Changes in the Role and Mode of Liver Resection for Hepatocellular Carcinoma Over 20 Years: A Single-Center Analysis.

INTRODUCTION: The aim of this study was to analyze changes in characteristics of HCC and the modes of LR over 20 years in order to show the impact of those changes in the outcome of LR. In addition, BCLC staging was used to assess the limitations of this classification system and changes over the decade. PATIENTS AND METHODS: In our department, 500 liver resections (LR) were performed for hepatocellular carcinoma (HCC) over the 20 years between January 2000 and February 2020. The 208 cases performed through 2009 were designated as Era 1, and the 292 cases between 2010 and February 2020 were termed Era 2. We analyzed changes in the characteristics of HCC and mode of LR (Study 1), and final outcomes of LR are shown according to the BCLC staging classifications and eras using data from the 5 years after LR (Study 2). RESULTS: In Era 1, the mean age of the patients was 68, while in Era 2 the mean age was 71, which was significantly older than the patients in Era 1. HCC that developed from non-B, non-C liver cirrhosis was significantly increased in Era 2 (45%) as compared to that in Era 1 (34%). Laboratory data were all comparable between the eras in patients undergoing LR for HCC. The size and numbers of the HCC as well as tumor markers were similar between the eras. As to the mode of LR, although the extent of LR was similar between the eras, the laparoscopic method was significantly increased in Era 2. Blood loss was significantly lower in Era 2 (mean 519 g) than in Era 1 (1,085 g). Patient survival and recurrence-free survival (RFS) were similar between the two eras, while RFS at 5 years after LR was better in Era 2. Even in the BCLC A category, only patients with a single HCC less than 5 cm showed best results, while patients with HCC within the rest of BCLC A and BCLC B showed a dismal outcome. There was no difference in OS and RFS between the eras after stratification by BCLC. CONCLUSION: There are conspicuous changes in the baseline characteristics and mode of LR over 20 years, which should be taken into account for patient care and informed consent for patients undergoing LR going forward.

Downstaging and Histological Effects Might Be Reliable Predictors of the Efficacy of DOC+CDDP+5-FU (DCF) as Neoadjuvant Therapy for Stage III or Borderline Resectable Esophageal Cancer: a Single Institute Experience.

PURPOSE: In Japan, two courses of CDDP+5-FU (CF) therapy followed by surgery are accepted as a standard treatment for stage II/III esophageal cancer (EC) based on the results of the JCOG9907 trial. To gain a better survival, benefit especially for stage III patients in comparison with CF therapy, a three-arm phase III trial (neoadjuvant setting: CF vs. CF + radiation vs. DOC+CF [DCF]) is ongoing. We have aggressively performed DCF therapy for stage III or IV patients since October 2014. We herein review the outcomes of DCF therapy. METHODS: We retrospectively reviewed the cases of 27 patients with stage III or IV EC (male, n = 24; female, n = 3; median age, 70.0 years) who received DCF therapy. RESULTS: The response rate was 48.1%. Downstaging was achieved over the course of treatment in 14 patients (51.9%). Twenty-six patients transitioned to surgery, with 25 receiving R0 resection. DCF-treated patients who achieved downstaging showed significantly longer relapse-free survival (RFS) than those without downstaging (p = 0.0002). DCF-treated patients with a grade ≥ 1b histological effect showed significantly longer RFS than those with a grade < 1b effect (p = 0.0282). The multivariate analysis showed that downstaging was the only factor significantly associated with RFS in DCF-treated patients. CONCLUSIONS: DCF therapy for stage ≥ III esophageal carcinoma is both feasible and effective. These findings suggest that downstaging and the histological effect might predict the effects of DCF therapy for EC.

Living donor liver transplantation for congenital absence of portal vein in portal venous reconstruction with a great saphenous vein graft.

BACKGROUND: Congenital absence of portal vein (CAPV) is a rare structural anomaly in which the portal vein (PV) blood that normally flow into the liver directly drains into the systemic venous system through other collateral circulation. Congenital portal vein shunts (CPSs) is classified into types I and II according to the absence or presence of the intrahepatic portal vein, respectively. The CPS type I is also known as CAPV. The liver transplantation may be the only treatment option for CAPV. The key point of liver transplantation for CAPV is the reconstruction of the PV. CASE PRESENTATION: A 29-year-old man was diagnosed with CAPV with splenomegaly and gastroesophageal varix when being treated for pancytopenia and liver dysfunction. A living donor liver transplantation was performed for him using the right lobe which had been donated by his mother. The PV was reconstructed using his own great saphenous vein (GSV) as a graft vein. The end of the GSV graft was anastomosed to the inferior mesenteric vein while the other end was anastomosed to the vein graft of the right hepatic vein from the explanted liver. CONCLUSION: Using the patient's own GSV for PV reconstruction during living donor transplantation in the patient with CAPV seems to be an effective method.

Relationship between various hepatic function scores and the formation of esophageal varices in patients with HIV/hepatitis C virus co-infection due to contaminated blood products for hemophilia.

AIM: It is reportedly difficult to accurately assess the liver reserve capacity of patients with HIV/hepatitis C virus (HCV) co-infection through contaminated blood products by the Child-Pugh (CP) classification. Therefore, we investigated a clinically applicable scoring system in determining the risk of esophageal varices in HIV/HCV co-infected patients, known as latent portal hypertension leading to esophageal varices. METHODS: Forty-three patients with HIV/HCV co-infection underwent clinical examinations, including endoscopy and assessment of hepatic reserve, in our department between 2009 and 2017. Child-Pugh score, the recently developed albumin-bilirubin (ALBI) grade, and the albumin-indocyanine green evaluation (ALICE) were compared to evaluate their diagnostic accuracy for the detection of esophageal varices using the area under the receiver operating characteristic curve (AUROC). RESULTS: The patients were all male hemophiliacs and were positive for both HIV and HCV antibodies, with a median age of 45 years (range, 29-66 years). Thirty-seven patients (84.1%) were classified as CP A at the examination. The comparison of AUROCs showed a superior diagnostic accuracy for ALICE (AUROC = 0.814) to detect esophageal varices. The positive prediction rate was the highest with ALICE if -2.325 was set, and the negative prediction rate was the highest with ALBI if -2.575 was set. The ALICE showed the highest accuracy compared to other two scores. CONCLUSION: The ALICE score was found to be the most valuable system for portal hypertension in HIV/HCV co-infected hemophilia patients. Because of its high specificity, ALICE for secondary surveillance could be used after other markers such as the aspartate aminotransferase to platelet ratio index and Fibrosis-4 index.

Surgical findings and technical knacks to performing living donor liver transplantation for hepatocellular carcinoma recurrence after carbon ion radiotherapy.

Although carbon-ion radiotherapy (CIRT) has been reported to achieve good local control of hepatocellular carcinoma (HCC), liver transplantation is still required in patients with tumor recurrence. However, few cases of living donor liver transplantation (LDLT) after curative CIRT for HCC has been reported. It would be of great interest to ascertain the true situation of the irradiated region as well as to clarify the surgical points. We herein report the surgical findings and our experience along with technical difficulties and knacks concerning two cases of LDLT for HCC after CIRT. Both patients suffered tumor recurrence after curative CIRT for HCC. Severe adhesions were found between the irradiated region and the surrounding tissues, which resulted in surgical difficulties. Histological findings showed severe tissue fibrosis in the CIRT area. We should pay attention to adhesions in the irradiated area caused by CIRT including the vascular reconstruction during surgery.

Preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced esophageal carcinosarcoma: a case report and review of the literature.

BACKGROUND: Esophageal carcinosarcoma is a relatively rare malignant neoplasm composed of both epithelial carcinomatous and mesenchymal sarcomatous elements. There is no recommended clinical treatment for esophageal carcinosarcoma because of the rarity of the disease. This report describes a case of esophageal carcinosarcoma that was effectively treated with docetaxel, cisplatin, and 5-fluorouracil as preoperative chemotherapy. CASE PRESENTATION: A 73-year-old man had a chief complaint of dysphagia with epigastric pain. Esophagogastroduodenoscopy (EGD) revealed a polypoid neoplasm combined with an infiltrative ulcer that exhibited a mixture of squamous cell carcinoma and spindle cell sarcoma histologically. Computed tomography findings showed swollen lymph nodes in the mediastinum and around the cardia. We diagnosed esophageal carcinosarcoma cT3N1M0 cStage III. After preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, the patient underwent thoracoscopic esophagectomy with three-field lymph node dissection. Histological findings revealed that the sarcomatous component had completely disappeared and the carcinomatous component was only confined by the basement membrane with scar formation of the muscularis propria. Mural fibrotic lesions were observed in several resected regional lymph nodes. Hence, immediately after preoperative therapy, the esophageal carcinosarcoma was diagnosed as ypTisN0M0 fStage I. The patient remained alive without tumor recurrence at 12 months after the operation. CONCLUSIONS: A review of the literature revealed that there is still no established therapeutic strategy for locally advanced esophageal carcinosarcoma, especially against the sarcomatous component. We herein provide the first report in which the sarcomatous component showed a complete response to preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil. Preoperative chemotherapy with docetaxel, cisplatin, and 5-fluorouracil followed by esophagectomy with extended lymphadenectomy may achieve definitive treatment for locally advanced esophageal carcinosarcoma.

Gallbladder small cell carcinoma: a case report and literature review.

Gallbladder small cell carcinoma (SCC) comprises only 0.5 % of all gallbladder cancer and consists of aggressive tumors with poor survival outcomes against current treatments. These tumors are most common in elderly females, particularly those with cholecystolithiasis. We report the case of a 79-year-old woman with gallbladder small cell carcinoma. The patient had intermittent right upper quadrant abdominal pain and was admitted to our hospital due to suspected acute cholecystitis. She regularly received medical treatment for diabetes, hypertension, and dyslipidemia. On initial laboratory evaluation, the levels of aspartate aminotransferase (AST), total bilirubin, and C-reactive protein (CRP) were markedly elevated. She underwent computed tomography (CT) for screening. CT images showed a thick-walled gallbladder containing multiple stones and multiple 3-cm-sized round nodular lesions, which were suggestive of metastatic lymph nodes. After percutaneous transhepatic gallbladder drainage was performed, endoscopic ultrasound-guided fine needle aspiration of enlarged lymph nodes resulted in a diagnosis of small cell carcinoma or adenocarcinoma. However, we could not identify the primary lesion before the surgery because of no decisive factors. We performed cholecystectomy because there was a possibility of cholecystitis recurrence risk and also partial liver resection because we suspected tumor invasion. The final pathological diagnosis was neuroendocrine carcinoma of the gallbladder, small cell type. The tumor stage was IVb, T3aN1M1. The patient died 13 weeks after the surgery. In the present paper, we review the current available English-language literature of gallbladder SCC.

Development of human Graafian follicles following transplantation of human ovarian tissue into NOD/SCID/gammac null mice.

PROBLEM: Transplantation of human ovarian cortex into host mice may permit various kinds of challenges in reproductive medicine. A novel immunodeficient mouse strain (NOD/SCID/gammacnull: NOG) has been developed as a host of transplantation of human tissue. METHOD OF STUDY: Human ovarian cortex was transplanted into various sites of NOG mice and human follicular development was examined by immunohistochemistry. RESULTS: Transplantation of human ovarian tissue into NOG mice resulted in approximately similar tissue survival and follicle growth as did transplantation into non-obese diabetic-severe combined immunodeficient mice. The human Graafian follicle from NOG mouse expressed the same steroidogenic enzymes as observed in human Graafian follicles, which developed in the human body. The NOG mice's ovarian bursa was better placed for transplantation than the back skin or kidney capsule. CONCLUSION: These results represent the successful generation and biological confirmation of the human Graafian follicles from the human ovarian cortex in the NOG mice.

Dynamics of microtubules and positioning of female pronucleus during bovine parthenogenesis.

The zygote centrosome, consisting of both paternal and maternal centrosomal components, is the microtubule-organizing center necessary for pronuclear migration and positioning in fertilization. Maternal centrosomal function in microtubule organization and pronuclear positioning, however, remains unclear. In the present study, we sought to elucidate the function of maternal centrosomes during bovine parthenotes in the microtubule organizational processes required to move the pronucleus to the cell center without sperm centrosomal components. Microtubule organization, pronuclear position, and distribution of gamma-tubulin, which is thought to be the major component of maternal centrosomal material, were imaged by immunocytochemistry and conventional epifluorescence microscopy. In bovine parthenotes treated with paclitaxel, a microtubule-stabilizing drug, the cytoplasmic microtubule asters became organized after chemical activation, and the microtubules radiated dynamically toward the female pronucleus. The microtubule patterns correlated well with pronuclear movement to the cell center. Microtubules aggregated at regions of gamma-tubulin concentration, but gamma-tubulin did not localize to a spot until the first interphase of bovine parthenogenesis. These findings indicate that gamma-tubulin is responsible for microtubule organization as the maternal centrosome. In bovine parthenogenesis, the maternal centrosome then organizes cytoplasmic microtubules to move the female pronucleus into the cell center. We propose that the maternal centrosome plays a role as a functional centrosome despite the lack of a sperm contribution, making this structure less competent for microtubule organization in comparison with centrosomes containing sperm centrosomal components.

A trial to restore defective human sperm centrosomal function.

BACKGROUND: In human fertilization, sperm centrosome function is essential for male and female pronuclear movement and fusion. In this study, we investigated the possibility of restoring human sperm centrosomal function in sperm exhibiting abnormalities in microtubule organization. METHODS: Semen was obtained from both a fertile donor and a patient with dysplasia of the fibrous sheath (DFS). Following heterologous ICSI using human sperm, we examined microtubules and chromatin configuration in bovine oocytes. Sperm were treated with dithiothreitol (DTT) prior to ICSI, while the oocytes were treated with the cytoskeletal stabilizer paclitaxel after ICSI. RESULTS: The combination of DTT and paclitaxel treatment induced microtubule organization in dead sperm from the fertile donor following heterologous ICSI. This treatment, however, was not effective for DFS sperm. In addition, expression of centrin, a protein functioning within the sperm centrosome, was reduced in DFS sperm from that of the normal levels observed in fertile donor sperm. CONCLUSION: These results indicate that sperm centrosomal function could be induced by the treatment of sperm with DTT before ICSI and of oocytes with paclitaxel after ICSI. DFS sperm are likely to exhibit such severe dysfunction of sperm centrosome that cannot be compensated for by this treatment; therefore, this method may be a practical way to discern the degree of sperm centrosomal dysfunction.