Liver Transplantation for Primary Sclerosing Cholangitis (PSC) With or Without Inflammatory Bowel Disease (IBD)-A European Society of Organ Transplantation (ESOT) Consensus Statement.

Primary sclerosing cholangitis (PSC) is the classical hepatobiliary manifestation of inflammatory bowel disease (IBD) and a lead indication for liver transplantation (LT) in the western world. In this article, we present a Consensus Statement on LT practice, developed by a dedicated Guidelines' Taskforce of the European Society of Organ Transplantation (ESOT). The overarching goal is to provide practical guidance on commonly debated topics, including indications and timing of LT, management of bile duct stenosis in patients on the transplant waiting list, technical aspects of transplantation, immunosuppressive strategies post-transplant, timing and extension of intestinal resection and futility criteria for re-transplantation.

The impact of ileal pouch-anal anastomosis on graft survival following liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Liver transplantation is the only life-extending intervention for primary sclerosing cholangitis (PSC). Given the co-existence with colitis, patients may also require colectomy; a factor potentially conferring improved post-transplant outcomes. AIM: To determine the impact of restorative surgery via ileal pouch-anal anastomosis (IPAA) vs retaining an end ileostomy on liver-related outcomes post-transplantation. METHODS: Graft survival was evaluated across a prospectively accrued transplant database, stratified according to colectomy status and type. RESULTS: Between 1990 and 2016, 240 individuals with PSC/colitis underwent transplantation (cumulative 1870 patient-years until first graft loss or last follow-up date), of whom 75 also required colectomy. A heightened incidence of graft loss was observed for the IPAA group vs those retaining an end ileostomy (2.8 vs 0.4 per 100 patient-years, log-rank P = 0.005), whereas rates between IPAA vs no colectomy groups were not significantly different (2.8 vs 1.7, P = 0.1). In addition, the ileostomy group experienced significantly lower graft loss rates vs. patients retaining an intact colon (P = 0.044). The risks conferred by IPAA persisted when taking into account timing of colectomy as related to liver transplantation via time-dependent Cox regression analysis. Hepatic artery thrombosis and biliary strictures were the principal aetiologies of graft loss overall. Incidence rates for both were not significantly different between IPAA and no colectomy groups (P = 0.092 and P = 0.358); however, end ileostomy appeared protective (P = 0.007 and 0.031, respectively). CONCLUSION: In PSC, liver transplantation, colectomy + IPAA is associated with similar incidence rates of hepatic artery thrombosis, recurrent biliary strictures and re-transplantation compared with no colectomy. Colectomy + end ileostomy confers more favourable graft outcomes.

Patients newly diagnosed with ulcerative colitis receive earlier treatment in surgical clinics.

AIM: The diagnosis and treatment of ulcerative colitis (UC) is traditionally the realm of gastroenterologists. However, the symptoms of UC overlap with those of bowel cancer and patients may be initially referred to colorectal surgery clinics. The aims of this study were to define which specialty most frequently diagnoses UC and to determine if there were differences in management between the two specialities. METHOD: The demographics, presenting symptoms and clinical management of patients with newly diagnosed UC were determined and compared by speciality clinic of initial referral. Histopathology reports and clinic letters were reviewed to identify patients newly diagnosed with UC at a large university teaching hospital from January 2007 to January 2012. RESULTS: Patients were more commonly referred to colorectal surgeons (74 vs 41 patients) than gastroenterologists. Patients referred to gastroenterology were younger (36.0 vs 59.6 years, P < 0.01) but there were no significant differences in gender, presenting symptoms or disease extent. Rigid sigmoidoscopy ± biopsy was more commonly performed in colorectal clinic (93.2 vs 31.7%, P < 0.01). There was a significantly shorter delay in starting disease-specific treatment for those patients referred initially to colorectal surgery (13.8 vs 33.6 days, P = 0.01). Performing rigid sigmoidoscopy in clinic was associated with starting disease-specific treatment at this visit. CONCLUSION: Patients with first presentation UC are more commonly seen in colorectal surgery clinics where rigid sigmoidoscopy is more frequently undertaken, allowing earlier commencement of UC treatment.

Indications, stains and techniques in chromoendoscopy.

Early detection of malignancies within the gastrointestinal tract is essential to improve the prognosis and outcome of affected patients. However, conventional white light endoscopy has a miss rate of up to 25% for gastrointestinal pathology, specifically in the context of small and flat lesions within the colon. Chromoendoscopy and other advanced imaging techniques aim at facilitating the visualization and detection of neoplastic lesions and have been applied throughout the gastrointestinal tract. Chromoendoscopy, particularly in combination with magnifying endoscopy has significantly improved means to detect neoplastic lesions in the gastrointestinal mucosa, particularly in ulcerative colitis and Crohn's colitis. In addition, chromoendoscopy is beneficial in the upper gastrointestinal tract, especially when evaluating Barrett's oesophagus (BO) for the presence of dysplasia. Furthermore, it also improves characterization, differentiation and diagnosis of endoscopically detected suspicious lesions, and helps to delineate the extent of neoplastic lesions that may be amenable to endoscopic resection. This review discusses the dyes, indications and advanced endoscopic imaging methods used in various chromoendoscopic techniques, and presents a critical overview of the existing evidence supporting their use in current practice with a particular emphasis on the role in inflammatory bowel disease and BO.

Review article: overlap syndromes and autoimmune liver disease.

BACKGROUND: Autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) all nestle within the family of autoimmune liver diseases, whereby the result of immune-mediated liver injury gives rise to varied clinical presentations. Some patients demonstrate a phenotype whereby there is evidence of either PBC or PSC together with overlapping features of AIH. Due to an absence of well-validated diagnostic criteria and a lack of large therapeutic trials, treatment of overlap conditions is empiric and extrapolated from data derived from the primary autoimmune liver diseases. AIMS: To review overlaps in the context of autoimmune liver diseases. METHODS: General and specific review of published articles using PubMed, Medline and Ovid search engines, alongside pre-existing clinical management protocols, guidelines, and the authors' own knowledge of the published literature. RESULTS: The challenges in diagnosis, clinical presentation, determining natural history and outcome of overlaps are presented, as well as present-day management suggestions, some based on evidence, others on consensus and opinion. CONCLUSIONS: Overlapping autoimmune features, be they clinical, serological, histological or radiological are not infrequent, but appropriate diagnosis remains hindered by a lack of standardised diagnostic criteria. Optimum care for those with suspected overlap should thus focus on attention to detail over the fundamental aspects of timely secure diagnosis of the dominant disease entity. Clinicians should counsel patients carefully with regard to the risks and benefits of treatment, bearing in mind the paucity of randomised and controlled outcome data for medical interventions.

PSC, AIH and overlap syndrome in inflammatory bowel disease.

Primary sclerosing cholangitis (PSC) is a progressive, cholestatic disorder characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include pruritus, fatigue and in advanced cases ascending cholangitis, cirrhosis and end-stage hepatic failure. Patients are at an increased risk of malignancy arising from the bile ducts, gallbladder, liver and colon. The majority (>80%) of Northern European patients with PSC also have inflammatory bowel disease (IBD), usually ulcerative colitis (UC). IBD commonly presents before the onset of PSC, although the opposite can occur and the onset of both conditions can be separated by many years. The colitis associated with PSC is characteristically mild although frequently involves the whole colon. Despite the majority of patients having relatively inactive colonic disease, paradoxically the risk of colorectal malignancy is substantially increased. Patients may also develop dominant, stenotic lesions of the biliary tree which may be difficult to differentiate from cholangiocarcinoma and the coexistence of IBD may influence the development of this complication. Ursodeoxycholic acid may offer a chemoprotective effect against colorectal malignancy and improve liver biochemical indices. Evidence of any beneficial effect on histological progression of hepatobiliary disease is less clear. High doses (∼25-30 mg/kg/d) may be harmful and should be avoided. Autoimmune hepatitis (AIH) is less common in patients with IBD than PSC, however, an association has been observed. A small subgroup may have an overlap syndrome between AIH and PSC and management should be individualised dependant on liver histology, serum immunoglobulin levels, autoantibodies, degree of biochemical cholestasis and cholangiography.

A new recurring chromosome 13 abnormality in two older patients with de novo acute myeloid leukemia: An Indian experience.

We report here two cases of trisomy 13 in acute myeloid leukemia M1 subtype. short-term unstimulated bone marrow and peripheral blood lymphocyte culture showed 47, XY, +13 in all metaphase plates and trisomy 13 was confirmed with whole chromosome paint probes. Trisomy 13 in AML-M1 is a rare numerical abnormality. This is the first Indian report of sole trisomy 13 in AML-M1. Here, we present two cases of elder male patients, which may constitute a distinct subtype.

Characterization of a familial small supernumerary marker chromosome in a patient with adult-onset tongue cancer.

Cytogenetic analysis in peripheral blood lymphocytes of a 50-year-old female with tongue cancer showed the presence of one to three copies of a small supernumerary marker chromosome (sSMC) in a mosaic state. Family studies also revealed the marker in mosaic form in four (age <29 years) of eleven clinically normal individuals studied from her family of 16 individuals spanning three generations. Due to the extremely small size of the marker chromosome, identification by classical cytogenetics was not informative. Multicolor FISH followed by whole chromosome painting identified the marker as a derivative of chromosome 21. This is the first report of sSMC21 in an adult-onset tongue cancer patient and some of her family members with no clinical symptoms.

A case of acute myeloid leukemia-M2 with trisomy 4 in addition to t(8;21).

t(8;21)(q22;q22) is the most frequently observed karyotypic abnormality associated with acute myeloid leukemia (AML), specifically in FAB-M2. Short-term unstimulated bone marrow (BM) and peripheral blood lymphocyte culture showed 47,XX, +4,t(8;21) in all metaphase plates; and interphase and metaphase results of AML-ETO fusion was positive and trisomy of 4 was confirmed with WCP probes. Trisomy 4 in AML with t(8;21) is a rare numerical abnormality. Here we present such case of patient which may constitute a distinctive subtype.

Constitutional tetrasomy 18p.

We present here the first case of constitutional tetrasomy 18p from India. A 3 year old female with developmental delay and dysmorphic features revealed 47,XX,+mar karyotype. The small meta-centric marker chromosome was identified as i(18p) with m-FISH followed by m-BAND. Parents and a normal sibling of the proband revealed normal karyotype. There was history of mental retardation and dysmorphic features in four cases on paternal side; however, their karyotype was also normal.