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Neoadjuvant therapy for resectable pancreatic cancer

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World Journal of Gastrointestinal Oncology 2017年第12期9卷 457-465页

作者： Sheikh Hasibur Rahman Robin Urquhart michele molinari Department of Surgery Dalhousie University Department of Surgery University of Pittsburgh Medical Center

The use of neoadjuvant therapies has played a major role for borderline resectable and locally advanced pancreatic cancers(PCs). For this group of patients, preoperative chemotherapy or chemoradiation has increased the likelihood of surgery with negative resection margins and overall survival. On the other hand, for patients with resectable PC, the main rationale for neoadjuvant therapy is that the overall survival with current strategies is unsatisfactory. There is a consensus that we need new treatments to improve the overall survival and quality of life of patients with PC. However, without strong scientific evidence supporting the theoretical advantages of neoadjuvant therapies, these potential benefits might turn out not to be worth the risk of tumors progression while waiting for surgery. The focus of this paper is to provide the readers an overview of the most recent evidence on this subject.

关键词： Pancreatic adenocarcinoma Neoadjuvant chemotherapy Neoadjuvant chemoradiation therapy Meta-analysis Decision analysis Borderline resectable Locally advanced Randomized controlled trial Phase I trial Phase II trial Phase III trial

Pathophysiology, epidemiology, classification and treatment options for polycystic liver diseases

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World Journal of Gastroenterology 2013年第35期19卷 5775-5786页

作者： Bassam Abu-Wasel Caolan Walsh Valerie Keough michele molinari Department of Surgery Dalhousie University Department of Radiolgoy Dalhousie University Department of Surgery and Community Health and Epidemiology Dalhousie University

Polycystic liver diseases(PLD)represent a group of genetic disorders in which cysts occur in the liver(autosomal dominant polycystic liver disease)or in combination with cysts in the kidneys(autosomal dominant polycystic kidney disease).Regardless of the genetic mutations,the natural history of these disorders is *** natural history of PLD is characterized by a continuous increase in the volume and the number of *** genders are affected;however,women have a higher *** patients with PLD are asymptomatic and can be managed *** symptoms can affect 20%of patients who develop massive hepatomegaly with compression of the surrounding ***,patients with PLD suffer from acutecomplications caused by the torsion of hepatic cysts,intraluminal cystic hemorrhage and *** most common methods for the diagnosis of PLD are cross sectional imaging *** ultrasound and computerized tomography are the two most frequently used *** resonance imaging is more sensitive and specific,and it is a valuable test for patients with intravenous contrast allergies or renal *** treatment modalities are available to physicians caring for these *** treatment has been *** sclerotherapy,transarterial embolization,cyst fenestration,hepatic resection and liver transplantation are indicated to specific groups of patients and have to be tailored according to the extent of *** review outlines the current knowledge of the pathophysiology,clinical course,diagnosis and treatment strategies of PLD.

关键词： Polycystic liver disease Hepatic Epidemiolgy Classification Therapy Genetic

Advances in diagnosis,treatment and palliation of cholangiocarcinoma:1990-2009

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World Journal of Gastroenterology 2009年第34期15卷 4240-4262页

作者： Murad Aljiffry Mark J Walsh michele molinari Department of Surgery Queen Elizabeth II Health Science CentreDalhousie University

Several advances in diagnosis,treatment and palliation of cholangiocarcinoma(CC)have occurred in the last decades.A multidisciplinary approach to this disease is therefore *** is a relatively rare tumor and the main risk factors are:chronic inflammation, genetic predisposition and congenital abnormalities of the biliary *** the incidence of intra-hepatic CC is increasing,the incidence of extra-hepatic CC is trending *** only curative treatment for CC is surgical resection with negative *** transplantation has been proposed only for selected patients with hilar CC that cannot be resected who have no metastatic disease after a period of neoadjuvant chemo-radiation *** resonance imaging/magnetic resonance cholangiopancreatography,positron emission tomography scan,endoscopic ultrasound and computed tomography scans are the most frequently used modalities for diagnosis and tumor *** therapy,palliative chemotherapy and radiotherapy have been relatively ineffective for inoperable *** most of these patients biliary stenting provides effective *** therapy is an emerging palliative treatment that seems to provide pain relief,improve biliary patency and increase survival. The clinical utility of other emerging therapies such as transarterial chemoembolization,hepatic arterial chemoinfusion and high intensity intraductal ultrasound needs further study.

关键词： Cholangiocarcinoma Epidemiology Diagnosis Therapy Palliation Systematic review

Rifaximin vs conventional oral therapy for hepatic encephalopathy:A meta-analysis

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World Journal of Gastroenterology 2012年第8期18卷 767-777页

作者： Karim M Eltawil Marie Laryea Kevork Peltekian michele molinari Department of Surgery and Transplantation Queen Elizabeth Ⅱ Health Sciences Center Dalhousie University Department of Medicine Hepatology and Transplantation Queen Elizabeth Ⅱ Health Sciences Center Dalhousie University

AIM: To characterize the efficacy of rifaximin in the management of hepatic encephalopathy (HE) as several randomized controlled studies have shown contradictory results on its effectiveness in comparison to other oral agents. METHODS: We performed a systematic review and random effects meta-analysis of all eligible trials identifi ed through electronic and manual searches. Twelve randomized controlled trials met the inclusion criteria with a total of 565 patients. RESULTS: The clinical effectiveness of rifaximin was equivalent to disaccharides or other oral antibiotics[odds ratio (OR) 0.96; 95% CI: 0.94-4.08] but with a better safety profi le (OR 0.27; 95% CI: 0.12-0.59). At the completion of treatment protocols, patients receiving rifaximin showed lower serum ammonia levels [weighted mean difference (WMD) = -10.65; 95% CI: -23.4-2.1; P = 0.10], better mental status (WMD = -0.24; 95% CI: -0.57-0.08; P = 0.15) and less asterixis (WMD -0.1; 95% CI -0.26-0.07; P = 0.25) without reaching statistical signifi cance. On the other hand, other psychometric outcomes such as electroencephalographic response and grades of portosystemic encephalopathy were superior in patients treated with rifaximin in comparison to the control group (WMD = 0.21, 95% CI: -0.33-0.09, P = 0.0004; and WMD = -2.33, 95% CI: -2.68-1.98, P = 0.00001, respectively). Subgroup and sensitivity analysis did not show any signifi cant difference in the above fi ndings. CONCLUSION: Rifaximin appears to be at least as effective as other conventional oral agents for the treatment of HE with a better safety profi le.

关键词： Hepatic encephalopathy Lactulose Neo-mycin Non-absorbable disaccharides Rifaximin

Trends of characteristics and outcomes of donors and recipients of deceased donor liver transplantation in the United States: 1990 to 2013

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World Journal of Transplantation 2018年第5期8卷 167-177页

作者： Subhashini Ayloo Sri Ram Pentakota michele molinari Department of Surgery Rutgers New Jersey Medical School Department of Surgery University of Pittsburgh Medical Center

AIM To compare trends in donor/recipient characteristics and outcomes using four period cohorts of liver transplant recipients from 1990 to 2009. METHODS Seventy thousand three hundred and seventy-seven adult first-time recipients of whole-organ deceased-donor liver grafts from 1990 to 2009 were followed up until September 2013. Four periods based on transplantation dates were considered to account for developments in transplantation. Descriptive statistics were used to describe donor/recipient characteristics and transplant outcomes. Statistical comparisons between periods were performed using χ~2/Fischer's exact test(categorical variables) and t-tests/Mann-Whitney U test(continuous variables). Univariate descriptive statistics/survival data were generated using Kaplan-Meier curves. Cox Proportional Hazards models were used for regression analyses of patient and graft *** Mean age(years), body mass index(kg/m^2), and the proportion of males were, respectively, 39.1(± 17.4), 25.9(± 5.7) and 60.3 for donors, and 51.3(± 10.5), 27.7(± 5.6), and 64.4 for recipients. Donor and transplantation rates differed between racial/ethnic groups. Median(Q1-Q3) cold and warm ischemia, waitlist, and hospital stay times were 8(6.0-10.0) h and 45(35-59) min, 93(21-278) d, and 12(8-20) d. Total functional assistance was required by 8% of recipients at wait-listing and 13.4% at transplantation. Overall survival at 1, 3, 5, 10, 15, and 20 years was 87.3%, 79.4%, 73.6%, 59.8%, 46.7%, and 35.9%, respectively. The 2005-2009 cohort had better patient and graft survival than the 1990-1994 cohort overall [HR 0.67(0.62-0.72) and 0.66(0.62-0.71)] and at five years [HR 0.73(0.66-0.80) and 0.71(0.65-0.77)]. CONCLUSION Despite changes in donor quality, recipient characteristics, and declining functional status among transplant recipients, overall patient survival is superior and posttransplant outcomes continue to improve.

关键词： UNOS database OPTN database Liver transplant surveillance Liver transplant outcomes Liver transplant survival

Impact of body mass index on outcomes of 48281 patients undergoing first time cadaveric liver transplantation

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World Journal of Transplantation 2016年第2期6卷 356-369页

作者： Subhashini Ayloo Scott Hurton Matthew Cwinn michele molinari Department of Surgery Victoria General HospitalDalhousie University Department of Public Health and Epide-miology Dalhousie University

AIM: To investigate possible disparities in perioperative morbidity and mortality among different body mass index(BMI) groups and to simulate the impact that these differences might have had on the cohort of patients undergoing cadaveric liver transplantation(LT).METHODS: All adult recipients undergoing first time LT for benign conditions and receiving a whole graft from brain-dead donors were selected from the united network of organ sharing registry. From January 1994 to June 2013, 48281 patients satisfied the inclusion criteria and were stratified by their BMI. The hypothesis that abnormal BMIs were independent predictors of inferior outcomes was tested with univariate and multivariate regression ***: In comparison to normal weight recipients, underweight and morbidly obese recipients had increased 90-d mortality(adjusted OR = 1.737; 95%CI: 1.185-2.548, P = 0.005)(adjusted OR = 1.956; 95%CI: 1.473-2.597, P = 0.000) respectively and inferior patients' survivals(adjusted HR = 1.265; 95%CI: 1.096-1.461, P = 0.000)(adjusted HR = 1.157; 95%CI: 1.031-1.299, P = 0.013) respectively. Overall, patients' 5-year survival were 73.9% for normal-weight, 71.1% for underweight, 74.0% for overweight, 74.4% for class Ⅰ obese, 75.0% for class Ⅱ obese and 71.5% for class Ⅲ obese recipients. Analysis of hypothetical exclusion of underweight and morbidly obese patients from the pool of potential LT candidates would have improved the overall survival of the entire cohort by2.7%(95%CI: 2.5%-3.6%).CONCLUSION: Selected morbidly obese patients undergoing LT for benign conditions had 5-year survival rates clinically comparable to normal weight recipients. Impact analysis showed that exclusion of high-risk recipients(underweight and morbid obese patients) would not significantly improve the overall survival of the entire cohort of patients requiring LT.

关键词： Obesity Impact analysis Survival Liver transplantation Body mass index

Obesity and liver transplantation

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World Journal of Transplantation 2015年第3期5卷 95-101页

作者： Subhashini Ayloo John Armstrong Scott Hurton michele molinari Department of Surgery Dalhousie University

The percentage of overweight and obese patients(OPs) waiting for a liver transplant continues to increase. Despite the significant advances occurred in bariatric medicine, obesity is still considered a relative contraindication to liver transplantation(LT). The main aim of this review is to appraise the literature on the outcomes of OPs undergoing LT, treatments that might reduce their weight before, during or after surgery, and discuss some of the controversies and limitations of the current knowledge with the intent of highlighting areas where future research is needed.

关键词： Liver transplantation Bariatric surgery Obesity End-stage liver disease Weight-loss Access to transplantation

Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010

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World Journal of Gastroenterology 2011年第7期17卷 867-897页

作者： Chakshu Sharma Karim M Eltawil Paul D Renfrew Mark J Walsh michele molinari Department of Surgery Queen Eliz-abeth Ⅱ Health Sciences Center Dalhousie University

Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.

关键词： Diagnosis Epidemiology Palliation Pancreatic cancer Therapy

Surgical management of genital lymphoedema:experience and critical considerations from a tricenter study

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Plastic and Aesthetic Research 2023年第1期10卷 629-642页

作者： Martino Guiotto michele Maruccia Rossella Elia Marco Fresa Lidia molinari Marie Nicod Lalonde Corrado Campisi Pietro Giovanni di Summa Department of Plastic and Hand Surgery Centre Hospitalier Universitaire Vaudois(CHUV)Lausanne 1011Switzerland Department of Plastic Surgery Bari University HospitalBari 70124Italy Angiology Department Centre Hospitalier Universitaire Vaudois(CHUV)Lausanne 1011Switzerland Department of Plastic Surgery Lymphatic UnitSan Martino HospitalGenova 16132Italy Nuclear Medicine and Molecular Imaging Centre Hospitalier Universitaire Vaudois(CHUV)Lausanne 1011Switzerland

Aim:Genital lymphoedema(GL)is a chronic and debilitating disease,which can severely affect the patient’s quality of life with significant socio-economic ***,no gold standard algorithm exists for GL from diagnosis to *** study proposes our therapeutic flowchart based on the three senior consultants’experience in lymphatic ***:A retrospective investigation was conducted on a prospectively maintained database(2018-2022).Inclusion criteria involved all patients who underwent surgical procedures for treating GL in three plastic surgery departments(Lausanne,Bari,and Genova).Outcomes were assessed in terms of oedema reduction,stage regression,and functional reported ***:16 patients with GL were included:50%underwent debulking surgery,18.8%microsurgery,and 31.2%debulking+*** recorded a significant regression of the GL stage:62.5%shifted from stage II/III to postoperative stage ***,we found an infection recurrency resolution in 50%,a scrotal oedema reduction in 62.5%,and a scrotal oedema resolution in 37.5%of the patients *** almost half of the patients(53.3%)with associated penile oedema described persistent postoperative penile oedema,only two patients complained of persistent ***:According to our clinical experience,preoperative and postoperative physical functional therapy is always *** stages I and IIA,after the failure of the conservative treatment,lymph-venous shunts and lymph node transplantation surgery are proposed at the early *** GL is already diagnosed at stages IIB and III,the debulking surgery,together with functional procedures,represents our first approach.

关键词： Genital lymphoedema debulking surgery functional surgery microsurgery lymphatic venous anastomosis multi lymphatic-venous anastomoses lymph node transplantation