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.

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.

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.

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.

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.

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.

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.

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.

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.

Reoperation following Pancreaticoduodenectomy.

Introduction. The literature on reoperation following pancreaticoduodenectomy is sparse and does not address all concerns. Aim. To analyze the incidence, causes, and outcome of patients undergoing reoperations following pancreaticoduodenectomy. Methods. Retrospective analysis of 520 consecutive patients undergoing pancreaticoduodenectomy from May 1989 to September 2010. Results. 96 patients (18.5%) were reoperated; 72 were early, 18 were late, and 6 underwent both early and late reoperations. Indications for early reoperation were post pancreatectomy hemorrhage in 53 (68%), pancreatico-enteric anastomotic leak in 10 (13%), hepaticojejunostomy leak in 3 (3.8%), duodenojejunostomy leak in 4 (5%), intestinal obstruction in 1 (1.2%) and miscellaneous causes in 7 (9%). Patients reoperated early did not fare poorly on long-term follow up. Indications for late reoperations were complications of index surgery (n = 12), recurrence of the primary disease (n = 8), complications of adjuvant radiotherapy (n = 3), and gastrointestinal bleed (n = 1). The median survival of 16 patients reoperated late without recurrent disease was 49 months. Conclusion. Early reoperations following pancreaticoduodenectomy, commonly for post pancreatectomy hemorrhage, carries a high mortality due to associated sepsis, but has no impact on long-term survival. Long-term complications related to pancreaticoduodenectomy and adjuvant radiotherapy can be managed successfully with good results.

Role of C-erbB2 expression in gallbladder cancer.

BACKGROUND: Gallbladder cancer (GBC) is a lethal malignancy presenting at an advanced stage. The pathogenesis is not well categorized, and surgery is the only treatment available at the early stage of the disease. There have been few reports on role of growth factor receptors in GBC. C-erbB2 is one such receptor whose over-expression is being explored in GBC as one of the factors involved in carcinogenesis and possible target for therapy. MATERIALS AND METHODS: One hundred and four consecutive cases of GBC were retrospectively studied with regard to clinical features, histological type, grade and stage of tumor. Immunohistochemistry for C-erbB2 was done and expression was correlated with different clinic-pathological parameters and survival. RESULTS: C-erbB2 overexpression was seen in 9.4% cases with complete staining and both complete and incomplete staining (2+ and 3+) was seen in 13.4% cases. Eighty percent of the C-erbB2 over-expressed cases were well differentiated and in stage II to stage IV disease. Dysplasia adjacent to carcinoma did not show any expression. No correlation was found with tumor grade, stage, gall stones, and patient survival. Xanthogranulomatous inflammation was inversely correlated with C-erbB2 over-expression. Median survival was 30 months in C-erbB2 over-expressed cases, and 12 months in C-erbB2 negative cases. CONCLUSION: We found complete membranous staining of C-erbB2 in 9.4% of GBC which was frequent in well differentiated and stage II to stage IV tumors. C-erbB2 tumors had longer median survival than C-erbB2 negative tumors. C-erbB2 is not involved early in the carcinogenetic process as none of the dysplasia showed expression. C-erbB2 over-expression may be considered as target for therapy in advanced stage of GBC.

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.

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.

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.

Role of E-cadherin gene in gall bladder cancer and its precursor lesions.

The aim was to investigate the genomic instability in the E-cadherin (CDH1) gene and to correlate it with its protein expression in gall bladder cancer (GBC) and in other gall bladder (GB) diseases viz. chronic cholecystitis (CC), xantho-granulomatous cholecystitis (XGC), and normal GB to explicate its role in GBC tumorigenesis. Microsatellite instability (MSI) and loss of heterozygosity (LOH) in CDH1 were studied using D16S421, D16S496, D16S503, D16S512, D16S2624, and D16S3021 microsatellite markers and D2S123 (2p16), D2S382 (2q24), D6S292 (6q21-23), D7S480 (7q31), and D17S796 (17p13.1-3) were used to investigate genomic instability at 2p, 2q, 6q, 7q, and 17p loci in 40 GBC, 50 CC, 34 XGC, and 15 normal GB cases. Immunohistochemistry was carried out to analyze the E-cadherin and p53 protein expression. Overall LOH in CDH1 and other markers was high in GBC and XGC as compared to CC; however, it did not correlate with its protein expression in GBC cases. Loss of E-cadherin expression was high in GBC (67%), while majority of the CC (94%) and XGC (91%) cases retained positive E-cadherin expression. Overexpression of p53 was high in GBC (43%) whereas CC, XGC, normal GB cases were negative for p53 overexpression. None of the normal GB cases showed genomic instability at any of the markers. High LOH in CDH1 and other chromosomal loci in GBC indicated that the genomic instability followed a GBC>XGC>CC trend during the process of neoplastic transformation in GB, highlighting the fact that CC might act as a precursor lesion of GBC.