Peri-operative outcomes for pancreatoduodenectomy in India: a multi-centric study

Background:

There have been an increasing number of reports world-wide relating improved outcomes after pancreatic resections to high volumes thereby supporting the idea of centralization of pancreatic resectional surgery. To date there has been no collective attempt from India at addressing this issue. This cohort study analysed peri-operative outcomes after pancreatoduodenectomy (PD) at seven major Indian centres.

Materials and Methods:

Between January 2005 and December 2007, retrospective data on PDs, including intra-operative and post-operative factors, were obtained from seven major centres for pancreatic surgery in India.

Results:

Between January 2005 and December 2007, a total of 718 PDs were performed in India at the seven centres. The median number of PDs performed per year was 34 (range 9–54). The median number of PDs per surgeon per year was 16 (range 7–38). Ninety-four per cent of surgeries were performed for suspected malignancy in the pancreatic head and periampullary region. The median mortality rate per centre was four (range 2–5%). Wound infections were the commonest complication with a median incidence per centre of 18% (range 9.3–32.2%), and the median post-operative duration of hospital stay was 16 days (range 4–100 days).

Conclusions:

This is the first multi-centric report of peri-operative outcomes of PD from India. The results from these specialist centers are very acceptable, and appear to support the thrust towards centralization.     

Carcinoid tumors and fibrosis: an association with no explanation

Carcinoid tumors are slow-growing neuroendocrine neoplasms most commonly associated with the gut and broncho-pulmonary system. In many instances, they are identified at surgery for unexplained bowel obstruction or during exploration of the small bowel in search of a primary tumor once distant metastases have been detected. Carcinoid tumors of the small bowel often present with pronounced fibrosis in the peri-tumoral tissues, distant in the heart or lungs, and locally in the peritoneal cavity. Despite medical and therapeutic advances that have alleviated symptoms and prolonged life, a substantial subset of patients develops mesenteric and small bowel carcinoid fibrosis and/or carcinoid heart disease. Fibrosis, and increasingly cardiac heart disease, are important components of intestinal carcinoid disease and are of considerable clinical concern, as both of these conditions reflect a connective tissue disorder whose etiology, biology, and therapy are unknown. In the past, individuals with carcinoid disease died of metastasis and uncontrollable symptomatology. Currently, there exists no clinical method to determine the development of fibrosis and little is understood about the biological basis of fibrosis. The elucidation of the biology and management of fibrosis is thus an issue of paramount clinical and scientific importance in determining appropriate diagnostic and therapeutic strategy. Therefore, the unraveling of the molecular events indicative of fibrosis in these cells and the identification of appropriate therapeutic targets is of considerable patient-care relevance. We have surveyed the world literature over the past 40 yr to evaluate both the incidence of carcinoid processes and track the evolving understanding of this process. In addition, we have provided more current mechanistic information in regard to the biological basis of fibrosis associated with small bowel carcinoid tumors.     

Cryptococcus neoformans-Cryptococcus gattii Species Complex: an International Study of Wild-Type Susceptibility Endpoint Distributions and Epidemiological Cutoff Values for Fluconazole,Itraconazole, Posaconazole,and Voriconazole

Epidemiological cutoff values (ECVs) for the Cryptococcus neoformans-Cryptococcus gattii species complex versus fluconazole, itraconazole, posaconazole, and voriconazole are not available. We established ECVs for these species and agents based on wild-type (WT) MIC distributions. A total of 2,985 to 5,733 CLSI MICs for C. neoformans (including isolates of molecular type VNI [MICs for 759 to 1,137 isolates] and VNII, VNIII, and VNIV [MICs for 24 to 57 isolates]) and 705 to 975 MICs for C. gattii (including 42 to 260 for VGI, VGII, VGIII, and VGIV isolates) were gathered in 15 to 24 laboratories (Europe, United States, Argentina, Australia, Brazil, Canada, Cuba, India, Mexico, and South Africa) and were aggregated for analysis. Additionally, 220 to 359 MICs measured using CLSI yeast nitrogen base (YNB) medium instead of CLSI RPMI medium for C. neoformans were evaluated. CLSI RPMI medium ECVs for distributions originating from at least three laboratories, which included ≥95% of the modeled WT population, were as follows: fluconazole, 8 μg/ml (VNI, C. gattii nontyped, VGI, VGIIa, and VGIII), 16 μg/ml (C. neoformans nontyped, VNIII, and VGIV), and 32 μg/ml (VGII); itraconazole, 0.25 μg/ml (VNI), 0.5 μg/ml (C. neoformans and C. gattii nontyped and VGI to VGIII), and 1 μg/ml (VGIV); posaconazole, 0.25 μg/ml (C. neoformans nontyped and VNI) and 0.5 μg/ml (C. gattii nontyped and VGI); and voriconazole, 0.12 μg/ml (VNIV), 0.25 μg/ml (C. neoformans and C. gattii nontyped, VNI, VNIII, VGII, and VGIIa,), and 0.5 μg/ml (VGI). The number of laboratories contributing data for other molecular types was too low to ascertain that the differences were due to factors other than assay variation. In the absence of clinical breakpoints, our ECVs may aid in the detection of isolates with acquired resistance mechanisms and should be listed in the revised CLSI M27-A3 and CLSI M27-S3 documents.     

Effect of vitamin A supplementation on measles-specific antibody levels in Guinea-Bissau

We have previously reported that vitamin A supplementation with measles vaccine at age 9 months increases measles-specific antibody concentrations in children at age 18 months compared with placebo. We examined these children when they reached age 6-8 years. Fewer vitamin A-supplemented children had non-protective antibody concentrations (p=0.0095); among children with protective antibody levels, vitamin A-supplemented children tended to have higher geometric mean antibody titres (p=0.09). Thus, simultaneous administration of vitamin A and measles vaccine at age 9 months had a long-term effect on measles-specific antibody levels and may contribute to improved measles control in less-developed countries.     

A Clinical Perspective on Gastric Neuroendocrine Neoplasia

The incidence of gastric neuroendocrine tumors (NETs) has increased exponentially based on widespread use of endoscopy and a greater pathological awareness of the condition. A key concern is the potential association with hypergastrinemia induced by proton pump inhibitor administration. Previous confusion regarding diagnosis and therapy has been diminished by a series of international consensus statements defining the biology and management strategies for the disease. Overall, gastric NETs are categorized as well-differentiated or poorly differentiated neoplasms. Well-differentiated gastric NETs are enterochromaffin-like (ECL) cell tumors subclassified into three types based on their relationship to gastrin, a key regulator of ECL cell neoplastic transformation. The treatment of type 1 and type 2 tumors depends on the size and invasiveness of the tumor, whereas type 3 tumors and poorly differentiated neuroendocrine carcinomas warrant aggressive surgical resection. The disease-specific 5-year survival ranges from about 95% in type 1 gastric carcinoids to about 25% in poorly differentiated gastric NECs. Elucidation of the precise biology of a gastric NET is critical to diagnosis and delineation of a type-specific management strategy.     

Drift, admixture, and selection in human evolution: a study with DNA polymorphisms.

Accuracy of evolutionary analysis of populations within a species requires the testing of a large number of genetic polymorphisms belonging to many loci. We report here a reconstruction of human differentiation based on 100 DNA polymorphisms tested in five populations from four continents. The results agree with earlier conclusions based on other classes of genetic markers but reveal that Europeans do not fit a simple model of independently evolving populations with equal evolutionary rates. Evolutionary models involving early admixture are compatible with the data. Taking one such model into account, we examined through simulation whether random genetic drift alone might explain the variation among gene frequencies across populations and genes. A measure of variation among populations was calculated for each polymorphism, and its distribution for the 100 polymorphisms was compared with that expected for a drift-only hypothesis. At least two-thirds of the polymorphisms appear to be selectively neutral, but there are significant deviations at the two ends of the observed distribution of the measure of variation: a slight excess of polymorphisms with low variation and a greater excess with high variation. This indicates that a few DNA polymorphisms are affected by natural selection, rarely heterotic, and more often disruptive, while most are selectively neutral.     

The effects of pyridoxine on pituitary hormone secretion in amenorrhea-galactorrhea syndromes

Six patients with amenorrhea, five of whom had galactorrhea and elevated PRL levels, were evaluated on a metabolic ward. All had normal sella tomograms, normal thyroid functions, and routine laboratory evaluations. None of the patients had taken any medication in the previous 6 months. On alternate days, five patients received 500 microgram of TRH iv with the measurement of PRL, TSH, FSh, LH, and hGH; 500 mg L-dopa orally with the measurement of PRL, FSH, and LH; a bolus infusion of 300 mg pyridoxine (B6) with measurement of PRL, hGH, TSH, FSH, and LH; and 25 mg chlorpromazine (CPZ) im with the measurement of PRL, LH, and FSH. The patients were then discharged on 600 mg oral pyridoxine/day and were readmitted for a repeat of the complete protocol 21 days later. The patients were continued on 600 mg oral pyridoxine for 3-4 months with monthly evaluations of serum PRL, LH, and FSH levels. These evaluations continued for 3 months after discontinuing pyridoxine. There was no demonstrable change in serum PRL after acute or chronic B6 therapy, mor was there a significant change in the response of PRL to CPZ, L-dopa, or TRH. The mean basal PRL was 97.5 +/- 9.7 ng/ml and after 3-4 months of oral pyridoxine was 97.1 +/- 14.8. In addition, there was no significant change in LH or FSH levels in response to acute or chronic B6, TRH, L-dopa, or CPZ. Neither acute B6 infusion nor chronic B6 therapy had any effect on TSH or the TSH response to TRH. Finally, acute B6 infusion had no effect on hGH levels and there were no paradoxical hGH responses to TRH. Two patients began having regular menses while on chronic pyridoxine. Their hormonal responses did not differ from those of the group, however.     

Membranoproliferative Glomerulonephritis in Pregnancy

Background

Membranoproliferative glomerulonephritis (MPGN) is an uncommon form of glomerulonephritis and it can be particularly difficult to predict outcomes and manage women with this disorder during pregnancy.

A clinical and microbiological study of approximal carious lesions. Part 1: the relationship between cavitation, radiographic lesion depth, the site-specific gingival index and the level of infection of the dentine

A clinical study was carried out to assess relationship between the presence of approximal cavitation, the radiographic depth of the lesion, the site-specific gingival index and the level of infection of the dentine. Adult patients assessed as needing operative treatment and presenting with approximal lesions visible in the outer third of dentine on bite-wing radiographs were included in the study. Direct lesion depth measurements were recorded from the radiographs and the site-specific gingival index adjacent to the lesion was noted. The presence or absence of a cavity was recorded on an impression following tooth separation. During operative treatment samples of dentine were taken on entry to the lesions to ascertain the level of infection of the dentine. Visual evaluation of 54 successfully recorded impressions revealed that 85% were cavitated. Cavitated lesions were found to have higher site-specific gingival index scores compared to non-cavitated lesions (p = 0.03). The probability of cavitation was greater for lesions >0.5 mm from the enamel-dentine junction on bite-wing radiographs (p<0.01). The level of infection of the dentine was significantly higher for cavitated lesions than for non-cavitated lesions (p = 0.02). However, the non-cavitated lesions were still infected.