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Aim: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) located in the posterosuperior segments (PS) have generally been considered more difficult than those for HCC in anterolateral segments (AL), but may be safe and feasible for selected patients with accumulated experience. In the present study, we investigated the effectiveness of LLR for single nodular HCCs ≤3 cm located in PS. Methods: In total, 473 patients who underwent partial liver resection for single nodular HCCs ≤3 cm at the 18 institutions belonging to the Kyusyu Study Group of Liver Surgery from January 2010 to December 2018 were enrolled. The short‐term outcomes of laparoscopic partial liver resection and open liver resection (OLR) for HCCs ≤3 cm, with subgroup analysis of PS and AL, were compared using propensity score‐matching analysis. Furthermore, results were also compared between LLR‐PS and LLR‐AL. Results: The original cohort of patients with HCC ≤3 cm included 328 patients with LLR and 145 with OLR. After matching, 140 patients with LLR and 140 with OLR were analyzed. Significant differences were found between groups in terms of volume of blood loss (median, 55 vs. 287 ml, p < 0.001), postoperative complications (0.71 vs. 8.57%, p = 0.003), and postoperative hospital stay (median, 9 vs. 14 days, p < 0.001). The results of subgroup analysis of PS were similar. Short‐term outcomes did not differ significantly between LLR‐PS and LLR‐AL after matching. Conclusions: Laparoscopic partial resection could be the preferred option for single nodular HCCs ≤3 cm located in PS. [ABSTRACT FROM AUTHOR]

The purpose of this study is to clarify the feasibility of left atrial (LA) volume measurement and CHA2DS2-VASc score for predicting the development of pulmonary vein (PV) stump thrombus after left upper lobectomy (LUL). The study population comprised 50 patients who underwent LUL for pulmonary lesions. All patients were evaluated for the development of PV stump thrombus at 7 days after LUL. LA volume was measured using preoperative CT and the CHA2DS2-VASc score was evaluated. LA volume and CHA2DS2-VASc score were compared between patients with and without the development of PV stump thrombus using the Mann–Whitney U test. Receiver–operating characteristic (ROC) curve analysis was performed to evaluate the accuracy of prediction of PV stump thrombus development. PV stump thrombus was detected in 17 (33.4%) of the 50 patients. LA volume was significantly greater in patients who developed PV stump thrombus than in those without thrombus (79.7 ± 19.4 vs. 66.6 ± 17.0 mL, p = 0.040). CHA2DS2-VASc score was significantly higher in patients with PV stump thrombosis than in those without thrombus (3.4 ± 1.5 vs. 2.5 ± 1.5, p = 0.039). Area under the ROC curve values for predicting PV stump thrombus were 0.679, 0.676, and 0.714 for LA volume, CHA2DS2-VASc score, and their combination, respectively. In conclusion, LA volume measured using preoperative CT and CHA2DS2-VASc score may help predict the development of PV stump thrombus after LUL. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the prevalence of microsatellite instability (MSI)-high status in hepato-biliary-pancreatic malignancies in clinical practice and the clinical characteristics of and therapeutic results of pembrolizumab on patients with MSI-high cancers. Methods: The subjects were 283 patients who had undergone MSI tests for unresectable, metastatic hepato-biliary-pancreatic malignancies at seven hospitals. The tests were polymerase chain reaction fragment analyses using the microsatellite markers consisting of BAT25, BAT26, NR21, NR24, and MONO27. Formalin-fixed, paraffin-embedded blocks, prepared according to the guidelines of the Japan Society of Pathology were used within 4 years after sampling. There were 13 patients with cancers high in MSI, including eight patients receiving pembrolizumab treatment. The clinical characteristics of these patients and therapeutic outcomes of their pembrolizumab treatment were investigated. Results: MSI-high was detected in 13 (4.6%) of the 283 patients with hepato-biliary-pancreatic malignancies. None of these 13 patients had been diagnosed with Lynch syndrome. Of the Eight patients receiving pembrolizumab, a complete response was observed in three patients, a partial response in one patient, and stable disease in three patients. The objective response rate was 50% and the disease control rate was 87.5%. Conclusion: MSI-high was detected in 4.6% of patients with hepato-biliary-pancreatic malignancies. There was a 50% objective response rate to pembrolizumab treatment for MSI-high cancers. The evaluation of MSI status by the current method using appropriately prepared tissue samples was to be a reliable and accurate approach to both the determination of MSI status and estimation of the effectiveness of pembrolizumab. [ABSTRACT FROM AUTHOR]

The Mycobacterium abscessus complex (MABC) comprises rapidly growing mycobacteria and has received increasing attention recently, with an increasing number of associated infections reported worldwide. However, the clinical features of MABC pulmonary disease (MABC-PD), especially in terms of the chest computed tomography (CT) findings, are not fully understood. Thus, this retrospective, cross-sectional study aimed to evaluate the clinical background and chest high-resolution CT (HRCT) findings of MABC-PD in comparison with those of Mycobacterium avium complex PD (MAC-PD). Accordingly, 36 patients with MABC-PD and 65 patients with MAC-PD (defined according to the American Thoracic Society criteria), who were newly diagnosed at four major hospitals in Okinawa (Japan) between January 2012 and December 2017, were analyzed. With respect to their clinical background, only cardiovascular diseases were significantly more common in patients with MABC-PD than in those with MAC-PD (38.9% vs. 18.5%, p = 0.0245). HRCT revealed a significantly higher incidence of low attenuation in patients with MABC-PD than in those with MAC-PD (63.9% vs. 10.8%, p<0.0001). On analyzing only never-smokers (20 and 47 patients with MABC-PD and MAC-PD, respectively), this significant difference remained (65.0% vs. 8.5%, p<0.0001), suggesting MABC infection itself caused low attenuation. In terms of the distribution of abnormal shadows, the involvement of the right lower, left upper, and left lower lobes was more common in patients with MABC-PD than in those with MAC-PD. Furthermore, the mean number of involved lung lobes was significantly higher in patients with MABC-PD than in those with MAC-PD (5.6 vs. 4.7, p<0.001). Although further studies are needed, we assume that the aforementioned radiological features of MABC-PD are due to the high virulence of MABC. [ABSTRACT FROM AUTHOR]

Pulmonary‐renal syndrome (PRS) is defined as a combination of diffuse alveolar haemorrhage and glomerulonephritis. An 18‐year‐old woman visited our hospital with a 2‐day history of fever, dyspnoea, and leg edema. Laboratory investigations revealed an elevated inflammatory reaction, increased serum creatinine levels, and normocytic anaemia. Additionally, the anti‐streptolysin‐O titre was positive, and complement component‐3 levels were decreased. Urinalysis revealed proteinuria and hematuria. Bronchoalveolar lavage aliquots were progressively more hemorrhagic. These findings supported a diagnosis of PRS secondary to streptococcal infection. The patient was treated with high‐dose methylprednisolone and antibiotics. After 4 days of treatment, her respiratory symptoms and serum creatinine levels improved. Steroid tapering was performed over 15 days. The findings in this case indicate that streptococcal infection is a potential cause of PRS, and that short‐term steroid therapy is an effective treatment. [ABSTRACT FROM AUTHOR]

This report presents a case of life‐threatening iliopsoas haematoma in an immunosuppressed 86‐year‐old man with a history of prostate cancer during the clinical course of coronavirus disease 2019 (COVID‐19). The patient was hospitalized for COVID‐19‐associated pneumonia. One week after admission, he complained of pain in his right thigh when he changed his position. Laboratory findings revealed markedly progressive anaemia and elevated creatine phosphokinase levels. Chest computed tomography revealed a massive haematoma in the right iliopsoas muscle spreading to the retroperitoneal space. Considering the advanced age and status of the patient, he was treated with red blood cell transfusions and bed rest. Fortunately, the anaemia was improved, and the haematoma gradually reduced in size. It should be noted that even during isolation, careful physical examination is important. In addition, physicians who administer heparin to patients with COVID‐19, even if prophylactic, should be aware of bleeding complications. [ABSTRACT FROM AUTHOR]

The purpose of this study is to determine whether multiparametric non-contrast MR imaging including diffusion-weighted imaging (DWI), arterial spin labeling (ASL), and amide proton transfer (APT) weighted imaging can help differentiate malignant from benign salivary gland lesions. The study population consisted of 42 patients, with 31 benign and 11 malignant salivary gland lesions. All patients were evaluated using DWI, three-dimensional pseudo-continuous ASL, and APT-weighted imaging on 3 T MR imaging before treatment. Apparent diffusion coefficient (ADC), tumor blood flow (TBF), and APT-related signal intensity (APTSI) values within the lesion were compared between the malignant and benign lesions by Mann–Whitney U test. For each parameter, optimal cutoff values were chosen using a threshold criterion that maximized the Youden index for predicting malignant lesions. The performance of ADC, TBF, APTSI, individually and combined, was evaluated in terms of diagnostic ability for malignant lesions. Diagnostic performance was compared by McNemar test. APTSI was significantly higher in malignant lesions (2.18 ± 0.89%) than in benign lesions (1.57 ± 1.09%, p = 0.047). There was no significant difference in ADC or TBF between benign and malignant lesions (p = 0.155 and 0.498, respectively). The accuracy of ADC, TBF, and APTSI for diagnosing malignant lesions was 47.6%, 50.0%, and 66.7%, respectively; whereas the accuracy of the three parameters combined was 85.7%, which was significantly higher than that of each parameter alone (p = 0.001, 0.001, and 0.008, respectively). Therefore, the combination of ADC, TBF, and APTSI can help differentiate malignant from benign salivary gland lesions. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether combined signal averaging and compressed sensing (CS averaging) improves the image quality of contrast-enhanced fat-suppressed T1-weighted three-dimensional turbo field-echo (FS T1W 3D-TFE) for evaluation of pharyngolaryngeal squamous cell carcinoma (PLSCC). Methods: This retrospective study included 27 patients with PLSCC. In all patients, contrast-enhanced FS T1W 3D-TFE imaging with CS averaging (number of excitations, 7) and that without CS averaging (number of excitations, 1) were obtained during the same acquisition time. Overall image quality, mucosal enhancement, vessel clarity, motion artifact, lesion conspicuity, and lesion edge sharpness were qualitatively evaluated using a 5-point scale. Images with and without CS averaging were compared using the Wilcoxon signed-rank test. Signal-to-noise ratio (SNR) of the lesion and the muscle structure were compared between the two imaging methods using a paired t-test. Results: Compared with the images without CS averaging, those with CS averaging showed significantly better overall image quality (p = 0.002), mucosal enhancement (p = 0.009), vessel clarity (p = 0.003), muscle edge clarity (p = 0.002), lesion conspicuity (p = 0.002), and lesion edge sharpness (p = 0.001); and less motion artifact (p < 0.001). The SNRs of the lesion and of the muscle structure were significantly higher for images with CS averaging than those without CS averaging (p < 0.001). Conclusion: CS averaging improves the image quality of contrast-enhanced FS T1W 3D-TFE MR images for evaluation of PLSCC without requiring additional acquisition time. [ABSTRACT FROM AUTHOR]

Non-tuberculous mycobacteria (NTM) cause several infectious diseases in humans. This study reports on Mycobacterium shimoidei infection in an immunosuppressed 61-year-old male with a background of emphysema. His chief complaint was haemoptysis. Chest computed tomography showed a large, thin-walled cavitary lesion in the upper right lobe. Although NTM were identified in two separate expectorated sputum samples, DNA-DNA hybridization (DDH) failed to identify the species. M. shimoidei was finally identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Following antimicrobial agent susceptibility tests, treatment with clarithromycin, levofloxacin, and ethambutol commenced. Six months post-treatment, acid-fast sputum culture was negative and repeat imaging demonstrated improvement of the radiographic abnormalities. This study aimed to assess the utility of MALDITOF MS for successful identification of rare NTM species that are not identifiable by DDH. It is the first report of M. shimoidei from Okinawa, which is the only prefecture in Japan categorized as subtropical. [ABSTRACT FROM AUTHOR]

Background: The clinical component of medical education for students and resident doctors in Japan occurs almost entirely in the hospital setting. Because of this inpatient focus, graduate medical education clinical training often fails to expose physicians-in-training to the challenges that patients may face in the outpatient or home setting. This is a descriptive study in which we explore what participating students and resident doctors learned through our brief home-based teaching experience. Methods: From June 2016 to December 2017, attending physicians on the internal medicine service had medical students and resident doctors accompany them on home care visits. Participants were selected by convenience sampling based on their rotation availability. After the home visit and the interactive discussion, the participants were expected to prepare a reflective journal on their experience and learning. Thematic analysis was applied, and key themes were developed based on Kolb’s ELT (Experiential learning theory). Three months after completion of the experience, semi-structured interviews were individually conducted assessing participants’ self-perceived changes. Results: Thirty-two medical students(10) or residents(22)participated in a home visit. Thirty of these learners were able to complete a reflective journal. Using thematic analysis, we identified 2 domains and 6 key themes from the participants’ perceptions. Participants recognized the importance of patient-centered care, inter-professional collaboration of the home care team, and reconceptualized the meaning of medical practice and their professional identity as a doctor. Three month post-experience interviews were completed on 12 of the original 30 participants who completed the reflective journal. 2 domains and 6 key themes from the residents’ experiences and perceptions were generated. The participants reported an increased attention to the daily lives and social situations of their hospitalized patients, and an extension of their focus beyond the clinical medical treatment of the patient. Conclusion: The experience of a brief visit to a patient’s home is a novel educational approach that may potentially provide medical students and resident doctors with opportunities to learn about out-of-hospital, patient-centered, home-based medical care. [ABSTRACT FROM AUTHOR]

The presence of foreign bodies (FB) in the airway is a potentially life‐threatening event. We encountered a rare case of long‐standing bronchial FB complicating with intermittent massive haemoptysis in a 42‐year‐old man. He denied any prior history of aspiration. The FB was buried deep in the bronchial epithelium and could not be removed using bronchoscopy. Bronchial angiography revealed marked dilation of the inferior lobe branch of the bronchial artery due to the FB. Bronchial artery embolization (BAE) was performed, which was followed by left lower lobectomy (LLL). The FB was keyhole‐shaped, composed of a plastic‐like material, with an appearance akin to an ancient Japanese burial mound. This case was extremely unique, since a strange FB remained in the bronchi for a long time, which caused massive haemoptysis due to the dilation of the bronchial artery.This case was a very unique in that a strange foreign body in the bronchi remained for a long time and massive haemoptysis was caused by dilation of the bronchial artery. [ABSTRACT FROM AUTHOR]

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is extremely poor. We reviewed the recent surgical treatments and outcomes of this form of advanced HCC. TT is classified into three types according to its anatomic location relative to the heart: the inferior hepatic type (type I), where the TT is in the IVC below the diaphragm; the superior hepatic type (type II), where the TT is in the IVC above the diaphragm, but still outside the RA; and the intracardiac type (type III), where the TT is above the diaphragm and has entered the RA. Type I can be treated relatively easily by standard radical hepatectomy. For type II, the intrathoracic IVC is approached via the abdominal cavity and an incision in the diaphragm with total hepatic vascular exclusion (THVE). For type III, hepatectomy plus thrombectomy is generally performed under cardiopulmonary bypass. If the TT is only just inside the RA, THVE can be performed by mobilizing the liver caudally. The median overall survival of HCC patients with TT in the IVC or RA, who undergo curative resection, is 19.0-30.8 months. As postoperative recurrence is likely to develop, even after curative surgery, effective postoperative adjuvant chemotherapy is required. [ABSTRACT FROM AUTHOR]

Aim: No effective therapies for extrahepatic metastases from hepatocellular carcinoma (HCC) have yet been identified. Previous studies suggested a potentially promising antitumor effect of combination therapy of S‐1, a novel oral dihydropyrimidine dehydrogenase inhibitor, and interferon (IFN)‐α. The present study aimed to investigate the clinical efficacy of single agent S‐1 and S‐1/IFN‐α for HCC patients with extrahepatic metastases in a randomized, open‐label, multicenter trial. Methods: A total of 103 patients with HCC with extrahepatic metastases were randomly assigned to the S‐1/IFN‐α group, receiving the combination of S‐1 and IFN‐α, or the S‐1 group, receiving the single agent of S‐1. Clinical efficacy and adverse events were compared between the two groups. Results: A total of 49 patients in the S‐1/IFN‐α group and 51 patients in the S‐1 group were included in the efficacy analysis. The response rate was 22.4% (11/49) in the S‐1/IFN‐α group and 13.7% (7/51) in the S‐1 group; there was no significant difference. Overall and progression‐free survival in the two groups were also not significantly different (1‐year overall survival 50.8% vs. 72.4%, median progression‐free survival 127 days vs. 157 days). The incidence of grade ≥3 adverse events in the S‐1/IFN‐α group was 62.7% (32/51), which tended to be higher than in the S‐1 group (43.1% [22/51]). Conclusions: Oncological outcomes in both treatment groups were favorable compared with previous reports, though there was no significant beneficial effect of adding IFN‐α to S‐1 for the treatment of HCC patients with extrahepatic metastases. [ABSTRACT FROM AUTHOR]

• ECV fraction measurement is helpful in diagnosing anterior mediastinal tumors. • ECV fraction differed significantly among the anterior mediastinal tumors. • High ECV fraction is suggestive of malignant tumors, especially thymic carcinomas. To assess the usefulness of extracellular volume (ECV) fraction derived from equilibrium contrast-enhanced CT (CECT) for diagnosing anterior mediastinal tumors. This study included 161 histologically confirmed anterior mediastinal tumors (55 low-risk thymomas, 57 high-risk thymomas, 32 thymic carcinomas, and 17 malignant lymphomas) that were assessed by pretreatment CECT. ECV fraction was calculated using measurements obtained within the lesion and the aorta on unenhanced and equilibrium phase CECT. ECV fraction was compared among anterior mediastinal tumors using one-way ANOVA or t -test. Receiver-operating characteristic (ROC) curve analysis was performed to evaluate the ability of ECV fraction to differentiate thymic carcinomas/lymphomas from thymomas. ECV fraction differed significantly among the anterior mediastinal tumors (p < 0.001). ECV fraction of thymic carcinomas was significantly higher than those of low-risk thymomas, high-risk thymomas, and lymphomas (p < 0.001, p < 0.001, and p = 0.006, respectively). ECV fraction of lymphomas was significantly higher than that of low-risk thymomas (p < 0.001). ECV fraction was significantly higher in thymic carcinomas/lymphomas than in thymomas (40.1 % vs. 27.7 %, p < 0.001). The optimal cutoff value to differentiate thymic carcinomas/lymphomas from thymomas was 38.5 % (AUC, 0.805; 95 %CI, 0.736–0.863). ECV fraction derived from equilibrium CECT is helpful in diagnosing anterior mediastinal tumors. High ECV fraction is indicative of thymic carcinomas/lymphomas, particularly thymic carcinomas. [ABSTRACT FROM AUTHOR]

Nontuberculous mycobacteria (NTM) lung disease is increasing globally. Although the etiological epidemiology of NTM is different across regions, Mycobacterium avium complex (MAC) is the leading cause of NTM lung disease in most countries, including mainland Japan. Okinawa is located in the southernmost region of Japan and is the only prefecture categorized as a subtropical region in Japan, it is therefore likely the etiological epidemiology of NTM lung disease is different from mainland Japan. From 2009 to 2015, the medical records of patients, with respiratory specimens positive for NTMs, visiting or admitted to two Okinawan hospitals, were retrospectively analyzed. NTM lung disease cases were defined according to the American Thoracic Society criteria and patient epidemiology and clinical information were evaluated. Results indicate four hundred sixteen patients had bacterial cultures positive for NTM. The most common NTM was M. abscessus complex (MABC) (n = 127; 30.5%), followed by M. intracellulare (n = 85; 20.4%). NTM lung disease was diagnosed in 114 patients. Of these cases, MABC was most common (n = 41; 36.0%), followed by M. intracellulare (n = 31; 27.2%). Chronic obstructive pulmonary disease (COPD) and tracheostomy patients were more likely to develop MABC than MAC lung disease. Multivariate analysis showed a probable association between COPD and MABC lung disease. Chest computed tomography (CT) evaluation revealed bronchiectasis, nodules, and consolidation were less frequently observed in MABC patients compared with MAC patients. Our data suggests Okinawa may be one of the few places where MABC is the predominant pathogen causing NTM lung disease and our results add new insight to MABC lung disease, which is not yet well understood. [ABSTRACT FROM AUTHOR]

The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5-37 months; 1-year OS rate, 46.8-100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT. [ABSTRACT FROM AUTHOR]

Background: Management of severe central airway obstruction due to advanced cancer is a medical and technical challenge. The impact of airway stenting on the clinical outcome of such patients is unclear. Method: This single-center, retrospective study evaluated 21 patients who underwent airway stenting for advanced cancer. We examined predictors of the post-stenting mortality, including age, serum albumin, tracheal diameter, smoking, opioid use, respiratory failure, and performance status (PS). We also compared survival according to the PS. Results: The mean survival period after stenting was 85.2 days. On univariate analysis, age, albumin, PS before airway stenting, respiratory failure, admission route, and PS grade were the candidates as possible predictors of prognosis after the procedure. On multivariate analysis, PS before airway stenting was identified as possible predictor of prognosis after stenting (HR 1.6180, 95% CI 0.969 to 2.7015, p = 0.066). The mean survival period after stenting was significantly longer in the good PS group, compared to the poor PS group (147.8 days vs. 38.2 days,p = 0.0346). Conclusion: Airway stenting for advanced cancer may be more effective for patients in good general condition than in those with poor performance status. [ABSTRACT FROM AUTHOR]

A Li 2 FeP 2 O 7 /Carbon (C) nanocomposite was successfully synthesized via a combination of spray pyrolysis and wet ball milling followed by annealing from a precursor solution; in which LiNO 3 , H 3 PO 4 and Fe(NO 3 ) 3 ·9H 2 O were stoichiometrically dissolved into distilled water. Ascorbic acid was added to the precursor solution as a reduction agent. The peaks of the Li 2 FeP 2 O 7 /C nanocomposite obtained by X-ray diffraction analysis were indexed to the monoclinic structure with the space group P 2 1 /c. The Li 2 FeP 2 O 7 /C nanocomposite cathode delivered a first discharge capacity of 100 mAh g −1 at 0.05 C, which corresponded to 91% of its theoretical capacity. After various higher discharge rates from 0.05 to 2 C in the cycle performance test, a discharge capacity of 93 mAh g −1 was achieved at 0.05 C, which showed an excellent capacity retention (93%) after 29 cycles. [ABSTRACT FROM AUTHOR]

Metabolism may determine the biologically malignant behavior of pancreatic cancer. To investigate the significance and prognostic value of cancer metabolism in cancer patients, we investigated the expression of two key enzymes in anaerobic glycolysis, hexokinase 2 (HK2) and pyruvate kinase isoenzyme type M2 (PKM2), in surgical specimens obtained from 36 patients who underwent curative resection of pancreatic ductal carcinoma. The HK2-glycolysis axis is a key system in the clinical imaging of tumors via positron emission tomography. Immunohistochemical staining for HK2 and PKM2 was performed and the data were statistically analyzed to evaluate their prognostic power. The expression of HK2 and PKM2 was associated with clinicopathological variables and patient prognosis, including overall survival, local recurrence-free survival and distant metastasis-free survival. Staining for HK2 was negative and positive in 42 and 58% of the patients, respectively, whereas staining for PKM2 was negative and positive in 56 and 44%, respectively; HK2-positive staining was correlated with progressive pathological tumor stage (pT3 vs. pT1 and pT2; P=0.017). In the univariate analysis, the positive expression of HK2 and PKM2, pathological stage (pT3 vs. pT1 and pT2) and nodal metastasis were significantly correlated with poor prognosis (P<0.03). In the multivariate analysis, pathological nodal metastasis was an independent prognostic factor for overall survival, whereas the positive expression of HK2 and PKM2 exhibited borderline significance (P=0.08 and 0.12, hazard ratio = 2.57 and 2.16, respectively). In addition, the combination of high expression of HK2 as well as PKM2 was found to be significant (P<0.05). These results suggested that the expression of HK2 and PKM2, particularly their combination, in surgical specimens obtained during curative resection, may predict an unfavorable clinical outcome in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Standardized adjuvant therapy is not performed after major hepatectomy for biliary tract cancer (BTC) because of frequent adverse events, which may be caused by insufficient liver function. Therefore, the aim of this multicenter study (KHBO1003) was to determine the safety protocol for adjuvant chemotherapy after major hepatectomy. Methods: Within 12 weeks of R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC, the following adjuvant chemotherapy was performed for 6 months: 800-1,000 mg/m gemcitabine on days 1, 8, and 15 and then every 3-4 weeks or 40-80 mg/m/day S-1 on days 1-28 and every 3-6 weeks. Major dose-limited toxicity (DLT) was defined as grade 4 hematotoxicity, grade 3/4 febrile neutropenia, grade 3/4 non-hematotoxicity, skipped gemcitabine on days 8 and 15, or halting the course at or after 14 days. Dose-escalation and de-escalation decisions were based on the continual reassessment method. Every three patients were alternately assigned to each arm. Results: Thirty-three patients (14 intrahepatic bile duct, 1 gall bladder, 18 extrahepatic bile duct) were enrolled in this study from February 2011 to July 2012 ( n = 18 gemcitabine, n = 15 S-1). At 10 % of DLT, the recommended dose was 1,000 mg/m gemcitabine biweekly and 80 mg/m/day S-1 on days 1-28 and every 6 weeks. Major DLT and adverse drug reactions were neutropenia. No grade 3 or 4 non-hematological adverse events were noted. Conclusion: We determined RDs for gemcitabine and S-1 adjuvant chemotherapy after major hepatectomy with a DLT that does not exceed 10 %. [ABSTRACT FROM AUTHOR]

Purpose: Use of the fourth-generation oral fluoropyrimidine S-1 together with gemcitabine has shown striking anticancer effects. In this single-arm phase I trial of preoperative combination therapy using gemcitabine and S-1 concurrently with radiotherapy, we verified the safety and feasibility and determined the maximum-tolerated dose of each drug in patients with resectable pancreatic cancer. Methods: A standard 3+3 dose escalation scheme was used. Patients with cytologically or histologically proven resectable pancreatic ductal adenocarcinoma were administered 30-min intravenous gemcitabine infusions on days 1, 8, 22, and 29 and S-1 orally on days 1-5, 8-12, 22-26, and 29-33. A total radiation dose of 50.4 Gy (1.8 Gy/day, 5 times per week, 28 fractions) was concurrently delivered. Surgical exploration was scheduled 4-7 weeks after the final radiation fraction. Results: Twenty-one patients were enrolled. No treatment-related deaths occurred during this study. Recommended doses were determined to be 80 mg/m of S-1 daily and 1,000 mg/m of gemcitabine. CA19-9 was reduced to <50 % of baseline values in 12 (75 %) of 16 measurable patients. Nineteen of 21 enrolled patients successfully underwent surgical resection. Conclusions: Preoperative chemoradiotherapy consisting of gemcitabine and S-1 concurrent with full-dose radiation is feasible and well tolerated. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to evaluate the surgical parameters and treatment outcomes of tumor hemodynamics-based pure laparoscopic (PURE) and laparoscopy-assisted (HYBRID) hepatectomy for small hepatocellular carcinoma (HCC) compared with those of open hepatectomy. Methods: Using a prospectively collected database from 1997 to 2011, we analyzed the data of 56 consecutive cases of laparoscopic hepatectomy for HCC (PURE, n = 24; HYBRID, n = 29; HALS, n = 3) from among 102 cases undergoing laparoscopic hepatectomy. We employed 27 cases treated by open hepatectomy during the same period as controls. Results: PURE was associated with lesser blood loss, lower weight of the resected liver, and a shorter skin incision than HYBRID and open hepatectomy [median blood loss (mL): PURE 7, HYBRID 380, Open 450; P < 0.05]. On the other hand, HYBRID hepatectomy was associated with a longer operation time [operation time (min): HYBRID 232, Open 185; P = 0.0226]. The length of hospitalization in the cases treated by PURE and HYBRID hepatectomy was shorter than that in the cases treated by open hepatectomy [length of hospitalization (days): PURE 11, HYBRID 12, Open 17; P < 0.05]. One case each of transfusion and morbidity was recorded in this series. There was no significant difference of the overall (OS) or disease-free survival (DFS) between the patients treated by laparoscopic and open hepatectomy (3-year OS: 100 vs. 100 %; DFS 50 vs. 62 %, respectively). Conclusions: Neither the surgical parameters nor the treatment outcomes of hemodynamics-based laparoscopic hepatectomy were inferior to those of open hepatectomy. [ABSTRACT FROM AUTHOR]

This report describes the case of an 81-year-old woman with sudden evisceration of the small intestine through the vagina. It occurred one year after repair of a vaginal vault prolapse, which was initially treated by vaginal hysterectomy and colporrhaphy three years prior to the repair. On examination, we found a 70-80-cm loop of bowel prolapsing through a 3-cm oval defect in the vaginal vault. The patient underwent emergency exploratory laparotomy under general anesthesia. After careful reduction of the eviscerated small intestine, the hernia hiatus was closed and the widened cul-de-sac was obliterated by performing a Moschcowitz culdoplasty. Rapid intervention by abdominovaginal surgery may enable smooth repositioning of the eviscerated intestine, thus preventing subsequent morbidity. [ABSTRACT FROM AUTHOR]

Background: To minimize bleeding and biliary leakage after open hepatectomy, fibrin sealing is undertaken at the transaction plane of the liver. Recently, clinicians have begun using polyglycolic acid PGA felt as an absorbable cross-linker. However, this method has not been well studied for laparoscopic hepatectomy because available laparoscopic devices are quite limited. This study aimed to investigate the feasibility and efficacy of using fibrin sealant with PGA felt in laparoscopic hepatectomy. Methods: A retrospective analysis of prospectively collected data from 1997 for laparoscopic hepatectomy was performed. Application of fibrin sealant with PGA felt in laparoscopic hepatectomy was begun in February 2009, and the data collected until November 2009 were used. The differences in the perioperative factors were compared including hematocrit and bilirubin concentration changes in the drainage fluid between the surgical procedures conducted with and without the use of fibrin sealant and PGA felt. Results: Fibrin sealant with PGA felt was used in 18 patients who underwent laparoscopic hepatectomy after February 2009. The data for these patients were compared with those for 22 patients who underwent laparoscopic hepatectomy before the start of fibrin sealant use. The operative procedure and devices differed according to the period. No significant differences in preoperative factors were observed between the groups. The use of fibrin sealant had no influence on the operation time or changes in the leukocyte count or serum C-reactive protein. No cases of postoperative bleeding or biliary leakage occurred in either group, and the time course of the perioperative hematocrit and drain bilirubin concentrations did not differ between the two groups. Conclusion: Use of fibrin sealant with PGA felt in laparoscopic hepatectomy appears to be feasible, and the outcomes are not inferior to those in the control group. [ABSTRACT FROM AUTHOR]

Background and Aim: Complications associated with live liver donor surgery should be minimized. There is little information on the impact of team experience and learning on the surgical outcome. The aim of this study was to clarify the impact of team experience in a single center on the outcome of live donor hepatectomy.Methods: Graft livers consisted of 56 right lobes, 40 left lobes with/without caudate, 36 left lateral section (LLS), and 11 right posterior section (RPS). Surgeries were divided according to the time of execution: era I (n=50), era II (n=50) and era III (n=43).Results: No postoperative mortality was recorded. Blood loss steadily decreased and operation time decreased after era II (P<0.0001). The overall frequency of postoperative morbidities by the Clavien system was significantly less for LLS graft [P=0.009, right lobe (42.9%) vs. LLS (13.9%)]. Multivariate risk factor analysis showed that donors in recent years were at low risk of morbidity and bile leakage (P=0.025 and 0.010, respectively). There was less impact for team experience on the outcome in LLS graft than other types of grafts.Conclusion: Our analysis demonstrated several learning steps in live liver donor surgery and confirmed their positive impact on surgical outcome. [ABSTRACT FROM AUTHOR]

Background/Aim: We previously reported the beneficial effects of a combination therapy of interferon (IFN)-α/5-fluorouracil (FU) for advanced hepatocellular carcinoma (HCC) with tumor thrombi in the major portal branches. This report describes the results of longer follow-up and includes more than twice the number of patients relative to the previous report; it also evaluates the clinical predictor on the response to the combination therapy and long-term survival. Methods: The study subjects were 102 patients with advanced HCC and tumor thrombi in the major branches of the portal vein (Vp3 or 4). They were treated with at least 2 courses of IFN-α/5-FU. Results: No major treatment-related complications were noted. In the 102 patients, 40 (39.2%) showed objective response [11 (10.8%) showed complete response, 29 (28.4%) partial response], 8 (7.9%) showed no response and 54 (52.9%) showed progressive disease. Conclusion: IFN-α/5-FU combination therapy is a promising modality for advanced HCC with tumor thrombi in the major portal branches. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Hand-sewn closures or stapler closures of the pancreatic remnant after a distal pancreatectomy have commonly been employed; however, the choice of technique in each patient depending on their clinical characteristics has not been discussed. Methods: Forty-eight patients who underwent a distal pancreatectomy at Osaka University Hospital between January 2007 and October 2009 were enrolled. A hand-sewn closure was planned during the 1st period (before June 2008, 26 consecutive patients), whereas a stapler closure was planned for the 2nd period (after June 2008, 22 consecutive patients). The incidence of pancreatic fistula and the patients' characteristics were retrospectively investigated. Results: Seven patients (27%) developed a fistula in the hand-sewn group, while 5 (23%) developed a fistula in the stapler group (p = n.s.). Using logistic regression analysis for all patients, younger age and the thickness of the pancreatic remnant were identified as independent risk factors for pancreatic fistula. In the stapler group, 50% of patients with a thick pancreas developed a pancreatic fistula, while no patients with a thin pancreas developed one. Conclusion: Thick pancreas is one of the risk factors for pancreatic fistula after a distal pancreatectomy; however, a stapler closure seems to be suitable at least for thin pancreas. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Minimally invasive approaches for small liver tumors are desirable. We describe a single-incision laparoscopic hepatectomy (SILH) using total laparoscopic surgery (TLS) technique. SILH was performed to remove a solitary 2-cm hepatocellular carcinoma located at segment 3. The technique included a one-inch skin incision with three ports (one 12 mm and two of 5 mm each). The liver was sealed and dissected by three different devices: Harmonic scalpel, TissueLink sealing dissector, and Endoclip. Operation time was 70 minutes and blood loss was trivial. The patient required no analgesia postoperatively and walked unaided the next day. Various aspects of the procedure were not different from TLS. SILH is a safe procedure with several advantages. The procedure is promising as minimally invasive liver surgery. [ABSTRACT FROM AUTHOR]

Because of the difficulties of low sensitivity for anticancer agents and giving a sufficient dose because of chronic liver dysfunction, chemotherapy may not play a central role in the treatment of hepatocellular carcinoma (HCC), especially those with liver cirrhosis. However, chemotherapy must be one of the important possibilities of multimodal treatment for advanced HCC, for which hepatic resection, percutaneous ablation, transcatheter arterial embolization and other general therapies would not be effective or even possible. Also, intraarterial perfusion chemotherapy is a common therapy for HCC and it is not difficult to maintain; but the effective rate is not sufficient. Recently, the combination therapy of subcutaneous interferon (IFN)-α and intraarterial 5-fluorouracil (5-FU) showed an outstanding response rate for intractable HCC (with portal vein thrombosis). In addition, recent preclinical and clinical studies have revealed that the mechanism of combination therapy may concern direct antitumor effects (through cell-cycle arrest and induction of apoptosis) and indirect actions (through immunocompetent cells and antiangiogenic effect). For the further advance of HCC treatment and prognosis, this therapy might be a promising treatment modality and is expected to develop. In this review, we summarize recent clinical and preclinical data regarding IFN-α and 5-FU combination therapy and discuss the further prospects of this therapy. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Previously, we reported guanylate-binding protein 2 (GBP2) and interferon regulatory factor 1 (IRF1) elevated in the rat peripheral blood during acute cellular rejection (ACR), which are identified from transcriptome analysis of liver graft, as leukocyte-related gene in liver. In this study, we investigated whether these two genes could differentially diagnose ACR from other types of liver dysfunction (LD) clinically. The mRNAs from leukocytes of 19 patients with ACR and 27 with LD, as well as from liver biopsies of 12 patients with ACR and 12 with LD, were analysed by real-time PCR for GBP2 and IRF1 expression. Sensitivity and specificity were calculated using receiver operator characteristic (ROC) curves. Guanylate-binding protein 2 (GBP2) and interferon regulatory factor 1 (IRF1) gene expression levels in ACR samples were higher than that in controls, and GBP2 expression in blood was higher than that in LD (26.4 ± 3.1 and 15.6 ± 1.9, P = 0.0203). Multivariate analysis showed that the ratio GBP2/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was independent of ACR-related factors (OR = 0.911, P = 0.035). GBP2 expression levels in ACR were also higher than that in liver transplantation patients with hepatitis C or no LD. Using a cut-off value of 20, the sensitivity and specificity of GBP2/GAPDH based on ROC curve analysis were 63% and 85% respectively. GBP2 in the patients with LD may be useful for diagnosis of ACR. [ABSTRACT FROM AUTHOR]

The aim of our study was to investigate the allogeneic influence inside and outside the liver in vitro following donor-specific cell injection (DSI). DA rats (RT1a) were used as donors and WS rats (RT1k) as recipients. WS were sensitized with DA spleen cells, followed 24 h later by total hepatectomy. The liver was transplanted into another WS (sensitized liver-grafted; SL-Grafted). The hepatectomized WS underwent liver transplantation from a naive WS (sensitized liver-removed; SL-Removed). Alloantigens accumulated in the liver in SL-Grafted and in the extrahepatic tissue/organ(s) in SL-Removed. DA hearts were transplanted 10 days after antigen administration. To analyze the immune responses, we measured Th1/Th2 cytokine profiles, and perform mRNA in various organs, allogeneic mixed lymphocyte reaction (MLR), and donor- specific immunoglobulin. Th1 cytokine levels in the liver of SL-Grafted and in spleen of SL-Removed were highly and rapidly upregulated but decreased thereafter. IFN-γ and perform mRNAs were significantly higher in SL-Grafted and lower in SL-Removed. MLR was significantly higher in SL-Grafted than SL-Removed and controls. There was no significant difference in the donor-specific immunoglobulin level. Our findings suggest that liver and other organs may behave differently to alloantigen. suggesting the importance of an early Th1 reaction in the liver and spleen. [ABSTRACT FROM AUTHOR]

A 54-year-old man underwent surgery for excision of a retroperitoneal tumor that measured 12 cm in diameter, and histopathological examination revealed the tumor was an extraadrenal retroperitoneal paraganglioma. He presented 9 years later with epigastric discomfort. Abdominal ultrasound showed a solitary liver tumor. The diagnosis, based on radiological workup, was metastatic paraganglioma. The tumor was surgically resected and the histological fi ndings resembled those of the primary tumor. The patient has been followed up for 3 years and remains recurrence-free. Surgical resection is an effective treatment approach for primary and secondary paragangliomas, but the resectability of liver metastatic lesions is usually low, although complete resection with a wide surgical margin was possible in this patient. This case suggests that a good prognosis after the resection of hepatic metastasis depends not only on the curative resection of the metastatic lesion but also on the tumor characteristics, such as slow growth or low aggressiveness. [ABSTRACT FROM AUTHOR]

The article discusses a study on the combination chemotherapy of S-1, a novel oral dehydropyrimidine dehydrogenase (DPD) inhibitor, and interferon (IFN)-α for advanced hepatocellular carcinoma (HCC) with extraheptic metastasis. Researchers knew that there is no effective treatment for extrahepatic metastasis of HCC. However, key findings indicated that combination therapy of S-1 and IFN-α appears to be highly effective, with low toxicity in patients with extrahepatic metastases of HCC.

The article details a study which examined the efficacy of interferon (IFN)-α/5-fluorouracil (5-FU) combination therapy in patients diagnosed with advanced hepatocellular carcinoma (HCC). The study included 30 patients with advanced HCC, tumor thrombi in the main trunk of portal vein and multiple nodules in the liver. It concluded that adjunct IFN/5 FU treatment regiment is effective for patients with advanced HCC, tumor thrombi in the main trunk of portal vein and multiple nodules in the liver.

Background: Patients with advanced hepatocellular carcinoma (HCC) need an effective treatment modality because of the poor prognosis of the disease. From an in vitro study, β-interferon (IFN-β) has been reported to enhance the antiproliferative effects of doxorubicin on HCC cell lines. In the present study, we investigated the therapeutic effects of combined IFN-β and doxorubicin intra-arterial injection therapy on patients with advanced HCC. Methods: IFN-β (3 MIU) and doxorubicin (10 mg/bodyweight) were given by one-shot intra-arterial injection through an arterial port to patients with advanced HCC. One treatment course consisted of three intra-arterial injections per week for 4 weeks. Three courses were conducted and evaluation was done monthly. Results: Eleven patients with advanced HCC were treated with combined IFN-β and doxorubicin. One patient enteredcomplete remission (CR), seven patients were evaluated as having stable disease (SD) and three as having progressive disease (PD). The mean overall survival was 10 months. The mean survival for CR and SD patients was 15 months, and that for PD patients was 6 months ( P = 0.0464, log–rank test). Decrease of serum total bilirubin was observed for all patients. Conclusion: Combined IFN-β and doxorubicin intra-arterial therapy offers an effective chemotherapy option for patients with advanced HCC by improving liver function and having tolerable side-effects. [ABSTRACT FROM AUTHOR]

Because of the difficulties of low sensitivity for anticancer agents and giving sufficient dose because of poor liver function, chemotherapy may not play a central role for treatment of hepatocellular carcinoma (HCC) patients, especially those with liver cirrhosis. However, chemotherapy must be one of the important possibilities of multimodal treatment for advanced HCC, for which hepatic resection, percutaneous ablation, transcatheter arterial embolization and other general therapies would not be effective or even possible. Also, intra-arterial perfusion chemotherapy is a common therapy for HCC and it is not difficult to maintain; but the effective rate is not sufficient. Recently, the combination therapy of s.c. interferon (IFN)-α and intra-arterial 5-fluorouracil (5-FU) showed an outstandingly effective rate for intractable HCC (with portal vein thrombosis). In addition,recent preclinical and clinical studies have revealed that the mechanism of combination therapy may concern direct antitumor effects (through cell-cycle arrest and induction of apoptosis) and indirect actions (through immunocompetent cells and anti-angiogenic effect). For the further advance of HCC treatment and prognosis, this therapy might be a promising treatment modality and is expected to develop. In this review, we summarize recent clinical and preclinical data regarding IFN-α and 5-FU combination therapy and discuss the further prospects of this therapy. [ABSTRACT FROM AUTHOR]

We report two cases of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and lymph node (LN) metastases successfully treated by hepatic arterial infusion of 5-fluorouracil (5-FU) combined with systemic injection of interferon (IFN)-α following hepatic resection for the liver tumor. Complete remission was obtained. Case 1 was a 51-year-old man who had HCC in the right lobe of the liver with PVTT and multiple intrahepatic metastases. He also had abdominal and mediastinal LN metastases. Case 2 was a 53-year-old man who had diffuse-type HCC in the right lobe of the liver with PVTT and intrahepatic metastases. A chest computed tomography scan revealed lymph nodes enlarged to 1.0 cm from the mediastinum to the left supraclavicular space. Both patients underwent the hepatectomy to reduce the tumor volumes and remove the PVTT to relieve portal vein obstruction. Following the surgery, the patients underwent IFN-α/5-FU combination therapy. Three months after this combined therapy, tumor markers (both α-fetoprotein and protein induced by vitamin K absence or antagonist II) returned to the normal range and residual tumors in the liver disappeared. The patients are alive without any recurrence more than 1 year after initial treatment. IFN-α/5-FU combined therapy following hepatic resection is a promising modality for the treatment of advanced HCC with LN metastasis. [ABSTRACT FROM AUTHOR]

We experienced a patient who received successful treatment for multiple hepatocellular carcinoma (HCC) nodules, with tumor thrombi in the major portal branches, with intraarterial 5-fluorouracil perfusion chemotherapy combined with subcutaneous interferon-alpha administration. The patient was a 50-year-old man with hepatitis C virus and HCC. The tumors consisted of a 5-cm main nodule in the right lobe (segment 8) and multiple intrahepatic metastases. The tumor also involved portal vein thrombosis throughout the right portal branch. After two cycles of interferon-alpha/5-fluorouracil combination chemotherapy, tumor markers demonstrated a decreasing tendency. Nine months after the initiation of this therapy, the tumors were limited to the right lobe and were surgically removed by S8 subsegmentectomy, S5 partial hepatectomy, and portal thrombectomy. The serum levels of both alpha-fetoprotein and protein induced by vitamin K absence II fell to normal levels after hepatic resection. Fifty-eight months after the first treatment, he is alive with several recurrent nodules in the liver. In conclusion, the interferon-alpha/5-fluorouracil combination therapy is a useful treatment for HCC in patients who have multiple intrahepatic metastases and portal vein thrombosis. In addition to this therapy, combined modality therapy including, for example, surgical resection, can sometimes have a dramatic therapeutic effect, shown by tumor markers reverting to normal levels. [ABSTRACT FROM AUTHOR]

Background/Aims: Several studies have reported the efficacy of combination therapy of interferon (IFN) α and 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). However, the mechanism underlying the clinical anti-tumor effects of this treatment is not well understood. The aim of this study was to determine the role of Fas/FasL signaling in the anti-tumor effect of this combination therapy. Methods and Results: We used six human hepatoma cell lines, three of which are known Fas-expressing cells. Growth of Fas-positive hepatoma cell lines was inhibited by an agonistic anti-Fas antibody in a dose-dependent manner, and these effects were enhanced by IFNα or 5-FU alone, but even more so by combination therapy using both agents. Annexin-V assay implicated apoptosis as the main mechanism underlying these growth inhibitory effects, although changes in Fas expression regulated by IFNα and/or 5-FU did not correlate with increased apoptosis. Caspase-3 activation was exclusively increased by IFNα/5-FU combination treatment, which was compatible with enhancement of the synergistic apoptotic effect, and other caspases and apoptotic factors (FLIP, BCL-xl, and Bax) were also regulated by IFNα/5-FU. 51Cr-release assay revealed that pretreatment with IFN activated cytotoxicity of peripheral blood mononuclear cells (PBMCs) against HCC cells. The largest interaction was observed when both PBMC and HCC cells were pretreated with the combination of IFNα/5-FU. These cytotoxicities were markedly inhibited by a neutralizing anti-Fas antibody. Co nclusions: Our results indicated that IFNα/5-FU combination treatment enhances the induction of apoptosis and the cytotoxic effect of PBMCs via the Fas/FasL pathway. The Fas/FasL pathway seems, at least in part, to contribute to the anti-tumor effects of IFNα/5-FU against HCCs. [Copyright &y& Elsevier]

Aim: Interferon (IFN)-α is a promising drug for the prevention and treatment of hepatocellular carcinoma (HCC). We reported that responders to IFN-α/5-fluorouracil combination therapy expressed higher IFN alpha receptor (IFNAR)2 in tumor. Herein we studied involvement of IFNARs in response to IFN-α in HCC cells. Methods: IFN-α sensitivity and expression of IFNARs were studied in six HCC cell lines (HuH7, PLC/PRF/5, HLE, HLF, HepG2, Hep3B) using growth-inhibitory and RT-PCR, Western blot assays. Short interfering RNAs (SiRNAs) against IFNAR1 and 2 were used to analyze the role of the IFNARs in IFN-α’s effect and signal transduction. Results: The expressions of IFNAR1 and 2c mRNAs were higher in PLC/PRF/5 cells than those in other cell lines, and PLC/PRF/5 cells expressed abundant IFNAR2c on their cell membrane. When we examined the sensitivity of the HCC cell lines to the growth-inhibitory effect of IFN-α, PLC/PRF/5 exhibited a significant response, while the other cells were much more resistant. Knockdown of either IFNAR1 or 2 using siRNAs suppressed the IFN-α’s signal transduction (2.5-fold), and decreased the growth-inhibitory effect (down by 69.9% and 67.3%). Conclusion: The results suggest that the expression of IFNAR1 and IFNAR2c independently are important for the antiproliferative effect of IFN-α in HCC cells. [ABSTRACT FROM AUTHOR]

A 54-year-old man was admitted Osaka University Hospital for hepatocellular carcinoma (HCC) with portal vein thrombus and multiple intrahepatic metastases that extended to the bilateral lobes of the liver. He underwent multimodal therapy, including extended left lobectomy followed by intra-arterial 5-fluorourcil (5-FU) infusion chemotherapy combined with subcutaneous interferon-α (IFN-α) to treat the lesions in the residual liver. Seven months after the initial resection, recurrent tumors in the spleen, lung, and residual liver were detected by follow-up examination. We started a new regimen of per oral administration of S-1 and subcutaneous IFN-α injection, because the combined therapy with intra-arterial 5-FU infusion was not considered effective for distant metastases. After two cycles of S-1 and IFN-α, the metastatic tumor in the spleen and the recurrence in the residual liver had disappeared, and the diagnosis was complete remission with no adverse effect; the pulmonary metastasis showed a partial response, and was finally resected. This patient is still alive with no recurrence 32 months after initial hepatic resection. This outcome suggests that combination therapy with S-1 and IFN-α may be a promising treatment modality against advanced HCC with distant metastasis. [ABSTRACT FROM AUTHOR]

Abstract: Several studies have recently reported the efficacy of combination therapy of interferon (IFN) α and 5-fluorouracil (5-FU) for hepatocellular carcinoma (HCC). However, the clinical effect of this treatment was not complete. The new therapeutic modality should be necessary to rise up this clinical response rate. Recently, the anti-tumor effect of Vitamin K2 has been reported in terms of decreased recurrence rate of HCC patients. The aim of this study was to explore the additive or synergistic effect of Vitamin K2 to combined therapy of interferon (IFN) α and 5-fluorouracil (5-FU) against hepatocellular carcinoma (HCCs). The study was conducted using three hepatoma cell lines (PLC/PRF/5, Hep3B and HepG2). The 3-(4-5-dimethylthiazol-2-yl)-2, 5-dyphenyl tetrazolium bromide (MTT) assay (48h) revealed anti-tumor effect of IFNα and 5-FU. Cell growth assay (3–7 days) showed growth inhibitory effect of Vitamin K2 on three cell lines after day 5. But additional effect of combination treatment of Vitamin K2 and IFNα/5-FU was not observed in any time course from 48h to 7 days. Cell cycles were assessed with flowcytometry. Although either Vitamin K2 or IFNα/5-FU alone has the influence to the cell cycles, no significant change was shown in the combination of Vitamin K2 and IFNα/5-FU. In conclusion, Vitamin K2 itself has potentially growth inhibitory effect for HCC cell lines, but does not enhance the anti-tumor effect of IFNα and 5-FU. [Copyright &y& Elsevier]

The clinical features of Allen''s type C of combined hepatocellular and cholangiocarcinoma (cHCC-CC) are not well known. In this study, we aim to define the clinicopathologic features of cHCC-CC and to evaluate the preoperative diagnosis and surgical treatment results in comparison with those of hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC). We retrospectively analyzed 13 patients with cHCC-CC, 509 patients with HCC, and 41 patients with CCC treated in our hospital within past two decades. Viral hepatitis B or C backgrounds were more prominent in HCC and cHCC-CC groups than in the CCC group. Elevated serum alpha-fetoprotein (AFP) levels were found in 60.3% of HCC patients and in 46.2% of cHCC-CC patients. Only one patient of cHCC-CC was correctly diagnosed before surgery. The postoperative survival rates between the cHCC-CC and HCC or the CCC group were not significantly different. Both intrahepatic and extrahepatic postoperative recurrences were frequent in cHCC-CC patients, and CCC component recurrences were more frequently seen. In conclusion, the preoperative diagnosis is difficult; liver masses similar to those of HCC, together with moderately elevated serum AFP and CA19-9 levels, are reliable indicators of cHCC-CC. Surgical resection of this tumor yields results intermediate between those of HCC and CCC in character. More cases are needed to further define the characteristics of this tumor. [Copyright &y& Elsevier]

Hepatocellular carcinoma (HCC) is a hypervascular tumor and angiogenesis plays an important role in its progression. Angiogenesis is regulated by a balance between pro and antiangiogenic molecules. The aim of this study was to investigate the expressions of angiogenic factors and elucidate their roles in angiogenesis in HCC. Methods: We investigated immunohistochemical expression of vascular endothelial growth factor (VEGF), angiopoietins (Ang-1 and Ang-2), hypoxia-induced factor-1α (HIF-1α) and thrombospondin-1 (TSP-1) in 60 specimens of surgically resected HCC. We investigated the relationship between their expressions and clinicopathological factors or prognosis. Results: Ang-2 staining had a significant correlation with the grade of differentiation of HCC cells ( P=0.0082). VEGF and Ang-2 expression correlated positively with microvessel density (MVD) ( P=0.0061 and 0.0374, respectively). MVD of well-differentiated HCC were significantly lower than those of moderately and poorly differentiated HCC. The disease-free survival time of patients with high Ang-2 and/or HIF-1α expression was significantly shorter than that of the low expression group ( P=0.0278 and 0.0374, respectively). Conclusion: Our study showed that the expression of VEGF and Ang-2 correlated with MVD. Strong Ang-2 expression and/or high nuclear expression of HIF-1α is a significant predictive factor for recurrence after curative resection in HCC patients. [ABSTRACT FROM AUTHOR]

Background/Aims: The prognosis of hepatocellular carcinoma (HCC) is poor because of frequent intrahepatic metastasis (IM) or multicentric carcinogenesis (MC). We compared the effectiveness of loss of heterozygosity (LOH) analysis in the diagnosis of these two forms with that of histopathological diagnosis.Methods: Using LOH analysis of 15 specific DNA microsatellite loci, tumor clonality was assessed in 37 cases.Results: LOH was observed in 30% of seven solitary tumors. According to these results, the selected threshold to diagnose MC was a difference in the LOH status at more than 30% of the analyzed loci, when comparing two samples in the same liver. In nine multiple HCCs, identical genetic and histopathological diagnoses were found in four (IM: 2, MC: 2). Of 21 recurrent tumors, 19 showed LOH for at least one marker. IM and MC were genetically diagnosed in five and ten patients, respectively. Genetic and histopathological diagnoses were identical in ten of 19 patients (IM: 5. MC: 5). Five genetic MC were histopathologically diagnosed as IM (3) and ‘undetermined’ (2).Conclusions: Genetic diagnosis by LOH analysis may be more strict and specific than histopathological diagnosis in the differential diagnosis of IM and MC. [Copyright &y& Elsevier]

Renal allograft protection with losartan in Fisher→Lewis rats: Hemodynamics, macrophages and cytokines. Background. We sought to assess the effects of angiotensin receptor blockade on glomerular hypertension, macrophage recruitment, and cytokine expression, all of which contribute to the development of chronic graft injury in this model. Methods. The effects of treatment with the specific angiotensin II type 1 (AT1 ) receptor antagonist, losartan, were assessed over 24 weeks in F344→LEW rats (LOS, N = 9) versus vehicle-treated F344→LEW controls (CON, N = 9). Results. Uprot V rose progressively in CON (from 7.0 ± 2.9 to 41 ± 17 mg/day at 24 wk) but remained at baseline in LOS (4.2 ± 0.6 to 9.4 ± 1.3 mg/day, P < 0.05 vs. CON). Glomerular capillary pressure (PGC ) was increased in CON (71 ± 1 mm Hg at week 20), but remained within the normal range in LOS rats (54 ± 2 mm Hg, P < 0.05). Glomerulosclerosis averaged 0.3 ± 0.2% in LOS versus 4 ± 2% in CON rats (P < 0.05). Tubulointerstitial injury was minimal in both LOS and CON rats (+). The overexpression of renal cortical cytokine mRNA levels for the monocyte chemoattractants, monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as interleukin-1, inducible nitric oxide synthase, and transforming growth factor-β, assessed by competitive reverse transcription-polymerase chain reaction, was suppressed in LOS versus CON rats at 20 weeks. Macrophage and T-cell numbers were decreased, and MCP-1, RANTES, and intercellular adhesion molecule-1 staining in the graft, identified by immunohistochemistry, were attenuated in LOS versus CON rats. Conclusions. The renoprotective effects of losartan in F344→LEW rats were associated with lowered PGC , inhibition of macrophage chemoattractants and recruitment, and suppression of macrophage-associated cytokines at 20 weeks. These findings suggest that chronic... [ABSTRACT FROM AUTHOR]

Recent advances in tumor immunology and molecular drug development have ushered in a new era of cancer immunotherapy. Immunotherapy has shown promising results for several types of tumors, such as advanced melanoma, non-small cell lung cancer, renal cell carcinoma, bladder cancers, and refractory Hodgkin's lymphoma. Similarly, efforts have been made to develop immunotherapies such as adoptive T-cell transplantation, peptide vaccines, and dendritic cell vaccines, specifically for gastrointestinal tumors. However, before the advent of immune checkpoint inhibitors, immunotherapy did not work as well as expected. In this article, we review immunotherapy, focusing on cancer vaccines for gastrointestinal tumors, which generally target eliciting tumor-specific CD8 + cytotoxic T lymphocytes (CTLs). We also review various vaccine therapies and describe the relationship between vaccines and adjuvants. Finally, we discuss prospects for the combination of immunotherapy with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Lafutidine, an antagonist of histamine H2-receptor, has gastroprotective activity associated with activation of capsaicin-mediated sensory nerves. The objective of this study was to investigate the efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy in patients with gynecological malignancies. Methods: Twenty patients with taxane-induced peripheral neuropathy during the treatment of gynecological malignancy were enrolled in this study. After obtaining their informed consent, lafutidine (20mg per day) was administered orally, the efficacy of which was assessed according to the Patient Neurotoxicity Questionnaire item 1. Results: Significant, moderate, slight, and no effects were observed in four, five, five, and six patients, respectively. The efficacy including significant and moderate effect was observed in nine (45%) of the 20 patients (95% confidence interval, 25.8%–65.8%). No adverse effects due to lafutidine were observed. Conclusion: This pilot study supports the relatively high efficacy of lafutidine for the treatment of taxane-induced peripheral neuropathy. Further prospective studies are warranted. [Copyright &y& Elsevier]

Simple Summary: Neoadjuvant chemotherapy (NAC) is effective in improving the prognosis of patients with resectable and borderline resectable pancreatic cancer (PC). A modified FOLFIRINOX (mFOLFIRINOX) regimen is widely used as the standard therapy. However, owing to its toxicity, it is not applied in patients older than 75 years. Furthermore, elderly patients often have concomitant conditions and are at high risk for adverse effects associated with chemotherapy. Given the rapid increase in the number of elderly patients, it is necessary to determine whether NAC can be performed in both non-elderly and elderly patients. Thus, in this study, we investigated the safety and feasibility of neoadjuvant mFOLFIRINOX in elderly patients with PC. We found that the perioperative and postoperative outcomes of elderly patients who received neoadjuvant mFOLFIRINOX were comparable to those of non-elderly patients. The optimal treatment strategy for neoadjuvant chemotherapy in elderly patients with pancreatic cancer (PC) remains unclear. Hence, this study was aimed at evaluating the safety and feasibility of neoadjuvant-modified FOLFIRINOX (mFOLFIRINOX) in elderly patients with PC. We retrospectively collected data from 62 patients who received neoadjuvant mFOLFIRINOX between May 2015 and October 2023 and comparatively analyzed the clinicopathological data and outcomes between the non-elderly group (age: <75 years) and elderly group (age: >75 years). The non-elderly and elderly groups comprised 39 and 23 patients, respectively. Although elevated levels of aspartate aminotransferase (p = 0.0173) and alanine aminotransferase (p = 0.0378) and nausea (p = 0.0177) were more frequent in the elderly group, the incidence of severe adverse events was similar between the groups. Intergroup differences in resection rate (p = 0.3381), postoperative severe complication rates (p = 0.2450), and postoperative hospital stay (p = 0.3496) were not significant. Furthermore, no significant intergroup differences were found in survival in either the whole or the resection cohorts. The perioperative and postoperative outcomes of elderly patients treated with neoadjuvant mFOLFIRINOX were comparable with those of non-elderly patients. Neoadjuvant mFOLFIRINOX should be considered a feasible option for elderly patients with PC. [ABSTRACT FROM AUTHOR]