Impact of age on short-term outcomes of liver surgery: Lessons learned in 10-years' experience in a tertiary referral hepato-pancreato-biliary center

We investigate the surgical outcomes of patients undergoing hepatectomy according to different age intervals, identify the clinical factors related to surgical outcomes, and propose clinical risk scores for severe morbidity and mortality based on the clinical factors.Eight hundred three patients undergoing liver resection were divided into 3 groups: young patients (YP), <65 years (n = 387), elderly patients (EP), from 65 to 74 years (n = 279); very-elderly patients (VEP), ≥75 years (n = 137).Severe morbidity was 10.6%, 12.2%, and 17.5% (P = .103), and mortality was 0.3%, 1.4%, and 4.4% (P = .002) in group YP, EP, and VEP, respectively. Ischemic heart disease, cirrhosis, major hepatectomy, biliary tract-associated procedure, and red blood cells (RBC) transfusion ≥3 U were related with severe morbidity. Ischemic heart disease, cirrhosis, major hepatectomy, and RBC transfusion were independent risk factors for postoperative mortality. Age did not result an independent factor related to mortality and severe morbidity. Two different scores were developed and have proved to be statistically related with severe morbidity and mortality. Moreover, in patients with score ≥2, severe morbidity increased from 24.2% in YP, to 29.3% in EP, and to 40.0% in VEP, P = .047. Likewise, mortality increased from 2.3% in YP, to 7.0% in EP, and to 22.7% in VEP, in patients with score ≥2, P = .017.Age alone should not be considered a contraindication for hepatectomy. We identified factors and proposed 2 scores that can be useful to stratify the risk of morbidity and mortality after hepatectomy. Moreover, severe morbidity and mortality increases according to the different age intervals in patients with scores ≥2

Long term results of down-staging and liver transplantation for patients with hepatocellular carcinoma beyond the conventional criteria

The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p < 0.005. After LT, the tumor recurrence rate was significantly different: MC 7.6%, Down-Achieved 20.9%, Down-not Achieved 31.6%, and No-Down 30.4% (p < 0.001). The survival rates at 5 years were: 63% in Down-Achieved, 62% in Down-not Achieved, 63% in No-Down, and 77% in MC (p = n.s.). The only variable related to a better outcome was the effective down-staging to T2 at the histological evaluation of the explanted liver: recurrence rate = 7.8% vs. 26% (p < 0.001) and 5-year patient survival = 76% vs. 67% (p < 0.05). The ATE estimation showed that the mean survival of T3-LT candidates was significantly better than that of T3 patients ineligible for LT [83.3 vs 39.2 months (+44.6 months); p < 0.001]. Long term outcome of T3 down-staged candidates was poorer than that of MC candidates, particularly for cases not achieving down-staging. However, their survival outcome was significantly better than that achieved with non-transplant therapies

Regulatory T cells from patients with end-stage organ disease can be isolated, expanded and cryopreserved according good manufacturing practice improving their function

Background Here, we isolated, expanded and functionally characterized regulatory T cells (Tregs) from patients with end stage kidney and liver disease, waiting for kidney/liver transplantation (KT/LT), with the aim to establish a suitable method to obtain large numbers of immunomodulatory cells for adoptive immunotherapy post-transplantation. Methods We first established a preclinical protocol for expansion/isolation of Tregs from peripheral blood of LT/KT patients. We then scaled up and optimized such protocol according to good manufacturing practice (GMP) to obtain high numbers of purified Tregs which were phenotypically and functionally characterized in vitro and in vivo in a xenogeneic acute graft-versus-host disease (aGVHD) mouse model. Specifically, immunodepressed mice (NOD-SCID-gamma KO mice) received human effector T cells with or without GMP-produced Tregs to prevent the onset of xenogeneic GVHD. Results Our small scale Treg isolation/expansion protocol generated functional Tregs. Interestingly, cryopreservation/thawing did not impair phenotype/function and DNA methylation pattern of FOXP3 gene of the expanded Tregs. Fully functional Tregs were also isolated/expanded from KT and LT patients according to GMP. In the mouse model, GMP Tregs from LT or KT patient proved to be safe and show a trend toward reduced lethality of acute GVHD. Conclusions These data demonstrate that expanded/thawed GMP-Tregs from patients with end-stage organ disease are fully functional in vitro. Moreover, their infusion is safe and results in a trend toward reduced lethality of acute GVHD in vivo, further supporting Tregs-based adoptive immunotherapy in solid organ transplantation

Persistent Mullerian duct syndrome: Report of two cases with phenotypical immunohistochemical profiling

INTRODUCTION:: Persistent Mullerian duct syndrome is a rare disorder of male organ development characterized by internal male pseudohermaphroditism. Persistent Mullerian duct syndrome is usually an incidental finding in patients presenting cryptorchidism, inguinal hernia, or a previous story of undescended testes. CASE DESCRIPTION:: We report on two cases of persistent Mullerian duct syndrome: an adult fertile male with uterus and ectopic prostate occurring as pelvic mass and a 75-year-old organ donor with uterus and two fallopian tubes, discovered in course of organ recruitment. We performed routine histological analysis and immunohistochemical profiling of the different tissue components. Examined tissues were all benign, and the living patient is well after surgery. CONCLUSION:: In order to prevent further complications such as infertility and potential malignant change, surgeons and surgical pathologists must be aware of this condition and should consider excision of the Mullerian remnant where possible

Total Dorsal Pancreatectomy, an Alternative to Total Pancreatectomy: Report of a New Case and Literature Review

Background: Total dorsal pancreatectomy (TDP) is a conservative pancreatic resection that should be considered in cases of benign or low malignant tumors confined to the dorsal pancreas to preserve the viability of both digestive and biliary tracts, and to avoid the endocrine and metabolic consequences of total pancreatectomy. We report a new case of TDP and provide a literature review of this procedure. Methods: The case reported was a 35-year-old female patient with a solid pseudopapillary tumor. We resected the dorsal segment of the pancreas while preserving the common bile duct, gastroduodenal artery, and pancreaticoduodenal arcades, and the spleen and splenic vessels. The MEDLINE\uae and Embase\uae databases were searched for English language studies, case series, or case reports published through August 31, 2017. Results: The postoperative course was uneventful and patient was discharged on postoperative day 11. The patient was alive and in good condition at the 10-year follow-up. To date in English literature, there are only 3 reported cases of TDP, and all cases were patients with intraductal papillary mucinous neoplasia and pancreas divisum. There was no postoperative mortality, and 2 grade B pancreatic fistulas healed 1 month postoperatively. Conclusions: TDP is a feasible and safe operation for benign or low grade malignant pancreatic tumors involving the dorsal pancreas, as an alternative to total pancreatectomy

Endoscopic transmural drainage of pseudocysts associated with pancreatic resections or pancreatitis: a comparative study

Background: Endoscopy has been regarded as an effective modality for draining pancreatic collections, pseudocysts, and abscesses. This study analyzes our experience with endoscopic transmural drainage of pancreatic pseudocysts and compares the outcomes in patients with postsurgical and pancreatitis-associated ones. Methods: Patients who underwent endoscopic drainage of a pancreatic pseudocyst from January 1999 through June 2008 were included in this retrospective analysis. The specific indication for attempting the procedure was the presence of direct contact between the pseudocyst and the gastric wall. All the drainages were carried out via a transgastric approach, and one or two straight plastic stents (10 or 11.5 French) were positioned. A comparative analysis of short- and long-term results was made between patients with postoperative pseudocysts (group A) and patients with pancreatitis-associated pseudocysts (group B). Results: Fifty-five patients were included in the study, 25 in group A and 30 in group B. Overall, a single stent was inserted in 84.0% of patients, while two stents were needed in the remaining 16.0%. The technical success rate was 78.2%, whereas procedure-related complications were 16.4%. Complications included pseudocyst superinfection and major bleeding and were managed mainly by surgery. Mortality rate was 1.8% (1 patient). There were no significant differences in the technical success rate and procedure-related complications between the two groups (p = 0.532 and 0.159, respectively) Recurrences were 13.9% and significantly more common in group B (p = 0.021). In such cases, a second endoscopic drainage was successfully performed. Conclusion: Transmural endoscopic treatment of pancreatic pseudocysts is feasible and has a technical success rate of 78.2%, without differences related to the pseudocyst etiology. Recurrences, on the other hand, are more common in patients with pancreatitis. Given the severe complications that may occur after the procedure, we recommend that endoscopic drainage be performed in a tertiary-care center with specific expertise in pancreatic surgery

Usefulness of contrast-enhanced intraoperative ultrasonography (CE-IOUS) in patients with colorectal liver metastases after preoperative chemotherapy.

The aim of this study was to evaluate the ability of contrast-enhanced intraoperative ultrasonography to detect colorectal liver metastases after preoperative chemotherapy compared with intraoperative ultrasound and preoperative imaging techniques.From January 2010 to December 2011, 28 patients with colorectal liver metastases underwent intraoperative ultrasonography and contrast-enhanced intraoperative ultrasonography during hepatectomy following preoperative chemotherapy. The findings were compared to preoperative imaging using contrast-enhanced ultrasonography, computed tomography, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography.Preoperative imaging techniques detected 58 metastatic lesions in 28 patients. In 32 % of patients (n\u2009=\u20099), intraoperative ultrasound detected 24 missed hepatic nodules. In 14 % of patients (n\u2009=\u20094), contrast-enhanced intraoperative ultrasonography detected an additional six nodules and change in operative management occurred in 18 % of patients. Using univariate analysis, we found three factors significantly related to detection of additional metastases with contrast-enhanced intraoperative ultrasonography: three or more metastases before chemotherapy (p\u2009=\u20090.047), resolution of at least one metastasis (p\u2009=\u20090.011), and small liver metastases (largest lesion size 6420 mm) after chemotherapy (p\u2009=\u20090.007).In patients undergoing surgery for colorectal liver metastases after chemotherapy, contrast-enhanced intraoperative ultrasonography improved both the sensitivity of intraoperative ultrasonography to detect liver metastases and the R0 hepatic resection rate