Identification of anaplastic lymphoma kinase fusion in clear cell renal carcinoma (ALK-tRCC): a precision oncology medicine case report.

BACKGROUND: Translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) is a rare subtype of adult renal cell carcinoma (RCC) reported in recent years. CASE PRESENTATION: A new Italian case of ALK-tRCC was reported. The patient was a female 44-year-old with a metastatic and pretreated RCC. The tumor showed a rearrangement of ALK gene in tumor cells detected by targeted next-generation sequencing panel. The patient received oral alectinib therapy and achieved a partial response. CONCLUSIONS: ALK-tRCC is a rare subtype of adult RCC. Its diagnosis is very difficult because the genomic alteration spectrum is very wide. We suggested that metastatic RCCs should be screened for uncommon genomic alterations expecially in good performance status pretreated resistant/refractory patients.

Pulmonary tumor embolization as early manifestation in patients with renal cell carcinoma and tumor thrombus: Perioperative management and outcomes.

BACKGROUND: Renal cell carcinoma (RCC) with tumor thrombus extending into the inferior vena cava (IVC) occurs in 4%-10% of cases. Within this subset, pulmonary tumor embolism (PTE) appears in approximately 0.9%-2.4% of cases. We wanted to review our experience in managing patients with RCC with IVC involvement and a preoperative diagnosis of PTE. METHODS: A total of seven patients presented at our center between January, 2005 and January, 2015 with RCC, IVC involvement, and PTE (diagnosed either by chest computerized tomography angiography or preoperative transesophageal echocardiogram). Each patient underwent a radical nephrectomy and tumor thrombectomy using an organ transplant-based approach. RESULTS: Surgical removal of the PTE was performed in three patients (tumor embolectomy in two cases, right lower lobe resection in one case); the PTEs in four patients were considered to be too small to undergo surgical resection. PTE pathology found neoplastic cells in each patient that had surgical removal. No postoperative complications were observed in any of the seven patients. All four patients who were metastasis-free preoperatively (with 2/4 having tumor embolectomy performed) developed distant metastasis; median time-to-developing metastatic disease was 6.5 months. With a median follow-up of 19 months, three deaths because the disease have occurred. CONCLUSION: Although RCC with IVC tumor thrombus complicated by PTE may not be catastrophic in most cases, it appears to be associated with an increased risk of developing metastatic disease. In addition, as the PTEs appear to contain neoplastic cells, pulmonary artery embolectomy at the time of nephrectomy should be performed whenever possible.

Selection Bias in Colorectal Surgery in a Non-Tertiary Hospital: Laparoscopic Versus Open Surgery.

INTRODUCTION: Laparoscopy is used increasingly to treat malignant and benign colorectal surgical diseases. However, this practice is still not offered to all patients. Many barriers halt the widespread use of laparoscopic colorectal surgery. Both surgeon's and patient's factors contribute to limit a wider use of laparoscopy in colorectal surgery. MATERIALS AND METHODS: We retrospectively analyzed 408 consecutive colorectal resections in a 4-year period, to find out if a selection bias exists in using laparotomy or laparoscopy for colorectal surgical diseases, and which factors are associated with a poor use of laparoscopy or to a preferred laparotomy. RESULTS: In our practice, advanced disease, American Society of Anesthesiologist class III and IV, and emergency status are all patient-related factors associated with laparotomy. Surgeon's age more than 52 years and lack of laparoscopic training are surgeon-related factors that negatively affect the chance of being operated on with the laparoscopic technique. CONCLUSIONS: An extensive laparoscopic colorectal training and a supporting environment, especially during the night shift, are needed to facilitate the use of laparoscopy in colorectal surgery avoiding a bias in selecting surgical candidates to one technique or another.

Radical surgery for gastric cancer in octogenarian patients.

To valuate feasibility and results of radical surgery in octogenarian patients with gastric cancer. We collected data on 60 patients that underwent gastrectomy with an R0 resection at our Institution from 2010 to 2015. Patients were divided into two groups: octogenarian (OG) (n = 26), consisting of patients aged 80-89 years, and younger (YG) (n = 34), consisting of patients under 80 years of age. All patients were treated with total or subtotal gastrectomy with lymphadenectomy. A D2-lymphadenectomy was performed in 11 and 24 patients, a D1+ in 5 and 4, a D1 in 8 and 6, and a D0 in 2 and 0 cases in OG and YG respectively. The overall morbidity rate was 42.3% (11/26) in OG and 29.4% (10/34) in YG, while 90-days mortality was observed in four (15.4%) and one (2.9%) patients in OG and YG, respectively. The median hospital stay was 9 days (2-31) and 9.5 days (6-66) in OG and YG, respectively. Gastrectomy with radical resection and limited lymphadenectomy should be recommended for octogenarian patients with good performance status and low co-morbidity.

Vitamin D and VDR in cancer cachexia and muscle regeneration.

Low circulating levels of vitamin D were associated with decreased muscle strength and physical performance. Along this line, the present study was aimed to investigate: i) the therapeutic potential of vitamin D in cancer-induced muscle wasting; ii) the mechanisms by which vitamin D affects muscle phenotype in tumor-bearing animals.Rats bearing the AH130 hepatoma showed decreased circulating vitamin D compared to control rats, while muscle vitamin D receptor (VDR) mRNA was up-regulated. Both circulating vitamin D and muscle VDR expression increased after vitamin D administration, without exerting appreciable effects on body weight and muscle mass.The effects of vitamin D on muscle cells were studied in C2C12 myocytes. Vitamin D-treated myoblasts did not differentiate properly, fusing only partially and forming multinucleated structures with aberrant shape and low myosin heavy chain content. Vitamin D treatment resulted in VDR overexpression and myogenin down-regulation. Silencing VDR expression in C2C12 cultures abrogated the inhibition of differentiation exerted by vitamin D treatment.These data suggest that VDR overexpression in tumor-bearing animals contributes to muscle wasting by impairing muscle regenerative program. In this regard, attention should be paid when considering vitamin D supplementation to patients affected by chronic pathologies where muscle regeneration may be involved.

Autophagy is induced in the skeletal muscle of cachectic cancer patients.

Basal rates of autophagy can be markedly accelerated by environmental stresses. Recently, autophagy has been involved in cancer-induced muscle wasting. Aim of this study has been to evaluate if autophagy is induced in the skeletal muscle of cancer patients. The expression (mRNA and protein) of autophagic markers has been evaluated in intraoperative muscle biopsies. Beclin-1 protein levels were increased in cachectic cancer patients, suggesting autophagy induction. LC3B-I protein levels were not significantly modified. LC3B-II protein levels were significantly increased in cachectic cancer patients suggesting either increased autophagosome formation or reduced autophagosome turnover. Conversely, p62 protein levels were increased in cachectic and non-cachectic cancer patients, suggesting impaired autophagosome clearance. As for mitophagy, both Bnip3 and Nix/Bnip3L show a trend to increase in cachectic patients. In the same patients, Parkin levels significantly increased, while PINK1 was unchanged. At gene level, Beclin-1, p-62, BNIP3, NIX/BNIP3L and TFEB mRNAs were not significantly modulated, while LC3B and PINK1 mRNA levels were increased and decreased, respectively, in cachectic cancer patients. Autophagy is induced in the skeletal muscle of cachectic cancer patients, although autophagosome clearance appears to be impaired. Further studies should evaluate whether modulation of autophagy could represent a relevant therapeutic strategy in cancer cachexia.

Collagenase isoforms for pancreas digestion.

The available information concerning the characteristics and composition of collagenase batches, which are effective in the digestion of human pancreas for islet transplants, is scarce and incomplete. A large inter- and intrabatched variability in activity and efficiency of blend enzymes available for isolation has been observed. The aim of this study was to characterize enzyme blend components. Liberase batches were characterized by SDS-PAGE analyses, microelectrophoresis, and then by MALDI-TOF MS analysis. Three main bands were detected by SDS-PAGE analysis and submitted to MALDI-TOF MS analysis. Two bands were found to correspond to class I (isoform beta and another of 106 kDa) and one to class II (isoform delta) collagenase. These results represent an important step towards a complete characterization of enzymes, with the final aim of identifying key components for a standardized product.

Arterial anastomosis in a pediatric patient receiving a right extended split liver transplant: a case report.

We report a case of a pediatric patient who received a right-extended liver transplant. The size of the recipient hepatic artery did not match with the donor right hepatic arterial stump. Moreover, recipient arterial anatomy made the direct anastomosis difficult or at increased risk for complications. The recipient's splenic artery was then mobilized, divided and anastomosed to the donor's right hepatic artery. The spleen was preserved and revascularization through collaterals is demonstrated by Angio CT Scan. Doppler US of the transplanted liver demonstrated good flow through the liver and the patient was discharged with perfect liver function. Splenic artery is perfectly suited for hepatic artery anastomosis. The use of splenic artery is favored in particular situations as in the case of a pediatric recipient receiving a right-extended liver graft with small caliber artery.

The role of basiliximab in the evolving renal transplantation immunosuppression protocol.

Basiliximab is a chimeric mouse-human monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor on activated T lymphocytes. It was shown in phase III trials to reduce the number and severity of acute rejection episodes in the first year following renal transplantation in adults and children, with a reasonable cost-benefit ratio. The drug does not increase the incidence of opportunistic infections or malignancies above baseline in patients treated with conventional calcineurin inhibitor-based immunosuppression. In the field of renal transplantation, basiliximab does not increase kidney or patient survival, despite the reduction in the number of rejection episodes. Basiliximab may reduce the incidence of delayed graft function. In comparison with lymphocyte-depleting antibodies basiliximab appears to have equal efficacy in standard immunological risk patients. Recently, IL-2 receptor monoclonal antibodies have been used with the objective of reducing or eliminating the more toxic elements of the standard immunosuppression protocol. Several trials have incorporated basiliximab in protocols designed to avoid or withdraw rapidly corticosteroids, as well as protocols which substitute target-of-rapamycin (TOR) inhibitors for calcineurin inhibitors.

Brittle type 1 diabetes mellitus.

A small group of patients affected by type 1 diabetes mellitus is characterized by a severe instability of glycemic values with frequent and unpredictable hypoglycemic and/or ketoacidosis episodes which cannot be explained by errors of patients or diabetologists. The quality of life of these patients is dramatically compromised in particular because of the frequency of acute events, hospital recoveries and precocious appearance of chronic complications. This clinical condition has been defined as "brittle diabetes". A precise quantification of these patients is difficult because diagnostic criteria are still not well defined and it is often difficult to verify errors of patients in terms of inappropriate conduct with the pathology. Even more than the other kinds of diabetes, therapy is based on education, glycemic control, intensive therapy and strict interaction between physicians and patients. The introduction of insulin analogous, with either ultra-fast and ultra-slow action and the use of subcutaneous insulin pumps have significantly increased the possibility of treating the most of these cases. However, there is a minority of patients resistant to the therapy. In similar cases, pancreas or islet transplantation represents an effective therapeutic option entailing good expected outcomes. The main limiting factor of beta cell function replacement by transplantation is so far represented by the potentially severe side effects of the immunosuppression therapy necessary to avoid graft rejection and recurrence of autoimmunity.

Comparison of two different techniques of reperfusion in adult orthotopic liver transplantation.

UNLABELLED: The aim of this study was to determine the impact of two reperfusion techniques on the peri-operative hemodynamic changes and early post-operative graft function of adult patients undergoing orthotopic liver transplantation. MATERIAL AND METHODS: From June 2003 to May 2004, 50 consecutive liver transplants were performed and divided into two groups: group A, 25 patients, portal vein flush with 500 cm(3) of Ringer's lactate without vena caval venting. Group B, 25 patients, vena caval venting with no portal vein flush. Donor and recipient characteristics were similar in both groups. Sixty-four different parameters were analyzed, and Pearson's chi(2) test and t-test were used for statistical analysis, p

Artificial organs as a bridge to transplantation.

Current organ shortage is estimated to keep outpacing demand for years to come. Among the advocated strategies, artificial and bioartificial devices may prove beneficial to a wide category of patients on transplant waiting lists. Bionic organ science allows to reproduce organ architecture and function through a complex interplay of cellular and mechanical elements. Some bioartificial organs may well be used to replace anatomical defects, while others allow to compensate for failing organ functions and to bridge patients to transplantation. Among these latter, bioartificial liver (BAL) systems bear the highest potential for clinical application, even if their use is raising several controversial issues. These latter regard the identification and stratification of patients fit for transplantation, timing and type of transplantation after recovery, appropriateness of double-blind, randomized clinical trials and safety of animal and/or human cell lines. Nonetheless, bionic organ science needs to be regarded as a useful adjunct in the armamentarium of organ replacement therapies for the third millennium.

Outcomes in 139 cases of biliary tract reconstructions from a transplant surgery center.

OBJECTIVES: The purpose of this study is to report our single institution transplant surgery referral center's experience with 139 consecutive biliary tract reconstructions performed in a mixed cohort of liver transplant recipients and patients with biliary tract malignancies, iatrogenic injuries, or other benign biliary pathology. MATERIALS AND METHODS: Between July 1999 and February 2003, 139 biliary tract reconstructions were performed in 119 patients, using five various types of biliary reconstructions. The records and operative notes of all patients were reviewed with particular attention to surgical technique, operative mortality, post-operative complications and post-operative liver function tests with respect to biliary function. RESULTS: The mean duration of follow-up was 19.4 months (range 1.0 - 44.7 months). We were pleased to find excellent results from bilio-enteric reconstruction as no patient in our series developed cholangitis, jaundice or liver failure. CONCLUSION: Our goal is to inform the hepatobiliary and general surgeons of the principles of restoring biliary drainage that have arisen from our experience in a variety of reconstruction.