Metaanalysis of the Resolution rate of Type 2 diabetes mellitus in patients undergoing Roux-en-Y gastric bypass surgery

Background One of the major comorbidities in obese and morbidly obese patients is Type 2 diabetes (T2DM) with approximately 20% of them suffering from this disease. The objective of this review was to determine the impact of Roux-en-Y gastric bypass (RYGB) surgery on the resolution rate of T2DM in obese diabetic patients.Methods A systematic review was made into the literature using MEDLINE database to search for relevant studies reporting the resolution or improvement of T2DM post RYGB. Data from the case series and systematic review were collected for different age groups and different degrees of obesity (obese,morbidly obese,super obese) and metaanalysed. The various other aspects of the surgery regarding the complications,mortality rate,cost analysis,improvement in quality of life were also reviewed. Results Data from 56 relevant studies were retrieved containing a total of 10289 patients. Metaanalysis of the data from case series and other systematic reviews showed that RYGB is an effective method for obtaining weight reduction in obese,morbidly obese patients and in elderly obese patients. The mean age of patients was 42.8 years,mean baseline BMI was 47.4 kg/m2.The mean percentage excess weight loss (%EWL) was 65.3% and mean change in BMI was 17.1 kg/m2.The mean resolution rate of diabetes was 76.4 % while the mean improved/resolved rate of T2DM was 87.4%. Conclusion RYGB is a highly effective method for patients of various degrees of obesity and different age groups for treatment of obesity and T2DM. It also appears to be an interesting option economically due to savings from diabetic medications which outweigh the costs of the surgery and follow-up coupled with increased quality of life.

Laparoscopic liver resection:Wedge resections to living donor hepatectomy, are we heading in the right direction?

Despite inception over 15 years ago and over 3000 completed procedures, laparoscopic liver resection has remained mainly in the domain of selected centers and enthusiasts. Requirement of extensive open liver resection(OLR) experience, in-depth understanding of anatomy and considerable laparoscopic technical expertise may have delayed wide application. However healthy scepticism of its actual benefits and presence of a potential publication bias; concern about its safety and technical learning curve, are probably equally responsible. Given that a large proportion of our work, at least in transplantation is still OLR, we have attempted to provide an entirely unbiased, mature opinion of its pros and cons in the current invited review. We have dividedthis review into two sections as we believe they merit separate attention on technical and ethical grounds. The first part deals with laparoscopic liver resection(LLR) in patients who present with benign or malignant liver pathology, wherein we have discussed its overall outcomes; its feasibility based on type of pathology and type of resection and included a small section on application of LLR in special scenarios like cirrhosis. The second part deals with the laparoscopic living donor hepatectomy(LDH) experience to date, including its potential impact on transplantation in general. Donor safety, graft outcomes after LDH and criterion to select ideal donors for LLR are discussed. Within each section we have provided practical points to improve safety in LLR and attempted to reach reasonable recommendations on the utilization of LLR for units that wish to develop such a service.

Interferon-γ inhibits ghrelin expression and secretion via a somatostatin-mediated mechanism

AIM:To investigate if and how the proinflammatory cytokine interferon γ(IFNγ) affects ghrelin expression in mice.METHODS:The plasma concentration of ghrelin,andgastric ghrelin and somatostatin expression,were examined in wild-type mice and mice infected with Helicobacter pylori(H.pylori).Furthermore,ghrelin expression was examined in two achlorhydric mouse models with varying degrees of gastritis due to bacterial overgrowth.To study the effect of IFNγ alone,mice were given a subcutaneous infusion of IFNγ for 7 d.Finally,the influence of IFNγ and somatostatin on the ghrelin promoter was characterized.RESULTS:H.pylori infection was associated with a 50% reduction in ghrelin expression and plasma concentration.Suppression of ghrelin expression was inversely correlated with gastric inflammation in achlorhdyric mouse models.Subcutaneous infusion of IFNγ suppressed fundic ghrelin mRNA expression and plasma ghrelin concentrations.Finally,we showed that the ghrelin promoter operates under the control of somatostatin but not under that of IFNγ.CONCLUSION:Gastric infection and inflammation is associated with increased IFNγ expression and reduced ghrelin expression.IFNγ does not directly control ghrelin expression but inhibits it indirectly via somatostatin.

Signet ring colorectal carcinoma:Do we need to improve the treatment algorithm?

AIM To elaborate about this peculiar variant from a tertiary cancer center from India.METHODS It's a retrospective study(2011-2014) of all patients diagnosed with signet ring colo-rectal cancer(SRCC). Various clinico-pathological variables were studied.RESULTS One hundred and seventy consecutive patients with SRCC were diagnosed(11.4% of all colorectal cancers). Median Age of the cohort was 41 years. Most common location was recto-sigmoid area(54.7%). Majority patients presented in stage III and IV(91.2%). Most of the stage IV patients had isolated peritoneal metastases(86.5%). Colonic tumors had higher incidence of peritoneal metastases(91.8% vs 83.3%) as well as isolated peritoneal recurrences(37.5% vs 16.7%) than rectal primaries. Thirty-seven point five percent of patients recurred after curative surgery. Amongst them 63.63% patients had isolated peritoneal recurrences. Circumferential resection margin(CRM) was involved in 17.9% patients. Median relapse free survival(RFS) and overall survival(OS) of the cohort were 14.9 and 18.13 mo respectively. CRM involvement, colonic primary were associated with poorer RFS and OS.CONCLUSION SRCC has predilection for peritoneal dissemination. More aggressive and/or extended chemotherapy schedules as well as prophylactic hyperthermic intra-peritoneal chemotherapy at the time of primary surgery may be attempted in these patients.

Intestinal anisakiasis treated successfully with conservative therapy:Importance of clinical diagnosis

Intestinal anisakiasis is not only a rare parasitic disease,but is also difficult to diagnose.The symptoms are not specific and are often very severe and abrupt,and the findings of clinical imaging are very remarkable.Therefore,intestinal anisakiasis is often misdiagnosed as acute abdomen or intestinal obstruction and is treated surgically.However,if intestinal anisakiasis could be diagnosed correctly,it is well treated conservatively.We experienced three cases of intestinal anisakiasis,which were diagnosed correctly and treated successfully with conservative therapy.A correct clinical history and imaging interpretation helped us diagnose intestinal anisakiasis correctly and thus treat the patients successfully with conservative therapy.

Involvement of methylation-associated silencing of formin 2 in colorectal carcinogenesis

AIM To investigate whether promoter methylation is responsible for the silencing of formin 2(FMN2) in colorectal cancer(CRC) and to analyze the association between FMN2 methylation and CRC. METHODS We first identified the expression levels and methylation levels of FMN2 in large-scale human CRC expression datasets, including GEO and TCGA, and analyzed the relationship between the expression and methylation levels. Then, the methylation levels in four CpG regions adjacent to the FMN2 promoter were assessed by MethylTarget? assays in CRC cells and in paired colorectal tumor samples and adjacent nontumor tissue samples. Furthermore, we inhibited DNA methylation in CRC cells with 5-Aza-2'-deoxycytidine and assessed the expression of FMN2 by q RT-PCR. Last, the association between FMN2 methylation patterns and clinical indicators was analyzed.RESULTS A statistically significant downregulation of FMN2 expression in large-scale human CRC expression datasets was found. Subsequent analysis showed that a high frequency of hypermethylation occurred in the FMN2 gene promoter in CRC tissues; operating characteristic curve analysis revealed that FMN2 gene methylation had a good capability for discriminating between CRC and nontumor tissue samples(AUC = 0.8432, P < 0.0001). Methyl Target? assays showed that CRC cells and tissues displayed higher methylation of these CpG regions than nontumor tissue samples. Correlation analysis showed a strong inverse correlation between methylation and FMN2 expression, and the inhibition of DNA methylation with 5-Aza significantly increased endogenous FMN2 expression. Analysis of the association between FMN2 methylation patterns and clinical indicators showed that FMN2 methylation was significantly associated with age, N stage, lymphovascular invasion, and pathologic tumor stage. Notably, the highest methylation of FMN2 occurred in tissues from cases of early-stage CRC, including cases with no regional lymph node metastasis(N0), cases in stages Ⅰ and Ⅱ, and cases with no lymphovascular invasion, but the methylation level began to decrease with tumor progression. Additionally, FMN2 promoter hypermethylation was more common in patients > 60 years old and in colon cancer tissue. CONCLUSION FMN2 promoter hypermethylation may be an important early event in CRC, most likely playing a critical role in cancer initiation, and can serve as an ideal diagnostic biomarker in elderly patients with early-stage colon cancer.

Phase Ⅱ study of docetaxel,cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer

AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric cancer.METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria,were treated with 4 cycles of docetaxel(60 mg/m2),cisplatin(60 mg/m2) and capecitabine(1.875 mg/m2 orally on day 1-14,two daily doses) repeated every three weeks,followed by surgery.Primary end point was the feasibility and toxicity/safety profile of DCC,secondary endpoints were pathological complete resection rate and pathological complete response(p CR) rate.RESULTS All of the patients(51) were assessable for the feasibility and safety of the regimen.The entire preoperative regimen was completed by 68.6% of the patients.Grade Ⅲ/Ⅳ febrile neutropenia occurred in 10% of all courses.Three patients died due to treatment related toxicity(5.9%),one of them(also) because of refusing further treatment for toxicity.Of the 45 patients who were evaluable for secondary endpoints,four developed metastatic disease and 76.5% received a curative resection.In 3 patients a p CR was seen(5.9%),two patients underwent a R1 resection(3.9%).CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding.The high occurrence of febrile neutropenia is of concern.To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colonystimulating factor(G-CSF) should be explored.A curative resection rate of 76.5% is acceptable.The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

Histologically proven hepatic steatosis associates with lower testosterone levels in men with obesity

Men with obesity often present with low testosterone(T)and sex hormone-binding globulin(SHBG)levels.Several mechanisms for this have been proposed,but as SHBG is secreted by hepatocytes and sex steroids undergo hepatic metabolization,this study investigates whether severity and histological components of nonalcoholic fatty liver disease(NAFLD)are associated with sex steroid levels in obese men.This cross-sectional study included 80 obese men(age:46±11 years;body mass index:42.2±5.5 kg m^-2).Serum levels of total T and estradiol(E.)were measured using liquid chromatography coupled with tandem mass spectroscopy(LC/MS-MS)and SHBG and gonadotropins by immunoassay.Liver biopsies were evaluated using Steatosis.Activity,and Fibrosis scoring.Participants with steatohepatitis had similar median(1st quartile-3rd quartile)total T levels(7.6[5.0-11.0]nmol l^-1 vs 8.2[7.2-10.9]nmol l^-1;P=0.147),lower calculated free T(cFT)levels(148.9[122.9-188.8]pmol 1-1 s 199.5[157.3-237.6] pmol l^-1;P=0.006),and higher free E.T ratios(10.0[6.4-13.9]×10^-3 vs 7.1[5.7-10.7]×10^-3;P=0.026)compared to men with only nonalcoholic fatty liver.Among the histological components of NAFLD.only steatosis was independently associated with total T(r=-0.331.P=0.003)and cFT levels(r=-0.255.P=0.025).Obese men with.steatohepatitis have even lower cFT levels compared to those without,an association mainly driven by grade of steatosis.Whether this reflects a subgroup of men with a more severe obesity-related phenotype or results from direct relations between hepatic steatosis and sex steroid metabolism needs further investigation.