Nariman Karanjia

Liposarcoma is the most common malignant soft tissue tumour in adults occurring predominantly in the retroperitoneum and extremities but very rarely within the gastrointestinal tract. We report on a 77-year-old gentleman who presented with a history of melaena and anaemia. On oesophagogastric duodenoscopy a duodenal polyp was identified. Surgical excision was performed and on histology, the duodenal polyp revealed a primary duodenal well differentiated liposarcoma. A literature review confirmed the rarity of primary duodenal liposarcomas, with only four cases previously reported.

Background Patients with chronic pancreatitis experience malnutrition, osteoporosis, pancreatic exocrine insufficiency and have a 80% lifetime risk of diabetes (1). These are progressive consequences and require proactive surveillance for detection and optimisation of treatment. The NICE pancreatitis guidelines recommend long-term follow up for patients with chronic pancreatitis (1). European guidelines recommend regular assessment of bone density, biochemical assessment of micronutrient status and a comprehensive nutritional assessment (2).   The aim of this survey was to assess compliance with the NICE guidelines by analysing current practice in patients with chronic pancreatitis after pancreaticoduodenectomy. Methods A UK wide electronic survey was developed using Qualtrics® software (SAP America Inc. USA) to capture all the nutritional aspects of follow-up thought to be relevant in the long term. Markers of endocrine failure and malnutrition (weight, nutritional assessment and b...

Background Pancreatico-duodenectomy (PD)  results in major anatomical changes that have an impact on nutritional status and quality of life. Issues such as pancreatic exocrine insufficiency (PEI), diabetes mellitus (DM), malnutrition, micronutrient deficiency, osteoporosis and other gastrointestinal diseases are common in the post-operative setting (1, 2). Appropriate treatment of these surgical consequences is associated with improved survival (3, 4), and should improve quality of life. The aim of this survey was to assess current practice and identify which disciplines were reviewing patients following PD, what format that review takes and the duration of follow up. Methods A UK wide electronic survey was developed using Qualtrics® software (SAP America Inc. USA) to capture all the nutritional aspects of follow up thought to be relevant in the long term. Markers of endocrine failure and malnutrition (weight, nutritional assessment and biochemical vitamin and mineral screens), smok...

Aims Homeobox (HOX) proteins are emerging as promising biomarkers and targets for gene-therapy in cancer; however, their role in colorectal liver metastases (CRLM) is unknown. This study aims to investigate the role of HOXB9 as prognostic marker and potential therapeutic target in CRLM. Methods Two patient-cohorts were included: a) Patients with colorectal cancer (CRC) from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database (n = 614) and b) Institutional patient cohort who underwent liver resection for CRLM (n = 110) between 2007-2014. Primary outcome was 10-year overall survival (OS). COX regression and Kaplan-Meier survival analyses were performed including HOXB9 expression, demographics, clinicopathological and treatment-related variables. HOXB9 gene expression was modulated to assess its impact on CRC cell growth in vitro. Therefore, we conducted experimental studies using plasmid-vector and siRNA-interference to overexpress and knockdown HOXB9 respectivel...

Intraductal papillary mucinous neoplasm (IPMN) is a unique pancreatic neoplasm developing in the ductal system. Two major histologic subtypes have been reported, that is the gastric type and the intestinal type. However, their histopathologic features, especially those of the gastric type, have not been fully described. To evaluate the features of these two types and refine their differences, we analyzed 80 IPMNs including 50 cases of the gastric type and 30 cases of the intestinal type with mucin immunohistochemistry. By defining a main duct-type lesion as predominantly involving the main pancreatic duct with or without branch ducts, and a branch duct-type lesion as exclusively centered on branch ducts or consisting of a collection of small cystic lesions, gastric-type IPMNs were mostly branch duct-type lesions (98%), whereas the intestinal-type IPMNs were usually main duct type (73%). The histologic grade of the intestinal type was generally higher than that of the gastric type. The intestinal type was also characterized by frequent intraluminal nodular growth, and severe atrophy and fibrosis of the surrounding parenchyma with mucous lake formation. In contrast, pyloric glandlike structures at the base of the papillae and pancreatic intraepithelial neoplasia (PanIN)-like complexes were more frequently observed in the gastric type. A significant difference was observed between the gastric type and the intestinal type with regard to all the above features (P<0.05). Seven cases (23%) of the intestinal type were associated with an invasive adenocarcinoma (6 mucinous and 1 ductal), versus only 1 case (2%) of the gastric type (invasive ductal carcinoma). All cases of both gastric and intestinal types expressed MUC5AC; however, high immunolabeling scores for MUC2 were mostly observed in the intestinal type (P<0.05). In conclusion, gastric and intestinal types of IPMNs have distinct histopathologic features and mucin profiles, suggesting that they may follow different biologic pathways.

Stage IV colorectal cancer encompasses a broad patient population in which both curative and palliative management strategies may be used. In a phase II study primarily designed to assess the efficacy of capecitabine and oxaliplatin, we were able to prospectively examine the outcomes of patients with stage IV colorectal cancer according to the baseline resectability status. At enrolment, patients were stratified into three subgroups according to the resectability of liver disease and treatment intent: palliative chemotherapy (subgroup A), conversion therapy (subgroup B) or neoadjuvant therapy (subgroup C). All patients received chemotherapy with capecitabine 2000 mg m(-2) on days 1-14 and oxaliplatin 130 mg m(-2) on day 1 repeated every 3 weeks. Imaging was repeated every four cycles where feasible liver resection was undertaken after four or eight cycles of chemotherapy. Of 128 enrolled patients, 74, 22 and 32 were stratified into subgroups A, B and C, respectively. Attempt at cura...

Introduction Afferent loop syndrome (ALS) is a recognised complication of foregut surgery caused by mechanical obstruction at the gastrojejunostomy anastomosis itself or at a point nearby. Acute ALS has only been reported following pancreaticoduodenectomy (PD) after several years due to recurrence of malignancy at the anastomotic site. We report five cases of acute ALS in the first postoperative week. Methods The presentation, clinical findings and successful management of the 5 patients with ALS were obtained from a prospectively collected database of 300 PDs. All five patients with early acute ALS presented with signs and symptoms of a bile leak. Since the fifth patient, the surgical technique has been modified with the creation of a larger window in the transverse mesocolon and a Braun enteroenterostomy. Results There have been no further incidents of ALS since the adoption of these modifications to the standard technique of PD and there has also been a reduction in postoperative...

ABSTRACT Emergency presentation of diseases of the upper gastrointestinal tract represents a significant proportion of the acute general surgical workload with gallstone disease representing only a slightly smaller burden than acute appendicitis. Peptic ulcer disease, gallstones and pancreatitis are the three most common emergency conditions of the supra-colic compartment and their initial management should be within the capabilities of all general surgeons who contribute to an emergency service. The clinician’s approach to all three conditions has undergone changes due to new pharmacological and technological advances, however a sound understanding of the clinical presentation and natural history remains essential to their safe management. This article will deal with practical aspects of dealing with these patients in the emergency setting.

Background The clinical benefits of enhanced recovery programs (ERPs) have been extensively researched, but few studies have evaluated their cost-effectiveness. Our ERP for open liver resection is based closely on the guidelines produced by the Enhanced Recovery After Surgery Society (2016). This study follows on from a previous randomized controlled trial. We also undertook a long-term follow-up of the patients enrolled in the original trial alongside an analysis of the associated health economics. Objective We aimed to undertake a health economic and long-term survival analysis as part of a trial investigating the implementation of an ERP for open liver resection. Methods The enhanced recovery elements utilized included extra preoperative education, carbohydrate loading, oral nutritional supplements, postresection goal-directed fluid therapy (LiDCOrapid), early mobilization, and physiotherapy (twice a day compared with once per day in the standard care group). A decision-analytic ...

Surgery for colorectal liver metastases results in an overall survival of about 40% at 5 years. Progression-free survival is increased with the addition of oxaliplatin and fluorouracil chemotherapy. The addition of cetuximab to these chemotherapy regimens results in an overall survival advantage in patients with advanced disease who have the KRAS exon 2 wild-type tumour genotype. We aimed to assess the benefit of addition of cetuximab to standard chemotherapy in patients with resectable colorectal liver metastasis. Patients with KRAS exon 2 wild-type resectable or suboptimally resectable colorectal liver metastases were randomised in a 1:1 ratio to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done using minimisation with factors of surgical centre, poor prognostic tumour (one or more of: ≥ 4 metastases, N2 disease, or poor differentiation of primary tumour), and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m(2) intravenously over 2 h and fluorouracil bolus 400 mg/m(2) intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m(2) repeated every 2 weeks (regimen one) or oxaliplatin 130 mg/m(2) intravenously over 2 h and oral capecitabine 1000 mg/m(2) twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m(2) intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given as an intravenous dose of 500 mg/m(2) every 2 weeks with regimen one and three or a loading dose of 400 mg/m(2) followed by a weekly infusion of 250 mg/m(2) with regimen two. The primary endpoint was progression-free survival. This is an interim analysis, up to Nov 1, 2012, when the trial was closed, having met protocol-defined futility criteria. This trial is registered, ISRCTN22944367. 128 KRAS exon 2 wild-type patients were randomised to chemotherapy alone and 129 to chemotherapy with cetuximab between Feb 26, 2007, and Nov 1, 2012. 117 patients in the chemotherapy alone group and 119 in the chemotherapy plus cetuximab group were included in the primary analysis. The median follow-up was 21.1 months (95% CI 12.6-33.8) in the chemotherapy alone group and 19.8 months (12.2-28.7) in the chemotherapy plus cetuximab group. With an overall median follow-up of 20.7 months (95% CI 17.9-25.6) and 123 (58%) of 212 required events observed, progression-free survival was significantly shorter in the chemotherapy plus cetuximab group than in the chemotherapy alone group (14.1 months [95% CI 11.8-15.9] vs 20.5 months [95% CI 16.8-26.7], hazard ratio 1.48, 95% CI 1.04-2.12, p=0.030). The most common grade 3 or 4 adverse events were low neutrophil count (15 [11%] preoperatively in the chemotherapy alone group vs six [4%] in the chemotherapy plus cetuximab group; four [4%] vs eight [8%] postoperatively), embolic events (six [4%] vs eight [6%] preoperatively; two [2%] vs three [3%] postoperatively), peripheral neuropathy (six [4%] vs one [1%] preoperatively; two [2%] vs four [4%] postoperatively), nausea or vomiting (four [3%] vs six [4%] preoperatively; four [4%] vs two [2%] postoperatively), and skin rash (two [1%] vs 21 [15%] preoperatively; 0 vs eight [8%] postoperatively). There were three deaths in the chemotherapy plus cetuximab group (one interstitial lung disease and pulmonary embolism, one bronchopneumonia, and one pulmonary embolism) and one in the chemotherapy alone group (heart failure) that might have been treatment related. Addition of cetuximab to chemotherapy and surgery for operable colorectal liver metastases in KRAS exon 2 wild-type patients results in shorter progression-free survival. Translational investigations to explore the molecular basis for this unexpected interaction are needed but at present the use of cetuximab in this setting cannot be recommended.

Aims Pre-B-cell Leukaemia (PBX) genes are important in organ development during embryogenesis. To date, four members of the PBX family (PBX1, PBX2, PBX3, PBX4) have been identified to be involved in human cancers, but little is known about their role in colorectal cancer (CRC). The aim of this study was to determine their differential expression, prognostic role and function in CRC. Methods Molecular and overall survival (OS) data from 614 patients with CRC were obtained from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database. To investigate the differential PBX gene mRNA expression, we performed a comparative cancer to normal computational analysis in edgeR. To determine PBXs prognostic value, we conducted Kaplan-Meier survival analysis and COX regression, selecting 10-year OS as primary outcome. Lastly, to explore the effect of PBX4 in CRC cell growth and angiogenesis, we performed gene expression modulation experiments using a PBX4-overexpressing plasmid-ve...

Aims Enhanced recovery after surgery (ERAS) has shown to reduce perioperative stress and improve short-term postoperative outcomes. However, little is known regarding the effect of ERAS on long-term oncological outcomes. This study aimed to investigate the impact of ERAS on overall survival in patients undergoing liver resection for colorectal liver metastases (CRLM). Methods Between 2006 and 2014, 387 patients underwent liver resection for CRLM at Royal Surrey County Hospital. The ERAS protocol after liver surgery was implemented in 2011. Data regarding patients’ demographics, oncological characteristics, long and short-term postoperative outcomes were obtained from a prospectively maintained institutional database. Comparative analysis was performed between the ERAS and non-ERAS patients. The primary objective was overall survival (OS) and secondary objective included identification of factors affecting OS. Results The groups were similar in terms of demographics, primary and seco...

Background: Colorectal cancer (CRC) is worldwide the third leading cause of cancer-related death, and despite therapeutic advances, survival remains low. Emerging evidence shows that Homeobox (HOX) genes are important in carcinogenesis, and their dysregulation has been linked with metastatic potential and poor prognosis. This systematic review aims to present the current evidence on the role of HOX genes as biomarkers in CRC and the impact of their modulation in tumour growth and progression. Methods: MEDLINE, EMBASE, Web of Science and Cochrane databases were searched by following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Eligible studies investigated two research questions: a) the clinicopathological and prognostic significance of HOX gene dysregulation in patients with CRC and b) the functional role of HOX genes in CRC progression. This study was registered in the international prospective register of systematic reviews (PROSPERO),...

Ovarian granulosa cell tumours (GCT) occur rarely and represent 2-3% of all ovarian tumours. Regarded as tumours with low malignant potential and renowned for late recurrences, these tumours occasionally metastasize to the liver. We present our experience with three patients who underwent secondary cytoreductive surgery including liver resection for recurrence of the disease resulting in greatly improved quality of life and disease-free interval.

In 40 patients with superficial femoral artery disease we prospectively evaluated the effect of angioplasty (n = 20) or femoropopliteal bypass (n = 20) on the ankle-brachial pressure index (ABI) using the Doppler ultrasound probe. The ABI was measured as a baseline 1 day before the procedure, 1 day after the procedure and 30 days later. In the angioplasty group the baseline ABI was 0.57 (0.11), increasing to 0.74 (0.26) 1 day postangioplasty and increasing further to 0.88 (0.26) after 30 days. The increase in ABI over 30 days was significantly greater than the increase over 1 day. In the femoropopliteal bypass group the baseline ABI was lower at 0.46 (0.17). However 1 day postoperatively it had increased to 0.92 (0.2) with almost no further increase at 30 days [0.95 (0.17)]. We concluded that by contrast to a surgical bypass where there was a large improvement in the ABI over the first day, the ABI following angioplasty continued to improve significantly beyond the first day.

AIMS: To evaluate the role of routine laparoscopy as a staging modality prior to laparotomy and hepatic resection for metastatic colorectal cancer. METHODS: Prospectively collected data were analysed from a database. In the first half of the series patients underwent ...

The anatomy facing a surgeon during cholecystectomy involves complex relationships between the hepatic artery, extrahepatic biliary tree, and gallbladder. A sound knowledge of the normal anatomy of the extrahepatic biliary tract is thus essential in the prevention of operative injury to it. Equally important, however, is an understanding of congenital variation of biliary and vascular anatomy, as the literature abounds with reports of specific anatomical variations, and their operative implications. This article reviews the world literature on congenital variation of extrahepatic biliary anatomy.

Providing nutrition for patients following pancreaticoduodenectomy (PD) is vital but can be challenging. Due to the lack of UK national guidelines for the provision of nutrition and nutritional pre-operative assessment regarding PD, a national survey was conducted. A questionnaire was sent to the Department of Nutrition and Dietetics at each of the 31 specialist pancreatic centres listed with the Pancreatic Society of Great Britain and Ireland. Questions were asked regarding the nutritional assessment and treatment of patients undergoing classical PD and pylorus-preserving PD (PPPD) resections. Twenty-two centres responded to the questionnaire. With regard to PD and PPPD, 82% routinely feed patients following resection, 32% have a regimen for staring feeds, 18% carry out pre-operative nutritional assessment, five centres have funding for an hepatobiliary dietition, and only four centres have a specialist hepatobiliary dietition employed. There was no consensus regarding the type or route of feeding, and at least one centre reported using parenteral nutrition exclusively. Very few centres in the UK have funding for a hepatobiliary dietition. Hence pre-operative nutritional assessment in patients undergoing PD and PPPD does not receive much input. Although the importance of postoperative feeding in these patients is appreciated in all major units, there is no consensus with regards to feeding regimens. The authors hope this observational study will address these issues with this important message and stimulate further study in this area.

We investigated the etiology of interstitial hypertension in chronic pancreatitis by examining the relationship between pancreatic ductal and interstitial pressures in cats. The main pancreatic duct was cannulated in the tail of the gland and perfused at 1, 2, or 5 ml/hr, to simulate pancreatic secretion. Intraductal and interstitial pressures were measured in four groups of animals: (1) normal cats; (2) normal cats after acutely narrowing the main duct to 25% of its original diameter; (3) normal cats after encasing the body and tail in a rigid latex capsule; and (4) cats with chronic pancreatitis created by narrowing the main duct five weeks earlier. Duct perfusion increased intraductal pressure in all of the cats, but significantly more in groups 2, 3, and 4 compared to group 1. Pancreatic interstitial pressure was unchanged by duct perfusion in groups 1 and 2, but increased in groups 3 and 4. We concluded that the compliant tissue of the normal pancreas expanded to effectively dissipate the increase in duct pressure associated with duct perfusion. In chronic pancreatitis, the inelastic parenchyma and capsule limited the distensibility of the gland, which resulted in elevated interstitial pressures during duct perfusion.

The cause of pain in chronic pancreatitis appears to be related to ductal and parenchymal hypertension and possibly to pancreatic ischemia. The management of pain needs a multidisciplinary approach. Medical measures such as abstinence from alcohol and therapy with mild analgesics are useful. Surgery should be considered when the pain begins to interfere with the patient's quality of life. Ductal drainage operations may be indicated when the duct is dilatated. The alternative is pancreatic resection, which, although safe and effective, creates diabetes when much of the pancreas is removed. Newer operations that relieve pain while preserving function are being devised.

Esophageal cancer recurrence rates after esophagectomy are high, and locally recurrent or distant metastatic disease has poor prognosis. Management is limited to palliative chemotherapy and symptomatic interventions. We report our experience of four patients who have undergone successful liver resection for metastases from esophageal cancer. All underwent esophagectomy and were referred to our unit with metastatic recurrent liver disease, two with solitary metastases and two with multi-focal disease. The patients underwent multidisciplinary assessment and proceeded to a course of neoadjuvant chemotherapy followed by open or laparoscopic liver resection. Three patients were male, and the mean age was 57.5 (range 44-71) years. Response to chemotherapy ranged from partial to complete response. Following liver resection, two patients developed recurrent disease at 5 and 15 months, and both had disease-specific mortality at 10 and 21 months, respectively. The other two patients remain di...

Chemotherapy for metastatic colorectal cancer is constantly advancing. Its use in the adjuvant and neoadjuvant setting is also increasing. However, while long-term survival is improving, clinicians must be aware of the possible adverse events that can occur when treating with adjuvant chemotherapy and liver resection. We present a case of a life-threatening delayed bile leak following a liver resection for metastatic colorectal cancer in association with adjuvant treatment with bevacizumab. A 53-year-old man was treated with neoadjuvant bevacizumab followed by liver resection for metastatic colorectal cancer. He made an uneventful recovery. Forty-three days post-surgery he received bevacizumab and developed acute life-threatening bile leaks from the cut surface of the liver. He spent a total of 65 days in hospital, and required ERCP repeatedly and eventually had a repeat liver resection to resolve the bile leak. This case reports a possible association between bevacizumab and a life...

The management of patients with colorectal liver metastases and loop ileostomies remains controversial. This study was performed to assess the outcome of combined liver resection and loop ileostomy closure. Analysis of prospectively collected perioperative data, including morbidity and mortality, of 283 consecutive hepatectomies for colorectal liver metastases was undertaken. Consecutive liver resections were performed from 1996 to 2006 in one centre by a single surgeon (NDK). Fourteen of these patients had combined liver resection and ileostomy closure. Case-matched analysis was undertaken. Six (2.2%) patients died in the hepatectomy only group and none died in the combined group. There was no difference in operative blood loss between the two groups (0.09). Perioperative morbidity was 36% in the combined group and 23% in the hepatectomy alone group (P = 0.33). Mean hospital stay was 14 days in the combined group and 11 days in the hepatectomy only group (P = 0.046). Case-matched a...