Hepatitis C virus (HCV) persistence in the host results from inefficiencies of innate and adaptive immune responses. Most studies addressing the role of innate immunity concentrated on peripheral ...blood (PB) natural killer (NK) cells, whereas only limited information is available on intrahepatic (IH) NK cells. We therefore examined phenotypic and functional features of IH and PB NK cells in paired liver biopsy and venous blood samples from 70 patients with chronic HCV infection and 26 control persons subjected to cholecystectomy for gallstones as controls. Ex vivo isolated IH NK cells from HCV‐infected patients displayed unique phenotypic features, including increased expression of NKp46‐activating receptor in the face of reduced tumor necrosis factor–related apoptosis‐inducing ligand (TRAIL) and cluster of differentiation (CD) 107a expression, which resulted in impaired degranulation compared with controls. To gain insights into the effect of HCV on NK cells, we exposed peripheral blood mononuclear cells (PBMCs) from patients and healthy donors to cell‐culture–derived HCV (HCVcc) and measured NK cell degranulation, TRAIL, and phosphorylated extracellular signal‐regulated kinase 1/2 (pERK1/2) expression. Exposure of PBMCs to HCVcc significantly boosted NK degranulation, pERK1/2, and TRAIL expression in healthy donors, but not in patients with chronic HCV infection, a defect that was completely reversed by interferon‐alpha. Purified NK cells showed a minimal, though significant, increase in degranulation and TRAIL expression, both in patients and controls, after exposure to HCVcc. Conclusions: These findings indicate dysfunctional IH NK cell cytotoxicity associated with TRAIL down‐regulation in chronic HCV infection, which may contribute to virus persistence. PB NK cell impairment upon exposure to HCVcc suggests the existence of an accessory cell‐dependent NK cell lytic defect in chronic HCV infection predominantly involving the TRAIL pathway. (HEPATOLOGY 2012;56:841–849)
Sacral chordoma (SC) is a neoplasm arising from residual notochordal cells degeneration. SC is difficult to manage mainly because of anatomic location and tendency to extensive spread. Carbon ion ...radiotherapy (CIRT) is highly precise to selectively deliver high biological effective dose to the tumor target sparing the anatomical structure on its path even if when SC is contiguous to the intestine, and a surgical spacer might be an advantageous tool to create a distance around the target volume allowing radical curative dose delivery with a safe dose gradient to the surrounding organs. This paper describes a double approach-open and hand-assisted laparoscopic-for a silicon spacer placement in patients affected by sacral chordoma undergoing carbon ion radiotherapy.
Six consecutive patients have been enrolled for surgical spacer placement-open (three) or hand-assisted (three)-prior carbon ion radiotherapy treatment in order to increase efficacy of carbon ion radiotherapy minimizing its side effects.
Results showed that silicon spacer placement for SC treatment is feasible both via laparoscopic and laparotomic approach.
Its use might improve CIRT safety and thus efficacy for SC treatment.
OBJECTIVE:To explore whether preoperative oral carbohydrate (CHO) loading could achieve a reduction in the occurrence of postoperative infections.
BACKGROUND:Hyperglycemia may increase the risk of ...infection. Preoperative CHO loading can achieve postoperative glycemic control.
METHODS:This was a randomized, controlled, multicenter, open-label trial. Nondiabetic adult patients who were candidates for elective major abdominal operation were randomized (1:1) to a CHO (preoperative oral intake of 800 mL of water containing 100 g of CHO) or placebo group (intake of 800 mL of water). The blood glucose level was measured every 4 hours for 4 days. Insulin was administered when the blood glucose level was >180 mg/dL. The primary endpoint was the occurrence of postoperative infection. The secondary endpoint was the number of patients needing insulin.
RESULTS:From January 2011 through December 2015, 880 patients were randomly allocated to the CHO (n = 438) or placebo (n = 442) group. From each group, 331 patients were available for the analysis. Postoperative infection occurred in 16.3% (54/331) of CHO group patients and 16.0% (53/331) of placebo group patients (relative risk 1.019, 95% confidence interval 0.720–1.442, P = 1.00). Insulin was needed in 8 (2.4%) CHO group patients and 53 (16.0%) placebo group patients (relative risk 0.15, 95% confidence interval 0.07–0.31, P < 0.001).
CONCLUSIONS:Oral preoperative CHO load is effective for avoiding a blood glucose level >180 mg/dL, but without affecting the risk of postoperative infectious complication.
Summary Reconstruction after circumferential pharyngolaryngectomy is a challenging problem. Reconstruction methods should ensure an appropriate mucosa lining of the digestive tract, preferably ...already tubulized, and peristalsis. Despite the high reported success rates, the jejunum flap is still occasionally lost due to thrombosis of the pedicle and/or fistula formation. Five cases of circumferential pharyngolaryngectomy in which failure of the jejunum loop was managed with a second free or pedicle flap are presented. A second free jejunum was reliable in selected patients, depending on time of detection of flap necrosis, on bacterial control of the wound and on the vascular or general conditions. For this reason, careful monitoring of the flap and clinical signs of necrosis in the first 5 post-operative days is crucial to prevent the formation of fistulas and infection and to increase the possibility of using this kind of salvage surgery. Pedicle flaps should be used only in the event of severe complications because of their high risk of post-operative salivary fistulas.
Reported herein is an unusual vascular tumor primary arising in the liver and exhibiting unique histopathological features. A 47‐year‐old woman underwent left hepatectomy because of a large hepatic ...mass. On histology the tumor had a composite pattern, consisting of angiomatous, retiform and solid areas, formed by oval to cuboidal to spindle cells, that expressed only endothelial markers (CD31 and factor VIII‐related antigen). These findings led to the diagnosis of a low‐grade vascular neoplasm with morphological features consistent with so‐called polymorphous hemangioendothelioma. The tumor was completely resected. At 24 month follow up the patient was alive, without evidence of disease. Polymorphous hemangioendothelioma is a rare vascular neoplasm, with borderline malignant potential, which usually occurs in lymph nodes and, rarely, at extranodal sites. Its classification as an entity has been questioned recently. The unusual morphological features of the present case, which do not fit neatly with any other recognized hemangioendothelioma subtype, indicate that the family of vascular tumors is broader than currently accepted. In addition the present case widens the spectrum of primary vascular tumors arising in the liver.
Background The clinical success of liver transplantation is founded upon years of experimental research. Since Kamada and colleagues developed the “two-cuff” technique, the rat has become the best ...model for extensive investigations. Although the Kamada technique is technically complex and not easy to master, it is still the mainstay of orthotopic liver transplantation in rodents. We have developed a modified three-cuff version of this technique that facilitates anastomosis and markedly reduces warm ischemia time. Materials and methods The new technique involves a set of five microinstruments (the Quick-Linker system) designed and manufactured by our group. It was tested in male Lewis rats (group 1, donors n = 10, recipients n = 10). The graft was explanted as usual and standard cuffs were attached to the portal vein and the supra- and infrahepatic vena cavae. Corresponding vessels in the recipient were isolated, and Quicker-Linker holding rings were attached to each. The vessels were then clamped and the native organ removed. Once the graft was positioned in the recipient's abdomen, the holding rings attached to the recipient vessels and the cuffs applied to graft vessels were automatically aligned and joined with the aid of a special alignment tool. Results Warm ischemia times were always inferior to 6 minutes. Survival at postoperative day 10 was 80%. Liver function was well preserved in all of the surviving rats. Conclusions The Quick-Linker technique significantly shortens warm ischemia time and allows rapid anastomosis that is relatively independent of operator skill. It can be considered a reliable option for microsurgeons looking for quick results and high success rates.
Surgical treatment of hypopharyngeal cancers with extension to the retrocricoid region generally requires a circumferential pharyngolaryngectomy followed by a reconstruction of the removed segment of ...the upper digestive tract. Historically, many techniques have been used in order to achieve a safe and functional reconstruction. Jejunum interposition is generally considered the best reconstructive technique.
This study examines the details of the surgical technique, the complications, the oncological and the functional results in a series of 29 consecutive patients submitted to circumferential pharyngoesophageal resection for advanced hypopharyngeal cancer followed by reconstruction with a free flap of jejunum.
Three of the transplants failed because of venous thrombosis. The overall success rate was 90%. There were no general complications. A good swallowing has been preserved in all our patients. All our patients where a phonatory prosthesis was positioned (20/29) were able to achieve speech following speech therapy and all were satisfied with their own capacity to communicate.
The prognosis of hypopharyngeal tumours (18-40% at 5 years) remains poor, but jejunum autografts are being shown to be an excellent choice for the reconstruction of the cervical hypopharyngo-oesophagus offering the patient fast rehabilitation and a reasonable quality of survival. Our experience confirm that this kind of reconstruction is safe with a good results in improving oncologic controls and restoring a good quality of life.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Gastrointestinal stromal tumors are mesenchymal tumors arising in the stomach and small bowel and more rarely in the rectum, esophagus, peritoneum and retroperitoneum. These tumors are ...characterized by KIT or PDGFRA mutations. KIT mutations are all in frame and lead to constitutive tyrosine kinase domain activation without ligand binding. Mutations concern four exons (9, 11, 13 and 17) but mainly exon 11.
In this work we report a case of a GIST patient with wild-type PDGFRA but bearing two mutations in KIT exon 9, i.e., the insertion mutation Y503_F504insAY and the missense mutation K509N.
The patient was treated with Imatinib at standard regimen dose (400 mg/day), and responded well.
Accordingly, in silico experiments were performed to disclose the effects exerted by these new mutations on the protein structure, its thermodynamic stability, and the ability to promote/interfere with Imatinib binding.
Direct drug binding thermodynamics and kinetics of the mutant KIT were measured using isothermal titration calorimetry. FInally, in vitro kinase assays were performed to monitor the phosphorylation status of this new mutant KIT.
The prototypical KIT mutations Δ559 and T670I were also analyzed in parallel for comparison.
To our knowledge, only AY 502-503 duplication/insertion and K509I substitution have been previously reported.
Citation Format: Erik Laurini, Suzana Aulic, Domenico Marson, Maurizio Fermeglia, Roberta Riboni, Marco Lucioni, Elena Dellera, Mario Alessiani, Vittorio Perfetti, Sabrina Pricl. New c-KIT mutations in GISTs: Bad for good abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 812.
Jejunal free flap (JFF) reconstruction is a popular treatment option for advanced hypopharyngeal cancer. Several factors including ischemia-reperfusion injury (IRI) can cause mucosal damage and ...progressive flap necrosis. We investigated the development and time-related progression of morphological and cellular changes in patients with JFF reconstruction including cold preservation of the graft.
Eleven patients were enrolled. Biopsies were taken during surgery from normally perfused tissue, before loop isolation (T0), at the end of back-table surgery (T1), immediately before reperfusion (T2), 15′ after reperfusion (T3), and at the end of the digestive anastomoses (T4) and from the external monitor daily from the 1st to the 5th postoperative day (M1–M5). Histomorphological and immunohistochemical parameters in the intraoperative and postoperative samples were evaluated and compared.
Delayed flap necrosis was observed in 2 patients. The cold ischemia phase did not negatively affect mucosal regeneration after reperfusion; morphological and cellular damage parameters returned to normal by the end of surgery or along the early postoperative period. Significant enterocyte replication activity was observed at the end of revascularization, which continued in the postoperative phase, leading to recovery of the epithelial morphological integrity and disappearance of apoptotic cells. An inflammatory infiltrate persisted in the M samples, and in a significant proportion of samples, mucosal fibrosis developed by the end of the postoperative observation.
Cold perfusion and preservation of the JFF can effectively limit the negative effects of IRI and to prevent short- and medium-term complications that can compromise the final outcome.
Kidney transplantation (Ktx) is generally performed during end stage renal disease due to a loss of the kidneys' ability to filter wastes from the circulatory system. Acute graft-versus-host disease ...(GVHD) after Ktx is a life-threatening complication that progresses to organ failure, systemic complications, and death. The current study evaluated the significance of histologic findings of GVHD as obtained from skin biopsies following Ktx in swine. A swine model of Ktx with tacrolimus-based immunosuppression was used to assess possible correlations between acute-graft-cellular rejection and skin histological findings for prediction of GVHD. Animals were divided into a Ktx treatment group or a control group with no Ktx and skin and kidney biopsies were histologically assessed at postoperative days 0, 15, 30, 45 and 60. Skin samples were analyzed and classified from grade 1 to 4 of skin GVHD and the major histopathological changes of kidney acute cellular rejection were described using Banff's score system. We observed a significant linear correlation between the histological grading values of skin biopsy changes and the histological grading values of kidney biopsies (Kendall's tau_b=0.993) in the Ktx experimental group. No histological changes were observed in controls. Our findings demonstrate the diagnostic value of staging skin GVHD after Ktx and suggest it's future utility for monitoring long term Ktx-induced changes.
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