Colorectal surgical management of colitis induced by vasculitis in the absence of inflammatory bowel disease: a case report and literature review.

Colitis caused by vasculitis is a rare and poorly understood pathology. Little evidence exists on its clinical presentation, path to diagnosis, and surgical management. In this report, we present a case report and literature review. A healthy 20-year-old male patient presented with hemorrhagic colitis requiring total colectomy with end ileostomy. Pathological examination showed pancolitis with multiple ulcers, transmural inflammation, hemorrhage, and microvascular thrombosis. Extensive serological testing revealed elevated cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) and eosinophilia, leading to a diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) and vasculitis-induced colitis. A literature review was subsequently conducted. Nineteen studies were found documenting vasculitis-induced colitis in the absence of inflammatory bowel disease (IBD). Systemic signs of vasculitis, hemorrhagic colitis, and progression to fulminant colitis were present. Of all patients, 40.0% required colorectal surgery and 62.5% of those patients received a stoma; 25% underwent emergency surgery following failed immunosuppression. All cases relied on clinical correlation with serology and/or histopathology to reach a final diagnosis. We report a case of vasculitis-induced colitis caused by c-ANCA-positive EGPA. The review shows that vasculitis-induced colitis without IBD is an important differential that clinicians should be aware of in patients presenting with colitis.

MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice.

MCC950 a potent, highly specific small molecule inhibitor of canonical and noncanonical activation of NLRP3 inflammasome has been evaluated in a multitude of NLRP3 driven inflammatory diseases. However, the effect of MCC950 on colonic inflammation has not yet been reported. In the present study we investigated the effect of MCC950 in a spontaneous chronic colitis mouse model Winnie, which mimics human ulcerative colitis. Oral administration of 40 mg/kg MCC950 commencing at Winnie week seven for three weeks significantly improved body weight gain, colon length, colon weight to body weight ratio, disease activity index and histopathological scores. MCC950 significantly suppressed release of proinflammatory cytokines IL-1ß, IL-18, IL1-α, IFNγ, TNF-α, IL6, IL17, chemokine MIP1a and Nitric Oxide in colonic explants. Moreover, MCC950 resulted in a significant decrease of IL-1ß release and activation of caspase-1 in colonic explants and macrophage cells isolated from Winnie. Complete inhibition with MCC950 in Winnie colonic explants shows, for the first time, the contribution of inflammatory effects resulting exclusively from canonical and noncanonical NLRP3 inflammasome activation in colitis. Taken together, our results illustrate the efficacy of MCC950 in the treatment of murine ulcerative colitis and provides avenue for a potential novel therapeutic agent for human inflammatory bowel diseases.

Characterisation of colonic dysplasia-like epithelial atypia in murine colitis.

AIM: To determine if exacerbation of pre-existing chronic colitis in Winnie (Muc2 mutant) mice induces colonic dysplasia. METHODS: Winnie mice and C57BL6 as a genotype control, were administered 1% w/v dextran sulphate sodium (DSS) orally, followed by drinking water alone in week-long cycles for a total of three cycles. After the third cycle, mice were killed and colonic tissue collected for histological and immunohistochemical evaluation. Inflammation and severity of dysplasia in the colonic mucosa were assessed in H&E sections of the colon. Epithelial cell proliferation was assessed using Ki67 and aberrant ß-catenin signalling assessed with enzyme-based immunohistochemistry. Extracted RNA from colonic segments was used for the analysis of gene expression using real-time quantitative PCR. Finally, the distribution of Cxcl5 was visualised using immunohistochemistry. RESULTS: Compared to controls, Winnie mice exposed to three cycles of DSS displayed inflammation mostly confined to the distal-mid colon with extensive mucosal hyperplasia and regenerative atypia resembling epithelial dysplasia. Dysplasia-like changes were observed in 100% of Winnie mice exposed to DSS, with 55% of these animals displaying changes similar to high-grade dysplasia, whereas high-grade changes were absent in wild-type mice. Occasional penetration of the muscularis mucosae by atypical crypts was observed in 27% of Winnie mice after DSS. Atypical crypts however displayed no evidence of oncogenic nuclear ß-catenin accumulation, regardless of histological severity. Expression of Cav1, Trp53 was differentially regulated in the distal colon of Winnie relative to wild-type mice. Expression of Myc and Ccl5 was increased by DSS treatment in Winnie only. Furthermore, increased Ccl5 expression correlated with increased complexity in abnormal crypts. While no overall difference in Cxcl5 mucosal expression was observed between treatment groups, epithelial Cxcl5 protein appeared to be diminished in the atypical epithelium. CONCLUSION: Alterations to the expression of Cav1, Ccl5, Myc and Trp53 in the chronically inflamed Winnie colon may influence the transition to dysplasia.

Diagnostic and therapeutic quandaries in a patient with primary hepatic lymphoma and concurrent hepatitis C infection.

Primary hepatic lymphoma (PHL) is a very rare sub-type of non-Hodgkin's lymphoma and hepatitis C infection may be a contributory factor. The association of hepatitis C infection and PHL causes difficulties in management since safety of rituximab in such situations is unclear due to lack of evidence. The role of anti-viral therapy in combination with chemotherapy is also uncertain. We describe the diagnostic and therapeutic challenges posed by a patient who was diagnosed with PHL and concurrent hepatitis C infection.

Adoption of endovenous laser treatment as the primary treatment modality for varicose veins: the Auckland City Hospital experience.

AIM: To assess the effectiveness of adopting endovenous laser treatment (EVLT) as the primary treatment modality for varicose veins at Auckland City Hospital (Auckland, New Zealand). METHODS: The outcomes of 354 consecutive EVLT procedures performed between 2007 and 2013 were reviewed. Data was collected from a prospectively maintained procedural database and by retrospective chart review. RESULTS: Of the 319 patients who had an ultrasound, at 1 month post-procedure there was a saphenous vein occlusion rate of 96%. Side effects were minimal with no cases of DVT or skin burns and one case of self-limiting neuralgia. The procedure was well tolerated with a median pain score of 3. Since the adoption of EVLT there has been a large increase in the number of patients treated for varicose veins (28 in 2007 compared to 176 in 2013). CONCLUSIONS: EVLT is a safe and effective treatment for varicose veins and its adoption has allowed a large increase in the number of varicose vein patients treated at Auckland City Hospital.

Transcriptionally active human papillomavirus is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma.

OBJECTIVES: The role of human papillomavirus (HPV) in Barrett's esophagus (BE) remains unclear. The few studies that have previously investigated HPV and esophageal adenocarcinoma (EAC) or BE have produced either negative data or positive results of doubtful clinical/etiological significance or have detected only low-risk HPV types. We therefore prospectively determined the prevalence of biologically active HPV in esophageal epithelium of patients representing the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. METHODS: HPV DNA was estimated by nested PCR and viral transcriptional activity detected by E6/7 oncogene mRNA expression and p16INK4A immunohistochemistry in fresh frozen and paraffin-embedded esophageal biopsies of patients with BE, Barrett's dysplasia (BD), and EAC, as well as controls. Biopsies were obtained from the transformation zone (squamocolumnar junction (SCJ)) and the lesion, or corresponding site in controls, i.e., 2 cm above the gastroesophageal junction (GEJ). RESULTS: Of the 261 patients, 81 were positive for HPV DNA. In controls and BE, the virus was mostly detected at the transformation zone. Compared with controls (18.0%), HPV positivity was significantly more common in BD (68.6%, incidence rate ratio (IRR) 2.94, 95% confidence interval (CI) 1.78-4.85, P<0.001) and EAC (66.7%, IRR 2.87, 95% CI 1.69-4.86, P<0.001), but not in BE (22.1%, IRR 1.06, 95% CI 0.60-1.85, P=0.85). Of the patients, 92.6% were high-risk (HR) HPV, i.e., types 16 and 18. Again, p16INK4A positivity was greatest in BD and EAC and much less in BE patients (44.1%, IRR 17.0 (95% CI 4.86-59.6, P<0.001), 44.4%, 17.0 (95% CI 4.87-59.4, P<0.001), and 10.6%, 3.93 (95% CI 1.01-15.3, P=0.048) respectively). In 66 HPV DNA-positive patients tested for E6/E7 mRNA, none of the control (n=16) or BE (n=13) individuals were positive, whereas 9/22 BD and 9/15 EAC patients demonstrated oncogene expression (P<0.001). When HPV DNA, p16INK4A, and E6/E7 mRNA were all positive, there was a very strong association with disease severity (SCJ: odds ratio (OR) 104, 95% CI 20.3-529, P<0.001; lesion: OR 62.2, 95% CI 12.4-311, P<0.001) than when all were negative. CONCLUSIONS: Transcriptionally active HR-HPV was strongly associated with BD and EAC, but was largely biologically irrelevant in BE and controls, suggesting a potential role in esophageal carcinogenesis. These data provide robust justification for further detailed longitudinal, interventional, and molecular studies.

Extramedullary plasmacytoma of the tonsil with nodal involvement.

We present a rare case of extramedullary plasmacytoma of the palatine tonsil with cervical lymph node involvement treated by surgical resection. A 58-year-old Caucasian male presented with a solitary 3 cm x 3 cm jugulodigastric lymph node and was found to have an ipsilateral tonsillar swelling. The involved tonsil and lymph node were surgically resected after two inconclusive fine-needle aspirates, and plasmacytoma was confirmed histologically and by immunocytochemistry. Adjuvant radiotherapy was not indicated as adequate resection was achieved at surgery. We also highlight the challenges of diagnosis when fine-needle aspiration is inconclusive and the need for careful planning before surgery.

Pancreatic panniculitis: A rare form of panniculitis.

Pancreatic panniculitis is rare form of panniculitis with associated pancreatic disease. The skin manifestations can occur at any time of the pancreatic pathology. Here we report a case of pancreatic panniculitis associated with underlying chronic pancreatitis. The patient presented with painful subcutaneous nodules and the histology revealed the characteristic features of pancreatic panniculitis.

An unusual presentation of female urethral leiomyoma.

Leiomyoma of the urethra is a rare clinical entity. We report an unusual presentation of this tumour, which led to a diagnostic and surgical dilemma. The patient was a 16-year old female who presented with a labial mass which was palpable abdominally. Imaging methods and laparoscopy demonstrated a well defined soft tissue mass arising from the pelvis, without any obvious involvement of the urinary tract. The tumour (8 x 10 cm) was completely excised with reconstruction of the bladder and urethra. Histology confirmed a cellular leiomyoma.