Five‐year effectiveness of bariatric surgery on disease remission, weight loss, and changes of metabolic parameters in obese patients with type 2 diabetes: A population‐based propensity score‐matched cohort study

Aims: To compare disease remission rates, weight loss, and changes of metabolic parameters of patients after bariatric surgery with nonsurgical patients. Methods: Based on the 2006‐2017 Hospital Authority database, a population‐based retrospective cohort of obese type 2 diabetes mellitus (T2DM) patients with and without bariatric surgery were identified. Surgical patients were matched with nonsurgical patients on 1‐to‐5 propensity score. Remission rates of diabetes, hypertension, and dyslipidaemia were reported annually up to 60 months. Changes in weight loss measurements (Body Mass Index [BMI], percentage of total weight loss [%TWL], percentage of excess weight loss [%EWL], and percentage of rebound in excess weight loss [%REWL]) and metabolic parameters (haemoglobin A1c [HbA1c], systolic blood pressure [SBP], diastolic blood pressure [DBP], and low‐density lipoprotein cholesterol [LDL‐C]) were measured for both groups. Results: Four hundred one surgical patients (310 restrictive surgeries; 91 bypass surgeries) and 1894 nonsurgical patients were included. Surgical patients had higher remission rates in diabetes and dyslipidaemia and better glycaemic control at 12 to 60 months (all Ps < .01). SBP and DBP were significantly lower for surgical group up to 12 months and similar between two groups after 12 months. Surgical patients had significantly lower BMI during follow‐up period. %TWL and %EWL were higher in the surgery group (15.7% vs 3.7%; 48.8% vs 12.0%) at 60 months (P < .001); differences in %REWL between two groups were insignificant. The effectiveness of restrictive and bypass surgeries was similar at 60 months, although restrictive surgeries were slightly more effective in T2DM remission. Conclusions: Bariatric surgery was effective in weight loss, remission of diabetes, and dyslipidaemia in 5‐year post‐surgery

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Management strategies for advanced stage of esophageal cancer

published_or_final_versionSurgeryMasterMaster of Surger

Surgical treatment for type II diabetes mellitus

Introduction: Historically, type 2 diabetes (T2DM) has been regarded as a progressive and degenerative disease and only minority of patients can have disease remission with conventional treatment. It was noticed that gastrointestinal surgery could induce complete remission of T2DM in most of morbidly obese patients. Compared to the West, the development of bariatric and metabolic surgery is slow in Hong Kong. It is unknown whether the knowledge and attitudes of medical doctors and patients towards surgical treatment for T2DM have impacts on the development in this field. The novel procedure sleeve gastrectomy (SG) had been shown to be effective in inducing T2DM remission in obese human. Duodenal jejunal bypass (DJB) and ileal transposition (IT) were reported to be effective for ameliorating T2DM in non-obese diabetic animal model. The anti-diabetic potency of DJB and IT is unknown in comparing to SG particularly in non-obese subjects. Currently, SG is the main procedure for morbidly obese patients with or without T2DM in the authors’ institution. Aims: The aims of the present thesis were to investigate the knowledge and attitudes of medical doctors and patients toward using surgery as a treatment for T2DM, to compare the anti-diabetic effect of SG, DJB and IT in non-obese T2DM animal model, and lastly, to review of outcomes of morbidly obese patients who underwent SG in authors’ institution. Methods: Survey was conducted using questionnaire for interview of both doctors and patients to investigate their knowledge and attitudes toward surgical treatment of T2DM. The anti-diabetic effects of novel surgical procedures SG, DJB and IT were compared using non-obese T2DM animal model (Goto Kakizaki rats). The outcomes were evaluation by measuring fasting glucose and glycosylated haemoglobin (HbA1c) levels. Other parameters including alteration in gut hormones and lipid profile were also analyzed. The outcomes of morbidly obese patients who underwent laparoscopic SG in last 5 years in the authors’ institution were retrospectively reviewed. Results: The knowledge of bariatric and metabolic surgery was inadequate both in medical doctors and patients. The attitude and pattern of referral from medical doctors depends on the amount of knowledge. Patients’ attitudes were positive and they accept surgery as a treatment option for T2DM as long as they were provided with adequate information. This implies that tremendous educational works are required both for medical doctors and patients for the development of bariatric and metabolic surgery in Hong Kong. All 3 procedures (SG, DJB and IT) significantly improved glucose homeostasis and the effect was more potent and durable in DJB and IT than SG. The improved glucose homeostasis in IT was resulted from increased GLP-1 and PYY secretion (hindgut theory). In DJB, GIP, GLP-1 and PYY were raised and the anti-diabetic effect could be explained both by the foregut and hindgut theories. SG reduced the diet triglyceride absorption. DJB reduced cholesterol absorption whereas IT reduced cholesterol but increase triglyceride absorption. The outcomes of SG for T2DM for morbidly obese patients were promising. More than 90% patients had T2DM ameliorated and 70% had complete remission. SG can effectively control the body weight of morbidly obese patients. Conclusion: Education, both to doctors and patients, was crucial to overcome the potential obstacles for the development of this newly specialty. The anti-diabetic effects of DJB and IT were more potent than SG in non-obese diabetic animal model. The lipid absorption varied in different surgical procedures. Application of these procedures in non-obese T2DM patients warrants individual consideration and further investigation. SG in the authors’ institution was effective to induce T2DM remission in morbidly obese patients.published_or_final_versionSurgeryDoctoralDoctor of Philosoph

Overexpression of microRNA-1288 in oesophageal squamous cell carcinoma

© 2016 Elsevier Inc. Purpose This study aims to examine the expression profiles miR-1288 in oesophageal squamous cell carcinoma (ESCC). The cellular implications and target interactions of ESCC cells following miR-1288 overexpression was also examined. Methods In total, 120 oesophageal tissues (90 primary ESCCs and 30 non-neoplastic tissues) were recruited for miR-1288 expression analysis using qRT-PCR. An exogenous miR-1288 mimic and its inhibitor were used to explore the in-vitro effects of miR-1288 on ESCC cells by performing cell proliferation, colony formation, cell invasion and migration assays. Localisation and modulatory changes of various miR-1288 regulated proteins such as FOXO1, p53, TAB3, BCL2 and kRAS was examined using immunofluorescence and western blot. Results Overexpression of miR-1288 was more often noted in ESCC tissues when compared to non-neoplastic oesophageal tissues. High expression was often noted in high grade carcinomas and with metastases. Patients with high levels of miR-1288 expression showed a slightly better survival compared to patients with low miR-1288 levels. Furthermore, overexpression of miR-1288 showed increased cell proliferation and colony formation, improved cell migration and enhanced cell invasion properties in ESCC cells. In addition, miR-1288 overexpression in ESCC cells showed repression of cytoplasmic tumour suppressor FOXO1 protein expression. Inversely, inhibition of miR-1288 expression exhibited remarkable upregulation of FOXO1 protein, while expressions of other tested proteins remain unchanged. Conclusions Up regulation of miR-1288 expression in ESCC tissues and miR-1288 induced oncogenic features of ESCC cells in-vitro indicates the oncogenic roles of miR-1288 in ESCCs. Overexpression of miR-1288 play a key role in the pathogenesis of ESCCs and its modulation may have potential therapeutic value in patients with ESCC.Link_to_subscribed_fulltex

A Versatile Orthotopic Nude Mouse Model for Study of Esophageal Squamous Cell Carcinoma

© 2015 Joseph Chok Yan Ip et al. Increasing evidence indicates tumor-stromal interactions play a crucial role in cancer. An in vivo esophageal squamous cell carcinoma (ESCC) orthotopic animal model was developed with bioluminescence imaging established with a real-time monitoring platform for functional and signaling investigation of tumor-stromal interactions. The model was produced by injection of luciferase-labelled ESCC cells into the intraesophageal wall of nude mice. Histological examination indicates this orthotopic model is highly reproducible with 100% tumorigenesis among the four ESCC cell lines tested. This new model recapitulates many clinical and pathological properties of human ESCC, including esophageal luminal stricture by squamous cell carcinoma with nodular tumor growth, adventitia invasion, lymphovascular invasion, and perineural infiltration. It was tested using an AKT shRNA knockdown of ESCC cell lines and the in vivo tumor suppressive effects of AKT knockdown were observed. In conclusion, this ESCC orthotopic mouse model allows investigation of gene functions of cancer cells in a more natural tumor microenvironment and has advantages over previous established models. It provides a versatile platform with potential application for metastasis and therapeutic regimen testing.Link_to_subscribed_fulltex

Nuclear Localization of DNAJB6 Is Associated with Survival of Patients with Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells

© 2015 AGA Institute. Background & Aims The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulates chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates β-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Methods We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients who underwent esophagectomy with no preoperative chemoradiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1 ± 2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs, or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. Results In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2 ± 1.8 months; 95% confidence interval [CI], 15.6-22.8 mo) than patients whose tumors had low nuclear levels of DNAJB6 (12.6 ± 1.4 mo; 95% CI, 9.8-15.4 mo; P =.004, log-rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than patients with low levels (hazard ratio, 0.562; 95% CI, 0.379-0.834; P =.004). Based on log-rank analysis and Cox regression analysis, the combination of the nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or bad outcomes (P < .0005 for both analyses). There was a negative association between the nuclear level of DNAJB6 and the presence of lymph node metastases (P =.022; Pearson Ï 2 test). Cancer cell lines that overexpressed DNAJB6a formed tumors more slowly in nude mice than control cells or cells that expressed a mutant form of DNAJB6a that did not localize to the nucleus. DNAJB6 knockdown in cancer cell lines promoted their growth as xenograft tumors in mice. A motif of histidine, proline, and aspartic acid in the J domain of DNAJB6a was required for its tumor-suppressive effects and signaling via AKT1. Loss of DNAJB6a resulted in up-regulation of AKT signaling in cancer cell lines and immortalized esophageal epithelial cells. Expression of a constitutively active form of AKT1 restored proliferation to tumor cells that overexpressed DNAJB6a, and DNAJB6a formed a complex with AKT1 in living cells. The expression of DNAJB6a reduced the sensitivity of ESCC to AKT inhibitors; the expression level of DNAJB6a affected AKT signaling in multiple cancer cell lines. Conclusions Nuclear localization of DNAJB6 is associated with longer survival times of patients with ESCC. DNAJB6a reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their proliferation and growth of xenograft tumors in mice. DNAJB6a might be developed as a biomarker for progression of ESCC.Link_to_subscribed_fulltex