Long-term outcome of prucalopride for chronic constipation: a single-centre study.

AIM: Newer 5-hydroxytryptamine agonists, such as prucalopride, have been demonstrated to be effective in the short term for treatment of chronic constipation. To date, few studies have investigated their medium- and long-term effectiveness. METHOD: An analysis was carried out of a prospectively maintained database of all patients started on prucalopride for chronic constipation between April 2011 and April 2014. Cleveland Clinic Constipation Score (CCCS) questionnaires were administered before starting treatment with prucalopride and at the first follow-up visit to assess change in CCCS scores in 50 randomly selected patients. RESULTS: A total of 155 patients (median age: 47 years; seven men) were started on prucalopride in this period. Of these, 16 (10%) had slow-transit constipation, 31 (20%) had obstructive defaecation syndrome and 30 (19%) had a combination of both. Of these 155 patients, 78% patients were on three or more laxatives at the time of starting prucalopride. Patients were started on 1 mg or 2 mg according to their age. The median follow-up period was 24 (range: 4-40) months. At the first follow-up visit, 106 (68%) patients reported good symptomatic improvement, whereas the remainder had no response. Third of initial responders showed decreased efficacy after a median duration of 6 months and needed regular laxatives/irrigation. Of the 50 patients who filled in the CCCS questionnaires (15 patients were nonresponders), 32 (64%) reported improved scores with a median improvement of two points per criterion. CONCLUSION: This study provides evidence that prolonged use of prucalopride is effective in achieving a sustained benefit in the majority of patients.

Clinicopathological Study of Lesions of Upper Gastrointestinal Tract.

Conditions affecting the upper digestive system are often seen in clinical practice and are associated with a high rate of death and disability. Histopathological confirmation is one of the foundations for good treatment planning and the definite diagnosis of illnesses of the upper gastrointestinal tract. The numerous methods employed in the diagnosis of gastrointestinal lesions have come a long way in the previous 25 years. The identification and diagnosis of gastrointestinal lesions have been substantially aided by the development of endoscopy, endoscopic biopsy, and other surgical techniques. This research aimed to examine the variety of gastrointestinal tract (GI) lesions and to draw connections between the clinical and pathological manifestations of these conditions. Materials and Methods: A two-year cross-sectional study was conducted in the Department of Pathology, from June 2018 to May 2020, which included surgical specimens of 140 cases from the upper gastrointestinal tract, of which 111 cases were biopsy, and 29 cases were resected surgical specimens. The data were analyzed using SPSS software. Furthermore, P values, sensitivity, specificity, positive predictive value, and negative predictive value were calculated. Results: This study was a two-year cross-sectional study conducted in the Department of Pathology during the period of June 2018-May 2020.

Adhesive intestinal obstruction in laparoscopic vs open colorectal resection.

AIM: While there is evidence that laparoscopy creates fewer adhesions, evidence regarding decreased episodes of adhesive obstruction in laparoscopic colorectal resection (LCR) is still lacking. The aim of our study was to compare the incidence of adhesion-related admissions/surgery in patients undergoing LCR and open colorectal resection (OCR). METHOD: We conducted a retrospective analysis of a prospectively collected database that included all patients undergoing LCR and OCR between 2001 and 2010. Patients with <6 months of follow-up were excluded. Patients who were converted to open surgery were included in the laparoscopic group. Details regarding readmission rates and surgery for adhesive obstruction were obtained from clinical portals and the theatre database. Statistical analysis was performed using Fisher's exact test, the Mann-Whitney U-test and the Student's t-test. RESULTS: One-hundred and forty-four patients had LCR with a median (range) follow-up of 24.5 (6-108) months. One-hundred and eighty-seven patients underwent OCR, with a median (range) follow-up of 49 (6-104) months. Six (4.2%) of 144 patients in the LCR group had adhesion-related admission/obstruction compared with 13 (6.95%) of 187 patients in the OCR group (P = 0.34). Three (2.1%) of 144 patients who had LCR required surgery for adhesive obstruction compared with five (2.7%) of 187 who had OCR (P = 0.73). CONCLUSION: In our study there was no statistically significant difference in the incidence of postoperative adhesive intestinal obstruction between LCR and OCR groups.

Rectal irrigation: a useful tool in the armamentarium for functional bowel disorders.

AIM: The efficacy of rectal irrigation (RI) was assessed in patients with various functional bowel disorders. METHOD: A prospective analysis was carried out of patients presenting to our functional bowel clinic from 2005 to 2009. The Cleveland Clinic Constipation and Incontinence Scores were used to assess outcomes following rectal irrigation. Patients were asked if they were satisfied with RI and would recommend it to a friend. RESULTS: Ninety-one patients (80 female, median age 51 (17-78) years had undergone rectal irrigation for the following indications: chronic constipation (n = 32), slow transit constipation (n = 18), obstructed defaecation (n = 10), and faecal incontinence (n = 31). Of the 60 patients with constipation, 50 (83%) were available for follow up. Mean constipation scores improved from 18.72 to 11.45 following rectal irrigation (P = 0.001). Twenty-five patients experienced failure of RI to control symptoms, 10 of whom were offered surgery. Of the patients with incontinence, 20 (67%) were available for follow up. Mean incontinence scores improved from 16.2 to 10.8 with rectal irrigation (P = 0.005). Twelve patients discontinued RI, the commonest reason being lack of improvement in symptoms. Seven of these patients were offered surgery. The only complication was in one patient with constipation who had minor rectal bleeding following irrigation, which was stopped. CONCLUSION: Rectal irrigation can be a useful tool in the management of functional bowel disorders and should be tried prior to the consideration of any surgery. However, further work is needed to define the precise indications and patient selection criteria.

A tool-kit for the quantitative assessment of proficiency in laparoscopic colorectal surgery.

AIM: Laparoscopic colorectal surgery includes operative procedures of varying complexity, and traditional assessment tools may not be enough to assess competence. This study defines quantitative tools for assessing proficiency in laparoscopic colorectal surgery. METHOD: A single surgeon's 11-year experience was subdivided into five phases with equal numbers of patients. A tool-kit, with specific tools defined as the complexity score, the conversion score, the technical score, the training score and the proficiency score, has been developed and used to evaluate each phase of the experience. RESULTS: There were 400 patients, with 80 in each of the five phases. The complexity score increased from 23.75 to 63.75 over the five phases. Similar increases were also demonstrable in the conversion score (from 0.45 to 15.45), the technical score (from 30 to 96.5), the training score (from 5.8 to 34.8) and the overall proficiency score (from 15 to 52.63). CONCLUSION: The results show that it is possible to quantify the workload in laparoscopic colorectal surgery and to assess increasing proficiency using a simple, reproducible and reliable tool-kit.

A unique approach to quantifying the changing workload and case mix in laparoscopic colorectal surgery.

AIM: Laparoscopic colorectal surgery includes a range of operations with differing technical difficulty, and traditional parameters, such as conversion and complication rates, may not be sensitive enough to assess the complexity of these procedures. This study aims to define a reproducible and reliable tool for quantifying the total workload and the complexity of the case mix. METHOD: This is a review of a single surgeon's 10-year experience. The intermediate equivalent value scoring system was used to code complexity of cases. To assess changes in the workload and case mix, the period has been divided into five phases. RESULTS: Three hundred and forty-nine laparoscopic operations were performed, of which there were 264 (75.6%) resections. The overall conversion rate was 17.8%, with progressive improvement over the phases. Complex major operation (CMO), as defined in the British United Provident Association (BUPA) schedule of procedures, accounted for 35% of the workload. In spite of similar numbers of cases in each phase, there was a steady increase in the workload score, correlating with the increasing complexity of the case mix. There was no significant difference in the conversion and complications rates between CMO and non-CMO. The paradoxical increase in the mean operating time with increasing experience corresponded to the progressive increase in the workload score, reflecting the increasing complexity of the case mix. CONCLUSION: This article establishes a reliable and reproducible tool for quantifying the total laparoscopic colorectal workload of an individual surgeon or of an entire department, while at the same time providing a measure of the complexity of the case mix.

Post-exposure prophylaxis for H1N1 with oseltamivir in renal allograft recipient--safe and effective without any immunosuppresive drug interaction.

Kidney transplant recipients are at a high risk for H1N1 infection associated complications during the current pandemic. Prevention of infection by immunization, together with early recognition and prompt antiviral treatment are critical. Post-exposure prophylaxis of H1N1 with oseltamivir was safe, effective and well tolerated to prevent H1N1 influenza A virus infection in newly transplanted renal allograft recipient receiving triple immunosuppression without any interaction with tacrolimus level. Oseltamivir was effective for post-exposure prophylaxis of H1N1 in close contact.

Lupus nephritis associated with CD20+ B-cell NHL.

The combination of NHL and documented malignancy-associated glomerulonephritis is uncommon. Also, no single renal pathological entity is consistently found in patients with NHL. Epstein-Barr virus (EBV) infection may manifest as systemic lupus erythematosus (SLE) and/or diffuse large cell lymphoma (DLBCL) in a genetically/ immunologically susceptible individual with defective cytotoxic T-cell response against EBV. We describe lupus nephritis in a 45 years old male suffering from untreated NHL. CD20+ DLBCL was demonstrated by immunohistochemistry of the neck lymph node (LN) biopsy performed for generalized lymphadenopathy. Renal biopsy revealed class V + IV lupus nephritis. Serology demonstrated EBV infection. Complete clinical remission of both SLE and DLBCL was achieved post-therapy with six-cycle rituximab, cyclophosphamide, vincristin, adriablastin, methylprednisolone (R-CHOP) regime. This case report demonstrated the complex relationships between NHL, SLE, EBV and membranous glomerulonephritis. The presented case is remarkable not only because of the rare association of SLE and DLBCL, but also because of its successful treatment with R-CHOP.

C1q Nephropathy in a Patient of Neurofibromatosis Type 1: A Rare Case Report.

C1q nephropathy is a rare glomerular disease defined by the presence of characteristic mesangial dominant or codominant C1q deposition on immunofluorescence microscopy. Neurofibromatosis type 1 (NF-1) is an autosomal dominant syndrome caused by a mutation of a gene located on chromosomal segment 17q11.2. Nephrotic syndrome has rarely been reported in patients of NF-1, and the relation of NF-1 with nephrotic syndrome is unclear. Here, we present a rare case of C1q nephropathy in a patient of NF-1.

Posttransplant diabetes mellitus: a single-center study.

BACKGROUND: Posttransplant diabetes mellitus (PTDM) is a common complication of renal transplantation. We evaluated risk factors for PTDM. PATIENTS AND METHODS: This retrospective evaluation of 1112 patients transplanted from January 2001 to July 2007 was performed based on PTDM diagnosis using The American Diabetes Association criteria. After informed consent, The Ahmedabad Tolerance induction protocol (ATIP) was carried out in 846 of 988 living-related donor (LRD) cases versus 266 who underwent grafting under conventional immunosuppression (controls). RESULTS: PTDM was observed in 6.6% ATIP and 19.1% controls. Mean body mass index increased by 5.2% posttransplant among PTDM versus 1.2% in non-PTDM patients. There were 14.2% hepatitis C virus (HCV)-positive patients treated with ATIP, 27.5% among the controls; 8.3% of ATIP patients developed PTDM versus 15.4% of controls. Mean PTDM age was 43.6 years versus 41.4 years in the non-PTDM group. In ATIP, 20% HCV-positive patients were on tacrolimus versus 33.3% of controls. Antirejection therapy was necessary in 5.3% ATIP, 31.6% controls with 20% of both cohorts developing PTDM. For PTDM control, none of the ATIP subjects required insulin but 39.3%, oral hypoglycemic agents (OHA) and 60.7% diet versus 22.2% of controls on insulin, 37% OHA, and 40.7% diet control. ATIP showed higher chances of PTDM in the early posttransplant period versus delayed-onset in the controls. Calcineurin inhibitors increased PTDM risk. Mean serum creatinine in PTDM was comparable in all groups. HCV positivity increased PTDM risk with 20% to 33% cumulative effect of bolus steroid and tacrolimus therapy. CONCLUSION: Risk factors for PTDM were higher HCV positivity, BMI, and use of tacrolimus, cyclosporine or pulse steroids. ATIP seemed to be safer than the controls.

Postrenal transplant hemolytic uremic syndrome/thrombotic microangiopathy: Ahmedabad experience.

BACKGROUND: Hemolytic uremic syndrome (HUS)/thrombotic microangiopathy (TMA) (tissue-limited HUS) is a well-recognized serious complication of renal transplantation, affecting 3% to 14% patients who are administered calcineurin inhibitor-based immunosuppression. We performed a retrospective study to examine the incidence, etiology, course, and outcome of HUS/TMA in our experience. PATIENTS AND METHODS: This retrospective study of 1540 renal allograft biopsies performed between January 2000 and October 2007 was performed to assess the incidence of HUS/TMA. Institute Transplant Registry records were reviewed for clinical history, laboratory findings, medications, and outcome. The offending drug was substituted in all subjects and plasmapheresis was added as an adjuvant until recovery of allograft function. RESULTS: TMA was observed in 17 (1.1%) biopsies. Two of 17 patients experienced recurrent HUS; 15 were drug-induced (12 with cyclosporine, three with Sirolimus); 10 were TMA; and five HUS. Nine patients developed HUS/TMA within 3 months of transplantation with eight developing it within 1 year posttransplantation. Graft function recovered in 12, while five did not recover. The HUS group showed 60% recovery compared with 80% among the TMA group. Two patients were lost; both displayed HCV seropositivity and one also showed anti-cardiolipin antibody. CONCLUSION: Early allograft biopsy with prompt diagnosis and management by drug substitution +/- plasmapheresis in posttransplant HUS/TMA plays an important role in allograft outcome. TMA showed better recovery than HUS.

In pursuit of the ultimate: the initial Ahmedabad journey toward transplantation tolerance.

We designed a prospective clinical trial of 357 patients divided in two groups--treated (n = 201) and controls (n = 156)--to evaluate effects of donor hematopoietic stem cell transplantation (HSCT) with minimal nonmyeloablative conditioning for tolerance induction in living related donor renal allograft recipients. Conditioning included donor leukocyte infusions, target-specific irradiation, anti-T-cell antibody, cyclophosphamide, cyclosporine (CsA), followed by bone marrow (BM)-derived and peripheral blood stem cell (PBSC) infusion into thymus, liver, BM, and periphery, with mean total dose of 20 x 10(8) nucleated cells/kg body weight (BW) (mean CD34(+) count: 0.9%) pretransplantation. CsA (3 mg/kg BW/d) and prednisolone (10 mg/d) were used for immunosuppression. Azathioprine/mycophenolate mofetil were added in the event of an acute rejection episode. The controls underwent transplantation with three drug immunosuppression. With a mean follow-up of 21.5 months, the treated cohort showed better allograft function with mean serum creatinine (SCr), 1.42 +/- 0.31 mg% in contrast with the controls mean SCr, 1.61 +/- 0.52 mg% (P < .0001) at 23.9 months follow-up. One-year allograft/patient survival was 95%/96.7% versus 89%/93.4%, respectively. Peripheral blood chimerism by fluorescent in situ hybridization was 0.8% +/- 0.2% in the subset of treated patients with gender-mismatched donors. No graft-versus-host disease was noted. Nine patients with donor-specific cytotoxic alloantibodies pretransplantation showed a decrease in positivity to <15% post-HSCT and were transplanted safely. A transient rise in donor-specific cytotoxic alloantibodies was noted in 19 treated patients post-HSCT, 14 of whom returned to the transplantable range within 2 weeks and five required a desensitization protocol. "Prope" tolerance may be induced in living related donor renal transplantation across major histocompatability complex barriers using HSCT with minimal nonmyeloablative conditioning.

Cadaveric renal transplantation: our experience at the Institute of Kidney Diseases & Research Centre, Institute of Transplantation Sciences, Ahmedabad.

In a developing country such as India, cadaveric renal transplantation accounts for only less than 1% of total renal transplantations. The reasons for such a low rate of cadaveric transplantation are many, ranging from lack of awareness to socioeconomic reasons. Our institute conducted a statewide public awareness program and initiated an intercity organ harvesting program. This doubled the cadaveric renal transplantations in the last 2 years. We performed 38 cadaveric transplantations among 190 renal transplantations in the last year (August 2005 to July 2006). We retrieved kidneys from 21 donors, of whom 9 were outside our city. From 21 donors we transplanted 38 recipients; out of whom 3 received dual kidneys and one kidney was discarded. The Mean age of the donors was 41.4 +/- 18.2 years with a mean cold ischemia time of 6.9 +/- 3.8 hours. Sixty-eight percent had delayed graft function. At the last follow-up, which was 190 +/- 98 days, patient survival rate was 90%: 4 patients died, including 2 due to bacterial sepsis and 2 due to cytomegalovirus (CMV) disease. The Graft survival rate was 85%, and the death-censored graft survival rate was 90%. Mean serum creatinine value at the last follow-up was 1.2 +/- 0.3 mg%. There were 5 episodes of acute rejection in 31 patients during first 3 months (16% acute rejection rate). The increase in cadaveric transplantations was associated with satisfactory patient and graft survival despite the high incidence of delayed graft function.

Embryonic stem cell derived and adult hematopoietic stem cell transplantation for tolerance induction in a renal allograft recipient:--a case report.

UNLABELLED: We generated an human embryonic stem cell (hESC) line to augment chimerism-associated tolerance. A 40-year-old African with chronic glomerulonephritis-chronic renal failure with 100% G6PD enzyme deficiency presented for renal transplantation with a 27-year-old, 6/6 HLA-matched sister as a willing donor. METHOD: We generated an hESC line from the donor's oocytes using long ovarian stimulation protocol simultaneously with tolerance induction protocol. A nuclear transfer (NT)-hESC line was derived by transferring a donor cumulus cell into an enucleated oocyte, subjected to electrical fusion, and cultured for 5 days. ESCs hatched from the blastocyst on day 6 were cocultured with her unmodified bone marrow for 2 days and suspended in Ringer's lactate. Five milliliters of suspension were collected for cell counting, viability, pluripotency, flow cytometry, and karyotyping. The remaining suspension was infused into the periphery of the recipient. Transplantation was performed 1 week later following a negative lymphocytotoxicity cross-match test using no immunosuppression. Peripheral blood chimerism (PBC) was studied using fluorescent in situ hybridization technique. Allograft biopsy was performed on day 7. RESULTS: NT-hESC CD34+ count was 7.6%, viability 100%, karyotyping normal, pluripotency markers: SSEA-1, SSEA-4, OCT-3/4, TRA-1/60:positive; 12% PBC was noted at 1 week after transplantation. Serum creatinine was 1.2 mg%, graft biopsy was unremarkable, and G6PD enzyme deficiency was corrected to 0% at 100 days posttransplant. Liver function tests and hematology profile were unremarkable for graft-versus-host disease. CONCLUSION: This is the first report of tolerance induction using NT-hESC-induced hematopoietic chimerism with synergistic use of adult bone marrow. It was safe and effective.

Laparoscopic colorectal surgery: learning curve and training implications.

AIMS: This paper is a review of experience of laparoscopic colorectal surgery at a district general hospital with particular emphasis on the learning curve and training implications. METHODS: All patients undergoing colorectal surgery where laparoscopy was attempted between March 1998 and October 2003 were included in this study. RESULTS: There were 80 patients of which 49 had malignancy. Twenty eight stomas and 52 bowel resections were performed laparoscopically. The conversion rate for bowel resection was 32% (decreasing from 38% to 44% to 22%). This was significant (p = 0.001) when compared with stoma formation (7%). The firm has support from a specialist registrar and staff grade surgeon. In 22% of cases, one of the middle grades was the principal operating surgeon, mainly laparoscopic mobilisation and stoma formation. Only 6% of resections were performed by the middle grades. Conversely, a middle grade was the main operating surgeon in 66% of open resections and 61% of stoma formations during the same period. There were in all two deaths and 14 postoperative complications. All patients who had laparoscopic resections for malignancy had clear resection margins. CONCLUSION: This audit highlights that there is a long learning curve in laparoscopic colorectal surgery with decrease in conversion rates with increasing experience. There is also a reduction in training opportunities in open surgery during the learning phase of the consultant, although this may be counterbalanced by the exposure to laparoscopic techniques. Laparoscopic colonic mobilisation, as a part of stoma formation, is a good starting point for specialist registrar training.

Splenic rupture following colonoscopy: rare in the UK?

Splenic injury following colonoscopy is rare, with only 28 cases reported so far in the English language literature. Direct trauma during colonoscopy or traction on the spleno-colic ligament is the proposed mechanism of injury. Computed tomography (CT) of the abdomen is usually considered to be the most sensitive and specific modality for diagnosis. We report a case of a 56-year-old female, who was diagnosed having a splenic rupture following a routine colonoscopy for investigation of anaemia. She underwent an emergency laparotomy with splenectomy and made a satisfactory recovery post-operatively. We wish to highlight that there should be a high index of suspicion of splenic rupture in patients presenting with abdominal pain and demonstrating a positive Kehr's sign following colonoscopy. Only two case reports from the United Kingdom have been published, raising the possibility of under-reporting of such cases.

C1q nephropathy in India: a single-center study.

C1q nephropathy (C1qN) is defined by conspicuous C1q deposits in the glomerular mesangial regions of patients who do not have any evidence of systemic lupus erythematosus (SLE). We present our experience with C1qN over the last three years. In total, 1775 native renal biopsies were reviewed and dominant/co-dominant C1q mesangial deposits in patients with absence of clinical and/or serological evidence of SLE were considered as C1qN. Their clinical profile and renal function status were studied and correlated. C1qN was observed in 11 patients (0.61%), and included eight males and three females; the mean age was 36.6 years. The most common presentation was nephrotic syndrome. Hematuria was noted in eight patients (72%). The mean serum creatinine was 2.78 mg/dL. Hypertension was seen in two patients (18%). Mesangial proliferative glomerulonephritis (MePGN) was the most common histological pattern, followed by focal and segmental glomerulosclerosis and other lesions. The common codeposits along with C1q were IgM, followed by C3 and others. MePGN had better prognosis than others. To conclude, C1qN was noted in 0.61% of all renal biopsies with bimodal age distribution and may present as podocytopathy or non-podocytopathy. The prognosis depends on the morphological pattern and C1q deposits per se are not prognostic indicators.