Hepatocellular Carcinoma Intrinsic Cell Death Regulates Immune Response and Prognosis.

Ablative and locoregional treatment options, such as radiofrequency, ethanol injection, microwave, and cryoablation, as well as irreversible electroporation, are effective therapies for early-stage hepatocellular carcinoma (HCC). Hepatocyte death caused by ablative procedures is known to increase the release of tumor-associated antigen, thus enhancing tumor immunogenicity. In addition, the heat ablative resection induces pyroptotic cell death accompanied by the release of several inflammatory factors and immune-related proteins, including damage-associated molecular patterns (DAMPs), heat shock proteins (HSPs), ficolin 3, ATP, and DNA/RNA, which potentiate the antitumoral immune response. Surgical approaches that enhance tumor necrosis and reduce hypoxia in the residual liver parenchyma have been shown to increase the disease-free survival rate by reducing the host's immunosuppressive response. Scalpel devices and targeted surgical approach combined with immune-modulating drugs are an interesting and promising area to maximize therapeutic outcomes after HCC ablation.

Heterotopic segmental liver transplantation on splenic vessels after splenectomy with delayed native hepatectomy after graft regeneration: A new technique to enhance liver transplantation.

We describe a patient with liver metastases from colorectal cancer treated with chemotherapy and hepatic resection, who developed unresectable multifocal liver recurrence and who received liver transplantation using a novel planned technique: heterotopic transplantation of segment 2-3 in the splenic fossa with splenectomy and delayed hepatectomy after regeneration of the transplanted graft. We transplanted a segmental liver graft after in-situ splitting without any impact on the waiting list, as it was previously rejected for pediatric and adult transplantation. The volume of the graft was insufficient to provide liver function to the recipient, so we performed this novel operation. The graft was anastomosed to the splenic vessels after splenectomy, and the native liver portal flow was modulated to enhance graft regeneration, leaving the native recipient liver intact. The volume of the graft doubled during the next 2 weeks and the native liver was removed. After 8 months, the patient lives with a functioning liver in the splenic fossa and without abdominal tumor recurrence. This is the first case reported of a segmental graft transplanted replacing the spleen and modulating the portal flow to favor graft growth, with delayed native hepatectomy.

Double Single-Side Kidney Transplants With Bench Vascular Reconstruction: A Further Challenge Beyond the Marginality Without Future Preclusions.

BACKGROUND: Double kidney transplantation allows the use of marginal kidneys with a significant improvement in the recovery of renal function expected after transplantation, although with a greater anesthesiologic and surgical risk. One-sided positioning, more cautious in the event of functional exhaustion, can be complex due to vascular anomalies. MATERIALS AND METHODS: We report the case of 2 double unilateral kidney transplants with vascular reconstructions. The first is a double kidney transplant from a 83-year-old donor. Both kidneys (score 5) had 2 arteries and the arterial patch was not usable. A cryopreserved arterial graft was used for the packaging of an arterial axis with which a single T-L anastomosis was performed; the 2 veins were also joined with the packaging of a single anastomosis. The second case is a double kidney transplant from a cadaveric donor performed on a recipient suffering from severe diffuse atheromasia. The right kidney had 2 arteries and the left kidney had 3 arteries (both score 5). The aortic patches and veins of the 2 kidneys were joined together and a single arterial and venous anastomosis was performed. RESULTS: The course has been uneventful. In both cases there were no perioperative vascular complications. CONCLUSIONS: The use of marginal organs is an increasingly common reality. Bench vascular reconstructions can further increase donation resources, safely enhancing the transplantation of already marginal organs that would otherwise not be usable and allowing the contralateral vascular axis to be kept intact.

Hypothermic Oxygenated Perfusion Versus Static Cold Storage for Expanded Criteria Donors in Liver and Kidney Transplantation: Protocol for a Single-Center Randomized Controlled Trial.

BACKGROUND: Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species-related damage. These mechanisms may improve graft function and survival. OBJECTIVE: With this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients. METHODS: This is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021. RESULTS: Dynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020. CONCLUSIONS: The proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3R. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13922.

Carcinogenesis and Metastasis in Liver: Cell Physiological Basis.

Hepatocellular carcinoma (HCC) incidence is rising. This paper summarises the current state of knowledge and recent discoveries in the cellular and physiological mechanisms leading to the development of liver cancer, especially HCC, and liver metastases. After reviewing normal hepatic cytoarchitecture and immunological characteristics, the paper addresses the pathophysiological factors that cause liver damage and predispose to neoplasia. Particular attention is given to chronic liver diseases, metabolic syndrome and the impact of altered gut microbiota, disrupted circadian rhythm and psychological stress. Improved knowledge of the multifactorial aetiology of HCC has important implications for the prevention and treatment of this cancer and of liver metastases in general.

Protection of the intrahepatic biliary tree by contemporaneous portal and arterial reperfusion: results of a prospective randomized pilot study.

Sequential portal and arterial revascularization (SPAr) is the most common method of graft reperfusion at liver transplantation (LT), contemporaneous portal and arterial revascularization (CPAr) was used to reduce arterial ischemia to the bile ducts. Aim of this pilot study is to prospectively compare SPAr (group 1 #38) versus CPAr (group 2 #42) in 80 consecutive LTs. Biliary anastomosis was always duct to duct [T-tube in 21 % of cases (p = 0.83) in both groups]. CPAr had longer warm ischemia 61 ± 10 versus 39 ± 13 min, p < 0.0001, while SPAr had longer arterial ischemia 96 ± 39 min (p = 0.0001). No PNF while DGF was encountered in 10 versus 5 % (p = 0.32). One-year graft and patient's survival were respectively 87 versus 93 % and 83 versus 88 % in groups 1 and 2 (p = 0.31 and p = 0.39). At a median follow-up of 19 ± 8 versus 17 ± 8 months (p = 0.24), biliary complications were 28 %, being 39 % in group 1 and 19 % in group 2 (p = 0.04). Anastomotic stenoses were present in 11 versus 12 % (p = 0.84), biliary leakage in 5 versus 5 % (p = 0.72) and intrahepatic non-anastomotic biliary strictures in 23 versus 0 % (p = 0.0008) in groups 1 and 2. CPAr is safe and feasible and reduces the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia to the intrahepatic bile ducts.

Mesenchymal chondrosarcoma of the spleen: report of a case.

BACKGROUND: Chondrosarcoma is a malignant tumor of chondrogenic origin and the mesenchymal type is a very rare finding. Mesenchymal chondrosarcoma tends to develop mostly in the skeleton but may also occur as a primary tumor in periosteal nervous and muscular tissues, the anterior cerebral falx, meninges, brain, maxillary sinus, eyelid, thyroid, pleura and mediastinum, while in the abdomen the most frequent locations are the kidney, retroperitoneum and even the perineum and the anogenital area. Apparently, the only splenic mesenchymal chondrosarcoma in the literature occurred in a dog. METHODS AND STUDY DESIGN: Our paper reports the case of a patient who had a diagnosis of mesenchymal chondrosarcoma of the spleen. Results. We adopted surgery as the main therapeutic procedure without achieving complete recovery but preserving a good quality of life for our patient, minimizing the repercussions of the disease on her working and relational life. CONCLUSIONS: The absence of important or invalidating symptoms and the persistence of good general conditions before and after each surgical operation encouraged us to adopt the surgical option as the most rational.

Non-erosive and uncomplicated erosive reflux diseases: Difference in physiopathological and symptom pattern.

AIM: To investigate differences in the physiopathological findings (manometry and pH monitoring) and symptoms between cases of non-erosive reflux disease (NERD) and erosive reflux disease (ERD) found positive at 24 h pH monitoring. METHODS: For a total of 670 patients who underwent 24 h pH monitoring, esophageal manometry and upper endoscopy were retrospectively evaluated, assessing the reflux symptoms, manometric characteristics of the lower esophageal sphincter (LES) and esophageal body and the presence or absence of esophagitis and hiatal hernia. Typical and atypical symptoms were also evaluated. For inclusion in the study, patients had to have NERD or ERD and be found positive on pH monitoring (NERD+). Patients with Gastroesophageal reflux disease (GERD) complicated by stenosis, ulcers or Barrett's esophagus were ruled out. RESULTS: 214 patients were involved in the study, i.e. 107 cases of NERD+ and 107 of ERD. There were no significant gender- or age-related differences between the two groups. The ERD group had more cases of hiatal hernia (P = 0.02) and more acid reflux, both in terms of number of reflux episodes (P = 0.01) and as a percentage of the total time with a pH < 4 (P = 0.00), when upright (P = 0.007) and supine (P = 0.00). The NERD+ cases had more reflux episodes while upright (P = 0.02) and the ERD cases while supine (P = 0.01). The LES pressure was higher in cases of NERD+ (P = 0.03) while the amplitude and duration of their esophageal peristaltic waves tended to be better than in the ERD group (P >0.05). The NERD+ patients presented more often with atypical symptoms (P = 0.01). CONCLUSION: The NERD+ patients' fewer reflux episodes and the fact that they occurred mainly while in the upright position (unlike the cases of ERD) may be two factors that do not favor the onset of esophagitis. The frequently atypical symptoms seen in patients with NERD+ need to be accurately evaluated for therapeutic purposes because patients with GERD and atypical symptoms generally respond only partially to medical and surgical treatments.

Liver resection for noncolorectal and nonneuroendocrine metastases: results of a study on 56 patients at a single institution.

The usefulness of surgical treatment for hepatic metastases of noncolorectal nonneuroendocrine (NCRNNE) tumors is not yet clear due to the natural history of these tumors, their frequent systemic dissemination and their histological heterogeneity. The aim of this study was to evaluate the long-term outcome of patients who underwent liver resection for NCRNNE metastases. For this purpose we retrospectively analyzed 202 patients who underwent liver resection for metastasis between January 1989 and December 2006 at the Department of Surgery of the University Hospital of Udine. Fifty-six patients underwent liver resection because of NCRNNE metastases. The preoperative assessment was based on hepatic ultrasonography and CT scan; PET was used in a few patients. All patients had intraoperative liver ultrasonography to evaluate the lesions and to define the resection. Gender, age, primary tumor site (gastrointestinal or nongastrointestinal), synchronous or metachronous metastasis, unilobar or bilobar localization, number and diameter of the lesion(s), type of resection, margin status, positive lymph nodes in the hepatoduodenal ligament, and time between surgery and diagnosis of liver metastases were evaluated as possible prognostic factors for survival. Univariate analysis showed that the location of the primary tumor and the disease-free interval since the treatment of the primary tumor were positive predictive factors for longer survival. Multivariate analysis showed that the only independent significant factor was gastrointestinal versus nongastrointestinal origin. Demographic data, the synchronous or metachronous appearance of metastases, their unilobar or bilobar location, number and size, the type of resection, the resection margin status and the involvement of lymph nodes did not prove to be prognostic factors.

Diaphragm rupture in a liver transplant patient under chronic immunosuppressive therapy with sirolimus: rare complication after liver transplantation.

A diaphragm rupture is a very rare event. A variety of conditions such as coughing, delivery, and vigorous exercise causing a sudden increase of the intra-abdominal pressure can result in diaphragm rupture [1]. The diagnosis can be difficult because of non-specific symptoms and no history of blunt or penetrating trauma. Due to anatomical reasons, diaphragmatic lesions in the left side are more common than those in the right side. Chronic immunosuppressive therapy in transplanted patients, especially with antiproliferative drugs such as mTOR inhibitor, has been considered as a risk factor for the development of incisional hernia [2, 3]. We present the case of diaphragm rupture in a liver transplant patient under chronic immunosuppressive therapy with sirolimus.

Combined approach for spontaneous rupture of hepatocellular carcinoma.

Ruptured hepatocellular carcinoma is a rare, emergency occurrence in western countries with high mortality risk. A number of hypotheses have been formulated in order to explain the precise mechanism that leads to hepatocellular carcinoma (HCC) rupture: sub-capsular location, dimensions, portal hypertension, tumour necrosis, local increase of venous pressure due to the outflow reduction caused by neoplastic invasion, and the presence of a previous vascular injury which might predispose to HCC rupture. There is still a debate in the literature concerning the best approach in cases of HCC rupture. Surgery is the first option for treatment of acute abdominal bleeding. However the advent of endovascular treatments widens the range of possible therapies for acute bleeding control and subsequent ablation purposes. We report a case of hemoperitoneum from spontaneous rupture of undiagnosed HCC, that was treated successfully by emergency surgical resection followed by transarterial chemo-embolization for local recurrence.

Post-Traumatic Right Lumbar Abscess as First Manifestation of Perforated Right Colon Cancer - A Case Report.

Besides most common signs and symptoms suggesting a colic cancer, sometimes the clinical presentation can be difficult. Extra-abdominal abscess as a first sign of perforated colon carcinoma is a very unusual finding. We report a case of an old male patient, in bad general condition, with a post-traumatic finding of right lumbar abscess. After the percutaneous drainage with discharge of fecal material and a postponed explorative laparotomy, we discovered a perforated right colon carcinoma with a covered perforation affecting the duodenum wall and spreading to the hepatic bedand over to the back lumbar muscular wall. Because of the diffusion of the tumor, the patient was treated with palliative surgery with duodenum suture, right colon segment resection and subsequent ileocolic anastomosis with an uneventful postoperative course. The patient died 2 months later because of neoplastic cachexia.

Disseminate fungal infection after acute pancreatitis in a simultaneous pancreas-kidney recipient.

Fungal infections after kidney transplantation are a major cause of morbidity and mortality, and Candida infection of the pancreas is considered an infrequent but important agent in necrotizing pancreatitis. We report the case of a 43-year-old Caucasian patient who underwent simultaneous pancreas-kidney transplantation because of diabetes type I, and chronic renal failure with peritoneal dialysis. The postoperative course was complicated by acute pancreatitis due to the thrombosis of the splenic artery of the graft, the subsequent acute rupture of the external iliac artery caused by fungal arteritis (Candida glabrata), and peritonitis a few days later caused by sigmoid perforation with detection of Candida glabrata infection of the resected intestinal tract. The present case remarks that awareness and prevention of fungal infection are major issues in the transplant field. Important information can be added by systematic culture of conservation perfusates but, probably, the best way for early recognition of a critical level of infectious risk remains the routine application of the colonization index screening. In cases of positive results, preemptive antifungal therapy could be warranted.

Steatosis of the hepatic graft as a risk factor for post-transplant biliary complications.

BACKGROUND: Despite recent advances in organ preservation, immunosuppression, and surgical techniques, the biliary tree is still considered the Achilles' heel of liver transplantation. The aim of this study is to retrospectively analyze the incidence of biliary complications and identify risk factors that might predispose to the development of biliary problems. METHODS: From January 2004 to December 2007, 117 consecutive liver transplantations were retrospectively analyzed for the development of biliary complications by the review of medical records. Patients were divided into group 1 with biliary complications (n = 43) and group 2 without biliary complications (n = 74). RESULTS: The overall biliary complication rate was 36.8% (leakage 6% and stricture 30.8%). Univariate analysis indicated that significant predictors of biliary complications were the time interval between portal and arterial reperfusion (p = 0.037) and macrovacuolar steatosis of the graft > 25% (p = 0.004). Stepwise logistic regression model demonstrated that a macrosteatosis of the graft > 25% (OR = 5.21 CI 95% [1.79-15.15], p = 0.002) was the only independent risk factor predicting biliary complications after liver transplantation. No differences in patient's and graft's survival were noted between the two groups. CONCLUSION: According to our experience, transplanting a liver with > 25% of steatosis is a risk factor for the development of biliary complication.