Does perioperative hydrocortisone or indomethacin improve pancreatoduodenectomy outcomes? A triple arm, randomized placebo-controlled trial.

Backgrounds/Aims: This trial evaluated whether anti-inflammatory agents hydrocortisone (H) and indomethacin (I) could reduce major complications after pancreatoduodenectomy (PD). Methods: Between June 2018 and June 2020, 105 patients undergoing PD with > 40% of acini on the intraoperative frozen section were randomized into three groups (35 patients per group): 1) intravenous H 100 mg 8 hourly, 2) rectal I suppository 100 mg 12 hourly, and 3) placebo (P) from postoperative day (POD) 0-2. Participants, investigators, and outcome assessors were blinded. The primary outcome was major complications (Clavien-Dindo grades 3-5). Secondary outcomes were overall complications (Clavien-Dindo grades 1-5), Clinically relevant postoperative pancreatic fistula (CR-POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), surgical site infections (SSI), length of stay, POD-3 serum amylase, readmission rate, and mortality. Results: Major complications were comparable (8.6%, 5.7%, and 8.6% in groups H, I, and P, respectively). However, overall complications were significantly lower in group H than in group P (45.7% vs. 80.0%, p = 0.006). CR-POPF (14.3% vs. 25.7%, p = 0.371), PPH (8.6% vs. 14.3%, p = 0.710), DGE (8.6% vs. 22.9%, p = 0.188), and SSI (14.3% vs. 25.7%, p = 0.371) were comparable between groups H and P. Major complications and overall complications in group I were 5.7% and 60.0%, respectively, which were comparable to those in groups P and H. CR-POPF rates in groups H, I, and P were 14.3%, 17.1%, and 25.7%, respectively, which was comparable. Conclusions: H and I did not decrease major complications in PD.

Association of Postoperative Hyperamylasemia With Clinically Relevant Postoperative Pancreatic Fistula in Pancreatoduodenectomy.

Background In this study, we aimed to determine the association between postoperative hyperamylasemia (POH) and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). Methodology A prospective observational study of 140 consecutive PDs between March 2020 and March 2022 was conducted. POH was defined as an elevation in serum pancreatic amylase levels above the institutional upper limit of normal on postoperative day (POD) 1 (>100 U/L). CR-POPF was defined as the International Study Group of Pancreatic Surgery Grade B or C POPF. The primary outcome was the rate of CR-POPF in the study population. The trial was prospectively registered with Clinicaltrials.gov (NCT04514198). Results In our study, 93 (66.42%) patients had POH (serum amylase >100 U/L). CR-POPF developed in 48 (34.28%) patients: 40 type B and 8 type C. CR-POPF rate was 43.01% (40/93) in patients with POH compared to 17.02% (8/47) in patients without POH (p = 0.0022). Patients with POH had a mean serum amylase of 422.7 ± 358.21 U/L on POD1 compared to 47.2 ± 20.19 U/L in those without POH (p < 0.001). Serum amylase >100 U/L on POD1 was strongly associated with developing CR-POPF (odds ratio = 3.71; 95% confidence interval = 1.31-10.37) on logistic regression, with a sensitivity and specificity of 83.3% and 42.4%, respectively. Blood loss >350 mL, pancreatic duct size <3 mm, and elevated POD1 serum amylase >100 U/L were predictive of CR-POPF on multivariate analysis (p < 0.001). Conclusions An elevated serum amylase on POD1 may help identify patients at risk for developing POPF following PD.

Re-intervention rates and symptom-free survival at 1 year after endoscopic versus surgical management of strictures in Crohn's disease: A propensity matched analysis of a prospective inflammatory bowel disease cohort.

BACKGROUND AND AIM: Resection for Crohn's disease (CD) related strictures is definitive but carries risk of morbidity, recurrence, and short bowel syndrome. On the contrary, the durability of endotherapy (ET) for CD-related strictures is questionable. Prospective comparative studies are limited. We aimed to prospectively compare the outcomes of ET in CD strictures with a case-matched surgical therapy (ST) cohort. METHODS: Patients undergoing ET or resection for primary CD strictures (symptomatic, non-traversable, < 5 cm length, n ≤ 3) between January 2021 and March 2022 in a high-volume tertiary center were compared with regard to recurrent symptoms, escalation of therapy, re-intervention, and re-operation based on propensity matched analysis. RESULTS: Fifty-nine patients [49% ET, 57.6% male, median (years): 34 (15-74)] had ≥ 12 months of follow up. Before propensity matching, cumulative re-intervention rate was significantly higher with ET [34.5% (10/29) vs 3.3% (1/30) ST, P = 0.002]. Recurrent symptoms (34.5% vs 26.7%, P = 0.42), escalation of medical therapy (27.5% vs 23.3%, P = 0.64), and re-operation (7.4% vs 3.1%, P = 0.55) were comparable. In propensity matched analysis adjusted for demographics, disease, and stricture characteristics [n = 42, 21 each, 62% male, median (years): 32 (15-60)], cumulative probability of re-intervention rates was higher in ET (28.6% vs 4.8%, P = 0.042). The cumulative probability of recurrent symptoms (ET: 33.3% vs surgery 33.3%, P = 0.93), therapy escalation (ET: 23.8% vs surgery 28.6%, P = 0.75), and re-operation (ET: 9.5% vs surgery 4.8%, P = 0.57) was similar. CONCLUSIONS: ET for CD strictures require higher re-interventions compared with resection although re-operation could be avoided in the majority with comparable symptom free survival at 1 year.

Lesser prevalence of polyps/WNT-dysregulation and concomitant upregulation of gamma-catenin/MYC point to alternate pathways in colorectal cancer in India.

Colorectal cancer (CRC) is known to follow adenoma carcinoma sequence (ACS) in majority of the tumors and the driver variants and associated pathways are well delineated. However, most of the published data are from the west and information in other ethnicities is sparse. We therefore comprehensively evaluated the CRC tumors from Indian ethnicity for the prevalence of ACS. In this cohort study, clinical data of 100,497 patients who attended hospital between 2013 and 2018 were accessed. Tumors from patients (n = 130) with CRC who were treated primarily by surgery were included. DNA and RNA were isolated to assess variants (direct sequencing) and WNT-pathway dysregulation in genes related to ACS. Global gene expression was generated and analyzed on microarrays (Affymetrix; N = 10) and next generation sequencing platforms (Illumina; N = 25). Gene expression at mRNA (qRT-PCR) and protein level (IHC) of JUP/CTNNB1/MYC were assessed. Correlation between expression of JUP and MYC was evaluated by Karl Pearson's correlation coefficient. The prevalence of polyps was 16.75%, while 18.26% variants in APC/CTNNB1, 20.00% in KRAS, and 18.33% WNT dysregulation were noted. Interestingly, 29/60 (48.33%) tumors showed only MYC upregulation with normal APC/CTNNB1 expression. Global gene expression and validation in an independent tumor cohort confirmed concomitant upregulation of JUP (gamma-catenin) & MYC (r = 0.71; p = 0.001) at mRNA and protein in sizeable number of tumors (45/96; 46.88%). Our study provides evidence for limited prevalence of ACS in the Indian ethnicity. Preventive colonoscopies for early identification and management of CRC may not be an effective strategy in this ethnicity.

Indocyanine green guided sentinel lymph node biopsy may have a high sensitivity for early (T1/T2) colon cancer: A prospective study in Indian patients.

Objectives: Indocyanine green (ICG) dye guided near infrared fluorescence (NIR) imaging is a promising tool for mapping lymphatics. The aim of this study was to evaluate the role of ICG guided SLN biopsy in Indian colon cancer patients. Material and Methods: Forty-eight patients of clinically staged T1-T3 node negative colon cancer underwent laparoscopic/open resection. Patients received colonoscopic peritumoral submucosal ICG injections for laparoscopic (n= 32) and subserosal injections for open resections (n= 16) followed by the detection of SLN using NIR camera. SLNs underwent conventional hematoxylin and eosin (H & E) staging with additional serial sectioning and immunohistochemistry for pancytokeratin antibody (ultra-staging). Detection rate and upstaging rate were the primary end points. Results: Forty-eight patients were recruited. An average of 2.08 ± 1.27 SLNs were identified in 45 patients at a mean time of 8.2 ± 3.68 minutes with a detection rate of 93.75%. Mean age and mean BMI were 59.7 ± 12.54 years and 24.8 ± 4.09 kg/m2 , respectively. Eighteen patients had node positive disease, and SLN was false negative in four of these patients resulting in a sensitivity of 77.77% with a trend towards higher sensitivity for T1-T2 tumours (90% vs. 62.5%, p= 0.068). Upstaging rate was 10%. Negative predictive value (NPV) and accuracy of the procedure were 87.09% and 91.11%, respectively. Conclusion: ICG guided SLN biopsy can identify metastatic lymph nodes in colon cancer patients that can be missed on H & E staging with relatively higher sensitivity for early (T1/T2) tumours.

Circulating tumor DNA for monitoring colorectal cancer: A prospective observational study to assess the presence of methylated SEPT9 and VIM promoter genes and its role as a biomarker in colorectal cancer management.

Objectives: Methylation status of Septin9 (SEPT9) and vimentin (VIM) genes in circulating tumor DNA of colorectal cancer (CRC) patients is a promising bio-marker for the early detection of CRC. The aim of the present study was to identify the methylation status in promoter regions of the SEPT9 and VIM genes in a cohort of Indian patients with biopsy proven colorectal cancer. Material and Methods: Forty-five consecutive patients of colorectal cancer were recruited. 10 mL venous samples were collected from each patient and processed for isolation of cell-free DNA, bisulfite conversion of cell-free DNA, polymerase chain reaction (PCR) amplification and detection of SEPT9 and VIM genes. Results: Partial methylation in vimentin was present in 42.22% of the patients and 57.78% showed no methylation and none of the tumors had complete methylation. Only three (6.66%) patients showed complete methylation patterns in SEPT9 and the remaining 42 (93.33%) tumors showed partial methylation. Considering the two genes together, only three (6.66%) out of 45 showed complete methylation. The association of methylation patterns in both genes (complete, partial, and no methylation) with sex, age, T stage, N stage, M stage, CEA, histology, and location (right or left colon) were explored and none of these parameters were statistically significant. Conclusion: In our study, only 6.66% CRC patients showed hypermethylation and there was no association of methylation patterns in the both genes (complete, partial, and no methylation) with any of the parameters like age, sex, TNM stage, CEA, and histology.

Practice Patterns and Survival in Patients with Resected Pancreatic Ductal Adenocarcinomas (PDAC) - Results from the Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) Study.

BACKGROUND: There is limited data from India with regard to presentation, practice patterns and survivals in resected pancreatic ductal adenocarcinomas (PDACs). METHODS: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP) included data from 8 major academic institutions across India and presents the outcomes in upfront resected PDACs from January 2015 to June 2019. RESULTS: Of 288 patients, R0 resection was achieved in 81% and adjuvant therapy was administered in 75% of patients. With a median follow-up of 42 months (95% CI: 39-45), median DFS for the entire cohort was 39 months (95% CI: 25.4-52.5), and median overall survival (OS) was 45 months (95% CI: 32.3-57.7). A separate analysis was done in which patients were divided into 3 groups: (a) those with stage I and absent PNI (SI&PNI-), (b) those with either stage II/III OR presence of PNI (SII/III/PNI+), and (c) those with stage II/III AND presence of PNI (SII/III&PNI+). The DFS was significantly lesser in patients with SII/III&PNI+ (median 25, 95% CI: 14.1-35.9 months), compared to SII/III/PNI + (median 40, 95% CI: 24-55 months) and SI&PNI- (median, not reached) (p = 0.036)). CONCLUSIONS: The MIPPAP study shows that resectable PDACs in India have survivals at par with previously published data. Adjuvant therapy was administered in 75% patients. Adjuvant radiotherapy does not seem to add to survival after R0 resection.

Diagnostic yield and technical performance of the novel motorized spiral enteroscopy compared with single-balloon enteroscopy in suspected Crohn's disease: a prospective study (with video).

BACKGROUND AND AIMS: Both single-balloon enteroscopy (SBE) and the novel motorized spiral enteroscopy (NMSE) are effective techniques for device-assisted enteroscopy (DAE). To date, no study has prospectively compared both modalities in suspected Crohn's disease (CD). METHODS: Patients with suspected CD undergoing either SBE or NMSE between March 2021 and December 2021 in a high-volume tertiary center were prospectively compared for technical success (ability to reach the lesion), diagnostic yield, depth of maximal insertion (DMI), procedure time, and total enteroscopy rates. RESULTS: One hundred seventy-seven patients (37.2% female; aged 7-75 years) with suspected CD underwent 201 DAEs. Technical success was 83% (SBE 81.5% vs NMSE 87.3%, P = .61) and impacted subsequent management in 92% (SBE 88.5% vs NMSE 97.8%, P = .2). Technical success with antegrade NMSE was significantly higher (81.4%) than antegrade SBE (33.3%, P = .007) for lesions in the proximal ileum and beyond. There was no significant difference in the diagnostic yield (SBE 80.8% vs NMSE 83.6%, P = .65). Median procedure time was significantly lower in both antegrade (NMSE, 40 minutes [range, 10-75]; SBE, 60 minutes [range, 20-180]; P < .0001) and retrograde (NMSE, 25 minutes [range, 20-60]; SBE, 60 minutes [range, 20-180]; P < .0001) NMSE. Median DMI was higher with antegrade NMSE (NMSE, 400 cm [range, 70-600]; SBE, 180 cm [range, 60-430]; P < .0001). The total enteroscopy rate was higher with NMSE (37% vs .7% with SBE, P < .0001). All adverse events were mild. CONCLUSIONS: Both NMSE and SBE are safe and effective for small-bowel evaluation in suspected CD. NMSE is superior to SBE with regard to deeper small-bowel evaluation with complete small-bowel coverage and shorter procedure time.

Proposal of novel staging system CNM (Crohn's primary site, nodes, mesentery) to predict postoperative recurrence of Crohn's disease.

After oncologic resection, histological grading and staging of the tumor give important prognostic information about the future risk of recurrence and hence influence the subsequent management plan. Several studies and their meta-analysis have shown that various histological features (e.g., microscopic positive resection margins, plexitis, granuloma, mesenteric inflammatory activity) can predict postoperative clinical/endoscopic/surgical recurrence after resection in Crohn's disease (CD). Inclusion of mesentery in surgical resection specimens has been shown to reduce surgical recurrence after ileocolonic resection in CD. However, there is no uniform histopathological staging system for risk stratification in postoperative CD to systematically predict postoperative recurrence. This is because the prediction to date is based on clinical characteristics (smoking status, disease phenotype, surgical history). Histopathological predictors are still not adopted in routine clinical practice due to the lack of a uniform staging system, heterogeneity of published studies and lack of standardized definition of histological features. In this article, we attempted to incorporate all such histological features in a single histological staging system CNM (Crohn's primary site [resection margin positivity, plexitis, granuloma, depth of infiltration], nodes [presence of granuloma], mesentery [involved or not]) in surgical resection specimen in CD. The proposed CNM classification would help to enable systematic reporting, design future clinical trials, stratify postoperative recurrence risk and choose appropriate postoperative prophylaxis.

Primary Pancreatic Leiomyosarcoma: A Rare Malignant Transformation of Primary Pancreatic Head Leiomyoma.

Primary pancreatic leiomyosarcoma and primary pancreatic leiomyoma are rare tumors of the pancreas. Primary pancreatic leiomyoma is a benign tumor and its conversion to leiomyosarcoma has never been reported. We report a case of malignant transformation of pancreatic leiomyoma. In this case, a 75-year-old male, who presented with a mass in the head of the pancreas, was diagnosed with primary pancreatic leiomyoma. The patient maintained well on symptomatic treatment for 13 years. However, later the patient presented with loss of appetite, significant weight loss, and an abdominal lump, which was diagnosed to be locally advanced primary pancreatic leiomyosarcoma. The patient was provided the best supportive care and died after 11 months of diagnosis. Hence, we conclude that a more radical treatment approach is needed in patients with primary pancreatic leiomyoma.

Is intraoperative enteroscopy still relevant in small bowel disorders in the era of capsule endoscopy and device-assisted enteroscopy? Real-world experience from a tertiary care hospital.

BACKGROUND AND AIM: With the advent of video capsule endoscopy (VCE) and device-assisted enteroscopy (DAE), the indication of intraoperative enteroscopy (IOE) has become limited due to reported high morbidity/mortality. Most of the earlier studies on IOE were small/from pre-VCE/DAE era. We aimed to evaluate the impact of IOE in management of small bowel disorders (SBD) in post-VCE/DAE era. METHODS: Patients with SBD undergoing IOE over last 15 years were evaluated retrospectively. Overall diagnostic/therapeutic yield, incremental diagnostic yield over preoperative investigations, and adverse events were noted. We also evaluated the number of cases in which IOE changed the management or guided surgical or endoscopic therapy. Rebleeding and recurrence were evaluated in patients with available follow-up data. RESULTS: A total of 89 patients (59 male, 9-82 years) were included in the study. Overall diagnostic and therapeutic yield were 92.1% and 85.4%, respectively. Common findings of IOE were benign ulcers/strictures (30.1%), vascular lesions (26%), diverticula (15.1%), and tumors (13.7%). A total of 49.4% (44/89), 36% (32/89), and 20.2% (18/89) underwent VCE, DAE, or both, respectively, before IOE. Incremental diagnostic yield over preoperative work-up was 31.5% (28/89), and IOE changed the management in 37.1% (33/89) patients. IOE was used to guide surgery/endotherapy in 39.3% (35/89) patients. Recurrent gastrointestinal bleed occurred in 21.2% (14/66) patients. Morbidity and mortality rates were 20.2% (18/89) and 3.4% (3/89), respectively. CONCLUSIONS: Intraoperative enteroscopy remains an essential technique to evaluate SBD and can detect new and additional lesions even after extensive preoperative evaluation. IOE is useful in guiding therapy in preoperatively identified lesions and can change management in a substantial proportion of patients. Hence, IOE has a definitive role in post-VCE/DAE era in carefully selected patients with SBD.

Gallstones: A Worldwide Multifaceted Disease and Its Correlations with Gallbladder Carcinoma.

BACKGROUND: Gallstones (GS) associated diseases are among the most recurrent and frequent diseases delineated in India and United Arab Emirates. Several reports suggest that the association of GS with gallbladder cancer (GBC) is very high in Northern part of India; however, its occurrence in UAE and Southern part of India is notably low. Therefore, in the present study, we aimed to perform compositional analysis of GS in three different geographical areas by Solid State Nuclear Magnetic Resonance and Fourier Transformed Infrared spectroscopy. METHODS: Natural abundance 13C cross polarization magic angle spinning Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy is employed for the analysis of human gallstone. RESULTS: Cholesterol, bilirubin and calcium carbonate were present in variant concentrations in GS obtained from three different geographical regions. Cholesterol was present predominantly in gallstones from North India. Bilirubin was found to be a main constituent in gallstones pertaining to South India. Whereas GS from UAE showed both cholesterol and bilirubin as their major constituents. Calcium carbonate was found in varying concentrations in gallstones acquired from different regions. CONCLUSION: Variation in environmental condition and dietary habits may contribute and affect the GS formation. Alterations in bile composition influence the GB and augment the crystallization of cholesterol. Analysis of different geographical regions GS could be an important stride to understand the etiology of GS diseases.

Interferon-γ Decreases Nuclear Localization of Pdx-1 and Triggers ß-Cell Dysfunction in Chronic Pancreatitis.

Interferon-gamma (IFN-γ) is shown to play a major role in ß-cell dysfunction in chronic pancreatitis (CP). However, the underlying mechanisms are to be elucidated. The present study was conducted to determine the role of IFN-γ subverting insulin gene expression in CP. Pancreatic tissues from control (n=15) and CP patients (n=30) were analyzed for nuclear localization of pancreatic and duodenal homeobox transcription factor (Pdx-1) after ascertaining their diabetic status. By immunofluorescence and western blot analysis, the influence of IFN-γ, anti-inflammatory cytokine (interleukin-10), and anti-IFN-γ agent epigallocatechin-3-gallate (EGCG) on nuclear localization of Pdx-1was examined in the islets isolated from resected normal pancreatic tissue. Nuclear localization of Pdx-1 was 20.25±2.19 in the islets of diabetic CP patients and 31.44±2.09 in nondiabetic CP patients as compared with controls (60.45±5.11) and the corresponding distribution of Pdx-1 protein in the nuclear compartment was also decreased. Exposure of normal islets to IFN-γ revealed decreased nuclear localization of Pdx-1. Pretreatment with polyphenolic compound EGCG restored the nuclear localization of Pdx-1. These results suggest that IFN-γ induced ß-cell dysfunction is mediated through decreased nuclear localization of Pdx-1.

MicroRNA profiling in periampullary carcinoma.

BACKGROUND: MicroRNA expression patterns in many physiological and oncogenic processes have been established. However, the role of aberrant miRNA expression in periampullary carcinoma (PAC) has not been elucidated. We hypothesize that PAC may have differential expression of miRNAs which may differentiate the tumor histological subtypes. METHODS: Fresh paired tumor and control samples were collected from the PAC patients undergoing Whipple's pancreaticoduodenectomy. Microarray miRNA profiling was performed utilizing tumor (n = 40) and control tissues; adjacent normal pancreas (n = 22), six each distal CBD, duodenum and ampulla. Data obtained was subjected to statistical and bioinformatic analysis. Differentially expressed miRNAs obtained were validated using qPCR in an independent set of samples. RESULTS: Comparison of PAC tissue samples with controls revealed 29 common and differentially expressed miRNAs (20 upregulated and 9 downregulated) with a higher statistical significance (p < 0.001) and fold change (log2 FC > 1.5). A subset of 16 miRNAs (15 overexpressed and 1 underexpressed) differed in expression levels between pancreatobiliary and intestinal subtypes. Among these, miR-375, miR-31 and miR-196a expressions varied significantly between histological subtypes. Differential expression profiles of miRNAs specific to TNM staging was also observed in PAC subtypes. Target gene prediction for the differentially expressed miRNAs in PAC revealed that target genes are enriched for certain pathways. Particularly, Wnt signaling pathway genes appear to be relevant targets for most of the differentially expressed miRNAs. CONCLUSION: Differentially expressed common miRNA signatures identified in PAC subgroups may have a role in pathogenesis of PAC and miR-375, miR-31 and miR-196a expression patterns may differentiate PAC subtypes.

The diagnostic accuracy and strength of agreement between endoscopic ultrasound and histopathology in the staging of ampullary tumors.

AIM: Ampullary tumors are rare. Reports on ampullary tumor staging are heterogeneous and combine both periampullary and ampullary tumors. This study assessed the performance of endoscopic ultrasound (EUS) in the local staging of ampullary tumors only. METHODS: Data were collected retrospectively. We included patients with an ampullary tumor who underwent EUS and surgical resection. Tumor (T) and nodal (N) TNM staging for EUS and histopathological (HP) staging were compared. RESULTS: From 2009 to 2010, a total of 79 patients with ampullary tumors were identified. Of these, 26 had both EUS and Whipple's surgery and were included (28 did not undergo resection, 13 had palliative surgery only and 12 had resection without EUS). For T staging by HP, there were 2 (7.7 %) T1, 11 (42.3 %) T2, 12 (46.2 %) T3 and 1 (3.8 %) T4 tumors. The accuracy of EUS T staging was 73.1 % with a Kappa value of 0.564 (p < 0.0001). The sensitivity, specificity, positive predictive value (PPV), negative predictive values (NPV) of EUS, respectively were 50.0 %, 91.7 %, 33.3 % and 95.7 % for T1 tumors; 81.8 %, 80.0 %, 75.0 % and 85.7 % for T2; 75.0 %, 92.9 %, 90.0 % and 81.3 % for T3 tumors. For N staging by HP, 17 (65.4 %) were N0 and 9 (34.6 %) N1. The N staging diagnostic accuracy was 80.8 % with a Kappa value of 0.586 (p = 0.003). The sensitivity, specificity, PPV, NPV for N0 disease were 82.4 %, 77.8 %, 87.5 % and 70.0 %, respectively while for N1 they were 77.8 %, 82.4 %, 70.0 % and 87.5 %, respectively. CONCLUSIONS: EUS had a moderate strength of agreement with histopathology for both T and N staging, and a high diagnostic accuracy for nodal staging.

HER2 expression in gastric cancer in Indian population--an immunohistochemistry and fluorescence in situ hybridization study.

AIM: Human epidermal growth factor receptor (HER2, also known neu, ERBB2) protein expression in gastric cancer is associated with poor prognosis, aggressive disease and poor response to chemotherapy. Trastuzumab, a monoclonal antibody against HER2, in combination with chemotherapy is currently advocated as a new standard option for patients with HER2-positive advanced gastric and gastroesophageal junction carcinoma. Frequency of HER2 expression in gastric cancer has been reported from different geographic zones with a wide range of 13 % to 91 %. There are no reported data of HER2 protein expression in gastric cancer tissue from India. The purpose of this study was to evaluate the frequency of HER2 expression in gastric cancer. METHODS: The frequency of HER2 expression in 52 patients with gastric adenocarcinoma was prospectively evaluated over a six month period at Asian Institute of Gastroenterology from January 2010 to July 2010, using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). RESULTS: HER2 overexpression was confirmed in 23 of 52 (44.2 %) patients. Two patients had equivocal result by IHC (2+), one of whom was positive on analysis by FISH. There was no difference in HER2 overexpression (positivity) or negativity in relation to age, gender, tumor site, histological subtype, tumor differentiation, serosal involvement or lymph nodal status. HER2 overexpression rates were similar for intestinal type as compared to diffuse histological type (OR 1.84), as also for proximal as compared to distal gastric cancers (OR 0.81). CONCLUSION: HER2 overexpression was observed in significant number of advanced gastric adenocarcinoma patients. There was no difference in HER2 overexpression in relation to clinicopathological parameters.

Robot-assisted endoscopic submucosal dissection is effective in treating patients with early-stage gastric neoplasia.

BACKGROUND & AIMS: Endoscopic submucosal dissection (ESD) is a new technique for endoscopic resection of early-stage gastrointestinal cancers. Though ESD achieves high rate of en bloc resection, it is technically difficult to master. The development of a novel robotic endoscopic system that has 2 arms attached to an ordinary endoscope-Master and Slave Transluminal Endoscopic Robot (MASTER)-has improved the performance of complex endoluminal procedures. We evaluated the efficacy of MASTER-assisted ESD in treatment of patients with early-stage gastric neoplasia. METHODS: We performed a multicenter prospective study of 5 patients with early-stage gastric neoplasia, limited to the mucosa. After markings and circumferential mucosal incision, all submucosal dissections were performed using the MASTER system. We measured baseline demographics, tumor characteristics, and perioperative and clinical outcomes. RESULTS: All patients underwent successful MASTER-assisted ESD. The mean submucosal dissection time was 18.6 minutes (median, 16 minutes; range, 3-50 minutes). No perioperative complications were encountered. Three patients were discharged from the hospital within 12 hours and 2 on the third day after the procedures. Two patients were found to have intramucosal adenocarcinoma, 1 had high-grade dysplasia, 1 had low-grade dysplasia, and 1 had a hyperplastic polyp. The resection margins were clear of tumors in all 5 patients. No complications were observed at the 30-day follow-up examination. Follow-up endoscopic examinations revealed that none of the patients had residual or recurrent tumors. CONCLUSIONS: A flexible endoscopy robotic system can be used to perform ESD and effectively treat patients with early gastric neoplasia.

Hepatic cholesterol transporter ABCG8 polymorphisms in gallstone disease in an Indian population.

BACKGROUND AND AIM: Gallstone formation is characterized by the abnormal regulation of cholesterol trafficking and solubilization. The prevalence of gallstone disease (GSD) differs between ethnic groups sharing the common environment. These differences can be explained by a genetic predisposition to gallstone formation. Studies have identified single nucleotide polymorphisms (SNP) D19H and T400K in the cholesterol transporter gene ATP-binding cassette, subfamily G, member 8 (ABCG8) in patients with cholesterol gallstones. The aim of this study was to analyze the relationship between D19H and T400K polymorphisms in the ABCG8 gene and GSD in an Indian population, and the effects of these polymorphisms on cholesterol levels in sera and bile. METHODS: A total of 226 patients with GSD were analyzed for their lipid profile in plasma and bile. A total of 289 controls were recruited, and their plasma lipid profile was analyzed by standard protocols. The genotype of SNP D19H and T400K of ABCG8 was analyzed in 226 patients and 222 control samples. SNP D19H was analyzed by direct sequencing, and SNP T400K genotyping was assayed by the amplification refractory mutation system-polymerase chain reaction. RESULTS: There was no significant difference in the allelic distribution of SNP T400K between the GSD and gallstone-free groups (P > 0.05), but the distribution of the SNP variant, D19H, was significantly higher (P = 0.017, odds ratio = 2.274) in patients compared to controls. The analysis of serum and bile cholesterol followed a strong association with genotypes. CONCLUSION: SNP D19H, but not SNP T400K, in the ABCG8 gene is significantly associated with GSD in an Indian population.