[An Examination of Colon Cancer Treatment Policies for the Elderly].

Currently, the rate of aging is increasing rapidly and the number of elderly patients in hospitals is rising in Japan. Under such circumstances, we established an emergency care unit for the elderly at our hospital in July 2014 to provide acute healthcare of the community. Our unit has been active in providing treatment for acute diseases in elderly individuals in the community. We are also pursuing continuous medical care for elderly individuals in collaboration with the community comprehensive care unit at our hospital and other facilities in the community, such as care facilities for the elderly and specialist elderly nursing homes. From January to December 2015, we examined treatment policies for colon cancer at our hospital. The presence or absence of dementia and patient's age are factors considered before treatment at our hospital; however, in many cases colon cancer was treated using surgery if the patient's generalcondition permitted it. In colon cancer patients, this takes into consideration the decreased quality of life resulting from losing the ability to eat due to bleeding and intestinal obstruction. We hereby report specific cases of colon cancer treatment policies for elderly patients at our hospital, together with a discussion of the literature.

[Advanced Digestive Cancer in Super Elderly Patients More Than 85 Years Old - Two Cases That Required Major Invasive Surgery].

Case 1 involved an 87-year-old woman. She had increased serum amylase levels, and intraductal papillary mucinous adenocarcinoma( IPMC)in the accessory pancreatic duct was diagnosed following various medical examinations. Radical surgery is possible for such a lesion when there are no issues detected following evaluation. The patient and her family decided that she should undergo surgery; therefore, pancreatoduodenectomy was performed for Stage III IPMC. Various morbidities required medical treatment, but she was finally discharged from hospital 89 days after surgery. She has had no recurrence 2 years and 11 months after surgery. Case 2 involved a 90-year-old man. He had liver dysfunction, and progressive hepatocellular carcinoma( HCC)was diagnosed based on computed tomography(CT)findings. The tumor size reduced to around 10 cm with enforced 2 degrees TACE. The patient and his family chose for him to undergo radical surgery; therefore, right trisegmentectomy of the liver was performed for Stage III HCC. He was discharged from the hospital 22 days after surgery, and has had no recurrence for the past 1.6 years. More careful examination and a general assessment are necessary to make decisions on surgical indications in super elderly patients.

[A Case That in Most Part of the Metastatic Liver Tumor Fell into Spontaneous Necrosis after Surgery of Rectal Cancer].

We present a case of a 74-year-old woman treated with maintenance dialysis for chronic renal failure. She had undergone intravascular treatment of lower limb arteriosclerosis obliterans 3 times. Low anterior resection was performed for rectal cancer StageⅡ, but adjuvant chemotherapy was not administered after the operation. S5/S6 partial hepatectomy was performed after confirming a liver metastatic recurrence 7 months after the first operation. Tumor pathology examination of the resected specimen revealed necrosis in most parts of the specimen. Residual primary lesion similar to adenocarcinoma tissue was found only in a small part of the specimen. Artery wall embolism and recanalization image with cholesterol crystals indicated a Grison's lesion, which was considered to have likely developed into tumor necrosis from the embolization. Spontaneous regression of a malignant tumor is a rare condition found 1 case in 6-10 ten thousand cases. In hepatocellular carcinoma, secondary tumor infarction from tumor invasion and tumor thrombus may occur. The present case was a metastatic liver cancer, in which the cholesterol crystal embolism possibly reached the tumor necrosis. The suggested cause of the cholesterol crystal embolism in this case was intravascular treatment related.

[Relapse-Free Survival Following Multidisciplinary Therapy for Hepatocellular Carcinoma with Multiple Lung Metastases--A Case Report].

Chemotherapy is not effective for metastatic hepatocellular carcinoma(HCC); however, prolonged survival can be expected for patients with multiple metastases who are treated with surgical resection in addition to chemotherapy. We present a case of a 36-year-old woman with hepatitis B who developed HCC with multiple intrahepatic and lung metastases after undergoing resection of HCC in 2010 in Canada. The patient returned to Japan for additional treatment. She was treated with TACE therapy and systemic chemotherapy, but her lung metastases did not improve. The patient's PIVKA-Ⅱ levels remained moderately elevated after initiation of chemotherapy. Therefore, we performed surgical resection of the lung metastases in March 2014. Five months later, the patient received additional TACE therapy when an isolated metastasis was found in the residual liver. Since then, no recurrence of HCC has been found, and the patient's PIVKA-Ⅱ levels have remained in the normal range. This case demonstrates that surgical resection for multiple lung metastases is possible in select patients.

Pilot study of preoperative immunonutrition with antioxidants in living donor liver transplantation donors.

INTRODUCTION: Previous studies have demonstrated that oxidative stress by mediating the excessive production of reactive oxygen species is involved in tissue damage and organ failure during and after surgery. The impact of the preoperative immunonutrition including antioxidants on the postoperative course of patients undergoing hepatic surgery was investigated in this pilot study. PATIENTS AND METHODS: Twenty-three living donor liver transplantation (LDLT) donors were randomly assigned to either an experimental (AO) group, received a commercial supplement enriched with antioxidant nutrients for each of the 5 days immediately prior to surgery while maintaining normal food intake, or a control (CT) group, administered no supplement. Antioxidative capacity was measured by spectrophotometry of patient serum using a free-radical analytical system. RESULTS: The antioxidative capacity of 90.9% patients in the AO group increased after immunonutrition. Compared to the CT group, the AO group was found to have higher antioxidant capacity and transferrin levels; lower WBC, lymphocyte, and neutrophil counts; and briefer duration of postoperative fever during the postsurgical period. No significant differences were found between the 2 groups regarding the nutritional parameters; liver functioning parameters; immunological parameters; intraoperative factors; postoperative outcomes. CONCLUSION: Preoperative immunonutrition including antioxidants might play a beneficial role in improving postsurgical immunological response but the modest biological advantage was not associated with any significant clinical outcome.

Spontaneous regression of multiple pulmonary recurrences of hepatocellular carcinoma after hepatectomy: report of a case.

Spontaneous regression of hepatocellular carcinoma (HCC) is an extremely rare phenomenon. We herein report the case of a 73-year-old man who showed the spontaneous regression of multiple pulmonary recurrences of HCC that had occurred after hepatectomy. The patient was undergoing dialysis due to diabetic renal failure when ultrasonography revealed a liver tumor (diameter ~ 10 cm). A preoperative diagnosis of HCC with hepatic vein thrombosis was made. The liver function was well preserved and then the right hepatic vein area was resected. Two months after hepatectomy the α-fetoprotein level increased, and multiple lung nodules were observed on follow-up computed tomography. A diagnosis of multiple lung metastases was made, but no therapy was started because of the patient's renal failure. Five months after hepatectomy the α-fetoprotein level normalized, and the metastases regressed completely. The patient is now doing well without any recurrence at 13 months after the surgery. The associated literature on spontaneous HCC regression is also reviewed.

Zero mortality in more than 300 hepatic resections: validity of preoperative volumetric analysis.

PURPOSE: We reviewed a series of patients who underwent hepatic resection at our institution, to investigate the risk factors for postoperative complications after hepatic resection of liver tumors and for procurement of living donor liver transplantation (LDLT) grafts. METHODS: Between April 2004 and August 2007, we performed 304 hepatic resections for liver tumors or to procure grafts for LDLT. Preoperative volumetric analysis was done using 3-dimensional computed tomography (3D-CT) prior to major hepatic resection. We compared the clinicopathological factors between patients with and without postoperative complications. RESULTS: There was no operative mortality. According to the 3D-CT volumetry, the mean error ratio between the actual and the estimated remnant liver volume was 13.4%. Postoperative complications developed in 96 (31.6%) patients. According to logistic regression analysis, histological liver cirrhosis and intraoperative blood loss >850 mL were significant risk factors of postoperative complications after hepatic resection. CONCLUSIONS: Meticulous preoperative evaluation based on volumetric analysis, together with sophisticated surgical techniques, achieved zero mortality and minimized intraoperative blood loss, which was classified as one of the most significant predictors of postoperative complications after major hepatic resection.

Assessment of delayed gastric emptying after major hepatectomy using a 13C-acetic acid breath test.

PURPOSES: Delayed gastric emptying (DGE) after hepatectomy affects the quality of life of patients, although the causes and related conditions have not been investigated. This study evaluated the relationship between hepatectomy and DGE by the objective assessment of gastric emptying (GE). METHODS: Nineteen patients who underwent major hepatectomy were prospectively enrolled in the study. Their GE was studied using the (13)C-acetic acid breath test before and after hepatectomy. The results of the GE analysis were correlated with the postoperative course after hepatectomy. RESULTS: Clinically evident DGE, which was defined as the inability to take in an appropriate amount of solid food orally by postoperative day 14, was not found in these patients, but the gastric half-emptying times before and after hepatectomy were 20.2 ± 9.7 and 28.6 ± 12.2 min, respectively (P = 0.01). The GE time was significantly delayed in patients aged ≥ 41 years, or who underwent right hemihepatectomy. CONCLUSIONS: Gastric emptying was significantly inhibited in patients who underwent major hepatectomy, and aging and a right-sided hemihepatectomy may be related to the development of DGE.

Predictors of extrahepatic recurrence after curative hepatectomy for hepatocellular carcinoma.

BACKGROUND: The aim of this study was to elucidate the predictors of extrahepatic hepatocellular carcinoma (HCC) recurrence after hepatectomy. MATERIALS AND METHODS: A cohort of 252 patients with HCC who underwent hepatectomy following a recurrence were reviewed. The patients were categorized into 2 groups according to the pattern of their initial recurrence. Clinicopathological and survival data were compared between the groups. RESULTS: Of the 252 patients, 218 had intrahepatic recurrence (IHR) (86.5%) and 34 had extrahepatic recurrence (EHR) (13.5%) as their initial recurrence. The mean duration of time until the initial recurrence after hepatectomy of the EHR and IHR groups was 1.8 and 2.2 years, respectively. The rate of recurrence within 6 months after hepatectomy of EHR and IHR groups was 35.3 and 14.2%, respectively (P = .002). The 3-, 5-, and 10-year cumulative survival rates of EHR group were 60.3, 24.0, and 6.0%, respectively, which were significantly lower than that of IHR group (74.5, 57.7, and 23.1%, P = .004). A multivariate analysis showed that blood loss during surgery and microscopic hepatic vein invasion remained as independent risk factors for increased EHR after hepatectomy for HCC. Furthermore, the combination of these 2 independent factors showed a significant association with the EHR. CONCLUSIONS: EHR of HCC was associated with early recurrence and a poor survival after a hepatectomy. The combination of 2 independent factors for EHR, the presence of microscopic hepatic vein invasion and the blood loss during surgery, may be useful for predicting the risk for occurrence of EHR during the follow-up period.

Significance of DNA polymerase delta catalytic subunit p125 induced by mutant p53 in the invasive potential of human hepatocellular carcinoma.

OBJECTIVE: To clarify the role of DNA polymerase delta in tumor progression, we examined the expression of its main catalytic subunit p125 encoded by POLD1 in hepatocellular carcinoma (HCC) and human HCC cell lines. METHODS: We examined the expression of p53 and p125 in HCC by using immunohistochemistry and Western blotting. Characteristic changes observed in human HCC cell lines after transfection were examined. RESULTS: Immunohistochemical examination revealed positive staining of p125 in HCC cell nuclei, but few positively stained cells were observed in noncancerous tissues (p < 0.0001). p125 expression in specimens significantly correlated with cellular differentiation (p = 0.0048) and the degree of vascular invasion (p = 0.0401). It also significantly correlated with abnormal p53 expression. In vivo studies showed that p125 was upregulated in mutant p53-transfected HepG2 cells, which had more invasive potential than did control cells. Furthermore, the expression and invasive potential were reduced by the silencer sequence for POLD1. CONCLUSIONS: These findings suggest that the DNA polymerase delta catalytic subunit p125 induced by mutant type p53 plays an important role in tumor invasion, which leads to a poorer prognosis in HCC.

New prediction factors of small-for-size syndrome in living donor adult liver transplantation for chronic liver disease.

Small-for-size syndrome (SFSS), which is characterized by synthetic dysfunction and prolonged cholestasis, is a major cause of worse short-term prognoses after living donor adult liver transplantation (LDALT). However, the risks of SFSS remain unclear. The aim of this study was to clarify the risks of SFSS, which were analysed in 172 patients who underwent LDALT for chronic liver disease. Graft types included left lobe with caudate lobe graft (n = 110) and right lobe graft (n = 62). Thirty-four cases (24 with left lobe grafts and 10 with right lobe grafts) were determined as SFSS. SFSS developed even if the actual graft-to-recipient standard liver volume ratio was >40%. Logistic regression analysis revealed three independent factors associated with SFSS development in left and right lobe grafts: donor age, actual graft-to-recipient native liver volume ratio, and Child's score. Donor age and actual graft-to-recipient native liver volume ratio may become predictive factors for SFSS development in left and right lobe grafts in patients undergoing LDALT.

Impact of preoperative serum sodium concentration in living donor liver transplantation.

BACKGROUND AND AIMS: The importance of hyponatremia in deceased donor liver transplantation (DDLT) has been recently discussed frequently. However, its impact on the outcomes in living donor liver transplantation (LDLT) has not yet been elucidated. The current study was designed to demonstrate the impact of pre-transplant sodium concentration on postoperative clinical outcomes. METHODS: One hundred and thirty-four patients who underwent LDLT for end-stage liver diseases were examined to evaluate the significance of pre-transplant hyponatremia (Na < or = 130 mEq/L) on the short-term clinical outcomes and the efficacy of the Model for End-Stage Liver Disease and serum sodium (MELD-Na) score using the sodium concentration and original MELD score. RESULTS: The preoperative sodium and MELD score for all patients were 133.9 mEq/L (range: 109-142) and 16.2 (range: 6-38), respectively. According to a multivariate analysis, not only the MELD score (P = 0.030) but also the sodium concentration (P = 0.005) were found to be significant predictive factors for short-term graft survival. Preoperative hyponatremia was a significant risk factor for the occurrence of sepsis (P < 0.001), renal dysfunction (P < 0.001) and encephalopathy (P = 0.026). The MELD-Na score was 19.6 (range: 6-51) and the area under the receiver-operator curve of that (c-statistics: 0.867) was higher than MELD score and sodium concentration (c-statistics: 0.820 and 0.842, respectively). CONCLUSION: Preoperative hyponatremia was a significant risk for postoperative complications and short-term graft loss. The addition of sodium concentration to MELD score might therefore be an effective predictor for post-transplant short-term mortality in LDLT.

Phase II trial of gemcitabine combined with 5-fluorouracil and cisplatin (GFP) chemotherapy in patients with advanced biliary tree cancers.

OBJECTIVE: Advanced biliary tree cancers are often diagnosed at an advanced or metastatic stage and have poor prognoses. We reported the promising anti-tumor activity of gemcitabine/5-fluorouracil (5-FU)/cisplatin (CDDP) therapy, called 'GFP chemotherapy' in a pilot study. METHODS: Twenty-one patients with advanced or metastatic biliary tree cancers with no prior chemotherapy were enrolled in this Phase II trial. Patients were treated on 4-week cycle GFP chemotherapy consisting of gemcitabine at 1000 mg/m(2) on days 1, 8 and 15, and 5-FU at 150 mg/m(2) and CDDP at 3 mg/m(2) on days 1-5, 8-12 and 15-19. After two cycles, a 4-week outpatient treatment of gemcitabine (1000 mg/m(2)) on days 1 and 15 combined with 5-FU (500 mg/m(2)) and CDDP (7 mg/m(2)) on days 1 and 15 was commenced. Treatment was repeated until tumor progression or remission allowing curative operation, or unacceptable toxicity occurred. RESULTS: Of these 21 patients, no complete responses were observed, but 7 patients (33.3%) demonstrated partial responses (PRs) with an additional 12 patients (57.2%) having stable diseases, as assessed by RECIST. Three patients with PRs were treated by curative operation after GFP chemotherapy, and all of them survived with no recurrence for over 3 years. The median overall survival time was 18.8 months, and median time to progression was 13.4 months. Grade 3 side effects such as leukopenia, thrombocytopenia and anemia were found in six patients (28.6%), but no patients dropped out because of toxicity. CONCLUSIONS: This GFP chemotherapy has promising anti-tumor activity and is well tolerated in patients with advanced biliary tree cancers.

Surgically resected undifferentiated carcinoma with osteoclast-like giant cells of the periampullary region involving the orifice of the papilla of Vater: Report of a case.

Undifferentiated carcinomas with osteoclast-like giant cells are rare periampullary neoplasms, which morphologically mimic giant cell tumors of the bone. The terminology, histogenesis, biological behavior, and chemosensitivity of these tumors, and their treatment protocol, remain controversial. We report the case of a 71-year-old man with periampullary carcinoma who underwent pancreaticoduodenectomy under the diagnosis of periampullary carcinoma. Histologically, the neoplasm was composed of undifferentiated cells and evenly spaced osteoclast-like giant cells. Liver and paraaortic lymph node metastases were detected 6 months later and were treated effectively with intravenous gemcitabine. The patient remains in remission 2 years after surgery.

Acute biliary obstruction due to a large intracholedochal hematoma after living-donor liver transplantation: Report of a case.

This report presents a rare case of an acute biliary obstruction caused by the postoperative development of an intracholedochal hematoma in a 57-year-old female patient who underwent living-donor liver transplantation for end-stage liver disease of cryptogenic origin. This is the first report to describe the development of an intracholedochal hematoma after livingdonor liver transplantation.

Early diagnosis and treatment resolved cholestatic hepatitis C without fibrosis after living donor liver transplantation: report of a case.

Cholestatic hepatitis is a life-threatening recurrent pattern of hepatitis C virus (HCV) in immunosuppressed patients, for which curative treatment has not yet been established. We report the successful treatment of cholestatic hepatitis in a 59-year-old man who had undergone right lobe living donor liver transplantation (LDLT) for liver cirrhosis (LC) caused by HCV. Following uneventful surgery and an uncomplicated posttransplant clinical course, there was an abrupt increase in total bilirubin in comparison to aminotransferase on postoperative day (POD) 60 (total bilirubin 16.2 mg/dl, alanine aminotransferase 100 U/l, HCV-RNA 390 kIU/ml). The histological findings of the liver tissue showed lymphocyte infiltration in the periportal zone and severe cholestasis. Considering the clinical course, cholestatic hepatitis was strongly suspected and pegylated interferon and ribavirin therapy was started immediately, resulting in not only a viral response, but minimal progression of fibrosis. This case serves to demonstrate that early diagnosis and timely initiation of optimal antiviral therapy is essential for the resolution of cholestatic hepatitis C.

The role of serum interleukin-8 in hepatic resections.

PURPOSE: Interleukin-8 (IL-8) is a neutrophil chemotactic factor, which is associated with some inflammatory diseases and various types of surgical stress. The aim of this study was to investigate whether the early postoperative serum IL-8 level may potentially be a new indicator of a surgical stress in patients undergoing a hepatic resection. METHODS: The serum IL-8 levels were measured in 37 patients who underwent a hepatectomy. The serum IL-8 levels were serially measured using an enzyme-linked immunosorbent assay both before and after a hepatic resection. In addition, the correlation between the postoperative IL-8 value and several clinical variables were examined. RESULTS: The mean level of IL-8 significantly increased immediately after the operation (P < 0.01 vs before the operation) and decreased on the first postoperative day (POD 1, P < 0.05 vs after the operation). The early postoperative IL-8 levels positively correlated with the length of the procedure (r = 0.383; P < 0.05), the estimated blood loss (r = 0.483; P < 0.01) and the serum bilirubin level on POD 1 (r = 0.390; P < 0.05), and inversely correlated with the white blood cell counts (r = -0.388; P < 0.05) and lymphocyte counts on POD 1 (r = -0.424; P < 0.05). In a comparison of the postoperative IL-8 levels with the surgical factors, there was a significant difference in the extension of the resection (P < 0.05) and in blood transfusion. The patients with a fever of more than 38 degrees C showed higher levels of IL-8 immediately after the operation than those without fever (P < 0.01). CONCLUSIONS: The early postoperative serum IL-8 level was found to correlate with the degree of the severity of surgery in patients undergoing a hepatic resection, and it is also considered to be a new indicator of surgical stress and liver injury.

De novo hepatocellular carcinoma in a liver graft with sustained hepatitis C virus clearance after living donor liver transplantation.

The occurrence of de novo hepatocellular carcinoma (HCC) after liver transplantation (LT) for advanced HCCs has been extremely limited. In this article, a case of de novo HCC in a liver graft with sustained hepatitis C virus clearance after living donor liver transplantation (LDLT) for multiple HCCs and hepatitis C cirrhosis is reported. The recipient was a 58-year-old female, and the left lobe living donor was the 30-year-old healthy daughter of the recipient. Three years after LDLT, the patient received 48 weeks of interferon treatment for recurrent hepatitis C with advanced fibrosis. The patient has shown successful viral clearance since then. However, an HCC was recognized in the liver graft during a follow-up computed tomography scan performed 6 years after LDLT, and it was surgically resected. To analyze its origin [either from the patient (metastatic) or from the living donor (de novo)], genotyping by microsatellite analysis of tissue and blood samples from the donor and recipient was performed, and it revealed that the HCC originated from the donor. To the best of our knowledge, this is the first report of de novo HCC in a liver graft with sustained hepatitis C virus clearance after LT for advanced HCCs and hepatitis C cirrhosis.

Both fibrous capsule formation and extracapsular penetration are powerful predictors of poor survival in human hepatocellular carcinoma: a histological assessment of 365 patients in Japan.

BACKGROUND: A new definition of infiltration to the capsule (fc-inf) has been proposed as a novel marker for predicting the prognosis of 88 patients with hepatocellular carcinoma (HCC). The current aim was to present evidence to develop the fibrous capsule and fc-inf, from the Japanese histological findings for HCC, and to validate their biological significances and predictive power of survival in a large series. METHODS: A total of 365 HCCs were divided into HCCs without the fibrous capsule (NC type; n = 135) and HCCs with the fibrous capsule (FC type; n = 230). Then, FC type was subclassified into two types: extracapsular infiltrating (EC) type (n = 125), in which cancer cells penetrated outside the fibrous capsule, and intracapsular (IC) type (n = 105), in which the infiltrating cancer cells stayed inside the fibrous capsule. RESULTS: The proportion of less histological differentiation and portal venous invasion was higher in FC type than in NC type. The fibrous capsule came to be observed according to the increase of tumor size (P < 0.0001). FC type had significantly poorer outcome for overall survival than NC type (P = 0.0022). EC type showed more intrahepatic metastasis than IC type. The macroscopic subclassifications were significantly affected the presence of fc-inf. EC type had significantly poorer outcome for disease-free survival than IC type (P = 0.0132) and was an independent prognostic factor for disease-free survival (P = 0.0482). CONCLUSIONS: Fc-inf defined as extracapsular penetration was verified to be a novel marker for predicting prognosis, and presence of fc-inf might be predicted by tumor gross features.

Long-term results of hepatic resection combined with intraoperative local ablation therapy for patients with multinodular hepatocellular carcinomas.

BACKGROUND: Recently, local ablation therapy has been widely used for treatment of small hepatocellular carcinoma (HCC). The present study assessed the outcome of hepatic resection combined with intraoperative local ablation therapy in patients with multinodular HCCs. METHODS: Forty-one patients with initial and multinodular HCCs underwent hepatic resection combined with intraoperative local ablation therapy. The mean maximum diameter of all tumors was 3.8 cm (range 2.1-16.0 cm), and the mean number of nodules was 3.2 (range 2-11). We evaluated the survival rates and assessed the prognostic factors associated with overall survival rates using Cox proportional hazard models. RESULTS: Intraoperative local ablation therapy was completed in all patients with no evidence of residual viable tumor on the first postoperative computed tomography (CT) scan. The 3-, 5- and 7-year overall survival rates were 84.3%, 61.2%, and 61.2%, respectively. Patients with preoperative des-gamma carboxyprothrombin (DCP) level >300 mAU/ml showed significantly worse overall survival than those with DCP level 300 mAU/ml was a significant prognostic factor of long-term overall survival.