Complications of pancreato-duodenectomy.

UNLABELLED: Pancreato-duodenectomy (PD) is the procedure of choice for management of resectable periampullary and pancreatic cancers and some patients with chronic pancreatitis. PD is one of the most major GI/ HPB surgical procedures performed involving resection of multiple organs and reconstruction with multiple anastomoses. While mortality of PD has been brought down to less than 5% morbidity still remains high.Patients undergoing PD are usually elderly with comorbidities - general complications of a major operation e.g. wound, chest, cardiac and venous thrombo-embolism, are common.The major intra-operative morbidity of PD is bleeding which can be from multiple sites viz. gall bladder bed, choledochal veins, gastro-colic trunk, pancreato-duodenal veins, jejunal veins, uncinate veins and cut surface of pancreas. An aberrant right hepatic artery (from the superior mesenteric artery) can be injured while dissecting the common bile duct.Pancreatic leak is defined as presence of amylase rich (>3x serum amylase) fluid in drain beyond 3 days. It is graded as A (no clinical impact), B (persists, infected) or C (systemic sepsis, reoperation). Investigation of choice is computed tomography; a localized collection can be drained percutaneously. Major leak requires reexploration at which lavage and drainage should be performed; no attempt should be made to repair or redo the anastomosis. Soft pancreas and undilated duct are the two most important risk factors for pancreatic anastomotic leak; role of octreotide to prevent the leak is debatable. Preoperative biliary drainage in the form of endoscopic stenting may reduce bleeding complications by controlling coagulopathy but increases the risk of infective complications.Postoperative bleed can be early or delayed and intra-luminal or intra-abdominal. Early intra-abdominal bleed is surgical - either a slipped ligature e.g. of the gastro-duodenal artery or one of the veins or from the pancreato-duodenal bed; reexploration should be done to control it if it is severe. Early intra-luminal bleed is from one of the anastomoses - commonest being the pancreatic. UGIE rules out bleed from the gastro/duodenal anastomosis (which if present, can be controlled endoscopically). Control of pancreatic stump bleed requires reoperation - taking down anterior layer of the anastomosis or a jejunotomy. Delayed intra-abdominal bleed is from a pseudo-aneurysm of an artery, usually gastro-duodenal caused by erosion by an abscess secondary to a leak; treatment of choice is angio-embolization. Delayed intra-luminal bleed is because of stress ulcers caused by systemic sepsis usually secondary to a leak and intra-abdominal sepsis.Other common complications include delayed gastric emptying and acute pancreatitis.Reoperations after PD are frequent - commonest cause is bleed, followed by leak; mortality of reexploration is high. Long term complications include anastomotic (PJ/ HJ) stricture, endocrine and exocrine insufficiency and inability to regain weight and poor quality of life. KEY WORDS: pancreato-duodenectomy complications.

Bile duct injury during cholecystectomy.

Laparoscopic cholecystectomy (LC) is the treatment of choice for gallstones, but is associated with increased risk of bile duct injury (BDI bile duct injury). If the BDI is detected during LC can be addressed immediately, if available hepatobiliary surgeon, but the easiest and safest procedure for the general surgeon is placing drains into subhepatic region and the transfer of acute BDI to controlled external biliary fistula (external Biliary fistula EBF). Most BDI is diagnosed when the postoperative period, when there is biliary leak. Therapy is a percutaneous catheter drainage and endoscopic stenting in the bile duct; early repair is not recommended. Repair in the form hepatico-jejunostomy (HJ) should be performed hepatobiliary surgeon at intervals of 46 weeks after it closes EBF. BDI is a frequent cause medico-legal actions and a substantial burden on health care costs. Most BDI can be avoided by adherence to the principles of safe cholecystectomy.

NMR spectroscopy-based analysis of gallstones of cancerous and benign gallbladders from different geographical regions of the Indian subcontinent.

Analysis of the chemical composition of gallstones is vital for the etiopathogenesis of gallstone diseases that can ultimately help in the prevention of its formation. In the present study, gallstones from seven different regions of India were analyzed to highlight the major difference in their composition. Also, gallstones of different pathological conditions i.e., benign (chronic cholecystitis, CC) and malignant gallbladder disease (gallbladder cancer GBC) were characterized. The type of polymorphs of cholesterol molecules was also studied to provide insight into the structure of gallstones. 1H solution state NMR spectroscopy 1D experiments were performed on a total of 94 gallstone (GS) samples collected from seven different geographical regions of India. Solid-State NMR spectroscopy 13C cross-polarization magic angle spinning (CPMAS) experiments were done on the 20 CC GS samples and 20 GBC GS samples of two regions. 1H NMR spectra from the solution state NMR of all the stones reveal that cholesterol was a major component of the maximum stones of the north India region while in south Indian regions, GS had very less cholesterol. 13C CPMAS experiments reveal that the quantity of cholesterol was significantly more in the GS of CC in the Lucknow region compared with GBC stones of Lucknow and Chandigarh. Our study also revealed that GS of the Lucknow region of both malignant and benign gallbladder diseases belong to the monohydrate crystalline form of cholesterol while GS of Chandigarh region of both malignant and benign gallbladder diseases exists in both monohydrate crystalline form with the amorphous type and anhydrous form. Gallstones have a complicated and poorly understood etiology. Therefore, it is important to understand the composition of gallstones, which can be found in various forms and clinical conditions. Variations in dietary practices, environmental conditions, and genetic factors may influence and contribute to the formation of GS. Prevention of gallstone formation may help in decreasing the cases of gallbladder cancer.

Esophageal Cancer: Whether and What Before or After Surgery?

Esophageal cancer is the eighth most common cancer and the sixth most common cause of cancer-related mortality worldwide. Surgery has been the mainstay of the treatment of esophageal cancer. However, given the dismal survival with surgery alone, other modalities, e.g., chemotherapy (CT) and radiotherapy (RT), have been used for the management of these cancers. This review aims to look at the evolution of multi-modality management of esophageal cancer and tries to answer certain questions pertaining to the management of these cancers.

Pancreas-preserving limited duodenal resection: Minimizing morbidity without compromising oncological adequacy.

Backgrounds/Aims: Pancreaticoduodenectomy is the most common procedure for the management of duodenal pathologies. However, it is associated with substantial morbidity and a low risk of mortality. Pancreas-preserving limited duodenal resection (PPLDR) can be performed under specific scenarios. We share our experience with PPLDR and its outcome. Methods: We retrospectively analyzed a prospectively maintained database of patients undergoing limited duodenal resection in the form of wedge (sleeve) resection or segmental resection of one or more duodenal segments from March 2016 to March 2021 at a tertiary care center in North India. Results: During the study period, 10 patients (including 9 males) underwent PPLDR. Five of these 10 patients showed primary duodenal or proximal jejunal pathology, while the remaining five had duodenal pathology involving an adjacent organ tumor. Four patients underwent wedge (sleeve) resection, while the remaining six underwent segmental duodenal resection of one or more duodenal segments. Mean hospital stay was 6 days (range, 3-11 days) without 30-day mortality. Morbidity occurred in 4 patients (Grade I-II, n = 3; Grade III, n = 1). All patients were alive and disease-free at the time of last follow-up. The mean follow-up duration was 23 months (range, 2-48 months). Conclusions: PPLDR is a safe and effective alternative for pancreaticoduodenectomy when selected carefully for specific tumor types and location.

Insulinoma-Accurate Preoperative Localization Is the Key to Management: An Initial Experience.

Insulinoma is the commonest functioning pancreatic neuroendocrine tumor. The only curative treatment is surgical excision after preoperative localization. A retrospective analysis of nine patients (February 2017-June 2020), 2 males and 7 females, was done for clinical presentation, biochemistry, localization methods, intraoperative findings, postoperative outcome, histopathology reports, and follow-up. Techniques for localization of the tumor were pancreatic protocol triple-phase multi-detector computed tomography (MDCT), endoscopic ultrasound (EUS), Ga 68 DOTANOC PET-CT, and Ga 68 NOTA-exendin-4 PET-CT (GLP1R scan). The mean age was 38 (range 20-68) years and mean duration of symptoms 34 (range 8-120) months, and symptoms of Whipple's triad were present in all cases after a supervised 72-h fast. MDCT localized tumor in 8/9 cases. EUS before MDCT in one patient had also localized tumors. Ga 68 DOTANOC PET-CT detected tumor in 2/4 patients. In one patient, MDCT or DOTANOC PET scan could not localize tumor; GLP1R scan localized tumor accurately. Two patients had associated MEN1 syndrome. All 9 patients underwent surgical resection (four open and five laparoscopic) of tumor-enucleation (3), distal pancreatectomy with splenectomy (3), and pancreatoduodenectomy (PD) (3). The last four procedures and all three enucleations were laparoscopic. Five patients developed postoperative pancreatic fistula (POPF), only one grade B which required percutaneous drain placement. One patient, who had initial open enucleation, developed hypoglycemia after 48 h; PD was performed. All patients were cured and all, except one (who died of upper GI bleed), were alive and disease-free during a mean follow-up of 26 (range 2-41) months. Preoperative localization of insulinoma is important and decides the outcome of surgery in terms of cure. MDCT can localize tumors in most patients; the last resort for localization is the GLP1R scan. Laparoscopic procedures are equally effective compared to open surgery. Considering the benign nature of the disease, enucleation is the procedure of choice.

Ethnomedicinal uses, phytochemistry and dermatological effects of Hippophae rhamnoides L.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Hippophae rhamnoides L. (family- Elaeagnaceae, common name- Sea buckthorn) is a flowering shrub native to cold temperate regions of Eurasia. Berries, seeds, and leaves of the plant are widely used as a folk medicine for the treatment of hypertension, oedema, inflammation, tissue-regeneration, skin-grafts, burns/injury, wounds, and ulcers. AIM OF THE REVIEW: This article reviews geographical distribution, botanical description, phytochemistry, ethnomedicinal uses, and dermatological activities including, cosmeceuticals of H. rhamnoides available in the market. MATERIALS AND METHODS: The data has been compiled employing the various search engines like Science Direct, Pub Med, Google, Google Scholar, EBSCO, SCOPUS, and SciVal. RESULTS AND DISCUSSION: H. rhamnoides is primarily found in cold-temperate regions of Eurasia and was first located in China. Berries are the most prominent feature of the plant. Phytochemical studies reveal the presence of a wide variety of compounds like flavonoids, carotenoids, polyunsaturated fatty acids, minerals, vitamins, Omega 3, 6, 9 and rarest Omega 7 and about 190 bioactive compounds. The pharmacological studies demonstrated, sea buckthorn to exhibit antibacterial, anti-sebum, antifungal, anti-psoriasis, anti-atopic dermatitis and wound healing activities. Besides, it has also been included in various cosmeceuticals for its use in skin-eventone, smoothening, rejuvenation, removal of wrinkles, scars, and pigmentation, and also in hair related problems. CONCLUSION: Pharmacological evaluation confirmed the ethnomedically claimed biological actions and other beneficial effects on the skin of H. rhamnoides using scientifically accepted protocols and controls, although some of the studies require more elaborative studies. Its full application in the dermatology may be attributed to the presence of a variety of flavonoids, vitamins, and unsaturated fatty acids. Great use of plant in the traditional system for dermatological aspect, demands further comprehensive phytochemical work based on its actual use by the traditional population. Demonstration of the plant in the traditional system, pharmacology, cosmeceuticals not only demands its further therapeutic studies but also warrants focus towards its cultivation and propagation across the globe.

p53, carcinoembryonic antigen and carbohydrate antigen 19.9 expression in gall bladder cancer, precursor epithelial lesions and xanthogranulomatous cholecystitis.

BACKGROUND: Gallbladder cancer (GBC) is the commonest gastrointestinal cancer in women of north India. Precursor epithelial lesions in GBC are known; however, the role of xanthogranulomatous (XG) inflammation in the pathogenesis of GBC is unknown. AIMS: To analyze the role of precursor lesions in the pathogenesis of GBC we studied the immunohistochemical (IHC) expression of p53, carcino-embryonic antigen (CEA) and carbohydrate antigen 19.9 (CA-19.9) in GBC, chronic cholecystitis (CC), XG cholecystitis (XGC) and precursor lesions. MATERIALS AND METHODS: The study included 51 GBC, 68 CC, 42 XGC and 10 normal gallbladders. All cases were evaluated for presence of precursor lesions and IHC was performed. RESULTS: p53 immunoreactivity was found in 55% GBC, 32% of dysplasia with malignancy and in 14% of dysplasia with CC. Sixteen percent GBC had associated XG inflammation. Normal and metaplastic epithelium in CC and in XGC did not express p53. CEA expression was apical in normal and inflammatory GBs (CC, XGC), while cytoplasmic focal to diffuse positivity was seen in 82% GBC. CA-19.9 expression was seen in all cases of normal and inflammatory GBs; however, foci of antral metaplasia were negative. Seventy-five percent of GBC expressed CA-19.9; all negative cases were high-grade on histology. CONCLUSIONS: Altered CEA expression is seen in GBC as compared to normal and inflammatory gallbladders. Loss of expression of CA19.9 in antral metaplasia and poorly differentiated GBC may indicate that it is a marker of biliary differentiation. p53 over-expression seen in GBC and in dysplasia associated with malignancy and with CC suggests that p53 mutation and dysplasia are early events in the evolution of GBC. Epithelial metaplasia and XG inflammation are often associated with GBC but do not appear to play a role in its pathogenesis through the p53 pathway.

Natural toxins and their therapeutic potential.

Plants have been extensively investigated for exploring their therapeutic potentials, but there are comparatively scanty reports on drugs derived from animal kingdom, except for hormones. During last decade, the toxins that are used for defense by the animals, have been isolated and found useful tools for physiological and pharmacological studies, besides giving valuable leads to drug development. Toxins with interesting results have been isolated from the venoms of snakes, scorpions, spiders, snails, lizards, frogs and fish. The present review describe about some toxins as drugs and their biological activities. Some fungal, bacterial and marine toxins have also been covered in this article.

Fragile histidine triad (FHIT) gene and its association with p53 protein expression in the progression of gall bladder cancer.

OBJECTIVE: Present study deals with LOH and MSI in FHIT gene and p53 expression in GBC, CC, XGC, and normal GB to elucidate the role of FHIT gene in gall bladder cancer. METHODS: Five microsatellite markers D3S1217, D3S1300, D3S1313, D3S1600, and D3S2757, were selected. RESULTS: Among GBC cases the frequency of MSI-H and LOH was 17.5% and 27.5%, respectively. Significant difference was found between GBC and normal GB (p = .02), and GBC and CC groups (p= .002) when LOH was compared. CONCLUSIONS: Our results suggested CC might act as a preinvasive stage in the pathogenesis of GBC.

Solid state (13)C 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.

Elucidation of the Chemopreventive Role of Stigmasterol Against Jab1 in Gall Bladder Carcinoma.

BACKGROUND: Plant sterols have proven a potent anti-proliferative and apoptosis inducing agent against several carcinomas including breast and prostate cancers. Jab1 has been reported to be involved in the progression of numerous carcinomas. However, antiproliferative effects of sterols against Jab1 in gall bladder cancer have not been explored yet. OBJECTIVE: In the current study, we elucidated the mechanism of action of stigmasterol regarding apoptosis induction mediated via downregulation of Jab1 protein in human gall bladder cancer cells. METHODS: In our study, we performed MTT and Trypan blue assay to assess the effect of stigmasterol on cell proliferation. In addition, RT-PCR and western blotting were performed to identify the effect of stigmasterol on Jab1 and p27 expression in human gall bladder cancer cells. We further performed cell cycle, Caspase-3, Hoechst and FITC-Annexin V analysis, to confirm the apoptosis induction in stigmasterol treated human gall bladder cancer cells. RESULTS: Our results clearly indicated that stigmasterol has up-regulated the p27 expression and down-regulated Jab1 gene. These modulations of genes might occur via mitochondrial apoptosis signaling pathway. Caspase-3 gets activated with the apoptotic induction. Increase in apoptotic cells and DNA were confirmed through annexin V staining, Hoechst staining, and cell cycle analysis. CONCLUSION: Thus, these results strongly suggest that stigmasterol has the potential to be considered as an anticancerous therapeutic agent against Jab1 in gall bladder cancer.

Splenic tuberculosis in an immunocompetent patient can be managed conservatively: a case report.

Tuberculosis is a significant health problem in developing countries. Splenic tuberculosis usually occurs as a part of miliary tuberculosis, and ranks third after lung and liver involvement, respectively. Splenic involvement is more common in immunocompromised patients and is very rarely found in immunocompetent patients. Here we report a case of splenic tuberculosis in an immunocompetent patient, which was managed successfully with conservative treatment.

One-step analysis of major bile components in human bile using 1H NMR spectroscopy.

Human gallbladder bile dissolved in dimethylsulfoxide provides sharp and resolved signals for major bile components in 1H NMR spectra. Characteristic well-resolved marker signals that invariably appear in 1H NMR spectra of bile were identified for cholesterol (H18 methyl signal at 0.643 ppm), lipids (glycerol CH signal at 5.064 ppm), total bile acids (H18 signals in the range 0.520-0.626 ppm), total glycine conjugated bile acids (NH signal at 6.958 ppm), total taurine conjugated bile acids (NH signal at 7.646 ppm), and urea (NH2 signal near 5.48 ppm), which enabled their rapid and accurate analysis. Excellent linearity and precision of quantitative analysis was observed for all the identified bile components (R2 > 0.99 for all). The method was demonstrated on gallbladder bile from 19 patients with gallbladder diseases. Urea in bile was identified by NMR for the first time and its quantitative analysis, along with several other bile components, is presented. The majority of the bile components could be analyzed in a single step. Accurate and rapid quantification of several bile components noninvasively by using the method presented herein may have far-reaching implications in the study of bile acid metabolism and pathophysiology of various hepatobiliary and gastrointestinal diseases.

Single-step analysis of individual conjugated bile acids in human bile using 1H NMR spectroscopy.

1H and 13C NMR spectra of intact human bile were assigned using one-dimensional (1H and 13C) and two-dimensional (1H-1H and 1H-13C) experiments. Individual conjugated bile acids--glycocholic acid, glycodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, taurodeoxycholic acid, and taurochenodeoxycholic acid--were identified. The bile acids were quantified accurately and individually in a single step by using distinct and characteristic amide signals. Making use of 13C NMR, the study also suggests a way to analyze unconjugated bile acids separately, if present. Chemical shift assignments and rapid single-step analysis of individual conjugated bile acids from intact bile presented herein may have immense utility in the study of bile acid metabolism and deeper understanding of hepatobiliary diseases.

Cholecystectomy in patients with asymptomatic gallstones to prevent gall bladder cancer--the case against.

Gallstones (GS) are common in northern India. GS are the most important risk factor for gall bladder cancer (GBC). Data from the West, however, indicate that the risk of GBC in persons with asymptomatic GS is very small and does not warrant prophylactic cholecystectomy. Can these recommendations be applied to northern India where incidence rates of GBC are one of the highest in the world? Not all persons with asymptomatic GS require cholecystectomy. There may, however, be a case for offering cholecystectomy to a young woman in northern India with a large GS or a gall bladder packed with GS, though there is no evidence to support this recommendation. Type of stone, tumor markers and genetic markers need to be investigated to identify those with asymptomatic GS who are at the highest risk of developing GBC so that they can selectively be offered pre-emptive cholecystectomy to prevent GBC.

Percutaneous Direct Needle Puncture and Transcatheter N-butyl Cyanoacrylate Injection Techniques for the Embolization of Pseudoaneurysms and Aneurysms of Arteries Supplying the Hepato-pancreato-biliary System and Gastrointestinal Tract.

AIMS: The aim of this study was to evaluate the safety and clinical efficacy of percutaneous direct needle puncture and transcatheter N-butyl cyanoacrylate (NBCA) injection techniques for the embolization of pseudoaneurysms and aneurysms of arteries supplying the hepato-pancreato-biliary (HPB) system and gastrointestinal (GI) tract. SUBJECTS AND METHODS: A hospital-based cross-sectional retrospective study was conducted, where the study group comprised 11 patients with pseudoaneurysms/aneurysms of arteries supplying the HPB system and GI tract presenting to a tertiary care center from January 2015 to June 2016. Four patients (36.4%) underwent percutaneous direct needle puncture of pseudoaneurysms with NBCA injection, 3 patients (27.3%) underwent transcatheter embolization with NBCA as sole embolic agent, and in 4 patients (36.4%), transcatheter NBCA injection was done along with coil embolization. RESULTS: This retrospective study comprised 11 patients (8 males and 3 females) with mean age of 35.8 years ± 1.6 (standard deviation [SD]). The mean volume of NBCA: ethiodized oil (lipiodol) mixture injected by percutaneous direct needle puncture was 0.62 ml ± 0.25 (SD) (range = 0.5-1 ml), and by transcatheter injection, it was 0.62 ml ± 0.37 (SD) (range = 0.3-1.4 ml). Embolization with NBCA was technically and clinically successful in all patients (100%). No recurrence of bleeding or recurrence of pseudoaneurysm/aneurysm was noted in our study. CONCLUSIONS: Percutaneous direct needle puncture of visceral artery pseudoaneurysms and NBCA glue injection and transcatheter NBCA injection for embolization of visceral artery pseudoaneurysms and aneurysms are cost-effective techniques that can be used when coil embolization is not feasible or has failed.

Adjuvant chemo-radiotherapy in ampullary cancers.

PURPOSE: Patterns of failure following surgical treatment of ampullary cancers indicate that up to 45% of patients develop loco-regional recurrence. The effect of adjuvant chemo-radiotherapy on survival and loco-regional control is not yet established in this malignancy. PATIENTS AND METHODS: From January 1989 to December 2000, 113 patients underwent pancreatico-duodenectomy for ampullary cancer. One hundred and four patients who survived the operation were available for analysis to study the effect of adjuvant chemo-radiotherapy on survival and loco-regional control. Forty-nine patients received adjuvant chemo-radiotherapy (median dose 50.4 Gy with concurrent 5-Flurouracil) and long-term outcome in these patients was compared with those 55 who did not receive adjuvant therapy. RESULTS: The overall median survival was 30.1 (range 1.6-140.0) months with actuarial 1, 3 and 5-year survival rates of 79, 43 and 33%, respectively. No significant difference in median survival (34.6 vs 24.5 months; P=0.3) and actuarial 5-year survival rates (38 vs 28%) was seen between those who received and those who did not receive adjuvant therapy. Adjuvant chemo-radiotherapy did not influence the survival in high-risk patients (P=0.84), in various T and N stages and had no impact on loco-regional recurrence (P=0.6). CONCLUSIONS: Adjuvant chemo-radiotherapy did not improve the long-term survival or decrease recurrence rates in patients with ampullary cancers who had undergone pancreatico-duodenectomy.

MUC 1 core protein as a marker of gallbladder malignancy.

AIM: The significance of MUC 1 expression in the gallbladder tissues in relation to cancer and non-cancer disease is not well understood. The aim of this study was to clarify the significance of MUC 1 expression. MATERIALS AND METHODS: A monoclonal antibody (CA 15--3; DF 3) was applied to stain MUC 1 core protein in surgical specimens. RESULTS: MUC 1 expression is significantly higher (p<0.0001) in gallbladder cancer (69/88) compare to non-cancerous tissue, while, very trace in normal and inflammatory tissues. The expression rate was significantly lower (p<0.0001) when the cancer did not penetrate the mucosal layer than when cancers did penetrate this layer. The MUC 1 expression rate was (4/14) in T1 tumours, (11/14) in T4, (40/45) in T3, and (14/15) in T2, respectively. Every cell of normal and inflammatory mucosa, and T1 cancers had the polarized pattern. The depolarized pattern was dominant in cancer cells from the advanced tumours of T2, T3 and T4. That is, (45/74) of cancer cells from the mucosal layer and (58/74) of penetrating cancer cells in submucosal layer had the depolarized pattern. There was no significant correlation of MUC 1 expression rate and staining pattern with cancer differentiation and microscopic venous invasion. On the other hand, lymphatic vessel invasion was significantly correlated with the staining pattern but not with expression rate. CONCLUSION: MUC 1 core protein expression rate and pattern are suggesting that MUC 1 core protein would be a marker of malignant transformation of gallbladder epithelium and its depolarized expression would also be a marker of invasion of gallbladder cancer.