Role of adjuvant therapy in resected periampullary adenocarcinoma: A propensity matched case-control study.

Backgrounds/Aims: The published data had contradictory information on the role of adjuvant therapy on resected periampullary carcinomas (PACA). The study was performed to evaluate the survival benefit of adjuvant treatment. Methods: This was a propensity score matched case-control study from a prospectively maintained database from 2004-2019. The study included patients with nonpancreatic PACA who underwent curative resection. The patients (cases) who received adjuvant chemotherapy were compared with patients (controls) who were observed alone after surgery. Results: Of 510 patients with PACA, 230 patients (cases = 107, controls = 123) formed the unmatched study cohort. After propensity score matching, 140 patients (cases = 70, controls = 70) formed the matched study cohort. The median overall survival (OS) was similar in cases than controls in the unmatched population but doubled non-significantly in cases after matching (unmatched population, 54 months vs. 54 months, p-value = 0.624; matched population, 71 months vs. 36 months, p-value = 0.087). However, the median recurrence-free survival (RFS) was non significantly higher in the control group (unmatched population, 59 months vs. 38 months, p-value = 0.195; matched population, 53 months vs. 40 months, p-value = 0.797). In cox regression analysis, age < 60 years, advanced T stage, and presence of perineural invasion were independent factors for worse RFS, while tumor recurrence was an independent factor for poor OS. Conclusions: Patients with nonpancreatic PACA may have an OS benefit from adjuvant chemotherapy, and this needs to be validated with large prospective randomized studies.

Solitary Fibrous Tumors of the Mesocolon: A Report of Two Cases and Review of Literature.

Solitary fibrous tumors (SFTs) are an uncommon group of neoplasms. The visceral pleura is the most common site of origin of these tumors. The colonic mesentery is an unusual site of origin of SFTs. A pre-operative diagnosis of SFT is challenging as there are no pathognomonic clinical or radiological signs. Most patients reported thus far were diagnosed post-operatively with the aid of immunohistochemical markers. Complete surgical excision is the treatment of choice for SFTs. Recurrences are uncommon. However, they can occasionally show aggressive behavior. In this report, we describe two cases of rare colonic mesentery SFTs.

The outcome of 100 patients with achalasia cardia following laparoscopic Heller myotomy with blunt dissection technique.

Background: Laparoscopic Heller myotomy (LHM) can be performed by blunt dissection technique (BDT). Only a few studies have assessed long-term outcomes and relief of dysphagia following LHM. The study reviews our long-term experience following LHM by BDT. Methods: This retrospective study was analysed from a prospectively maintained database (from 2013 to 2021) of a single unit of the Department of Gastrointestinal Surgery at G. B. Pant Institute of Postgraduate Medical Education and Research, New Delhi. The myotomy was performed by BDT in all patients. A fundoplication was added in selected patients. Post-operative Eckardt score >3 was considered treatment failure. Results: A total of 100 patients underwent surgery during the study period. Of them, 66 patients underwent LHM, 27 underwent LHM with Dor fundoplication and 7 underwent LHM with Toupet fundoplication. The median length of myotomy was 7 cm. The mean operative time was 77 ± 29.27 min and the mean blood loss of 28.05 ± 16.06 ml. Five patients had intraoperative oesophageal perforation. The median length of hospital stay was 2 days. There was no hospital mortality. The post-operative integrated relaxation pressure (IRP) was significantly lower than the mean pre-operative IRP (9.78 vs. 24.77). Eleven patients developed treatment failure, of which ten patients presented with recurrence of dysphagia. There was no difference in symptom-free survival amongst various types of achalasia cardia (P = 0.816). Conclusion: LHM performed by BDT has a 90% success rate. Complication using this technique is rare, and recurrence post-surgery can be managed with endoscopic dilatation.

An audit of Complicated Choledochal Cysts- 15-years' experience at a tertiary care center.

PURPOSE: Complicated choledochal cysts (CDC) have a variable presentation, and their management differs from an uncomplicated CDC. They are infrequently reported. We present our 15 years of experience in the management of complicated CDC. METHODOLOGY: We reviewed the data of patients with CDCs managed at a tertiary level center from 2005 to 2020 from a prospectively maintained database. RESULTS: Of 215 patients with CDC, 123 patients presented with complicated CDC. The median age of complicated CDC was 31 years with a female preponderance (62.6%). The most common type of CDC associated with complications was type I (69.1%), followed by type IVA (29.3%). The Complicated CDC was presented as cholangitis with or without cystolithiasis (n = 45), cystolithiasis and hepatolithiasis(n = 44), malignancy(n = 10), complications associated with incomplete cyst excision (n = 10), acute pancreatitis (n = 8), chronic pancreatitis(n = 8), portal hypertension (n = 6), spontaneous rupture (n = 4), gastric outlet obstruction (n = 1). These patients were managed as a one-stage approach (52.03%) and a two-stage approach (47.96%). On univariate and multivariate analysis, increasing age, prolonged duration of symptoms, and presence of abnormal pancreaticobiliary ductal junction (APBDJ) were significantly associated with complicated CDC. CONCLUSION: The management of complicated CDC varied depending on the associated pathology, many of them required a staged approach. Increasing age, prolonged duration of symptoms, and presence of APBDJ were significantly associated with complicated CDC.

Primary Hepatic Choriocarcinoma with Pregnancy: A Diagnostic and Therapeutic Challenge.

Choriocarcinoma occurs mainly in the gonads, but an extragonadal origin has been reported, albeit infrequently. Primary hepatic choriocarcinoma (PHC) is a rare malignancy, with only 11 cases reported. Most cases reported were in males, with none reported in pregnant females. A 23-year-old primigravida presented with a large liver lesion involving the right lobe of the liver at 28 weeks of pregnancy. Preoperative imaging was suggestive of hepatocellular carcinoma. She underwent a non-anatomical resection of the liver lesion. Surprisingly, her postoperative histopathology revealed a diagnosis of PHC. Her blood workup showed elevated beta human chorionic gonadotrophin. She underwent a termination of her pregnancy at 32 weeks. Before initiating adjuvant chemotherapy four weeks after surgery, a whole-body PET scan revealed multiple bi-lobar liver and pelvic deposits. After a multidisciplinary team discussion, she was started on adjuvant chemotherapy. She is currently under regular follow-up, seven months post-surgery. PHC, one of the vascular lesions of the liver, poses a diagnostic and therapeutic challenge, warranting a multidisciplinary approach.

Molecular aspects of ABCB1 and ABCG2 in Gallbladder cancer and its clinical relevance.

The function of ABC transporters in the body is manifold; such as maintenance of homeostasis, effect on multi-drug resistance and their role in tumor initiation & progression. Evidence pointing towards the direct or indirect role of ABC transporter genes in particular; ABCB1 and ABCG2 in cancer genesis is increasing. However, their role in gallbladder cancer is unexplored. Therefore, we investigated the methylation status and expression pattern of ABCB1 and ABCG2in gallbladder carcinogenesis. The methylation and expression study of ABCB1/MDR1 and ABCG2/BCRP was performed in tumour and normal fresh tissue samples collected from 61 histopathologically diagnosed gallbladder cancer patients. The methylation status was analysed by Methylation-Specific PCR and expression was determined by Real-Time PCR and Immunohistochemistry. Hypomethylation of ABCB1 and ABCG2 was found in 44 (72.13%) and 48 (78.6%) cases, respectively. ABCB1 hypomethylation pattern showed association with female patients (p = 0.040) and GradeII tumors (p = 0.036) while, ABCG2 hypomethylation was more frequent in early tumors (T1-T2). The mRNA expression ofABCB1 and ABCG2 was up-regulated in 33 (54.10%) and 41 (67.21%) patients with fold change of 4.7 and 5.5, respectively. The mRNA expression of both genes showed association with Grade II tumours and the increased fold change of ABCG2 was higher in (T1-T2) depth of invasion (p = 0.02) and Stage I-II disease (p = 0.08). The protein expression on IHC was strongly positive for ABCB1/MDR1and ABCG2/BCRP in 32 (52.46%) and 45 (73.77%) patients, respectively. The protein expression in ABCG2 showed association with patients age > 50 years (p = 0.04) and GradeII differentiation (p = 0.07). Interestingly, the hypomethylation of both the genes showed significant correlation with increased expression. ABCB1/MDR1 and ABCG2/BCRP hypomethylation and overexpression could have a potential role in gallbladder cancer tumorigenesis especially in early stages. The epigenetic change might be a plausible factor for altered gene expression of ABCB1 and ABCG2 in gallbladder cancer.

Is central pancreatectomy an effective alternative to distal pancreatectomy for low-grade pancreatic neck and body tumors: A 20-year single-center propensity score-matched case-control study.

Backgrounds/Aims: Central pancreatectomy (CP) is associated with a higher rate of postoperative pancreatic fistula (POPF), and it is less preferred over distal pancreatectomy (DP). We compared the short- and long-term outcomes between CP and DP for low-grade pancreatic neck and body tumors. Methods: This was a propensity score-matched case-control study of patients who underwent either CP or DP for low-grade pancreatic neck and body tumors from 2003 to 2020 in a tertiary care unit in southern India. Patients with a tumor >10 cm or a distal residual stump length of < 4 cm were excluded. Demographics, clinical profile, intraoperative and postoperative parameters, and the long-term postoperative outcomes for exocrine and endocrine insufficiency, weight gain, and the 36-Item Short Form Survey (SF-36) quality of life questionnaire were compared. Results: Eighty-eight patients (CP: n=37 [cases], DP: n=51 [control]) were included in the unmatched group after excluding 21 patients (meeting exclusion criteria). After matching, both groups had 37 patients. The clinical and demographic profiles were comparable between the two groups. Blood loss and POPF rates were significantly higher in the CP group. However, Clavien-Dindo grades of complications were similar between the two groups (p = 0.27). At a median follow-up of 38 months (range = 187 months), exocrine sufficiency was similar between the two groups. Endocrine sufficiency, weight gain, SF-36 pain control score, and general health score were significantly better in the CP group. Conclusions: Despite equivalent clinically significant morbidities, long-term outcomes are better after CP compared to DP in low-grade pancreatic body tumors.

A case series of choledochal cyst with pancreatic divisum: A rare association.

Choledochal cysts (CC) are congenital cystic dilations of the biliary tree usually associated with abnormal pancreaticobiliary ductal junction (APBDJ), but its association with pancreatic divisum has been rarely described. We encountered four cases of CC associated with pancreatic divisum (PD). Three had Type 3 PD and one had Type 1 PD. Two cases presented with pancreatic complications, with one case requiring preoperative minor papilla sphincterotomy for recurrent pancreatitis. The association of CC with PD is infrequent, and the variable presentation alters management strategy. PD may be one of the factors responsible for complications associated with CC.

Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection.

BACKGROUND: Gallbladder carcinoma (GBC) has a dismal prognosis even after curative resection. The objective of the study was to evaluate the effect of adjuvant chemotherapy in patients with GBC undergoing curative resection in a randomized control trial (RCT). METHODS: A single-center open-labeled prospective RCT was done from January 2012 to June 2018. R0 curative resected GBC patients were randomized in 1:1 to either surveillance alone (control group) or adjuvant chemotherapy (gemcitabine and cisplatin (GemCis group)) for 6 cycles. The primary outcome was disease-free survival (DFS), and the secondary outcomes were overall survival (OS) and toxicity profile. RESULTS: On the evaluation of 362 patients with GBC, 50 patients were enrolled in each control or GemCis group. Per protocol (PP), it comprised 96 patients. The demographic and clinical profile was similar between the two groups except in the lower nodal stage where patients were higher in the control group (p = 0.01). Recurrences were similar between groups (control 44% vs GemCis 56%; p = 0.23). On the intention to treat (ITT), analyses of median DFS (not reached vs. 24 months, p = 0.14) and OS (not reached vs. 31 months, p = 0.10) were similar between groups. On PP, analyses of median DFS (not reached vs. 24 months, p = 0.16) and OS (not reached vs. 31 months, p = 0.09) were similar between groups. The common toxicity profile was hematological followed by gastrointestinal symptoms. CONCLUSIONS: Adjuvant GemCis therapy for 6 cycles does not improve DFS or OS than R0 surgery alone patients with GBC. TRIAL REGISTRATION: NCT02778308 ( https://www.clinicaltrials.gov ).

Laparoscopic versus open surgical management of patients with chronic pancreatitis: Amatched case-control study.

BACKGROUND: The safety and feasibility of laparoscopic surgery in patients with chronic pancreatitis (CP) have been established, but its outcome has not been compared to that of open surgery. PATIENTS AND METHODS: This retrospective study was conducted on patients with CP who were treated by a single surgical team from 2012 to 2018. The medical records of patients with surgical treatment of CP were reviewed. Patients were divided into laparoscopic group (LG) and open group (OG). Both the groups were matched for age and procedures. The matched groups were compared. RESULTS: The total number of unmatched patients was 99 and post matching, there were 38 patients in each group. The demographic, aetiological, clinical and laboratory parameters were comparable. The number of each surgical procedure including bilio-enteric anastomosis was also similar. Lateral pancreaticojejunostomy was the most common surgical procedure in both the groups. An additional surgical procedure (bilio-enteric bypass) was required in 10.5% of the patients in LG and 21% of the patients in OG groups (P = 0.3). Significantly lower blood loss (100 vs. 120 ml) and higher operation time (300 vs. 210 min) were observed in LG. The post-operative complication rate was 7.9% in LG group versus 10.5% in OG group. More than 85% of the patients in both the groups had a significant relief from pain. The impact of exocrine and endocrine insufficiency was not remarkable in both the groups. The requirement of an additional surgical procedure was associated with a high conversion rate. CONCLUSIONS: The outcomes of laparoscopic surgery in patients with CP were similar to that of open surgery, and requirement of an additional surgical procedure is associated with a high conversion rate.

Bi-segmentectomy versus wedge hepatic resection in extended cholecystectomy for T2 and T3 gallbladder cancer: A matched case-control study.

BACKGROUNDS/AIMS: Extended cholecystectomy (EC) is the mainstay of treatment in most patients with potentially curable gallbladder cancer (GBC). The optimum extent of hepatic resection in EC is debatable. METHODS: This retrospective study was conducted on patients with GBC who received EC from May 2009 to February 2019. Based on the extent of hepatic resection, patients were divided into ECB (EC involving bi-segmentectomy s4b&5) and ECW (EC involving wedge hepatic resection) groups. Patients with T1 GBC, T4 GBC, and benign diseases were excluded. Post-exclusion, both groups were matched for T and N stage. Matched groups were then compared. RESULTS: Out of a total of 161 patients who received EC, 86 patients had ECB and 75 patients had ECW. After exclusion and matching, both ECB and ECW groups had 35 patients. Their demographic and clinical profiles were comparable. Surgical blood loss (p = 0.005) and postoperative complication rate (p = 0.035) were significantly less in the ECB group. For ECB vs. ECW, mean recurrence-free survival (RFS) was 58.2 months vs. 42.3 months (p = 0.264) and overall survival (OS) was 61.5 months vs. 43.4 months (p = 0.161). On univariate analysis, higher T and N stages were associated with poor prognosis. On multivariate analysis, higher T stage, N stage, and American Society of Anaesthesiologists grade were associated with poor RFS and OS. CONCLUSIONS: The survival after ECB for T2 and T3 GBC was not significantly superior to that after ECW. However, surgical blood loss and postoperative complications were lower following ECB.

Management of Obscurely Dilated Common Bile Duct with Normal Liver Function Tests: A Pragmatic Approach.

OBJECTIVE: Dilated common bile duct (CBD) (8-15 mm) with normal liver function tests is seen not infrequently, while management of such patients is ambiguous. We propose a treatment algorithm for this cohort of patients after observing them over a period of 8 years. METHODS: Seventy-eight such patients were managed from 2009 to 2017 and categorized as: Group A-dilated CBD with post-cholecystectomy status (n = 15); B-dilated CBD with cholelithiasis (n = 34); C-dilated CBD without cholelithiasis (n = 16); D-dilated CBD with no cause identified and underwent CBD excision (n = 13). Causes for CBD dilatation were evaluated. The outcome of patients in Group B + C without any cause (n = 33) was compared with Group D. RESULT: Median age, CBD diameter, bilirubin and alkaline phosphatase were 51 years (13-79), 10 mm (8-20), 0.6 mg/dl (0.2-2.5) and 126 IU (60-214), respectively. Group-A patients who did not manifest any cause of CBD dilatation were managed conservatively. The aetiology was identified in 17/50 patients in Group B & C [acute pancreatitis (n = 6), passed CBD calculi (n = 3), perivaterian diverticulum (n = 3), viral aetiology (n = 4) and tumour (n-1)]. In Group-C, 7 patients with no obvious cause underwent endoscopic sphincterotomy, pancreatoduodenectomy (n = 1), and the rest were managed conservatively (n = 8). There was no significant difference in the complication between Group B + C (without any cause) and Group D (3/33 vs. 1/13; p = 0.58) at a median follow-up of 72 months (30-90). CONCLUSION: Dilated CBD with normal LFT's without apparent cause is mostly benign and of no consequence. Excision of the CBD is not required for most of these patients.

Laparoscopic versus open extended cholecystectomy with bi-segmentectomy (s4b and s5) in patients with gallbladder cancer.

INTRODUCTION: The outcome of laparoscopic extended cholecystectomy (EC) with wedge hepatic resection (LECW) in patients with gallbladder cancer (GBC) has been compared with that of open EC with wedge hepatic resection (OECW), but studies comparing laparoscopic EC with bi-segmentectomy (LECB) with open EC with bi-segmentectomy (OECB) are lacking. PATIENTS AND METHODS: This retrospective study comprised of 68 patients with GBC who were offered either LECB or OECB from July 2011 to July 2018. Patients were divided into laparoscopic group (LG) and open group (OG), and appropriate statistical methods were used for comparison. RESULTS: Out of the total 68 patients, 30 patients were in LG and 38 patients were in OG. Demographic, clinical and biochemical characteristics were similar except significantly higher number of male patients in OG (P = 0.01). In LG versus OG, the mean operation time was 286 versus 274 min (P = 0.565), mean blood loss was 158 versus 219 ml (P = 0.006) and mean hospital stay was 6.4 versus 9 days (P = 0.0001). The complication rate was 16.6% in LG and 31.5% in OG, but this difference was not statistically significant (P = 0.259). The median number of lymph nodes was 12 in both LG and OG (P = 0.62). Distribution of patients among American Joint Committee on Cancer stages I to IV was similar in both the groups (P = 0.5). Fifty percent of the patients in both the groups received adjuvant treatment (P = 1). In LG versus OG, the recurrence rate was 20% versus 28.9% (P = 0.4), mean recurrence-free survival was 48 months versus 44 months (P = 0.35) and overall survival was 51 months versus 46 months (P = 0.45). In LG versus OG, 1, 3 and 5-year survival was 96% versus 94%, 79% versus 72% and 79% versus 62% (P = 0.45). The median follow-up was statistically significantly shorter (24 vs. 36 months) in LG versus OG (P = 0.0001). CONCLUSIONS: The oncological outcome and survival after LECB in patients with resectable GBC is not inferior to that after OECB. Laparoscopic approach has a potential to improve perioperative outcome in patients with GBC.

Raised CA19-9 and CEA have prognostic relevance in gallbladder carcinoma.

BACKGROUND: Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoma embryonic antigen (CEA) in patients with GBC. METHODS: Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19-9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence. RESULTS: The median value of Ca19-9 was significantly higher in metastatic group [resectable: 21.3, unresectable: 53.9 and metastatic: 79; p < 0.001] but not for CEA [3.5, 7.8 and 5 ng/ml (p = 0.20)]. A cutoff value of 72 IU/ml for CA19-9, 5 ng/ml for CEA had a sensitivity and specificity of 52 and 80%, 51 and 72% respectively for detection of metastatic disease. Median, 3-year & 5-year survival were significantly lower in patients with CEA > 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8). CONCLUSIONS: Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence.

Laparoscopic versus open surgical management of patients with Mirizzi's syndrome: A comparative study.

INTRODUCTION: Open surgical management is considered as 'standard of care' for patients with Mirizzi's syndrome (MS). Laparoscopic management of MS has been reported, but comparative studies are lacking. PATIENTS AND METHODS: This retrospective study included patients with MS who were treated by a single surgical team from May 2009 to December 2017. Patients with total laparoscopic surgery were included in laparoscopic group (LG) and patients with total open surgery were included in open group (OG). Patients with conversion to open surgery and patients with gallbladder cancer (GBC) were excluded from the study. RESULTS: Total patients were 75; six patients with GBC and 11 patients with open conversion were excluded from comparison. LG had 32 patients and OG had 26 patients. Demographic, clinical and laboratory parameters were similar. Laparoscopic versus open preoperative diagnosis rate was 87.5% versus 69.2% (P = 0.08), respectively. OG had a large number of patients with concomitant bile duct stone; therefore, bile duct exploration rate was higher in OG (P = 0.009). Laparoscopic versus open, mean duration of surgery - 137 min versus 145 min (P = 0.664); mean blood loss - 45 mL versus 70 mL (P = 0.04); mean hospital stay - 4.5 versus 8.1 days (P = 0.027). Post-operative complication rate was 21.8% in LG and 42.3% in OG (P = 0.355); bile leak was noted in OG only (P = 0.042). LG versus OG mean follow-up was 50 versus 38 months (P = 0.189); no remote complication was observed in both groups. CONCLUSION: The results of laparoscopic surgery in patients with Mirizzi's syndrome are not inferior to that of open surgery; rather it may help to improve perioperative outcome in selected patients.