Survival benefit of neoadjuvant FOLFIRINOX for patients with borderline resectable pancreatic cancer.

Backgrounds/Aims: While patients with borderline resectable pancreatic cancer (BRPC) are a target population for neoadjuvant chemotherapy (NAC), formal guidelines for neoadjuvant therapy are lacking. We assessed the perioperative and oncological outcomes in patients with BRPC undergoing NAC with FOLFIRINOX for patients undergoing upfront surgery (US). Methods: The AHPBA criteria for borderline resectability and/or a CA19-9 level > 100 µ/mL defined borderline resectable tumors retrieved from a prospectively populated institutional registry from 2007 to 2020. The primary outcome was overall survival (OS) at 1 and 3 years. A Cox Proportional Hazard model based on intention to treat was used. A receiver-operator characteristics (ROC) curve was constructed to assess the discriminatory capability of the use of CA19-9 > 100 µ/mL to predict resectability and mortality. Results: Forty BRPC patients underwent NAC, while 46 underwent US. The median OS with NAC was 19.8 months (interquartile range [IQR], 10.3-44.24) vs. 10.6 months (IQR, 6.37-17.6) with US. At 1 year, 70% of the NAC group and 41.3% of the US group survived (p = 0.008). At 3 years, 42.5 % of the NAC group and 10.9% of the US group survived (p = 0.001). NAC significantly reduced the hazard of death (adjusted hazard ratio, 0.20; 95% confidence interval, 0.07-0.54; p = 0.001). CA19-9 > 100 µ/mL showed poor discrimination in predicting mortality, but was a moderate predictor of resectability. Conclusions: We found a survival benefit of NAC with FOLFIRINOX for BRPC. Greater pre-treatment of CA19-9 and multivessel involvement on initial imaging were associated with progression of the disease following NAC.

Liver transplantation with donation after medical assistance in dying: Case series and systematic review of the literature.

Medical assistance in dying (MAiD) has been a legally approved practice in Canada since 2016. Only recently have patients undergoing MAiD also been considered as donors for liver transplantation (LT). This study aimed to evaluate a case series of LT outcomes for recipients with MAiD donors and was paired with a systematic literature review of studies assessing the efficacy of MAiD-associated liver donation. A retrospective chart review of patients registered within the LT Registry at London Health Sciences Centre (LHSC) in London, Ontario, Canada, that had received MAiD donor LT was conducted to develop a case series. Descriptive statistics were produced based on available patient outcomes information. The systematic review included euthanasia due to MAiD being a term exclusive to Canada. Case series had a 100% 1-year graft survival rate, with 50% of patients experiencing early allograft dysfunction but having no significant clinical outcome. A single case of postoperative biliary complication was reported. Median warm ischemic time ranged from 7.8-13 minutes among case series and literature reviews. Utilization of donation after circulatory death allografts procured after MAiD appears to be promising. Mechanisms associated with potential impact in postoperative outcomes include relatively lower warm ischemic time relative to donation after circulatory death Maastricht III graft recipients.

The role of associating liver partition and portal vein ligation for staged hepatectomy in the management of patients with colorectal liver metastasis.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) approach emerged as a promising surgical strategy for rapid and large hypertrophy of the future liver remnant (FLR) when a major liver resection is necessary. Colorectal liver metastasis (CRLM) is their main indication. However, the promising results published so far, are very difficult to interpret since they usually focus on the technique and not on the underlying disease. Moreover, they are usually made up of complex populations, which received different chemotherapy schemes, with the ALPPS technical variations implemented over time and without consistent long-term follow-up results as well. Whereby, its role in CRLM should be analyzed as carefully as possible to indicate and select the best candidates who will benefit the most from this approach. We conducted a computerized search using PubMed and Google Scholar for reports published so far, using mesh headings and keywords related to the ALPPS and CRLM.

Liver transplantation for non-resectable colorectal liver metastasis: where we are and where we are going.

PURPOSE: Almost 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastasis (LM). Although their only long-term curative treatment is surgery, less than half of these patients can be eventually resected. Therefore, palliative chemotherapy is offered as a definitive option, though with poor results. Recently, the University of Oslo group has published encouraging results in the treatment of these patients with liver transplantation (LT), whereby worldwide interest in this option has been renewed. METHODS: A literature review of LT for patients with unresectable colorectal metastasis was performed. This included information regarding patient selection, complications, overall survival (OS) and disease-free survival (DFS), immunosuppression, chemotherapy, and description of the ongoing trials. RESULTS: Improvements in OS and DFS have been observed in consecutive published prospective trials, as patient selection has been refined. Papers reporting OS of patients who randomly presented similar selection criteria also exhibited good results. CONCLUSION: LT within the available therapeutic options in patients with CRC-LM seems to be a compelling alternative in carefully selected patients. The ongoing trials will provide valuable information regarding selection criteria, immunosuppressive therapy and different modalities of adjuvant chemotherapy, which are, to our knowledge, the vital platform of LT in CRC-LM. Although some of the developing techniques involve living donors, graft availability for these patients remains a matter of major concern.

Early pancreatic cancer in IgG4-related pancreatic mass: A case report.

BACKGROUND: IgG4-related disease can manifest diversely, including autoimmune pancreatitis and IgG4-related cholangiopathy. We are reporting a very unusual cause of pancreatic cancer triggered in a previously unknown IgG4-related disease. CASE SUMMARY: A 75-year-old man was diagnosed with a 43 mm × 33 mm pancreatic head tumor after consulting for abdominal pain and jaundice. A pancreaticoduodenectomy was carried out uneventfully, and the histopathology report showed an early stage of acinar-cell pancreatic cancer. The patient reconsulted on the 30th postoperative day with fever, jaundice and asthenia. Magnetic resonance cholangiopancreatography evidenced an extense bile duct stricture. A percutaneous biliary drainage proved to be ineffective, even after exchanging it with larger bore drainage. Reviewing the surgical specimen, features compatible with IgG4-related disease were observed. Consequently, empiric treatment with steroids was initiated achieving excellent results. CONCLUSION: IgG4-related disease may cause chronic inflammation of the pancreas and can condition pancreatic malignancies.

The pancreas as a target of metastasis from renal cell carcinoma: Results of surgical treatment in a single institution.

BACKGROUNDS/AIMS: Metastasis in the pancreatic gland is infrequent, representing between 2-5% of the tumors that affect this organ. However, secondary lesions of clear cell renal carcinoma (CCRC) can occur mainly in this location and it is frequently the only site of dissemination. Treatment of choice is resection in surgically fit patients, as it has been shown that it improves the quality of life and prognosis substantially. We retrospectively reviewed the clinical data of patients with pancreatic resections for metastatic CCRC since there are no reports of the treatment modality of this singular entity in Argentina. METHODS: Retrospective cohort analysis over a 10-year period including eight patients who underwent pancreatic resection for metastatic CCRC. RESULTS: 75% of patients were male with an average age of 65.5 years. The pancreatic surgery occurred at a median time of 9.2 years (1-24.8) from the renal operation. The pancreatic lesions were mostly solitary and asymptomatic. A pancreaticoduodenectomy (PD) was performed in 4 patients (50%). Distal pancreatectomy (DP) was performed in 3 patients (37.3%) and one patient (12.5%) underwent a total pancreaticoduodenectomy. All the patients presented a confirmatory biopsy of pancreatic metastasis of CCRC. Complications were recorded in 3 patients (42.85%). No intraoperative or postoperative mortality was registered. With a median follow-up of 45 months, three patients presented recurrence at 32, 46 and 51 months, respectively. Only one patient showed death due to recurrence at 7.8 month. CONCLUSIONS: CCRC pancreatic metastases treated surgically have a low morbidity and mortality rate in high volume centers, showing excellent long-term survival.

Biliary reconstruction before clamp removal to avoid portal vein thrombosis in pediatric living-donor liver transplantation using hyper-reduced left lateral segment grafts: A novel technical strategy.

LT has become the treatment of choice for children with end-stage liver disease. The scarcity of donors and the considerable mortality on waiting lists have propelled the related living-donor techniques, especially in small children. This population need smaller and good quality grafts and are usually candidates to receive a LLS from a related donor. Many times this grafts are still large and do not fit in the receptor's abdomen, so a further hyper-reduction may be required. Despite all advances in LT field, vascular complications still occur in a considerable proportion remaining as a significant cause of morbidity, graft loss, and mortality. Technical issues currently play an essential role in its genesis. The widely spread technique for biliary and vascular reconstruction in living donor LT (LDLT) nowadays implies removal of the portal vein (PV) clamp after the venous anastomosis, then the arterial reconstruction is done, followed by the biliary reconstruction. However, due to the posterior location of the LLS bile duct, for its reconstruction, a rotation of the liver is required risking a potential transient PV occlusion leading to thrombosis afterward. We describe a new technique that involves performing biliary reconstruction after the PV anastomosis and before removing the vascular clamp, thus allowing to freely rotate the liver with less risk of PV occlusion and thrombosis.

Malignant transformation of hepatocellular adenoma in a young female patient after ovulation induction fertility treatment: A case report.

BACKGROUND: Hepatocellular adenoma (HCA) is a rare benign liver tumor usually affecting young women with a history of prolonged use of hormonal contraception. Although the majority is asymptomatic, a low proportion may have significant complications such as bleeding or malignancy. Despite responding to the hormonal stimulus, the desire for pregnancy in patients with small HCA is not contraindicated. However, through this work we demonstrate that intensive hormonal therapies such as those used in the treatment of infertility can trigger serious complications. CASE SUMMARY: A 33-year-old female with a 10-year history of oral contraceptive use was diagnosed with a hepatic tumor as an incidental finding in an abdominal ultrasound. The patient showed no symptoms and physical examination was unremarkable. Laboratory functional tests were within normal limits and tests for serum tumor markers were negative. An abdominal magnetic resonance imaging (MRI) was performed, showing a 30 mm × 29 mm focal lesion in segment VI of the liver compatible with HCA or Focal Nodular Hyperplasia with atypical behavior. After a total of six years of follow-up, the patient underwent ovulation induction treatment for infertility. On a following MRI, a suspected malignancy was warned and hence, surgery was decided. The surgical specimen revealed malignant transformation of HCA towards trabecular hepatocarcinoma with dedifferentiated areas. There was non-evidence of tumor recurrence after three years of clinical and imaging follow-up. CONCLUSION: HCAs can be malignant regardless its size and low-risk appearance on MRI when an ovultation induction therapy is indicated.

Tratamiento quirúrgico de las metástasis pancreáticas de cáncer renal de células claras en una institución de la Argentina / Surgical treatment of pancreatic metastases from renal clear cell carcinoma

Isolated pancreatic metastases of clear cell renal carcinoma are rare. Clear cell renal carcinoma (CCRC) is responsible for approximately 20-30 % of cases that present metastases at diagnosis. Despite that pancreatic involvement is inusual, this is an organ were particularly and frequently place as the only dissemination site. The aim of this report was to evaluate the surgical and oncological results of patients submitted to pancreatectomy consecutively to a CCRC. Patients with pancreatectomy because of metastases were selected in a 10 -year period. Clear cell renal carcinoma spreads both by direct perinephric extension and by hematogenous and lymphatic routed. The treatment of localized CCRC is surgical. For patients with metastatic CCRC, no efficacious agent has ever been identified, and there is no standard or accepted therapy. The results of this study are presented and discussed

Use of radiotherapy in patients with palliative double bypass for locally advanced pancreatic adenocarcinoma.

PURPOSE: Pancreatic cancer (PC) has not changed overall survival in recent years despite therapeutic efforts. Surgery with curative intent has shown the best long-term oncological results. However, 80%-85% of patients with these tumors are unresectable at the time of diagnosis. In those patients, first therapeutic attempts are minimally invasive or surgical procedures to alleviate symptoms. The addition of radiotherapy (RT) to standard chemotherapy, ergo chemoradiation, in patients with locally advanced pancreatic cancer (LAPC) is still controversial. The study aims to compare outcomes in patients with a double bypass surgery due to LAPC treated or not with RT. MATERIALS AND METHODS: A retrospective cohort study of patients with double bypass for LAPC were registered and divided into two groups: treated or not with postoperative RT. Baseline characteristics, postoperative complications, those related to RT and their relation to the main event (mortality) were compared. RESULTS: Seventy-four patients were included. Surgical complications between the groups did not offer significant differences. Complications related to RT were mostly mild, and 86% of patients completed the treatment. Overall survival at 1 and 2 years for patients in the exposed group was 64% and 35% vs. 50% and 28% in the non-exposed group, respectively (p = 0.11; power 72%; hazard ratio = 0.53; 95% confidence interval, 0.24-1.18). CONCLUSION: We observed a tendency for survival improvement in patients with postoperative RT. However, we've not had enough power to demonstrate this difference, possibly due to the small sample size. It is indispensable to develop randomized and prospective trials to guide more specific treatment lines in this patients.

Extended antibiotic therapy versus placebo after laparoscopic cholecystectomy for mild and moderate acute calculous cholecystitis: A randomized double-blind clinical trial.

BACKGROUND: Acute calculous cholecystitis (ACC) is the most common complication of cholelithiasis. Laparoscopic cholecystectomy (LC) is the gold standard treatment in mild and moderate forms. Currently there is consensus for the use of antibiotics in the preoperative phase of ACC. However, the need for antibiotic therapy after surgery remains undefined with a low level of scientific evidence. METHODS: The CHART (Cholecystectomy Antibiotic Randomised Trial) study is a single-center, prospective, double blind, and randomized trial. Patients with mild to moderate ACC operated by LC were randomly assigned to receive antibiotic (amoxicillin/clavulanic acid) or placebo treatment for 5 consecutive days. The primary endpoint was postoperative infectious complications. Secondary endpoints were as follows: (1) duration of hospital stay, (2) readmissions, (3) reintervention, and (4) overall mortality. RESULTS: In the per-protocol analysis, 6 of 104 patients (5.8%) in the placebo arm and 6 of 91 patients (6.6%) in the antibiotic arm developed postoperative infectious complications (absolute difference 0.82 (95% confidence interval, -5.96 to 7.61, P = .81). The median hospital stay was 3 days. There was no mortality. There were no differences regarding readmissions and reoperations between the 2 groups. CONCLUSION: Although this trial failed to show noninferiority of postoperative placebo compared to antibiotic treatment after LC for mild and moderate ACC within a noninferiority margin of 5%, the use of antibiotics in the postoperative period does not seem justified, because it was not associated with a decrease in the incidence of infectious and other types of morbidity in the present study.

Intrahepatic cholangiojejunostomy for complex biliary stenosis after pediatric living-donor liver transplantation.

The treatment of biliary stenosis after pediatric LDLT is challenging. We describe an innovative technique of peripheral IHCJ for the treatment of patients with complex biliary stenosis after pediatric LDLT in whom percutaneous treatment failed. During surgery, the percutaneous biliary drainage is removed and a flexible metal stylet is introduced trough the tract. Subsequently, the most superficial aspect of the biliary tree is recognized by palpation of the stylet's round tip in the liver surface. The liver parenchyma is then transected until the bile duct is reached. A side-to-side anastomosis to the previous Roux-en-Y limb is performed over a silicone stent. Among 328 pediatric liver transplants performed between 1988 and 2015, 26 patients developed biliary stenosis. From nine patients requiring surgery, three patients who had received left lateral grafts from living-related donors due to biliary atresia were successfully treated with IHCJ. After a mean of 45.6 months, all patients are alive with normal liver morphological and function tests. The presented technique was a feasible and safe surgical option to treat selected pediatric recipients with complex biliary stenosis in whom percutaneous procedures or rehepaticojejunostomy were not possible, allowing complete resolution of cholestasis and thus avoiding liver retransplantation.

Protocol for extended antibiotic therapy after laparoscopic cholecystectomy for acute calculous cholecystitis (Cholecystectomy Antibiotic Randomised Trial, CHART).

INTRODUCTION: Acute calculous cholecystitis represents one of the most common complications of cholelithiasis. While laparoscopic cholecystectomy is the standard treatment in mild and moderate forms, the need for antibiotic therapy after surgery remains undefined. The aim of the randomised controlled Cholecystectomy Antibiotic Randomised Trial (CHART) is therefore to assess if there are benefits in the use of postoperative antibiotics in patients with mild or moderate acute cholecystitis in whom a laparoscopic cholecystectomy is performed. METHODS AND ANALYSIS: A single-centre, double-blind, randomised trial. After screening for eligibility and informed consent, 300 patients admitted for acute calculus cholecystitis will be randomised into two groups of treatment, either receiving amoxicillin/clavulanic acid or placebo for 5 consecutive days. Postoperative evaluation will take place during the first 30 days. Postoperative infectious complications are the primary end point. Secondary end points are length of hospital stay, readmissions, need of reintervention (percutaneous or surgical reinterventions) and overall mortality. The results of this trial will provide strong evidence to either support or abandon the use of antibiotics after surgery, impacting directly in the incidence of adverse events associated with the use of antibiotics, the emergence of bacterial resistance and treatment costs. ETHICS AND DISSEMINATION: This study and informed consent sheets have been approved by the Research Projects Evaluating Committee (CEPI) of Hospital Italiano de Buenos Aires (protocol N° 2111). RESULTS: The results of the trial will be reported in a peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT02057679.