A dangerous loop

Key Clinical Message: A 76-year-old man developed a hemoperitoneum after ERCP for choledocholithiasis. He underwent a laparotomy and splenectomy for a capsular tear at the splenic hilum, a rare complication of ERCP. “Bowing” of the endoscope with torsion on the greater curvature of the stomach may lead to shear forces causing splenic injury

Pancreas preserving distal duodenectomy: a versatile operation for a range of infra-papillary pathologies

AIM To investigate the range of pathologies treated by pancreas preserving distal duodenectomy (PPDD) and present the outcome of follow-up. METHODS Neoplastic lesions of the duodenum are treated conventionally by pancreaticoduodenectomy. Lesions distal to the major papilla may be suitable for a pancreas-preserving distal duodenectomy, potentially reducing morbidity and mortality. We present our experience with this procedure. Selective intraoperative duodenoscopy assessed the relationship of the papilla to the lesion. After duodenal mobilisation and confirmation of the site of the lesion, the duodenum was transected distal to the papilla and beyond the duodenojejunal flexure and a side-to-side duodenojejunal anastomosis was formed. Patients were identified from a prospectively maintained database and outcomes determined from digital health records with a dataset including demographics, co-morbidities, mode of presentation, preoperative imaging and assessment, nutritional support needs, technical operative details, blood transfusion requirements, length of stay, pathology including lymph node yield and lymph node involvement, length of follow-up, complications and outcomes. Related published literature was also reviewed. RESULTS Twenty-four patients had surgery with the intent of performing PPDD from 2003 to 2016. Nineteen underwent PPDD successfully. Two patients planned for PPDD proceeded to formal pancreaticoduodenectomy (PD) while three had unresectable disease. Median post-operative follow-up was 32 mo. Pathologies resected included duodenal adenocarcinoma (n = 6), adenomas (n = 5), gastrointestinal stromal tumours (n = 4) and lipoma, bleeding duodenal diverticulum, locally advanced colonic adenocarcinoma and extrinsic compression (n = 1 each). Median postoperative length of stay (LOS) was 8 d and morbidity was low [pain and nausea/vomiting (n = 2), anastomotic stricture (n = 1), pneumonia (n = 1), and overwhelming postsplenectomy sepsis (n = 1, asplenic patient)]. PPDD was associated with a significantly shorter LOS than a contemporaneous PD series [PPDD 8 (6-14) d vs PD 11 (10-16) d, median (IQR), P = 0.026]. The 30-d mortality was zero and 16 of 19 patients are alive to date. One patient died of recurrent duodenal adenocarcinoma 18 mo postoperatively and two died of unrelated disease (at 2 mo and at 8 years respectively). CONCLUSION PPDD is a versatile operation that can provide definitive treatment for a range of duodenal pathologies including adenocarcinoma

DNA content analysis of colorectal cancer defines a distinct ‘microsatellite and chromosome stable’ group but does not predict response to radiotherapy

Colorectal cancers (CRC) are thought to have genetic instability in the form of either microsatellite instability (MSI) or chromosomal instability (CIN). Recently, tumours have been described without either MSI or CIN, that is, microsatellite and chromosome stable (MACS) CRCs. We investigated the (i) frequency of the MACS-CRCs and (ii) whether this genotype predicted responsiveness to neoadjuvant chemoradiotherapy. To examine the frequency of MACS-CRCs, DNA content (ploidy) was examined in 89 sporadic microsatellite-stable CRCs using flow cytometry. The tumours were also screened for mutations in KRAS/BRAF/TP53/PIK3CA by QMC-PCR. To examine the value of tumour ploidy in predicting response to chemoradiotherapy, DNA content was tested in a separate group of 62 rectal cancers treated with neoadjuvant chemoradiotherapy. Fifty-one of 89 CRCs (57%) were aneuploid and 38 (43%) were diploid. There was no significant association between mutations in TP53/KRAS/BRAF/PIK3CA and ploidy. Testing of association between mutations revealed only mutual exclusivity of KRAS/BRAF mutation (P < 0.001). Of the 62 rectal cancers treated with neoadjuvant chemoradiotherapy, 22 had responded (Mandard tumour regression grade 1/2) and 40 failed to respond (Grade 3–5). Twenty-five of 62 (40%) tumours were diploid, but there was no association between ploidy and response to therapy. We conclude that MACS-CRCs form a significant proportion of microsatellite-stable CRCs with a mutation profile overlapping that of CRCs with CIN. A diploid genotype does not, however, predict the responsiveness to radiotherapy

A recurrent retrohepatic abscess secondary to a dropped appendicolith

Appendicoliths can drop into the peritoneal cavity during the course of an appendicectomy, or more commonly as a result of perforated appendicitis. We report the case of a patient with a history of recurrent retrohepatic abscesses over 7-year period due to a retained appendicolith and review the literature on perihepatic abscesses caused by retained appendicoliths. The abscess had been drained percutaneously 4 times without retrieval of the appendicolith and eventually the patient needed a laparotomy, drainage of the abscess, and extraction of the appendicolith. Treatment of abscesses secondary to dropped appendicoliths may be percutaneous, laparoscopic, or via conventional open surgery, but it is important to retrieve the appendicolith if recurrent abscess formation is to be avoided

Immunohistochemical inflammation in histologically normal appendices in patients with right iliac fossa pain

BackgroundHistologically normal appendices resected for right iliac fossa pain in children demonstrate immunohistochemical markers of inflammation. We aimed to establish if subclinical inflammation was present in histologically normal appendices resected from adults with right iliac fossa pain.MethodsImmunohistochemistry was performed on formalin-fixed paraffin-embedded appendices for tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R and serotonin in four groups: Group I (n = 120): uncomplicated appendicitis, Group II (n = 118): complicated appendicitis (perforation or gangrene), Group III (n = 104): histologically normal appendices resected for right iliac fossa pain and Group IV (n = 106) appendices resected at elective colectomy. Expression was quantified using the H-scoring system.ResultsMedian, interquartile range expression of TNF-α was increased in Groups I (5.9, 3.1–9.8), II (6.8, 3.6–12.1) and III (9.8, 6.2–15.2) when compared with Group IV (3.0, 1.4–4.7, p ≤ 0.01). Epithelial expression of IL-6 in Groups II (44.0, 8.0–97.0) and III (71.0, 18.5–130.0) was increased when compared with Group IV (9.5, 1.0–60.2, p ≤ 0.01). Expression of mucosal IL-2R in Groups I (47.4, 34.8–69.0), II (37.8, 25.4–60.4) and III (18.4, 10.1–34.7) was increased when compared with Group IV (2.8, 1.2–5.7, p ≤ 0.01). Serotonin content in Groups I (3.0, 0–30.0) and II (0, 0–8.5) was decreased when compared with Groups III (49.7, 16.7–107.5) and IV (43.5, 9.5–115.8, p ≤ 0.01).ConclusionHistologically normal appendices resected from symptomatic patients exhibited increased proinflammatory cytokine expression on immunohistochemistry suggesting the presence of an inflammatory process not detected on conventional microscopy

Intrahepatic Sarcomatoid Cholangiocarcinoma

Intrahepatic sarcomatoid cholangiocarcinoma is a rare but an aggressive variant of cholangiocarcinoma with a very poor prognosis. We report the first caucasian patient who presented with a rapidly enlarging liver mass requiring hepatic resection. Detailed histopathological analyses including immunohistochemistry and electron microscopy confirmed sarcomatoid cholangiocarcinoma. The patient had early onset disease recurrence within 5 weeks of surgery. Here we demonstrate that combination chemotherapy with gemcitabine and cisplatin is a potential treatment option in patients with advanced sarcomatous cholangiocarcinoma. The patient achieved sustained partial remission with combination chemotherapy and remains alive and well more than 29 months since initial surgery

Thioredoxin system protein expression in carcinomas of the pancreas, bile duct and ampulla

Background: Pancreatic cancer (PC), including the ampulla and bile duct, is very aggressive, and thus difficult to treat with effective therapies. The current treatment options have failed to improve PC five-year survival rates over the last 30 to 40 years, which remain very low, at ~3%; there is, therefore, an urgent need to identify new targets and treatment modalities (1). Methods: The protein expression of thioredoxin (Trx), thioredoxin reductase (TrxR) and thioredoxin interacting protein (TxNIP) was assessed in two cancer patient cohorts by standard immunohistochemistry using tissue microarrays. The first cohort was composed of 85 pancreatic adenocarcinomas (PAD) and the second of 145 cancers of the bile duct and ampulla. Results: In the PAD cohort, high cytoplasmic TrxR expression significantly associated with lymph node metastasis (P = 0.033). High expression of cytoplasmic (P = 0.018) and nuclear (P = 0.006) Trx were significantly associated with better overall survival, with nuclear Trx expression remaining significantly associated with survival in multivariate Cox-regression (Hazard Ratio (HR) 0.316; 95% Confidence Interval (95% CI) 0.174-0.573; P < 0.0001) when potentially confounding factors were included (gender, age, tumour size, tumour grade, tumour stage, lymph node status, perineural and venous invasion). In cancers of the bile duct and ampulla, high expression of nuclear TrxR and high cytoplasmic TxNIP were associated with patients aged above 60 years (P = 0.024 and P = 0.049 respectively). Associations were also observed between high nuclear TrxR expression and the presence of venous (P = 0.001) and perineural (P = 0.021) invasion. Low cytoplasmic TxNIP expression was also associated with the presence of perineural invasion (P = 0.025). High expression of cytoplasmic TxNIP was significantly associated with better overall survival (P = 0.0002), which remained significant in multivariate Cox-regression analysis (HR 0.548; 95% CI 0.340-0.882; P = 0.013) when potentially confounding factors were included (tumour grade, stage, lymph node status, perineural and venous invasion). Conclusion: Current findings demonstrate the prognostic importance of Trx system protein expression in pancreatic, bile duct and ampullary cancers, with expression of certain members potentially being involved in disease progression. Current findings warrant a larger follow-up study

Small bowel perforation by a piece of china with a synchronous asymptomatic sigmoid carcinoma: A case report

A 75 year old gentleman who presented with an incarcerated paraumibilical hernia was found intraoperatively to have small bowel perforation due to a piece of china with a synchronous asymptomatic sigmoid carcinoma

The active form of Helicobacter pylori vacuolating cytotoxin induces decay-accelerating factor CD55 in association with intestinal metaplasia in the human gastric mucosa

High-level expression of decay-accelerating factor, CD55, has previously been found in human gastric cancer (GC) and intestinal metaplasia (IM) tissues. Therapeutic effects of CD55 inhibition in cancer have been reported. However, the role of Helicobacter pylori infection and virulence factors in the induction of CD55 and its association with histological changes of the human gastric mucosa remain incompletely understood. We hypothesised that CD55 would be increased during infection with more virulent strains of H. pylori, and with more marked gastric mucosal pathology. RT-qPCR and immunohistochemical analyses of gastric biopsy samples from 42 H. pylori-infected and 42 uninfected patients revealed that CD55 mRNA and protein were significantly higher in the gastric antrum of H. pylori-infected patients, and this was associated with the presence of IM, but not atrophy, or inflammation. Increased gastric CD55 and IM were both linked with colonisation by vacA i1-type strains independently of cagA status, and in vitro studies using isogenic mutants of vacA confirmed the ability of VacA to induce CD55 and sCD55 in gastric epithelial cell lines. siRNA experiments to investigate the function of H. pylori-induced CD55 showed that CD55 knockdown in gastric epithelial cells partially reduced IL-8 secretion in response to H. pylori, but this was not due to modulation of bacterial adhesion or cytotoxicity. Finally, plasma samples taken from the same patients were analysed for the soluble form of CD55 (sCD55) by ELISA. sCD55 levels were not influenced by IM and did not correlate with gastric CD55 mRNA levels. These results suggest a new link between active vacA i1-type H. pylori, IM, and CD55, and identify CD55 as a molecule of potential interest in the management of IM as well as GC treatment. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Helicobacter pylori vacA transcription is genetically-determined and stratifies the level of human gastric inflammation and atrophy

Aims Helicobacter pylori infection is the major cause of peptic ulceration and gastric cancer, and an important virulence determinant is its vacuolating cytotoxin, vacA. Previously, we have described allelic variation in vacA which determines toxin activity and disease risk. We now aimed to quantify vacA mRNA expression in the human stomach, define its genetic determinants and assess how well itpredicted gastric pathology. Methods Gastric biopsies were donated by 39 H. pylori-infected patients attending for endoscopy at Queen’s Medical Centre, Nottingham, UK. Total RNA was extracted, and vacA mRNA quantified by reverse transcriptase quantitative polymerase chain reaction. Separate biopsies were histologically scored for inflammation and atrophy using the updated Sydney system. H. pylori strains were isolated from further biopsies, and the nucleotide sequence upstream of vacA determined. Results vacA mRNA levels in human stomachs varied by two orders of magnitude independently of vacA allelic type. Among vacA i1-type (toxic) strains, increased vacA expression was strongly associated with higher grade gastric inflammation (