Search

Background/aim: Osteopenia, the loss of bone mineral density (BMD), was recently reported as a prognostic factor in various cancers. However, the prognostic significance of preoperative osteopenia in breast cancer remains unclear. This study aimed to clarify the clinical significance of preoperative osteopenia in breast cancer., Patients and Methods: We retrospectively analyzed the relationship between osteopenia and clinical factors and prognosis in 532 patients with pathological Stage I-III primary breast cancer between 2009 and 2017. Osteopenia was assessed by measuring the average pixel density (Hounsfield unit) in the midvertebral core of the 11 th thoracic vertebra on enhanced preoperative computed tomography., Results: Osteopenia was diagnosed in 186 (35.0%) patients. The recurrence-free survival (RFS) rate was significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0275), but there was no significant difference in overall survival (OS) between the two groups. When evaluated by menopausal status, RFS and OS were significantly worse in the osteopenia group than in the non-osteopenia group (p=0.0094 and p=0.0264, respectively) in premenopausal patients. However, there were no significant differences in RFS and OS between the two groups among postmenopausal patients. In premenopausal patients, osteopenia was an independent prognostic factor for RFS in a multivariate analysis (p=0.0266)., Conclusion: Preoperative osteopenia was independently associated with recurrence of breast cancer., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The efficacy of neoadjuvant chemotherapy (NAC) for colon cancer remains unestablished. This study aimed to investigate the outcomes of NAC in patients with locally advanced T4b or obstructive T4a colon cancers (LACC)., Patients and Methods: Data of patients with LACC who underwent colon surgery between 2010 and 2022 after NAC at our institution were retrospectively reviewed. Patient characteristics, surgical outcomes, tumor features, and prognosis were analyzed., Results: Among 800 patients with LACC who underwent radical resection, 11 received NAC because of cT4b or cT4a with mechanical obstruction. NAC, administered as a doublet regimen, had a median duration of three months, without grade ≥3 adverse events. R0 resection was achieved in all patients and downstaging was observed in eight patients. One patient developed a postoperative abdominal abscess, and adjuvant chemotherapy was administered to eight patients. Four patients experienced recurrence: liver metastasis in two, and local recurrence in two. Among these, three patients underwent resection of recurrent tumors. Median follow-up was 30 months., Conclusion: NAC is feasible for T4b or obstructive T4a colon cancer and may be a treatment option for LACC. Further large-scale studies are required to confirm the efficacy of NAC in these patients., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study examined the clinical significance of very high preoperative carbohydrate antigen 19-9 (CA19-9) levels in patients with early-stage colorectal cancer (CRC)., Patients and Methods: We retrospectively analyzed the clinicopathological data of patients who underwent curative resection for primary CRC (c-Stage I-III) between 2004 and 2022 in our facility. The patients were classified into three groups according to the preoperative CA19-9 level: normal (≤37.0 U/ml), high (>37.0 to ≤100.0 U/ml), and very high (>100.0 U/ml)., Results: Of 971 patients, 885 (91.1%), 67 (6.9%), and 19 (2.0%) had normal, high, and very high CA19-9 levels, respectively. Overall survival (very high vs. normal: p<0.0001, very high vs. high: p=0.01) and recurrence-free survival (very high vs. normal: p<0.0001, very high vs. high: p=0.18) were significantly worse in the very high group. On multivariate analysis including TNM stage, very high preoperative CA19-9 levels were independently associated with worse overall (odds ratio=4.54; 95% confidence interval=2.03-10.16; p=0.0002) and recurrence-free survival (odds ratio=3.49; 95% confidence interval=1.82-6.69; p=0.0002)., Conclusion: High preoperative CA19-9 levels were associated with poor survival in early-stage CRC. Careful intraoperative observation and close follow-up might be necessary., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Recent advances in surgery, such as thoracoscopic surgery, have made it possible to treat patients with chronic obstructive pulmonary disease (COPD) more safely than before. This study evaluated the short- and long-term prognosis of lobectomy in non-small cell lung cancer (NSCLC) patients with COPD., Patients and Methods: This retrospective, propensity-matched, cohort analysis was conducted from January 2014 to December 2018. Among 441 patients who underwent lobectomy for NSCLC, 158 (35.8%) had a preoperative diagnosis of COPD. Propensity-matched analysis, incorporating preoperative variables, was used to compare postoperative hospital stay and complications, and long-term prognosis between the groups., Results: Propensity matching estimated 145 patients in each group. There was no difference between the two groups for length of postoperative hospital stay (12 vs. 11 days, p=0.306). Postoperative complications were more frequent in the COPD group (24.1%) than in the non-COPD group (16.6%), but the difference was not significant (p=0.108). The 5-year overall survival rate was 86.2% in the COPD group and 82.1% in the non-COPD group after matching (p=0.580). The corresponding 5-year recurrence-free survival rate was 72.8% in the COPD group and 67.2% in the non-COPD group after matching (p=0.601)., Conclusion: In case of Global Initiative for Chronic Obstructive Lung Disease (GOLD) I/II classification, COPD did not significantly worsen the prognosis of patients with NSCLC after lobectomy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Tumour lysis syndrome (TLS) is a life-threatening oncological emergency. TLS is rare and associated with a higher mortality rate in solid tumours than in haematological malignancies. Our case report and literature review aimed to identify the distinctive features and hazards of TLS in breast cancer., Case Report: A 41-year-old woman complained of vomiting and epigastric pain and was diagnosed with HER2-positive, hormone-receptor-positive breast cancer with multiple liver and bone metastases and lymphangitis carcinomatosis. She had several risk factors for TLS: high tumour volume, high sensitivity to antineoplastic treatment, multiple liver metastases, high lactate dehydrogenase levels, and hyperuricaemia. To prevent TLS, she was treated with hydration and febuxostat. One day after the first course of trastuzumab and pertuzumab, she was diagnosed with disseminated intravascular coagulation (DIC). After 3 further days of observation, she was relieved of DIC and administered a reduced dose of paclitaxel without life-threatening complications. The patient achieved a partial response after four cycles of anti-HER2 therapy and chemotherapy., Conclusion: TLS in solid tumours is a lethal situation and can be complicated by DIC. Early recognition of patients who are at risk of TLS and initiation of therapy is essential to avoid fatal situations., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Mac2-binding protein glycosylation isomer (M2BPGi) is a non-invasive marker for assessing liver fibrosis. This was a retrospective study investigating whether M2BPGi predicts recurrence of hepatocellular carcinoma (HCC) after hepatectomy in patients with HCC who achieved a sustained virological response (SVR)., Patients and Methods: We retrospectively reviewed the clinicopathological factors from 60 patients who underwent hepatectomy for HCC after achieving a SVR. We divided all patients into high M2BPGi and low M2BPGi groups and analyzed the clinicopathological and surgical outcomes., Results: High M2BPGi (>1.54, n=23) was significantly associated with lower serum albumin, higher ICGR15, higher Fib-4 index, large blood loss, and worse recurrence-free survival compared to low M2BPGi (≤1.54, n=37). Multivariate analysis identified high M2BPGi and large tumor size as being associated with reduced recurrence-free survival. Multivariate analysis identified lower serum albumin, larger tumor size and higher DCP as associated with reduced overall survival. There was no difference regarding recurrence pattern., Conclusion: Preoperative M2BPGi is a useful biomarker for HCC recurrence after hepatectomy for SVR-HCC., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The Geriatric Nutritional Risk Index (GNRI) is a prognostic indicator for several cancers; however, the association between the GNRI and colorectal liver metastasis (CRLM) remains unknown., Patients and Methods: Eighty patients who underwent hepatectomy for synchronous CRLM were divided into two groups based on the GNRI., Results: The preoperative CA19-9 levels were significantly higher in the low (GNRI ≤98; n=30) than the normal GNRI group (GNRI >98; n=50). Patients in the low GNRI group had poorer outcomes than those in the normal GNRI group. A low GNRI was an independent prognostic factor for recurrence-free survival and overall survival. Among 50 patients who experienced recurrence, only 16 of 22 patients (72.7%) in the low GNRI group could receive intensive treatment and 27 of 28 patients (96.4%) in the normal GNRI group., Conclusion: The GNRI is a simplified prognostic factor for patients with CRLM., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC., Materials and Methods: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC., Results: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis., Conclusion: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To investigate whether liver fibrosis can be predicted by quantifying the deformity of the liver obtained based on computed tomographic (CT) images scanned under respiratory control., Materials and Methods: For dynamic CT of 47 patients, portal venous and equilibrium phases were scanned during inspiration and expiration, respectively. After rigid registration of the two images, non-rigid registration of the liver was performed, and the amount and direction of each voxel's shift during non-rigid registration was defined as the deformation vector. The correlation of each CT parameter for the obtained deformation vectors with the pathologically-proven degree of liver fibrosis was assessed using Spearman's rank correlation test. Receiver operating characteristic curve analysis was conducted for prediction of liver fibrosis., Results: The standard deviation, coefficient of variance (CV) and skewness were significantly negatively correlated with the degree of liver fibrosis (p=0.030, 0.009 and 0.037, respectively). Of these measures, CV was best correlated and significantly decreased as liver fibrosis progressed (rho=-0.376). CV showed accuracies of 66.0-70.2%, and the areas under curves were 0.654-0.727 for prediction of fibrosis of grade F1 or greater, F2 or greater, F3 or greater and F4 fibrosis., Conclusion: The deformation vector is a potential CT parameter for evaluating liver fibrosis., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Intrahepatic cholangiocarcinoma (IHCC) is characterized by poor prognosis, and postoperative recurrence remains a problem. Thus, prognostic markers for IHCC are greatly needed. Recently, inflammatory factors were reported to be related to tumor progression and recurrence in various cancers. Therefore, the present study aimed to evaluate the prognostic ability of inflammatory factors., Materials and Methods: Forty-four patients with mass-forming IHCC (m-IHCC) were retrospectively evaluated and the correlations between inflammatory markers, including neutrophil-to-lymphocyte ratio and, modified Glasgow prognostic score, and patient survival were assessed., Results: The absolute neutrophil count (ANC) was significantly higher in the recurrence group than in the non-recurrence group (p=0.00568) and the most significant prognostic factor by multivariate analysis. Poor recurrence-free survival (RFS; p=0.00452) and cancer-specific survival (CSS; p=0.0323) were associated with high neutrophil levels. Moreover, neutrophil infiltration in the tumor site was positively correlated with ANC., Conclusion: ANC is associated with poor RFS, and could be used to predict recurrence in patients with m-IHCC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Computed tomography (CT) has recently been applied to measure bone mineral density (BMD). However, the definition of osteopenia, which means depletion of BMD, using CT remains controversial. The aim of this study was to establish formulae to calculate standard BMD., Patients and Methods: Fifty healthy donors for liver transplantation underwent CT. BMD was measured as cross-sectional average pixel density (Hounsfield units) only in trabecular-bone at Th11 bottom. Validation was performed on another 50 healthy donors to check the accuracy of formulae for standard BMD., Results: Measured BMD was significantly correlated with age in both males and females (p<0.0001). The formulae to calculate standard BMD were 308.82-2.49 × Age in males and 311.84-2.41 × Age in females. Estimated BMD was significantly correlated with measured BMD in males and females (p<0.0001)., Conclusion: Osteopenia can be defined by the difference between measured data and calculated data using our new formula based on each age., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study's aim was to investigate the safety and effectiveness of asunaprevir and daclatasvir treatment for recurrent hepatitis C virus (HCV) infection in transplant recipients. The study cohort comprised 14 transplant recipients with recurrent hepatitis C who were receiving asunaprevir and daclatasvir., Patients and Methods: Serum concentrations of asunaprevir and daclatasvir, their therapeutic effects, trough concentrations/dose ratios of tacrolimus, and adverse effects were evaluated., Results: Hepatitis C virus was still undetectable in 12 (85.7%) out of 14 patients 12 weeks after completing treatment. One week after starting treatment, asunaprevir concentrations were significantly higher in patients with baseline albumin concentrations ≤3.6 g/dl than in those with baseline albumin concentrations >3.6 g/dl. No marked fluctuations were identified in tacrolimus trough concentrations/dose ratios during the 24 weeks of therapy., Conclusion: Full doses of asunaprevir and daclatasvir-based treatment can be safely and effectively administered to liver transplant recipients for recurrent HCV genotype 1b after living donor liver transplantation (LDLT) with little effect on blood concentrations of tacrolimus., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer after hepatocellular carcinoma, and has a poor prognosis. Surgical resection is the only option for a cure of ICC. Here we attempted to define the cure rate after hepatic resection for ICC and to identify the predictors for a cure., Patients and Methods: Among the 96 patients who underwent R0 resections for primary ICC between 1990 and 2011 at the Kumamoto University Hospital and Kyushu University Hospital, those who were followed for ≥5 years after surgery were enrolled. "Cure" was defined as recurrence-free survival (RFS) of ≥5 years after surgery., Results: A total of 81 patients were eligible. A cure was achieved in 37 patients (45.7%). The 5-year overall survival and RFS rates were 55.0% and 41.7%, respectively. A multivariate logistic regression analysis identified the absence of lymph node metastasis (relative risk (RR) 7.5, p=0.011) and the absence of microvascular invasion (RR 5.5, p=0.0137) as the independent predictors of achieving a cure., Conclusion: R0 resections achieved a cure in 45.7% of this series of ICC patients. The predictors of a cure identified here, i.e., absence of lymph node metastasis and absence of microvascular invasion, could contribute to the selection of patients who are not candidates for adjuvant chemotherapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection., Patients and Methods: We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factors., Results: Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection., Conclusion: Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: De novo malignancy, including primary lung cancer, is one of the limitations to long-term survival after liver transplantation. The purpose of this study was to describe patients who developed de novo lung cancer after living-donor liver transplantation (LDLT) and investigate their clinicopathological features as well as the feasibility of surgical resection., Patients and Methods: We investigated 554 patients who underwent LDLT., Results: De novo lung cancer after LDLT was observed in five (0.9%) out of 554 studied patients: four men and one woman, aged 61-78 years (mean=67 years). All four men had a smoking history. Clinical stages of de novo lung cancer were stage IA in three patients, and stage IB and IV in one patient each. Three out of five patients underwent pulmonary lobectomy and pathological stage was IA in two patients and IIA in one. All patients who underwent surgery stopped immunosuppressive therapy 1 day preoperatively and restarted on postoperative day 1. There were no serious postoperative complications. All three patients are still alive without any recurrence, with survival ranging from 8 to 29 months, with an average of 16.3 months after diagnosis of lung cancer., Conclusion: Although the study population was small, these results suggest that pulmonary lobectomy of de novo lung cancer after LDLT, even under immunosuppressive conditions, is a feasible procedure and may yield a survival benefit., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: To assess the correlations among pancreatic fibrosis, pancreatic stiffness, and postoperative pancreatic fistula (PF)., Patients and Methods: The study population consisted of 17 consecutively enrolled patients who underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD). The liver fibrosis (LF) index as pancreatic stiffness was measured by real-time tissue elastography (RTE) before SSPPD. We also obtained the pathological fibrosis assessment of the pancreatic stump after SSPPD., Results: The LF index was significantly correlated with pathological pancreatic stump fibrosis. The LF index of patients without PF was significantly higher than that of patients with PF. The optimal cut-off value of the LF index to predict postoperative PF was defined as an LF index ≤1.91. Multivariate analysis revealed that a preoperative LF index ≤1.91 was an independent predictive factor of postoperative PF., Conclusion: Evaluation of pancreatic stiffness using RTE might be an objective index to estimate pancreatic fibrosis and predict postoperative PF., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Refractory ascites is a serious post-hepatectomy complication in cirrhotic patients with hepatocellular carcinoma (HCC). In order to avoid this complication, surgeons should preserve as much liver parenchyma as possible in performing hepatectomy in such patients. However, we still occasionally encounter refractory ascites even after limited or small hepatectomy. The aim of this study was to identify risk factors for post-hepatectomy refractory ascites in cirrhotic patients, focusing on limited or small hepatectomy., Patients and Methods: The data of 73 cirrhotic patients with HCC who underwent limited or small hepatectomy were analyzed. Limited or small hepatectomy was defined as hepatectomy equal to or of less than subsegmentectomy. We compared the clinicopathological factors between patients with and without postoperative refractory ascites., Results: Fourteen cirrhotic patients suffered postoperative refractory ascites. Total cholesterol, duration of operation, duration of Pringle maneuver, resection of segment VII, intraoperative blood loss, and intraoperative blood transfusion were found to be significant risk factors for postoperative refractory ascites in univariate analyses. Multivariate analysis revealed that resection of segment VII was an independent risk factor., Conclusion: Resection of segment VII necessitates extensive dissection of the right triangular or coronary ligaments, which could explain that it was an independent risk factor for post-hepatectomy refractory ascites. Surgeons should avoid extensive dissection of these ligaments in order to avoid this detrimental complication., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Treatment strategies for lymph node (LN) metastasis after liver transplantation (LT) for hepatocellular carcinoma (HCC) have not been studied., Patients and Methods: The treatment modes and outcomes in patients with LN metastasis after LT (n=6) for HCC were reviewed., Results: The mean time from LT to LN recurrence was 2.0±1.3 years, and the locations of the LNs recurrences included the phrenic (n=2), common hepatic artery (n=2), inferior vena cava (n=1) and gastric (n=1) regions. Treatments included surgery alone (n=3), surgery followed by chemoradiation (n=1), radiation followed by chemotherapy (n=1), and chemotherapy, radiation and sorafenib (n=1). Although the patients receiving non-surgical treatments (n=3) died within 1.2 years, those who underwent surgical removal of the metastatic LNs survived 11.2 years, 4.5 years and 0.8 years, respectively, without any signs of re-recurrence., Conclusion: Surgical resection is the only feasible and potentially curative treatment for LN metastasis after LT for HCC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Surgical resection of retrocaval giant pheochromocytomas (PCs) and of extra-adrenal paragangliomas (EAPs) is a technically challenging procedure but data on these procedures are scarce. The purpose of this study was to present and evaluate our surgical results for such tumors., Patients and Methods: We retrospectively analyzed four consecutive patients who had surgery for giant retro-caval PCs and EAPs in terms of surgical technique, resectability of the tumor, requirement for bypass, and postoperative complications. A laparoscopic approach was not feasible in all cases because of the undesirable location of the tumors., Results: In all cases, the liver was completely mobilized from the right side to expose and control the supra- and infra-hepatic inferior vena cava. Resection of the tumors was feasible for all patients with a minimum titration of blood pressure during surgery. None of the cases required venous bypass. In the patient who had the largest tumor, the infra-hepatic inferior vena cava was transected temporally to obtain direct and maximum exposure of the tumor. None of the patients have had any postoperative complications and all are currently alive without recurrence and use of antihypertensive drugs., Conclusion: Resection of retrocaval giant PCs and EAPs is a safe procedure. Temporal transection of the infra-hepatic inferior vena cava can offer excellent exposure, especially for an extremely large tumor, without compromising hepatic and systemic hemodynamics., (Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Inflammation-besed prognostic score including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS) and prognostic nutritional index (PNI) have prognostic value in various malignancies., Patients and Methods: We retrospectively investigated their prognostic value in 213 patients with living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). Disease-free survival (DFS) following LDLT was calculated; NLR, PLR, PNI and mGPS values in patients with and without recurrence were compared. Risk factors for HCC recurrence were identified by univariate and multivariate analyses., Results: Both NLR and PLR were significantly increased in patients with recurrence. Multivariate analysis showed that des-gamma-carboxy prothrombin (DCP) ≥300 mAU/ml, NLR ≥2.66, <3 months between last HCC treatment to LDLT were independent predictors of DFS., Conclusion: Preoperative NLR was an independent, inflammation-based prognostic marker of DFS and was predictive of recurrence following LDLT., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To evaluate the efficacy of age on the surgical outcomes in hepatic or pancreatic resection., Patients and Methods: We performed 50 hepatic or pancreatic resections in our community hospital and divided them into 2 groups based on age: patients aged ≥85 years old and patients aged <85 years old. We calculated the Estimation of Physiologic Ability and Surgical Stress (E-PASS) score and the Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) system and compared the surgical outcome between the two groups., Results: There was no significant difference between the two groups with regard to E-PASS and POSSUM scores. Patients aged ≥85 years had a significantly higher frequency of anti-platelet agents. The incidence of postoperative complications and mortality in patients ≥85 years old were comparable to those in patients aged <85 years old., Conclusion: Hepatic or pancreatic resection for elderly patients aged 85 years or older can be safely performed under a given careful patient selection., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To compare outcomes of patients with primary hepatocellular carcinoma (HCC) and portal hypertension (PHT) who underwent laparoscopic liver resection (LLR), open liver resection (OLR) or radiofrequency ablation (RFA)., Patients and Methods: We retrospectively reviewed 88 patients with primary HCC and PHT who underwent LLR (n=20), OLR (n=48) or RFA (n=20) and analyzed their outcomes by treatment group. To reduce selection bias, covariate distributions in groups were adjusted using inverse probability treatment weighting (IPTW)., Results: Five-year recurrence-free survival (RFS) was significantly better in the LLR and OLR than in the RFA group both before and after IPTW adjustment. The OLR group had significantly more postoperative complications than the RFA group; however, there was no significant difference in the postoperative complication rate between LLR and RFA groups., Conclusion: LLR may be a feasible treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or advanced hepatocellular carcinoma (A HCC) and PHT., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: We aimed to evaluate the effect of body composition on the outcome of living-donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC)., Patients and Methods: We performed LDLT in 153 patients with HCC and divided the patients into two groups based on skeletal muscle mass-to-visceral fat area ratio (SVR), as assessed by computed tomography (CT) measurement, namely a low-SVR group (n=38) and a not-low SVR group (n=112). We compared surgical outcomes between the two groups., Results: A low SVR was significantly correlated with a higher body mass index and male sex. No differences were found between the two groups in terms of other factors. The patients in the low-SVR group had a significantly poorer prognosis than those in the not-low SVR group in terms of recurrence-free (p=0.01) and overall (p=0.03) survival. The results of the multivariate analysis showed low SVR to be an independent and prognostic indicator for patients with HCC who had undergone LDLT., Conclusion: Pre-transplant body composition measured by CT is a major determinant of prognosis in LDLT for HCC in Japan., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Postoperative pancreatic fistula (POPF) remains a major complication after pancreaticoduodenectomy (PD), and the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC) after PD is poor., Patients and Methods: A multi-institutional retrospective study was performed in 174 patients who underwent PD for PDAC from 2007 to 2012. The details of clinical data were examined, and risk factors for POPF and poor prognostic factors after PD were identified., Results: POPF occured in 26 patients (15%), and 18 patients (10%) were diagnosed as Grade B/C POPF. The independent risk factors for Grade B/C POPF were body mass index (BMI) ≥25 (Odds Ratio [OR]=21.1, p=0.006) and absence of post-operative enteral nutrition (EN) (OR=10.2, p=0.04). The 1-, 3-, and 5-year overall survivals of patients with PDAC after PD were 76%, 35%, and 18%, respectively. R1/2 operation was identified as the only independent poor prognostic factor (Hazard Ratio=3.66; p=0.0002)., Conclusion: Patients with BMI ≥25 should be closely monitored for POPF after PD. Post-operative EN might help prevent POPF. Performing R0 resection is an important goal for ensuring patient survival after PD for PDAC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Early treatment of disseminated intravascular coagulation (DIC) can be associated with improved early outcomes. We aimed to evaluate the effectiveness of recombinant human soluble thrombomodulin (rTM) administration in patients with peritonitis-induced DIC., Patients and Methods: We treated 39 patients with DIC or pre-DIC caused by peritonitis at the Department of Surgery and Science, Kyushu University, and related facilities between January and December 2013., Results: Patients surviving to 28 days after DIC treatment had significantly better platelet counts, DIC scores, and sequential organ failure assessment scores at 7 days than did those who died earlier than 28 days. Patients receiving rTM had significantly better overall survival rates at 28 days and the results of multivariate analysis showed that rTM administration for DIC treatment was a prognostic indicator of 28-day survival in patients with peritonitis., Conclusion: rTM administration for the treatment of DIC or pre-DIC complicated by peritonitis had acceptable early outcomes., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: The rupture of hepatocellular carcinoma (HCC) is defined as a detrimental staging factor. The aim of the present study was to elucidate whether the prognosis of surgical patients with ruptured HCC was truly appalling., Patients and Methods: The data obtained from the medical records of 1,031 patients who underwent primary R0 hepatecomy for HCC between August 2003 and November 2014 at the Department of Surgery and Science, Kyushu University Hospital and its two affiliated hospitals, were retrospectively analyzed. Twenty-seven patients had ruptured HCC., Results: The recurrence-free and overall survival for patients with ruptured HCC were favorable. All 19 patients with ruptured HCC who experienced recurrence had intrahepatic recurrence, while only three had peritoneal recurrence. The multivariate risk factor analyses showed that rupture itself was not relevant to recurrence-free survival nor to overall patient survival., Conclusion: Rupture itself does not have much relevance to the outcome for patients who undergo hepatectomy., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The aim of the present study was to clarify the outcome of living donor liver transplantation (LDLT) in patients with hepatocellular carcinoma (HCC) within Milan criteria., Patients and Methods: The study comprised of 197 adult patients. One hundred twenty-nine patients were within Milan criteria. The overall and recurrence-free survival rates after the LDLT were calculated., Results: The 1-, 5- and 10-year overall survival rates were 94.5%, 89.9% and 88.6%, respectively. The 1-, 5- and 10-year recurrence-free survival rates were 100%, 97.0% and 94.0%, respectively. Four patients had HCC recurrence. The mean neutrophil to lymphocyte ratio (NLR) (6.75 vs. 2.75, p=0.002) or alpha-fetoprotein (AFP) (3,239 vs. 197, p<0.001) of these four recipients was significantly higher compared to that of 125 recipients without HCC recurrence., Conclusion: The outcome of LDLT for patients with HCC within Milan criteria was outstanding. Careful follow-up after LDLT is necessary for patients with high NLR or AFP., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: This retrospective study investigated outcomes after laparoscopic hepatectomy in the semi-prone position compared to open hepatectomy in the conventional supine position, for HCC (hepatocellular carcinoma) located in segment 6, 7, or 8., Patients and Methods: Patients were divided into two groups according to the surgical approach. The clinicopathological and surgical outcomes were analyzed., Results: There were no significant differences in patient-related or tumor-related factors between the two groups. The laparoscopic-hepatectomy group had significantly less blood loss, fewer postoperative complications, and a shorter hospital stay than the open-hepatectomy group. There were no in-hospital deaths. The postoperative change in the serum C-reactive protein was a significantly larger decrease in the group treated with laparoscopic hepatectomy than that in the open-hepatectomy group., Conclusion: Laparoscopic hepatectomy in the semi-prone position for HCC is safe and minimally invasive, and can reduce intraoperative bleeding, postoperative complications, and hospital stay compared to open hepatectomy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: To describe a patient with hepatocellular carcinoma (HCC), accompanied by hypersplenism and portal hypertension caused by macroglobulinemia, who underwent splenectomy followed by hepatectomy., Case Report: A 74-year-old man was admitted to our Hospital. He had previously developed primary macroglobulinemia, which had been completely cured by chemotherapy. At admission, he had a low platelet count (52 × 10(3)/μl), and his liver function was impaired. Imaging showed a 5-cm-sized tumor, an esophageal varix, and splenomegaly, but not liver cirrhosis. The patient underwent splenectomy for hypersplenism and portal hypertension; the weight of his spleen was 2,400 g. After splenectomy, his platelet count increased to 259 × 10(3)/μl and his liver function was improved. He safely underwent hepatectomy for HCC. The patient was discharged 14 days later without morbidity., Conclusion: These findings suggest that hepatectomy following splenectomy for hypersplenism and portal hypertension caused by macroglobulinemia, may effectively cure HCC in patients with liver dysfunction and thrombocytopenia., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: With the recent popularization of living-donor liver transplantation (LDLT), it has become important to provide treatment for comorbidities in recipients. We report the case of a patient who was successfully treated with LDLT, followed by left upper lobectomy for lung cancer concomitant with decompensated liver cirrhosis., Case Report: A 67-year-old female was admitted for treatment for severe liver cirrhosis. The lung cancer was identified preoperatively using computed tomography. We initially performed LDLT to improve liver function and coagulopathy; the patient was discharged postoperatively on day 39 without complication. Three months after LDLT, we performed a left upper lobectomy., Results: The patient's postoperative course was uneventful and she was discharged after 11 days., Conclusion: We conclude that an aggressive and appropriate surgical strategy, including LDLT, is an effective curative treatment in patients with controllable malignancy, concomitant with severe liver dysfunction., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

We describe a very rare case of recurrent hepatocellular carcinoma (HCC) after living donor liver transplantation (LDLT). A 47-year-old female underwent LDLT for HCC within Milan criteria, receiving a left liver lobe from her 38-year-old husband with an incompatible blood type. Thirty months after LDLT, however, enhanced computed tomography (CT) showed a tumor in her left adrenal gland; after another six months, enhanced CT and positron-emission tomography detected a frontal head bone tumor; enhanced CT performed 54 months after LDLT revealed a recurrent HCC in the liver graft. Each of these three tumors was surgically resected. Two months after hepatic partial resection, an enhanced CT showed another HCC in her liver graft, which was treated with local ablation therapy. One year after the last ablation treatment, the recipient is doing well without evidence of recurrence. At the time of detection of each of these tumors, the patient's serum concentration of hepatitis B virus surface antigen was elevated. Pathological examination showed that the resected tumors were moderately differentiated HCCs. Genotyping by microsatellite analysis confirmed their origin to be metastases of the primary HCC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

A 63-year-old man diagnosed with locally advanced pancreatic ductal adenocarcinoma (PDAC; stage IIa) was treated with chemotherapy (gemcitabine, 5-fluorouracil and cisplatin) followed by radiotherapy. He had complete response by imaging and relapse-free survival for 11 years. However, he subsequently presented with local tumor recurrence and underwent pancreaticoduodenectomy followed by chemotherapy; a partial response was achieved. As in liver metastasis of colonic cancer, complete response by imaging in PDAC may not mean pathological complete response. We would propose the importance of adjuvant surgery for a patient with PDAC with complete response by imaging after chemoradiotherapy., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Survival of patients with multiple recurrences (MR) of hepatocellular carcinoma (HCC) is very poor as recurrent tumors are usually aggressive and not amenable to curative resection. The present study aimed to investigate retrospectively predictors of intrahepatic MR of HCC after hepatectomy., Patients and Methods: We reviewed 416 patients who underwent hepatectomy and developed intrahepatic recurrence during the follow-up period. According to the recurrence pattern, the patients were divided into two groups: 83 who had four or more recurrent lesions in the remnant liver were defined as the MR group and the others who constituted the control group., Results: Multivariate analysis showed that micro-intrahepatic metastasis, α-fetoprotein and tumor size were independent risk factors for MR after hepatectomy. The combination of these three independent factors was significantly associated with MR. The recurrence rates within 1 year after hepatectomy of MR and control groups were 53.0% and 27.6%, respectively (p=0.0001). The 5-year overall survival rate of the MR group was 39%, which was significantly less than that of the control group (68%, p<0.0001)., Conclusions: MR of HCC was associated with an earlier recurrence and poorer survival after hepatectomy. The combination of three independent factors for MR might help predict MR occurrence during the follow-up period., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background/aim: Combined hepatocellular-cholangiocarcinoma (cHC-CC) is found unexpectedly in explanted or resected liver specimens. The current study evaluated the longterm outcomes of living-donor liver transplantation (LDLT) between patients with cHC-CC and hepatocellular carcinoma (HCC)., Patients and Methods: We performed 178 LDLT including 8 patients of pathologically and immunohistochemically diagnosed cHC-CC who all underwent LDLT with a preoperative diagnosis of HCC by imaging study., Results: Out of the 8 patients, 6 were within the Milan criteria and all were within the Kyushu University criteria. The 1-, 5- and 10-year overall survival (OS) and disease-free survival (DFS) rates after LDLT for patients with cHC-CC were 87.5, 72.9 and 48.6% and 85.7, 85.7 and 85.7%, respectively. The OS and DFS between patients with cHC-CC and HCC were not statistically different., Conclusion: LDLT for patients with cHC-CC using the Milan criteria or the Kyushu University criteria, as well as HCC, could have an acceptable long-term outcome., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: The apelin-APJ system regulates angiogenesis, and is overexpressed in several types of cancer. The aim of this study was to clarify the role of the apelin-APJ system in the angiogenesis of hepatocellular carcinoma (HCC)., Materials and Methods: Expressions of angiogenic factors and vascular markers were investigated in specimens from 90 HCC patients. A subcutaneous HCC tumor mouse model was treated with the APJ antagonist, F13A, and tumor growth and vascular development were assessed., Results: APJ expression was observed in arteriole-smooth muscle. Higher amounts of APJ(+)-arteriole and apelin were detected in tumors (p<0.001 for both). APJ(+)-arteriole and apelin expression were more commonly observed in moderately- and poorly-differentiated than in well-differentiated HCC (p ≤ 0.003). HCC with irregular dilated arteries expressed higher levels of apelin (p=0.012). Tumor growth was inhibited by treatment with F13A (p<0.001), and arterioles were decreased in the treated group (p=0.047), in vivo., Conclusion: Apelin-APJ is overexpressed, and works as a signal for arteriogenesis in HCC., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: For eradicating portal venous tumor extension and intrahepatic metastasis in hepatocellular carcinoma (HCC), anatomical resection is, in theory, preferable., Patients and Methods: We carried-out a retrospective cohort study in 110 patients who underwent curative hepatic resection (anatomical resection; n=20, and limited resection; n=90) for solitary recurrent HCC from 1990-2010., Results: No significant difference was found in short-term surgical results such as mortality, morbidity, and duration of hospital stay between the two groups. Anatomical resection did not influence overall and disease-free survival for all patients with a solitary recurrent HCC. In patients with cancer spread, such as pathological vascular invasion and intrahepatic metastasis (n=61), or with des-γ-carboxy prothrombin (DCP) ≥ 100 mAU/ml (n=73), the disease-free survival rate in the anatomical-resection group was significantly better than that in the limited-resection group (p=0.0452 and p=0.0345, respectively)., Conclusion: Anatomical resection should be recommended only for HCC suspected of exhibiting cancer spread as reflected by DCP ≥ 100 mAU/ml in patients with solitary recurrent HCC., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: With the recent popularization of living donor liver transplantation (LDLT), providing treatment for comorbidities in LDLT recipients has become important. We report the first case of a patient who was successfully treated with LDLT followed by total gastrectomy for early gastric cancer concomitant with decompensated liver cirrhosis., Case Report: A 64-year-old female was admitted for the treatment of severe liver cirrhosis. The patient's preoperative liver function was evaluated as Child-Pugh classification grade C. Upper gastrointestinal endoscopy revealed early gastric cancer. We first performed LDLT to improve her liver function and coagulopathy. Nineteen days after the LDLT, we performed total gastrectomy., Results: The patient's postoperative course was uneventful and she left our hospital on the 18th day after gastrectomy. The final pathological diagnosis of gastric cancer was Stage IA., Conclusion: Aggressive and adequate surgical strategy including LDLT is effective as curative treatment in patients with controllable malignancy concomitant with severe liver dysfunction., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Advanced biliary tree cancers have poor prognosis and chemotherapy has been shown to have little impact. To date, no standard chemotherapy regimens have been established. A pilot study to evaluate gemcitabine/5-Fluorouracil(5-FU)/cisplatin(CDDP) (GFP) chemotherapy in patients with advanced biliary tree cancers was performed., Patients and Methods: Eight patients with advanced intrahepatic cholangiocarcinoma and gallbladder carcinoma with no prior chemotherapy were treated with a 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m2 on days 1, 8, and 15, and of 5-FU at 250 mg/patient and CDDP at 5 mg/patient on days 1 to 5, 8 to 12 and 22 to 26., Results: Of these 8 patients, no complete responses (CR) were observed, but 3 patients (37.5%) demonstrated partial responses (PR) with an additional 3 patients (37.5%) having stable diseases (SD), as assessed by RECIST. Two patients with PR and 1 patient with SD were treated by curative operation after GFP chemotherapy and all of them survived with no recurrence. The median overall survival time was 23.5 months, and median time to progression was 14.5 months. Grade 3/4 side-effects, such as leukopenia, thrombocytepenia and anemia were found in 4 patients (50%), but no patients dropped out because of toxicity., Conclusion: This GFP chemotherapy has promising antitumor activity and is well tolerated in patients with advanced biliary tree cancers. This regimen warrants further evaluation in a phase II study including larger numbers of patients.