Management of Patients Receiving Antiplatelet Therapy During Gastroenterological Surgery: A Multicenter Prospective Cohort Study (GSATT).

OBJECTIVE: This study aimed to evaluate the effect of continuing preoperative aspirin monotherapy on surgical outcomes in patients receiving antiplatelet therapy (APT). SUMMARY BACKGROUND DATA: The effectiveness of continuing preoperative aspirin monotherapy in patients undergoing APT in preventing thromboembolic consequences is mostly unknown. METHODS: This prospective multicenter cohort study on the Safety and Feasibility of Gastroenterological Surgery in Patients Undergoing Antithrombotic Therapy (GSATT study) conducted at 14 clinical centers enrolled and screened patients between October 2019 and December 2021. The participants (n=1,170) were assigned to the continued APT group, discontinued APT group, or non-APT group, and the surgical outcomes of each group were compared. Propensity score matching was performed between the continued and discontinued APT groups to investigate the effect of continuing preoperative aspirin therapy on thromboembolic complications. RESULTS: The rate of thromboembolic complications in the continued APT group was substantially lower than that in the non-APT or discontinued APT groups (0.5% vs. 2.6% vs. 2.9%; P=0.027). Multivariate investigation of the entire cohort revealed that discontinuation of APT (P<0.001) and chronic anticoagulant use (P<0.001) were independent risk factors for postoperative thromboembolism. The post-matching evaluation demonstrated that the rates of thromboembolic complications were significantly different between the continued and discontinued APT groups (0.6% vs. 3.3%; P=0.012). CONCLUSIONS: APT discontinuation following elective gastroenterological surgery increases the risk of thromboembolic consequences, whereas continuing preoperative aspirin greatly reduces this risk. The continuation of preoperative aspirin therapy in APT-received patients is considered one of the best alternatives for preventing thromboembolism during elective gastroenterological surgery.

Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase?

Antibody-mediated rejection (AMR) is a refractory rejection after donor-specific antibody-positive or ABO blood-type incompatible (ABOi) organ transplantation. Rituximab dramatically improved the outcome of ABOi living-donor liver transplantation (LDLT); however, an effective treatment for posttransplant AMR, once occurred, is yet to be established. A 44-year-old woman with biliary cirrhosis underwent ABOi-LDLT from her sister (AB-to-A). Pretransplant rituximab diminished CD19/20-positive B lymphocytes to 0.6%/0.0%; however, AMR occurred on posttransplant day-6 with marked increase in both CD19/20 cells (17.1%/5.8%) and anti-B IgM/G-titers (1024/512). Despite rituximab readministration, steroid-pulse, intravenous immunoglobulin, and plasmapheresis, AMR was uncontrollable, with further increasing CD19/20 cells (23.0%/0.0%) and antibody-titers (2048/512). Bortezomib (1.0 mg/m2) was thus administered on posttransplant day-9, immediately ameliorating CD19/20 cells (1.3%/0.0%) and antibody-titers (<256/128). Complete remission of refractory AMR was obtained by just 2 doses of bortezomib. Her liver function has been stable thereafter for over 3 years. This case highlighted the efficacy of bortezomib against refractory AMR after ABOi-LDLT. Unlike previous reports, the efficacy was very dramatic, presumably due to the administration timing near the peak of acute-phase AMR.

Elevated levels of circulating ITIH4 are associated with hepatocellular carcinoma with nonalcoholic fatty liver disease: from pig model to human study.

BACKGROUND: Noninvasive biomarkers are urgently needed for optimal management of nonalcoholic fatty liver disease (NAFLD) for the prevention of disease progression into nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In order to identify the biomarkers, we generated the swine hepatocellular carcinoma (HCC) model associated with NAFLD and performed serum proteomics on the model. METHODS: Microminipigs were fed a high-fat diet to induce NAFLD and a normal diet as the control. To induce HCC, diethylnitrosamine was intraperitoneally administered. Biopsied liver samples were histopathologically analyzed every 12 weeks. Serum proteins were separated by blue native two-dimensional gel electrophoresis and proteins of interest were subsequently identified by MALDI-TOF MS/MS. Human serum samples were analyzed to validate the candidate protein using antibody-mediated characterization. RESULTS: In the NAFLD pigs, hepatic histology of nonalcoholic steatohepatitis (NASH) was observed at 36 weeks, and HCC developed at 60 weeks. Among serum proteins identified with MALDI-TOF MS/MS, serum inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4), an acute response protein which is secreted primarily by liver, was identified as the most characteristic protein corresponding with NAFLD progression and HCC development in the NAFLD pigs. With immunoassay, serum ITIH4 levels in the NAFLD pigs were chronologically increased in comparison with those in control animal. Furthermore, immunohistochemistry showed ITIH4 expression in hepatocytes also increased in both the cancer lesions and parenchyma as NAFLD progressed. Human study is also consistent with this observation because serum ITIH4 levels were significantly higher in HCC-NAFLD patients than in the simple steatosis, NASH, and virus-related HCC patients. Of note, HCC-NAFLD patients who had higher serum ITIH4 levels exhibited poorer prognosis after hepatectomy. CONCLUSIONS: We established an HCC pig model associated with NAFLD. Serum proteomics on the swine HCC with NAFLD model implicated ITIH4 as a non-invasive biomarker reflecting NAFLD progression as well as subsequent HCC development. Most importantly, the results in the swine study have been validated in human cohort studies. Dissecting speciation of serum ITIH4 promises to have clinical utility in monitoring the disease.

CAAT/enhancer binding protein-homologous protein deficiency attenuates liver ischemia/reperfusion injury in mice.

Ischemia/reperfusion injury (IRI) is one of the main causes of liver dysfunction after liver surgery. Involvement of endoplasmic reticulum (ER) stress in various diseases has been demonstrated, and CAAT/enhancer binding protein-homologous protein (CHOP) is a transcriptional regulator that is induced by ER stress. It is also a key regulator of ER stress-mediated apoptosis. The aim of this study was to investigate the role of CHOP in liver IRI. Wild type (WT) and CAAT/enhancer binding protein-homologous protein knockout (CHOP-/-) mice were subjected to 70% liver warm ischemia/reperfusion for 60 minutes. At different times after reperfusion, liver tissues and blood samples were collected for evaluation. Induction of ER stress including CHOP expression was ascertained. Liver damage was evaluated based on serum liver enzymes, liver histology, and neutrophil infiltration. Hepatocyte death including apoptosis was assessed. Liver warm IRI induced ER stress in both WT and CHOP-/- mice. In addition, CHOP expression was up-regulated in WT mice. At 6 hours after reperfusion, liver damage was attenuated in CHOP-/- mice. On the basis of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining, apoptotic and necrotic cells were significantly reduced in CHOP-/- mice. CHOP deficiency also reduced the cleavage of caspase 3 and expression of the proapoptotic protein B cell lymphoma 2-associated X protein. Liver IRI induces CHOP expression, and CHOP deficiency attenuates liver IRI by inhibiting apoptosis. Elucidation of the function of CHOP in liver IRI may contribute to further investigation for a therapy against liver IRI associated with the ER stress pathway. Liver Transplantation 24 645-654 2018 AASLD.

Is routine abdominal drainage necessary after liver resection?

PURPOSE: Prophylactic abdominal drainage is performed routinely after liver resection in many centers. The aim of this study was to examine the safety and validity of liver resection without abdominal drainage and to clarify whether routine abdominal drainage after liver resection is necessary. METHODS: Patients who underwent elective liver resection without bilio-enteric anastomosis between July, 2006 and June, 2012 were divided into two groups, based on whether surgery was performed before or after, we adopted the no-drain strategy. The "former group" comprised 256 patients operated on between July, 2006 and June, 2009 and the "latter group" comprised 218 patients operated between July, 2009 and June, 2012. We compared the postoperative complications, percutaneous drainage, and postoperative hospital stay between the groups, retrospectively. RESULTS: There were no significant differences in the rates of postoperative bleeding, intraabdominal infection, or bile leakage between the groups. Drain insertion after liver resection did not reduce the rate of percutaneous drainage. Postoperative hospital stay was significantly shorter in the latter group. CONCLUSION: Routine abdominal drainage is unnecessary after liver resection without bilio-enteric anastomosis.

How far can we lower graft-to-recipient weight ratio for living donor liver transplantation under modulation of portal venous pressure?

BACKGROUND: Smaller size grafts for living donor liver transplantation (LDLT) can enhance donor safety and expand donor availability. We previously reported that modulation of portal venous pressure (PVP) was key for successful LDLT with small grafts, and that it actively lowered graft-to-recipient weight ratio (GRWR) for adult-to-adult LDLT. This retrospective study investigated the outcome of LDLT using small grafts with PVP modulation. METHOD: This study analyzed 221 adult LDLT patients between March 2008 and December 2013 and divided them into 3 groups based on GRWR: large (L), GRWR ≥ 0.8% (n = 154), medium (M), ≥ 0.7% GRWR < 0.8% (n = 38); and small (S) GRWR < 0.7% (n = 29). Donor and recipient factors, PVP, pressure gradient between PVP and central venous pressure (CVP), occurrence of small for size syndrome (SFSS), ascites, and posttransplant laboratory data were compared across the 3 groups. Patient and graft survival were compared using Kaplan-Meier methods. RESULTS: There was no difference in patient or graft survival between the 3 groups. Amount of posttransplant ascites and posttransplant International Normalized Ratio were similar, but the S and M groups had more prolonged cholestasis. SFSS was identified in 17%, 13%, and 13% in the S, M, and L groups, respectively (P = NS). Patients with a final PVP of ≤15 mmHg had better survival than patients with a final PVP of >15 mmHg (P < .001). Multivariate analysis showed that donor age >40 years old, final PVP of >15 mmHg, and pressure gradient of PVP-CVP >5 mmHg were risk factors for inferior patient survival. CONCLUSION: We achieved satisfactory outcomes in LDLT with GRWR as low as 0.6% using PVP modulation. Thus, we currently set a lower limit of GRWR at 0.6% while protecting donor safety and expanding donor availability.

Timing of laparoscopic cholecystectomy for mild and moderate acute cholecystitis.

BACKGROUND/AIMS: The timing of a laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) remains controversial. Traditionally, LC for AC is performed within 3 days. We designed this study so that the cut-off time of LC for AC was within 7 days of admission, based on severity. METHODOLOGY: A total of 103 patients were divided into 2 groups: patients undergoing LC within 7 days of admission [early LC (ELC), n = 41] and patients undergoing LC between 8 days and 5 weeks of admission [delayed LC (DLC), n = 62]. The outcomes compared were complication rate, conversion rate, postoperative hospital days, and operation time. Statistical analyses were performed in mild, moderate and all AC cases. Results: Of all AC cases, successful LC was performed in 93 patients, and no significant difference was observed between the 2 groups. In DLC for moderate AC, percutaneous cholecystectomy (PC) with or without endoscopic nasal bile drainage (ENBD) was performed more frequently than ELC. CONCLUSIONS: DLC had no advantage over ELC. ELC for AC is preferable in cost­effect. Even if the operation cannot be scheduled early, proper initial treatment, including percutaneous cholecystectomy with or without endoscopic nasal bile drainage for moderate AC, enables DLC a safe option.

A large retroperitoneal malignant solitary fibrous tumor.

We report on a large, retroperitoneal, malignant, solitary fibrous tumor (SFT) with high proliferation activity. A 43-year-old man was admitted to our department complaining of a palpable mass. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a large retroperitoneal tumor occupying the entire abdominal cavity. A laparotomy was performed for diagnosis and treatment, which revealed a tumor in the retroperitoneum but with no invasion to the surrounding organs, thereby allowing safe macroscopic excision. Histologically, the tumor was composed of spindle-shaped cells with patternless pattern and a hemangiopericytomatous appearance. Moreover, immunohistochemical staining was positive for CD34, vimentin, Bcl-2, and CD99 and negative for desmin, S-100p, and smooth muscle actin (AMA). The tumor exhibited high cellularity, moderate mitotic activity, pleomorphism, necrosis, and hemorrhagic changes. In addition, the Ki-67 labeling index was 37%. These findings confirmed the diagnosis of malignant SFT with high proliferation activity. Subsequently, adjuvant doxorubicin plus ifosfamide chemotherapy was performed. No signs of recurrence were observed 12 months after the surgery.

[A case of metastatic acsending colon cancer showing sustained complete response to chemotherapy with SOX and followed UFT].

A 72-year-old woman was diagnosed as Stage IV ascending colon cancer, with metastasis of lung and para-aortic lymph node. She received laparoscopic assisted right hemicolectomy for the local control. After the operation, we performed chemotherapy. We report a case of metastatic ascending colon cancer showing complete response(CR)to 3 courses of S-1/ oxaliplatin(SOX)regimen, and maintaining a CR status while being followed with UFT for 20 months.

Laparoscopic splenectomy for a large multilocular splenic cyst with elevated CA19-9: Report of a case.

INTRODUCTION: Because splenic cysts are rare, a definitive treatment regime for these cysts remains unclear. We report a case of a large multilocular splenic cyst with elevated carbohydrate antigen 19-9 (CA19-9) levels, which was successfully treated with laparoscopic splenectomy. PRESENTATION OF CASE: A 22-year-old female was admitted to our hospital with severe left upper abdominal pain. Serum CA19-9 level was mildly elevated (65U/ml). Computed tomography revealed a 25-cm long spleen with multilocular cystic lesions, for which an emergency laparoscopic splenectomy was performed. Histological findings revealed that the lesion was a benign true cyst, and immunostaining analyses showed that the epithelium was CA19-9-positive. DISCUSSION: Although some spleen-preserving approaches have been reportedly used, splenic cyst recurrence usually occurs in true cyst cases, wherein the cyst is incompletely removed. Most reported cases of splenic cysts producing CA19-9 are true cysts. CONCLUSION: The treatment approach should be decided on the basis of the type, shape, location, and even CA19-9 levels of the splenic cyst.

[A case of stage IV gastric cancer with multiple liver metastases responding to chemotherapy with weekly PTX after failure of chemotherapy with S-1 and CDDP combination].

A 65-year-old male with type 5 gastric cancer and two lesions of liver metastases was initially treated with S-1/CDDP. After completion of the second course, however, the progression of liver metastases and appearance of massive ascites were detected with CT scan, and dysphagia appeared. Total gastrectomy was performed to improve the symptoms. Later, chemotherapy with weekly PTX was performed, demonstrating the regression of liver metastases and disappearance of ascites after 2 courses. Thus, partial liver resection for liver metastases was performed. PTX has been readministered weekly, and the patient is currently attending the outpatient clinic without recurrence, although two years have passed since his first examination.