 1330 ml; P = 0.004). The mean operative time was significantly less in the enucleation group as compared to the resection group (170 min versus 230 min; P = 0.035). Five patients had major postoperative morbidity in the resection group as compared to none in the enucleation group (P = 0.045). The duration of hospital stay was significantly longer in the resection group.(9.9 days versus 5.6 days; P = 0.005). CONCLUSIONS Enucleation of liver haemangiomas is safer, quicker and associated with less morbidity than liver resection. Except for some situations, such as uncertain diagnosis or total replacement of a lobe, we recommend enucleation as the surgical procedures of choice for the treatment of hepatic haemangiomas.

Ets-1 and VEGF expression correlates with tumor angiogenesis, lymph node metastasis, and patient survival in esophageal squamous cell carcinoma

PurposeEsophageal squamous cell carcinoma (ESCC) in the Indian population exhibits insidious symptomatology, late clinical presentation, aggressive behavior, and high propensity for metastasis. Ets-1, a transcription factor, is expressed in esophageal tumors and associated with poor prognosis. The aim of the present study was to determine the relationship between Ets-1 expression, tumor angiogenesis [vascular endothelial growth factor (VEGF) and microvessel density (MVD)] and the biological behavior of ESCCs.MethodsIn a prospective study the expression of Ets-1, VEGF, and PECAM-1 (CD-31) was determined in 55 ESCCs, by immunohistochemical analysis, correlated with clinicopathological parameters and outcome of the patients.ResultsOverexpression of Ets-1 and VEGF proteins was observed in 44/55 (80%) and 38/55 (69%) of ESCCs, respectively. VEGF immunopositivity was associated with lymph node metastasis (P=0.002). Analysis of mRNA isoforms using RT-PCR revealed increased expression of VEGF 121 transcripts in ESCCs and MVD was correlated with de-differentiation status of the tumors (P=0.049). Kaplan-Meier survival analysis showed significant correlation between poor disease-free survival and tumor stage (P=0.02) and with nodal metastasis (P=0.05). Concomitant expression of VEGF, Ets-1 proteins, and high MVD was correlated with poor disease-free survival (P=0.004).ConclusionSignificant association of Ets-1 and VEGF proteins with tumor angiogenesis (MVD), lymph node invasion, and poor disease-free survival underscores their relevance regarding aggressive tumor behavior and highlights their potential utility as adverse prognostic factors in esophageal carcinomas.

Outcome following emergency surgery for refractory severe ulcerative colitis in a tertiary care centre in India

BackgroundSteroid-based intensive medical therapy for severe ulcerative colitis is successful in 60–70% of such patients. Patients with complications or those refractory to medical therapy require emergency colectomy for salvage. Little is known about the impact of timing of surgical intervention and surgical outcomes of such patients undergoing emergency surgery in India where the diagnosis is often delayed or missed in patients who are poor, malnourished and non-compliant to medical treatment.MethodsThe clinical records of all patients undergoing emergency surgery for severe ulcerative colitis or its complication in the Department of GI surgery AIIMS, New Delhi, India, between January 1985 and December 2003 were retrieved and data pertaining to demographic features, duration of intensive medical therapy, presence of complications, time from admission to emergency surgery, surgical procedure, in-hospital morbidity and mortality and follow up status extracted.ResultsA total of 72 patients underwent emergency surgery (Subtotal colectomy: 60; ileostomy alone under local anaesthesia: 12). Poor nutritional status was seen in 61% of the patients.Twenty-one patients (29%) underwent emergency surgery for complications of severe ulcerative colitis such as colonic perforation (spontaneous 6, iatrogenic 4), massive lower gastrointestinal haemorrhage (5), toxic megacolon (4) and large bowel obstruction (2). The remaining patients (n = 51) underwent emergency surgery following failed intensive therapy; 17 underwent surgery ≤5 days (Group I) and 34 were operated >5 days (Group II) after initiation of intensive therapy. In this group all the post-operative deaths (n = 8) occurred in those who were operated after 5 days. The difference in mortality in these two groups (i.e. surgical intervention ≤ or >5 days) was statistically significant {0/17 (Group I) vs 8/34 (Group II); p = 0.03}.Overall, 12 patients died (in-hospital mortality: 16.7%). The mortality was higher (10/43; 23.3%) in our early experience (i.e. 1985–1995) when compared to our subsequent experience (2/29; 6.9%) (1996–2003).A total of 48 patients (including 3 awaiting a restorative procedure) are alive on follow up (66.7%; 3 patients lost to follow up). A restorative procedure could be successfully completed in 81% of the survivors of the emergency procedure.ConclusionTo optimize the outcome, a combined team of physicians and surgeons should be involved in the management of patients with severe ulcerative colitis with focus on nutritional support, correction of metabolic derangements, close clinical monitoring and timely assessment for the need for emergency surgery. This retrospective analysis shows that improved results can be achieved with experience and by following a policy of early surgical intervention within 5 days, especially in patients who have failed intensive medical therapy.

Prognostic Significance of Stromelysin-3 and Tissue Inhibitor of Matrix Metalloproteinase-2 in Esophageal Cancer

Objective: Stromelysins (matrix metalloproteinases: MMP-10 or ST-2 and MMP-11 or ST-3) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) have been shown to be associated with human tumor progression, invasion and metastasis. The aim of the present study was to determine the prognostic significance of these proteins in esophageal squamous cell carcinoma (ESCC). Methods: Immunohistochemical analysis was carried out in 65 surgically resected ESCCs and 49 distant histologically normal esophageal tissues and 16 cases of dysplasias. Statistical analyses were performed to determine the associations between the protein expression and clinicopathological parameters and survival of esophageal cancer patients. Results: Expression of ST-2, ST-3, TIMP-1 and TIMP-2 was observed in 43/65 (66%), 51/65 (78%), 43/65 (66%) and 47/65 (72%) ESCC cases, respectively. Univariate analysis showed that TIMP-2 expression was associated with tumor site (OR = 2.63, p = 0.017). TIMP-1+/TIMP-2+ phenotype was inversely correlated with nodal invasiveness of the tumor (OR = 0.4, p = 0.04). Interestingly, p53 expression was associated with increased levels of ST-3 (OR = 0.11, p = 0.02) and TIMP-1 (OR = 3.2, p = 0.007) suggesting possible involvement of p53 in the regulation of these proteins. An increased expression of ST-2, ST-3, TIMP-1 and TIMP-2 was observed in 11/16 (69%), 7/17 (44%), 11/16 (69%) and 8/16 (50%) dysplasias also suggesting that these alterations are early events in esophageal tumorigenesis. All the ESCC patients were followed up postesophagectomy for a maximum period of 59 months (mean disease-free survival = 12 months). Kaplan-Meier survival analysis showed that patients with ST-3-positive and TIMP-2-negative carcinoma had a significantly shorter disease-free survival (median disease-free survival time of 4 months) as compared to patients in the other groups (median disease-free survival time of 20 months; p = 0.0016). To our knowledge this is the first report showing that ST-3+/TIMP-2– phenotype remained of significant predictive value for disease-free survival (p = 0.0007) in multivariate analysis including a conventional clinicopathological factor, tumor stage (p = 0.051). Conclusion: Our results suggest that ST-3+/TIMP-2– phenotype is an adverse prognosticator in esophageal cancer patients.

Clinical significance of sperm protein 17 expression and immunogenicity in esophageal cancer.

We recently identified sperm protein 17 (Sp17) transcripts in esophageal squamous cell carcinomas (ESCCs) by differential display. This study was designed to determine the clinical significance of Sp17 protein in different stages of esophageal tumorigenesis and to test the hypothesis that aberrant localization of Sp17 protein to immunosurveillant site may lead to production of anti‐Sp17 antibodies in serum, which may be of clinical relevance in ESCCs. Sp17 transcripts were detected by RT‐PCR in 26 of 30 (86%) ESCCs, while no transcripts were detected in normal esophageal tissues. Rabbit polyclonal antibody was raised against an immunogenic peptide of Sp17 and used to evaluate protein expression by immunohistochemistry. Expression of Sp17 protein was observed in 60/80 (75%) of ESCCs and 27/30 (90%) dysplastic tissues, while no detectable Sp17 expression was observed in 13 distant histologically normal epithelia. Sixteen of the 60 immunopositive ESCCs showed nuclear expression in addition to cytoplasmic localization of the protein. The circulating levels of anti‐Sp17 antibodies, determined by ELISA, were significantly elevated in ESCC patients when compared with normal subjects (p < 0.001). Increasing Sp17 antibody titers were observed to be associated with the progressive disease in 4 patients. In conclusion, the study demonstrates expression of Sp17 protein in esophageal tumor as well as dysplastic tissues, suggesting it to be an early event in the development of ESCC. To our knowledge, this is the first report showing elevated levels of anti‐Sp17 antibodies in ESCC patients.