Anu Behari

Longterm survival after extended resections in patients with gallbladder cancer

BACKGROUND Surgery is the treatment of choice for gallbladder cancer, but the extent of resection and its benefits remain unclear. STUDY DESIGN Survival analysis of 42 patients who underwent extended resections for gallbladder cancer was performed. Resections were labeled R0 (curative) or R1 (noncurative) based on histopathologic evaluation. Survival curves were constructed using the Kaplan-Meier method, and survival data were analyzed by univariate and multivariate analyses to identify factors associated with longterm (>2 years) survival. RESULTS R0 status was achieved in 18 patients (43%): 100%, 100%, 45%, and 0% in stages I, II, III, and IV, respectively. Patients with R0 resections had a significantly better survival than those with R1 resections (median 25.8 months versus 17.0 months; p = 0.03). R0 status was achieved in only 3 of 20 patients (15%) with node positive (N1) disease compared with 14 of 17 patients (82%) with node negative (N0) disease. Patients with N0 disease had a significantly better survival than those with N1 disease (median not reached versus 17 months; p = 0.01). None of the patients with N1 disease survived 5 years; 5-year survival for N0 patients was 58%. Adjuvant therapy did not have a significant effect on survival. CONCLUSIONS In patients with gallbladder cancer, R0 status could be achieved in only 43% of patients undergoing extended resections. R0 status and N0 disease were associated with better longterm survival.

Early gallbladder cancer1 1No competing interests declared.

Abstract Background: The majority of patients with gallbladder cancer (GBC) have advanced disease at the time of diagnosis and are unresectable. Longterm survival is usually seen in a subset of patients with early GBC (EGBC)—cancer confined to the mucosa (pT1a) and muscularis (pT1b). Management guidelines of EGBC are not yet defined and are controversial. The purpose of this article is to evaluate the diagnostic aspects and effects of resectional procedures on survival outcome in patients with EGBC. Study Design: EGBC was defined as cancer confined to the mucosa (pT1a) or muscularis (pT1b) according to the TNM classification. Clinicopathological details and survival data of 14 patients who had EGBC were analyzed. There were 9 women and 5 men, with a mean age of 60 years. Results: A definite preoperative diagnosis was possible in only three patients and three patients were diagnosed at surgery; the majority of patients were diagnosed incidentally after cholecystectomy for associated gallstones. Two patients underwent extended cholecystectomy and 12 patients underwent simple cholecystectomy. Two patients had pT1a and 12 had pT1b lesions. Mean (SD) survival was 71.5 (12.2) months and median survival was 42 months. There were five treatment failures with locoregional recurrence and death. All patients with pT1b tumors were treated by simple cholecystectomy. Cumulative 1-, 3-, and 5-year survival was 92%, 68%, and 68% respectively. Conclusions: Simple cholecystectomy is an adequate treatment only for mucosal GBC. Patients with pT1b tumors require extended cholecystectomy. Incidental GBC extending up to the muscularis merits early reoperation for completion of extended cholecystectomy, which offers the only chance of cure.

Anterior resection for rectal carcinoma - risk factors for anastomotic leaks and strictures.

AIM To determine the incidence and factors responsible for anastomotic leaks and stricture following anterior resection (AR) and its subsequent management. METHODS Retrospective analysis of data from 108 patients with rectal carcinoma who underwent AR or low anterior resection (LAR) to identify the various preoperative, operative, and post operative factors that might have influence on anastomotic leaks and strictures. RESULTS There were 68 males and 40 females with an average of 47 years (range 21-75 years). The median distance of the tumor from the anal verge was 8 cm (range 3-15 cm). Sixty (55.6%) patients underwent handsewn anastomosis and 48 (44.4%) were stapled. The median operating time was 3.5 h (range 2.0-7.5 h). Sixteen (14.6%) patients had an anastomotic leak. Among these, 11 patients required re-exploration and five were managed expectantly. The anastomotic leak rate was similar in patients with and without diverting stoma (8/60, 13.4% with stoma and 8/48; 16.7% without stoma). In 15 (13.9%) patients, resection margins were positive for malignancy. Nineteen (17.6%) patients developed anastomotic strictures at a median duration of 8 mo (range 3-20 mo). Among these, 15 patients were successfully managed with per-anal dilatation. On multivariate analysis, advance age (> 60 years) was the only risk factor for anastomotic leak (P = 0.004). On the other hand, anastomotic leak (P = 0.00), mucin positive tumor (P = 0.021), and lower rectal growth (P = 0.011) were found as risk factors for the development of an anastomotic stricture. CONCLUSION Advance age is a risk factor for an anastomotic leak. An anastomotic leak, a mucin-secreting tumor, and lower rectal growth predispose patients to develop anastomotic strictures.

Laparoscopic Staging in Gallbladder Cancer

Purpose: Laparoscopy is beneficial in the staging of pancreatic and upper gastrointestinal malignancies but its role in gallbladder cancer has not been investigated. We evaluated the role of laparoscopy in the staging of gallbladder cancer. Methods: From 1989 through 2001, 91 patients with gallbladder cancer, without any evidence of metastatic disease on imaging (ultrasound and/or computed tomographic scan), underwent staging laparoscopy. Peritoneal and surface liver metastases were looked for and assessment of local spread was done if possible. Assessment was based on visual impression and biopsies were not obtained routinely. Results: At laparoscopy, 34 (37%) patients had disseminated disease in the form of liver and/or peritoneal deposits; no further surgery was performed in 29 of these patients while 5 patients underwent surgical bypass procedures. Liver metastases were missed at laparoscopy in 2 patients and were subsequently found at laparotomy. Assessment of the gallbladder mass was possible in 33 (36%) patients, 6 of these were found to have extensive local disease and did not undergo any further surgery. Laparoscopic staging, thus avoided further surgery in 35 (38%) patients. Of the 51 patients without metastatic disease, who underwent laparotomy, 11 were found to have nonresectable locally advanced disease while 1 had liver metastases, which were missed at laparoscopy; 7 underwent bypass procedures only; 21 underwent simple cholecystectomy and extended cholecystectomy was done in 11 patients. The resectability rate (number of resections/operations) in patients undergoing laparoscopic staging was 57% (32/56) as compared with 43% (142/328) in those who did not undergo laparoscopy. Conclusions: Staging laparoscopy in patients with gallbladder cancer detected liver and peritoneal metastases that were missed on imaging. It reduced the number of unnecessary surgical explorations and improved the resectability rate.

Asymptomatic Gallstones (AsGS) – To Treat or Not to?

With ready availability of abdominal ultrasound, asymptomatic gallstones (AsGS) are being diagnosed with increasing frequency. Management decisions need to take into account the natural history of AsGS as well as the risks of cholecystectomy. Long-term follow up studies from the West have consistently shown that only a small minority of asymptomatic gallstones lead to development of symptoms or complications. Some sub-groups of patients (eg those with chronic hemolytic syndromes) have been shown to be at a higher risk of developing symptoms and complications and prophylactic cholecystectomy has been advised for them. Clear division of patients into low or high risk categories is still far from ideal and better identification of risk factors and risk stratification is needed. Overall, both open and laparoscopic cholecystectomy, are generally safe procedures. However, the incidence of bile duct injury (with all its serious consequences) continues to be higher with laparoscopic cholecystectomy and this should receive due consideration before offering prophylactic cholecystectomy to an asymptomatic patient who is not expected to receive any clinical benefit from it. Gallbladder cancer is rare in most of the developed world and prophylactic cholecystectomy has generally not been recommended to prevent development of GBC. Considering the wide geographical/ethnic variation in incidence of GBC across the world and the strong association of GBC with gallstones, it may not be prudent to extrapolate the results of studies of natural history of AsGS from one part of the world to another. Since northern India has one of the highest incidences of GBC in the world, it is imperative to have data on natural history of AsGS in patients from this area to allow formulation of precise guidelines for management of AsGs.

Post-endoscopic retrograde cholangiopancreatography perforation managed by surgery or percutaneous drainage

PurposePost-endoscopic retrograde cholangiopancreatography (ERCP) perforation usually resolves conservatively; however, intervention is sometimes needed, and there is a paucity of literature regarding the best management approach. We evaluated our experience of managing post-ERCP perforations to help define the role of surgery with percutaneous drainage (PCD).MethodsA retrospective chart review revealed 14 cases of post-ERCP perforation with intra-abdominal sepsis referred for intervention. We analyzed data pertaining to clinical details, management, and outcome.ResultsThere were 12 patients with duodenal perforation and 2 with biliary perforation. Most (10/14; 72%) had symptom onset within 48 h, but delayed diagnosis or referral resulted in a mean delay until intervention of 6.6 days (range 1–18 days). Computed tomography revealed localized collections in 9 (64%) patients. Seven patients with localized collections and no or minimal contrast leak underwent PCD and rest, and 7 underwent surgery. The indications for surgery were free perforation, generalized peritonitis, and major contrast leak. Overall morbidity was 50% and there was one early postoperative death, caused by severe sepsis.ConclusionThere should be a high index of suspicion of perforation when abdominal signs and symptoms develop after ERCP. Computed tomography is the investigation of choice for diagnosis and guiding therapy. With judicious selection of surgery or PCD based on clinical and imaging features, patients can be managed with acceptable morbidity and low mortality.

Solid state 13C NMR analysis of human gallstones from cancer and benign gall bladder diseases

Natural abundance (13)C cross polarized (CP) magic angle spinning (MAS) nuclear magnetic resonance (NMR) analysis of human gall bladder stones collected from patients suffering from malignant and benign gall bladder disease was carried out which revealed different polymorphs of cholesterol in these stones. All gall bladder stones in present study had cholesterol as their main constituent. (13)C CP-MAS NMR analysis revealed three forms of cholesterol molecules in these stones, which are anhydrous form, monohydrate crystalline with amorphous form and monohydrate crystalline form. Our study revealed that stones collected from patients associated with chronic cholecystitis (CC) disease have mostly different polymorph of cholesterol than stones collected from patients associated with gall bladder cancer (GBC). Such study will be helpful in understanding the mechanism of formation of gallstones which are associated with different gall bladder diseases. This is the first study by solid state NMR revealing different crystal polymorphism of cholesterol in human gallstones, extending the applicability of (13)C CP-MAS NMR technique for the routine study of gallstones.

Surgical management of patients with post-cholecystectomy benign biliary stricture complicated by atrophy–hypertrophy complex of the liver

BACKGROUND Atrophy-hypertrophy complex (AHC) of the liver rarely complicates post-cholecystectomy benign biliary strictures (BBS). This study aimed to analyse the effect of AHC on the surgical management of patients with BBS. METHODS Between 1989 and 2005, 362 patients underwent surgical repair for BBS at a tertiary referral centre in northern India. A total of 36 (10%) patients had AHC. Patients with AHC (n= 36) were compared with those without (n= 336) to define the factors associated with the development of AHC. RESULTS Overall, 35 patients with AHC underwent Roux-en-Y hepaticojejunostomy; right hepatectomy was performed in one patient. The interval between bile duct injury and stricture repair did not influence the development of AHC (mean 24 months in AHC patients vs. 19 months in non-AHC patients; P= 0.522). Of the 36 patients with AHC, 26 (72%) had hilar strictures (Bismuths types III, IV, V), as did 163 of the 326 (50%) patients without AHC (P= 0.012). Patients with AHC had more blood loss at surgery (mean blood loss 340 ml in the AHC group vs. 190 ml in the non-AHC group; P= 0.004) and required more blood transfusion (mean blood transfused 300 ml vs. 120 ml; P= 0.001). Surgery was prolonged in AHC patients (mean duration of operation 4.2 hours in the AHC group vs. 2.8 hours in the non-AHC group; P= 0.001). Over a mean follow-up of 43 months (range 6-163 months), three of 36 (8%) AHC patients required re-intervention for recurrent strictures, compared with nine of 326 (3%) non-AHC patients (P= 0.006). CONCLUSIONS Iatrogenic injury at the hepatic hilum predisposes for the development of AHC. Surgery is more difficult and blood transfusion requirements are higher in patients with AHC during surgical repair of BBS. Atrophy-hypertrophy complex is a risk factor for recurrent stricture formation after hepaticojejunostomy.

Lipid profiling of cancerous and benign gallbladder tissues by 1H NMR spectroscopy.

Qualitative and quantitative 1H NMR analysis of lipid extracts of gallbladder tissue in chronic cholecystitis (CC, benign) (n = 14), xanthogranulomatous cholecystitis (XGC, intermediate) (n = 9) and gallbladder cancer (GBC, malignant) (n = 8) was carried out to understand the mechanisms involved in the transformation of benign gallbladder tissue to intermediate and malignant tissue. The results revealed alterations in various tissue lipid components in gallbladder in CC, XGC and GBC. The difference in the nature of lipid components in benign and malignant disease may aid in the identification of the biological pathways involved in the etiopathogenesis of GBC. This is the first study on lipid profiling of gallbladder tissue by 1H NMR spectroscopy, and has possible implications for the development of future diagnostic approaches. Copyright

1 H NMR metabolic profiling of human serum associated with benign and malignant gallstone diseases

Proton NMR based metabolic profile of serum associated with different gallbladder pathologies is presented. Quantitative and qualitative variations in the metabolic profile of serum in control samples and three different pathologies of gallbladder, chronic cholecystitis, xanthogranulomatous cholecystitis and carcinoma of gallbladder has been evaluated by use of 1H NMR based metabonomics and multivariate chemometric methods. Multivariate partial least square discriminant analysis of 1H NMR spectra showed a clear discrimination between control and diseased groups on the basis of quantitative and qualitative metabolic variations. Increased levels of lactate and pyruvate whereas decreased levels of glucose, some amino acids and low density lipoprotein/very low density lipoprotein (LDL/VLDL) were observed. These metabolites, responsible for class discrimination, from different metabolic pathways could be considered as the signatures of the carcinoma of gallbladder.