LUBAC enables tumor-promoting LTß receptor signaling by activating canonical NF-κB.

Lymphotoxin ß receptor (LTßR), a member of the TNF receptor superfamily (TNFR-SF), is essential for development and maturation of lymphoid organs. In addition, LTßR activation promotes carcinogenesis by inducing a proinflammatory secretome. Yet, we currently lack a detailed understanding of LTßR signaling. In this study we discovered the linear ubiquitin chain assembly complex (LUBAC) as a previously unrecognized and functionally crucial component of the native LTßR signaling complex (LTßR-SC). Mechanistically, LUBAC-generated linear ubiquitin chains enable recruitment of NEMO, OPTN and A20 to the LTßR-SC, where they act coordinately to regulate the balance between canonical and non-canonical NF-κB pathways. Thus, different from death receptor signaling, where LUBAC prevents inflammation through inhibition of cell death, in LTßR signaling LUBAC is required for inflammatory signaling by enabling canonical and interfering with non-canonical NF-κB activation. This results in a LUBAC-dependent LTßR-driven inflammatory, protumorigenic secretome. Intriguingly, in liver cancer patients with high LTßR expression, high expression of LUBAC correlates with poor prognosis, providing clinical relevance for LUBAC-mediated inflammatory LTßR signaling.

Cholecystoenteric fistula in a patient with advanced gallbladder cancer: A case report and review of literature.

BACKGROUND: Cholecystoenteric fistula (CEF) involves the formation of a spontaneous anomalous tract between the gallbladder and the adjacent gastrointestinal tract. Chronic gallbladder inflammation can lead to tissue necrosis, perforation, and fistulogenesis. The most prevalent cause of CEF is chronic cholelithiasis, which rarely results from malignancy. Because the symptoms and laboratory findings associated with CEF are nonspecific, the condition is often misdiagnosed, presenting a challenge to the surgeon when detected intraoperatively. Therefore, a preoperative diagnosis of CEF is crucial. CASE SUMMARY: We present the case of a 57-year-old male with advanced gallbladder cancer (GBC) who arrived at the emergency room with persistent vomiting, abdominal pain, and diarrhea. An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second portion of the duodenum and transverse colon. We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula (CDF) or a cholecystocolonic fistula (CCF). He underwent multiple examinations, including esophagogastroduodenoscopy, an upper gastrointestinal series, colonoscopy, and magnetic resonance cholangiopancreatography; the results of these tests confirmed a diagnosis of synchronous CDF and CCF. The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon. His symptoms improved with supportive treatment while hospitalized. He initiated oral targeted therapy with lenvatinib for further anticancer treatment. CONCLUSION: The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.

Long-term oncologic result of laparoscopic versus open gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: Laparoscopic gastrectomy is an acceptable procedure for early-stage gastric cancer; however, most patients are diagnosed at an advanced stage and older age in Taiwan. The feasibility and safety of applying laparoscopic gastrectomy in daily practice remain unclear. This study aimed to examine the short- and long-term outcomes of laparoscopic gastrectomy versus open procedures. METHODS: From 2007 to 2015, 192 patients who underwent open gastrectomy and 189 patients who underwent laparoscopic gastrectomy for gastric cancer at a single center were included. Propensity score matching analysis was used to adjust selection biases associated with age, preoperative hemoglobin, the extent of resection, tumor size, and stage of the disease. The demographics, perioperative parameters, short-term postoperative results, and 5-year survival data were analyzed. RESULTS: Open gastrectomy was more frequently performed in the elderly, larger tumor size, advanced stage of the disease, and disease requiring total gastrectomy or combined organ resection. After propensity score matching, 108 patients with laparoscopic gastrectomy were compared to 108 patients with open gastrectomy. The morbidity rates were not different in both groups (25.9%), while hospital stay was shorter in the laparoscopic group (16.0 vs. 18.8 days, p = 0.04). The 5-year overall survival and disease-free survival were superior in the laparoscopic group (p = 0.03 and p = 0.01, respectively); however, the survival differences were not significant in the subgroup analysis by stage. Laparoscopic gastrectomy had fewer recurrences than open gastrectomy. The pattern of recurrence was not different between the groups. CONCLUSIONS: Laparoscopic gastrectomy can be safely applied in both early and locally advanced gastric cancer without compromising oncologic outcomes. TRIAL REGISTRATION: Retrospective registration.

Twice-Weekly Tacrolimus Can Overcome Pharmacologic Interaction and Help in the Successful Treatment of Pulmonary Aspergillosis in a Liver Transplant Recipient.

Drug-drug interactions between azoles and calcineurin inhibitors can cause issues for organ transplant specialists. Clinical practice guidelines for the treatment of solid-organ transplant recipients with invasive aspergillosis infection are lacking. Here, we present a patient who developed pulmonary aspergillosis after liver transplant. The patient had prolonged treatment with echinocandin that was not effective. A drug-drug interaction between azoles and tacrolimus caused issues for the clinical physician. We adjusted the doses, and the patient was successfully treated. A reduction in the tacrolimus dose, intensive monitoring of associated parameters, and elimination of risk exposures are important for a favorable outcome.

Retransplant as Rescue Treatment for ABO-Compatible Living-Donor Liver Transplant Related Antibody-Mediated Rejection: A Case Report.

Antibody-mediated rejection after liver transplant, especially when the donor is not a direct relative; it is associated with additional inconvenience for patients. We encountered a case in which antibody-mediated rejection because of de novo donor specific antibodies against donor human leukocyte antigen developed 6 months after ABO-compatible living-donor liver transplant and was treated with retransplant. A 38-year-old man with hepatitis B virus-related hepatocellular carcinoma underwent living-donor liver transplant with a graft from his wife. Six months later, he experienced fatigue and jaundice. Liver biopsy revealed C4d deposits, and histologic examination showed an antibody-mediated rejection pattern. We re-evaluated recipient-donor human leukocyte antigen matching and tested the patient's blood for antihuman leukocyte antigen donor-specific antibodies against donor human leukocyte antigen. De novo auto-antibodies against human leukocyte antigen-DQ6 were identified by Luminex single antigen beads.Because exhausting all treatment options, a rescue second living-donor liver transplant was planned with the patient's stepdaughter as the donor. Pretransplant human leukocyte antigen matching was performed, and the patient was discharged without event. Two months later, hyperbilirubinemia was noted, and a residual common bile duct from the first donor with chronic fibrosis and stricture was strongly suspected. Redo hepaticojejunostomy was successfully performed, with no problems during 1-years' follow-up. Thus, liver retransplant could be a rescue treatment for antibody-mediated rejection complicated with hepatic failure.

Rescue strategy for advanced liver malignancy with retrohepatic inferior vena cava thrombi: experience to promote surgical oncological benefit.

BACKGROUND: The prognosis of advanced liver malignancy with inferior vena cava (IVC) thrombi is poor. Many therapeutic policies are challenging for long-term prognosis. We performed the modified effective technique of transdiaphragmatic intrapericardial IVC isolation for curative resection of IVC tumors and prolonged survival time. METHODS: Between 2003 and 2015, 10 patients, sustained liver malignancy with IVC thrombi, underwent surgical intervention. Liver resection with thrombectomy under total hepatic vascular exclusion via the transdiaphragmatic intrapericardial IVC isolation method was performed for these 10 patients. The first 4 patients underwent retrohepatic IVC resection in order to complete resection, and the other 6 patients preserved the retrohepatic IVC. The last 3 patients received preoperative locoregional therapies, and all 10 patients received postoperative adjuvant chemotherapies immediately. RESULTS: All 10 patients underwent gross en bloc tumor resections with thrombectomy with R0 resection. There was no surgical mortality. Shortening of operation time and reduction of both intraoperative blood loss and hospital stay were demonstrated in the last 6 patients with preserving the retrohepatic IVC. However, similar time to recurrence and survival time were noted in the first 7 patients. The last 3 patients, who had received preoperative locoregional therapies, have better disease-free survival time. CONCLUSION: Simplified surgical procedure combined with preoperative locoregional therapies and rapid postoperative adjuvant treatment may provide a greater advantage for these patients.

Oncological safety and outcomes of nipple-sparing mastectomy with breast reconstruction: a single-centered experience in Taiwan.

INTRODUCTION: Nipple-sparing mastectomy has become a contemporary surgical treatment that achieves improved cosmetic outcomes for patients with breast cancer in Western countries. We examined oncological and cosmetic outcomes in Asian women who underwent nipple-sparing mastectomy in Taiwan. METHODS: Between 2006 and 2011, 42 patients with breast cancer who underwent 44 nipple-sparing mastectomy operations with immediate reconstruction at the Tri-Service General Hospital were reviewed. The cancer type, tumor stage, reconstruction method, presence of local recurrence, presence of distant metastasis, mortality, and complications were assessed and documented. Questionnaires were used to assess and rate patients' satisfaction with regard to appearance, sensation, symmetry, color, arousal, and texture. RESULTS: The mean follow-up period was 40.9 months (median, 45.5 months; range, 13-72 months). Among the 42 cases, only one case (2.4%) of local recurrence was observed and treated by nipple-areola complex resection. The overall complication rate was 25%, with nipple necrosis comprising 13.6%. CONCLUSION: Nipple-sparing mastectomy is a safe procedure in properly selected patients with breast cancer. This procedure yields similar oncological safety and cosmetic outcomes among Asians and women from Western countries.

Thyroid storm following trauma: a pitfall in the emergency department.

We present a case of a patient with thyroid storm exhibiting symptoms similar to those of traumatic injury. This patient presented multiple traumatic wounds on his limbs and face, loss of consciousness, and tachycardia. Diagnosis was initially confounded by the similarity between the symptoms of traumatic hypovolemic shock and trauma-induced thyroid storm. This case report discusses the factors leading to the diagnostic delay and highlights the dangerous manifestations of thyroid storm.

Meckel's diverticulum incarcerated in a transmesocolic internal hernia.

Intestinal obstruction is a common complication associated with Meckel's diverticulum in adults. The diverticulum itself or its fibrous band can lead to an intestinal volvulus, intussusceptions, or closed-loop obstructions, which require surgery. The incarceration of Meckel's diverticulum in either inguinal or femoral hernia sacs (Littre's hernia) is another, less common, etiology underlying intestinal obstruction. This case report describes a 45-year-old man who had an obstruction associated with a Meckel's diverticulum that passed through a congenital defect in the mesocolon into the right subphrenic space. The patient, who had not undergone abdominal surgery previously, came to the emergency room with acute onset of intermittent epigastric pain and abdominal distention. Computed tomography images showed the presence of a segment of the small bowel and a diverticulum in the right subphrenic space and paracolic gutter. The twisted mesentery and the dilated loops of the proximal small bowel were indicative of an intestinal volvulus and obstruction. Meckel's diverticulum complicated by a transmesocolic internal hernia was diagnosed, and this condition was confirmed during emergency surgery. The patient's postoperative recovery was uneventful. This case report highlights another presentation of Meckel's diverticulum, that is, in combination with a transmesocolic internal hernia. This etiology may lead to an intestinal volvulus and necessitate early surgery.

Locoregional therapy-induced tumor necrosis as a predictor of recurrence after liver transplant in patients with hepatocellular carcinoma.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) often undergo locoregional therapy before liver transplant either to downstage the tumor or as bridge therapy. Our goal was to assess the risk factors for posttransplant tumor recurrence, specifically the extent of necrosis induced by locoregional therapy. METHODS: We conducted a hospital-based retrospective analysis of 100 patients with HCC who received a liver transplant, 86 of whom had received pretransplant locoregional therapy. We evaluated various patient- and tumor-related parameters to determine the risk factors for recurrence. Furthermore, we grouped patients by the degree of tumor necrosis after locoregional therapy and identified the factors that were associated with a favorable tumor response. RESULTS: Initial tumor extent beyond the University of San Francisco (UCSF) criteria, microvascular invasion, and attainment of less than 90% tumor necrosis after locoregional therapy were independent risk factors for tumor recurrence. In addition, there was a significant correlation between the tumor necrosis percentage and disease-specific survival rate. Among patients whose tumors initially exceeded the UCSF criteria, those with extensive locoregional therapy-induced tumor necrosis had lower recurrence rates. All recurrences after transplant occurred within 3 years, and recurrence rates in patients with extensive tumor necrosis at 1, 2, and 3 years were 3%, 6%, and 10%, respectively. Female gender and a solitary tumor were independently associated with extensive tumor necrosis. CONCLUSIONS: In HCC patients who are transplant candidates and undergo pretransplant locoregional therapy, the degree of induced tumor necrosis affects both tumor recurrence and survival rate.