Depletion of plasma thymidine results in growth retardation and mitochondrial myopathy in mice overexpressing human thymidine phosphorylase.

Plasma thymidine levels in rodents are higher than in other mammals including humans, possibly due to a different pattern and lower level of thymidine phosphorylase expression. Here, we generated a novel knock-in (KI) mouse line with high systemic expression of human thymidine phosphorylase to investigate this difference in nucleotide metabolism in rodents. The KI mice showed growth retardation around weaning and died by 4 weeks of age with a decrease in plasma thymidine level compared with the litter-control WT mice. These phenotypes were completely or partially rescued by administration of the thymidine phosphorylase inhibitor 5-chloro-6-(2-iminopyrrolidin-1-yl) methyl-2,4(1H,3H)-pyrimidinedione hydrochloride or thymidine, respectively. Interestingly, when thymidine phosphorylase inhibitor administration was discontinued in adult animals, KI mice showed deteriorated grip strength and locomotor activity, decreased bodyweight, and subsequent hind-limb paralysis. Upon histological analyses, we observed axonal degeneration in the spinal cord, muscular atrophy with morphologically abnormal mitochondria in quadriceps, retinal degeneration, and abnormality in the exocrine pancreas. Moreover, we detected mitochondrial DNA depletion in multiple tissues of KI mice. These results indicate that the KI mouse represents a new animal model for mitochondrial diseases and should be applicable for the study of differences in nucleotide metabolism between humans and mice.

Prognostic implications of histologic growth patterns and tumor-infiltrating macrophages in colorectal liver metastases.

PURPOSE: Histopathologic patterns at the invasion fronts of tumors predict metastatic potential and prognosis in several cancers. We examined whether such patterns at the interface between colorectal liver metastases and hepatic parenchyma have similar prognostic value. METHODS: Microscopic growth patterns at edges of metastases including desmoplasia, pushing borders, and replacement of hepatocytes were retrospectively analyzed with respect to surgical outcomes in 142 patients who underwent hepatectomy for colorectal metastases. RESULTS: Patterns included desmoplasia in 58 patients (41%), hepatocyte replacement in 41 (29%), and pushing borders in 43 (30%). Maximum metastasis diameter and serum carcinoembryonic antigen concentration in patients showing desmoplastic tumor growth were lower than those in others (P < 0.05 and P < 0.01). Disease-free survival and overall survival were better in patients showing desmoplastic growth, while a non-desmoplastic tumor growth pattern showed a negative influence. More cluster of differentiation (CD) 68-positive M1 macrophages and fewer CD206-positive M2 macrophages were demonstrated at interfaces of tumors with hepatic parenchyma when desmoplasia was present, although markers for proliferative activity (MIB1 index) and metastatic potential (E-cadherin expression) appeared uninfluenced by desmoplasia. CONCLUSION: Better long-term results were associated with metastatic tumors showing desmoplastic growth patterns at invasion fronts, which may reflect local immune state in a prognostically useful manner.

Failure of peritoneal lavage to prevent operative site infection and peritoneal tumor recurrence in pancreatic surgery.

BACKGROUND: Although intraoperative peritoneal lavage often is performed routinely with the aim of reducing peritoneal contamination, evidence of lavage benefit in elective pancreatic surgery is limited. METHODS: We retrospectively classified patients who had undergone pancreatic surgery to groups given or not given peritoneal lavage, then comparing clinical results. This saline lavage was performed at the end of the operation. The primary endpoint was rate of surgical site infection. Frequency of peritoneal recurrence also was evaluated. RESULTS: Among all 104 patients in the study, incidence of infectious complications in the lavage group (n = 65) was significantly higher than in the non-lavage group (n = 39; 35% vs. 15%, P = 0.041), while incidences of postoperative complications overall and surgical site infection did not differ between lavage (80% and 26%) and non-lavage groups (67% and 10%, P = 0.162 and 0.076, respectively). Among 63 patients undergoing pancratoduodenectomy, frequencies of positive bacterial cultures of drainage fluids on postoperative days 1 and 3 were greater in the non-lavage group (P < 0.001 and P = 0.012), but surgical site infection was significantly more frequent in the lavage group (P = 0.043). Among patients with pancreatic and biliary cancers, lavage did not affect frequency of peritoneal recurrence. CONCLUSION: Intraoperative lavage did not prevent surgical site infection or peritoneal recurrence of pancreatobiliary cancer.

Benefit of laparoscopic compared to standard open gastric cancer surgery for sarcopenic patients: a propensity score-matching analysis.

BACKGROUND: Laparoscopic gastrectomy (LG) is performed widely, but whether LG is the optimal treatment for sarcopenic gastric cancer patients is unclear. This study aimed to determine whether LG is particularly beneficial for gastric cancer patients with sarcopenia. METHODS: We collected data concerning 604 consecutive patients who underwent gastrectomy for gastric cancer between January 2003 and December 2019. After adjustment using one-to-one propensity score matching, short-term and long-term outcomes were compared between LG and open gastrectomy (OG) groups among patients with sarcopenia and those without. RESULTS: Among patients with and without sarcopenia, the LG group had a significantly longer operative time but less blood loss than the OG group. The two groups showed no significant differences regarding complications. Although 5-year overall and disease-specific survival were similar between LG and OG groups among patients with and without sarcopenia, LG was associated with greater 5-year non-gastric cancer-related survival than OG among patients with sarcopenia (88.3% vs. 78.1%, P = 0.048), but not those without. CONCLUSION: LG for resectable gastric cancer was not inferior to OG regarding complications and outcomes in patients with or without sarcopenia. No difference in overall survival was evident between these approaches, but LG may lessen mortality from conditions unrelated to gastric cancer in sarcopenic patients.

Absence of a weekday effect on short- and long-term oncologic outcomes of gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: Day of the week when elective gastrointestinal surgery is performed may be influenced by various background and tumor-related factors. Relationships between postoperative outcome and when in the week gastrectomy is performed remain controversial. We undertook this study to evaluate whether weekday of gastrectomy influenced outcomes of gastric cancer treatment ("weekday effect"). METHODS: Patients who underwent curative surgery for gastric cancer between 2004 and 2017 were included in this retrospective study. To obtain 2 cohorts well balanced for variables that might influence clinical outcomes, patients whose gastrectomy was performed early in the week (EW group) were matched 1:1 with others undergoing gastrectomy later in the week (LW group) by use of propensity scores. RESULTS: Among 554 patients, 216 were selected from each group by propensity score matching. Incidence of postoperative complications classified as Clavien-Dindo grade II or higher was similar between EW and LW groups (20.4% vs. 24.1%; P = 0.418). Five-year overall and recurrence-free survival were 86.0% and 81.9% in the EW group, and 86.2% and 81.1% in the LW group (P = 0.981 and P = 0.835, respectively). CONCLUSIONS: Short- and long-term outcomes were comparable between gastric cancer patients who underwent gastrectomy early and late in the week.

[Prehepatectomy Chemotherapy Using Circadian Chrono-HAI for Liver Metastases from Colorectal Cancer].

We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.

dUTPase inhibition confers susceptibility to a thymidylate synthase inhibitor in DNA-repair-defective human cancer cells.

Deficiency in DNA repair proteins confers susceptibility to DNA damage, making cancer cells vulnerable to various cancer chemotherapies. 5-Fluorouracil (5-FU) is an anticancer nucleoside analog that both inhibits thymidylate synthase (TS) and causes DNA damage via the misincorporation of FdUTP and dUTP into DNA under the conditions of dTTP depletion. However, the role of the DNA damage response to its antitumor activity is still unclear. To determine which DNA repair pathway contributes to DNA damage caused by 5-FU and uracil misincorporation, we examined cancer cells treated with 2'-deoxy-5-fluorouridine (FdUrd) in the presence of TAS-114, a highly potent inhibitor of dUTPase that restricts aberrant base misincorporation. Addition of TAS-114 increased FdUTP and dUTP levels in HeLa cells and facilitated 5-FU and uracil misincorporation into DNA, but did not alter TS inhibition or 5-FU incorporation into RNA. TAS-114 showed synergistic potentiation of FdUrd cytotoxicity and caused aberrant base misincorporation, leading to DNA damage and induced cell death even after short-term exposure to FdUrd. Base excision repair (BER) and homologous recombination (HR) were found to be involved in the DNA repair of 5-FU and uracil misincorporation caused by dUTPase inhibition in genetically modified chicken DT40 cell lines and siRNA-treated HeLa cells. These results suggested that BER and HR are major pathways that protect cells from the antitumor effects of massive incorporation of 5-FU and uracil. Further, dUTPase inhibition has the potential to maximize the antitumor activity of fluoropyrimidines in cancers that are defective in BER or HR.

Liver regeneration after performing associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) is histologically similar to that occurring after liver transplantation using a small-for-size graft.

PURPOSE: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can achieve marked future liver remnant (FLR) hypertrophy but this procedure is associated with a risk of mortality due to liver failure because of an insufficient FLR functional increase, a situation comparable to small-for-size syndrome (SFSS) after living-donor liver transplantation (LDLT). METHODS: The clinical data, morphologic volume changes, and histopathologic and immunohistochemical findings in hepatocytes and bile ductules were compared between ALPPS (n = 10) and LDLT with a risk for SFSS (n = 12). RESULTS: Although the patient characteristics and short-term outcome differed between the groups, the mean hypertrophy ratios with respect to liver volume for the FLR after performing the first-stage ALPPS procedures resembled those in small-for-size grafts after similar time intervals: 1.702 ± 0.407 in ALPPS vs. 1.948 ± 0.252 in LDLT (P = 0.205). The histologic grades for sinusoidal dilation (P = 0.896), congestion (P = 0.922), vacuolar change (P = 0.964), hepatocanalicular cholestasis (P = 0.969), and ductular reaction (P = 0.728) within the FLR at the second-stage operation during ALPPS or implanted graft were all similar between the groups. CONCLUSIONS: The hepatic regenerative process may be similar in ALPPS and LDLT using a small-for-size graft. Reducing the hepatic vascular inflow that may be excessive for the FLR volume during the first stage of ALPPS might enhance the functional recovery since measures with a similar effect appear to lessen the likelihood of SFSS.

Association between low preoperative skeletal muscle quality and infectious complications following gastrectomy for gastric cancer.

PURPOSE: It is known that sarcopenia affects the overall short- and long-term outcomes of patients with gastric cancer (GC); however, the effect of muscle quality on infectious complications after gastrectomy for GC remains unclear. We investigated the associations between the preoperative quantity and quality of skeletal muscle on infectious complications following gastrectomy for GC. METHODS: The subjects of this retrospective study were 353 GC patients who underwent radical gastrectomy between 2009 and 2018. We examined the relationships between their clinical factors, including skeletal muscle mass index and intramuscular adipose tissue content (IMAC), and infectious complications after gastrectomy. RESULTS: Infectious complications developed in 59 patients (16.7%). The independent risk factors for infectious complications identified by multivariate analysis were male gender (P < 0.001), prognostic nutritional index below 45 (P = 0.006), and high IMAC (P = 0.011). Patients with a high IMAC were older and had a higher body mass index, as well as a greater age-adjusted Charlson comorbidity index, than those with low or normal IMAC. CONCLUSIONS: Low skeletal muscle quality defined by a high IMAC is a risk factor for infectious complications following gastrectomy. When feasible, preoperative nutritional intervention and rehabilitation aiming to improve muscle quality could reduce infectious complications after gastrectomy for GC.

Acquired resistance to trastuzumab/pertuzumab or to T-DM1 in vivo can be overcome by HER2 kinase inhibition with TAS0728.

HER2-targeting antibodies (trastuzumab, pertuzumab) and a HER2-directed antibody-drug conjugate (trastuzumab emtansine: T-DM1) are used for the treatment of HER2-overexpressing breast cancer. However, these treatments eventually become ineffective due to acquired resistance and there is an urgent need for alternative therapies. TAS0728 is a small-molecule, irreversible selective HER2 kinase inhibitor. In the present study, we established new in vivo models of cancer resistance by continuous exposure to a combination of trastuzumab and pertuzumab or to T-DM1 for evaluating the effect of TAS0728 on HER2 antibody-resistant populations. Treatment with trastuzumab and pertuzumab or with T-DM1 initially induced tumor regression in NCI-N87 xenografts. However, tumor regrowth during treatment indicated loss of drug effectiveness. In tumors with acquired resistance to trastuzumab and pertuzumab or to T-DM1, HER2-HER3 phosphorylation was retained. Switching to TAS0728 resulted in a significant anti-tumor effect associated with HER2-HER3 signal inhibition. No alternative receptor tyrosine kinase activation was observed in these resistant tumors. Furthermore, in a patient-derived xenograft model derived from breast cancer refractory to both trastuzumab/pertuzumab and T-DM1, TAS0728 exerted a potent anti-tumor effect. These results suggest that tumors with acquired resistance to trastuzumab and pertuzumab and to T-DM1 are still dependent on oncogenic HER2-HER3 signaling and are vulnerable to HER2 signal inhibition by TAS0728. These results provide a rationale for TAS0728 therapy for breast cancers that are refractory to established anti-HER2 therapies.

Can the location of the mural nodule indicate benign or malignant in branch duct-type intraductal papillary mucinous neoplasm of the pancreas?

BACKGROUND/OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are classified into main duct (MD)-type IPMNs, branch duct (BD)-type IPMNs, and mixed type IPMNs. While MD-type IPMN has a high risk of malignancy and should therefore be considered for resection if the patient is fit, BD-type IPMN needs to be carefully judged for surgical indication. The decision to resect BD-type IPMN is often based on international consensus Fukuoka guidelines 2017, but further investigation is required. In this study, we focused on whether the location of the mural nodule (MN) could be an indicator of malignancy. METHODS: We enrolled 17 cases who had been diagnosed BD-type IPMNs which were surgically resected from January 2016 to December 2019. These cases were classified into benign and malignant group. Subsequently, a clinicopathological study was conducted based on the localization of MN (MN-central type or MN-peripheral type). RESULTS: Although MN was found in 57% (4/11) in the benign group, 88% (7/8) was noted in the malignant group, indicating the presence of MN to be more common in the malignant group. Those with MN consisted of 6 cases of MN-central type and 5 cases of MN-peripheral type. All cases of central type were malignant compared to only one case of the peripheral group being confirmed on histology as cancer. CONCLUSION: BD-IPMN with central mural nodule should be considered high risk for malignancy.

Body composition as reflected by intramuscular adipose tissue content may influence short- and long-term outcome following 2-stage liver resection for colorectal liver metastases.

INTRODUCTION: For many kinds of cancer, body composition and immunonutritional status have been reported to influence postoperative outcome. We assessed their impact on short- and long-term outcome in patients with colorectal liver metastases who underwent 2-stage liver resections. METHODS: Short- and long-term outcomes for 47 patients with 2-stage hepatectomies were assessed retrospectively in terms of data obtained before preoperative chemotherapy, before the first hepatectomy, and before the second hepatectomy. RESULTS: Although immunonutritional status and body composition did not affect short-term outcome, high intramuscular fat content before the second hepatectomy was a poor prognostic factor for overall survival (HR, 5.829; 95% CI, 1.611-21.090; p = 0.007) and for recurrence-free survival (HR, 2.787; 95% CI, 1.301-5.973; p = 0.008). Patients with high intramuscular fat before the second hepatectomy also showed shorter intervals from recurrence to treatment failure. CONCLUSION: Intramuscular fat before the second hepatectomy is an important negative prognosticator in 2-stage liver resection for colorectal liver metastases.

Activity of TAS4464, a novel NEDD8 activating enzyme E1 inhibitor, against multiple myeloma via inactivation of nuclear factor κB pathways.

The ubiquitin proteasome pathway is essential for the proliferation and survival of multiple myeloma (MM) cells. TAS4464, a novel highly potent inhibitor of NEDD8 activating enzyme, selectively inactivates cullin-RING ubiquitin E3 ligases, resulting in accumulation of their substrates. Here, we examined 14 MM cell lines treated with TAS4464. TAS4464 induced growth arrest and cell death in the MM cell lines even in the presence of bone marrow stromal cells. It also induced the accumulation of phospho-inhibitor of κBα and phospho-p100, impaired the activities of nuclear factor κB (NF-κB) transcription factors p65 and RelB, and decreased the expression of NF-κB target genes, suggesting that TAS4464 inhibits both the canonical and non-canonical NF-κB pathways. TAS4464 had similar effects in an in vivo human-MM xenograft mouse model in which it was also observed to have strong antitumor effects. TAS4464 synergistically enhanced the antitumor activities of the standard MM chemotherapies bortezomib, lenalidomide/dexamethasone, daratumumab and elotuzumab. Together, these results suggest that the anti-MM activity of TAS4464 occurs via inhibition of the NF-κB pathways, and that treatment with TAS4464 is a potential approach for treating MM by single and combination therapies.

[A Case of Gastric Cancer with Necrotic Lymph Node Perforation in the Stomach during Chemotherapy].

A 63-year-old man was diagnosed with gastric cancer. Distal gastrectomywas performed in November 2011. The pathologic finding was pT3N2M0, Stage ⅢA. S-1 was administered as adjuvant chemotherapy. However, in August 2012, computed tomographyrevealed a tumor measuring 3 cm in size in the dorsal pancreas. Based on endoscopic ultrasound-guided fine- needle aspiration, he was diagnosed with lymph node recurrence of gastric cancer. Injection chemotherapy of CDDP/CPT-11 was initiated in November 2012. In January 2013, the patient developed fever owing to a ruptured abscess from the posterior wall in the stomach. In the 6 years since, although the patient has not undergone chemotherapy, recurrence has not been observed.

Effective Sequential Combined Chemotherapy with Trifluridine/Tipiracil and Regorafenib in Human Colorectal Cancer Cells.

Salvage chemotherapy for refractory metastatic colorectal cancer using trifluridine/tipiracil (FTD/TPI) and regorafenib has shown survival benefits. We evaluated the antitumor effects of FTD or FTD/TPI combined with regorafenib in vitro and in vivo. SW620, HCT 116, and HT-29 human colorectal cancer cell lines were treated with FTD and regorafenib simultaneously and sequentially. Cell death, incorporation of FTD into DNA, and molecules related to FTD and regorafenib-associated cell death were investigated. The antitumor effects of FTD combined with regorafenib in SW620 and COLO205 xenografts were also evaluated. Cell death was greater after sequential treatment with FTD followed by regorafenib in SW620 cells, but not in HCT 116 and HT-29 cells, than after treatment with FTD alone, which was attributable to thymidylate synthase reduction with the induction of apoptosis. In contrast, simultaneous and sequential exposure to regorafenib followed by FTD, but not FTD alone, attenuated the cell death effect. Furthermore, combined FTD/TPI treatment followed by regorafenib had greater antitumor activity than either monotherapy in SW620 and COLO205 xenograft models. Treatment results following regorafenib administration subsequent to FTD or FTD/TPI suggest that sequential therapy with FTD/TPI prior to regorafenib may be effective in a clinical setting.

Modified ALPPS Procedures Avoiding Division of Portal Pedicles.

OBJECTIVE: We describe a modified procedure associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) including portal pedicle preservation during parenchymal division, thus avoiding necrosis. BACKGROUND: Although ALPPS recently has been advocated for treating advanced liver tumors, sepsis originating from the ischemic area produced by parenchymal division increases mortality, accounting for one-third of postoperative deaths. METHODS: Our procedure differs from the original ALPPS technique by sparing portal pedicles at the transection plane, thus maintaining blood supply. The preserved pedicles are segment 4 (S4) in right lobectomy plus right portal vein ligation (PVL), S1 in extended right hepatectomy (extended to S1) plus right PVL, lateral portal pedicles of the right paramedian sector (RPS) in extended right lateral sectoriectomy plus lateral PVL, and both portal pedicles of the lateral RPS and S1 in extended right lateral sectoriectomy with S1 resection plus lateral PVL. RESULTS: These procedures were performed in 5 patients. Morbidity rates at first- and second-stage operations were 0% and 80%, without mortality. Mean hypertrophy of the future liver remnant was 1.638 ±â€Š0.384 a week after the first-stage procedure. CONCLUSIONS: Our technique stimulates rapid hypertrophy and may improve safety in ALPPS.

Immaturity of Bile Canalicular-Ductule Networks in the Future Liver Remnant While Associating Liver Partition and Portal Vein Occlusion for Staged Hepatectomy (ALPPS).

BACKGROUND: We studied histologic changes of bile canalicular-ductule networks in the future liver remnant (FLR) while associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS), since little is known about regeneration of these networks during the relatively short interval between procedures in ALPPS. METHODS: Bile canalicular-ductule networks were examined in specimens from eight patients treated with ALPPS and six patients undergoing hepatectomy following portal vein embolization (PVE). Expression of multidrug resistance-1 (MDR1), a membrane transporter in bile canaliculi (BC), was analyzed immunohistochemistcally. Morphologic changes of BC and tight junctions (TJs) adjoining BC were also assessed electron microscopically. RESULTS: Extrapolated kinetic growth of the FLR was greater during ALPPS (17.2 ± 6.8 mL/day) than after PVE (6.3 ± 3.4 mL/day; p = 0.005), and continuity of the MDR1-positive bile canalicular networks was less evident in ALPPS than PVE (p < 0.001). Electron microscopically, no significant difference was evident in numbers of BC or BC lumen size between the two groups; however, development of microvilli in BC was poorer in the ALPPS group than in the PVE group (p < 0.001). TJ/desmosome complexes were shorter in the ALPPS group (0.69 ± 0.52 µm) than in the PVE group (1.09 ± 0.50 µm; p < 0.001), and leaky TJs were seen more frequently in the ALPPS group (64.9 vs. 23.6%; p = 0.001). CONCLUSIONS: Regeneration of bile canalicular-ductule networks in the FLR was poorer in ALPPS than PVE, which may be associated with prolonged cholestasis following final hepatectomy in ALPPS.

Naso-esophageal extraluminal drainage for postoperative anastomotic leak after thoracic esophagectomy for patients with esophageal cancer.

Postoperative anastomotic leaks and subsequent mediastinal abscess are serious complications. The purpose of this study was to assess the efficacy of naso-esophageal extraluminal drainage after thoracic esophagectomy with gastric conduit reconstruction using a posterior mediastinal route. About 50 of 365 patients (13.7%) with esophageal cancer and postoperative anastomotic leak after curative esophagectomy was investigated. Beginning in June 2009, naso-esophageal extraluminal drainage by inserting a naso-esophageal aspiration tube into the abscess cavity when percutaneous abscess drainage was introduced which was ineffective or technically impossible. Twenty-five patients underwent naso-esophageal extraluminal drainage concomitantly with enteral nutrition. Twenty-one (84%) patients had major leaks, one (4%) minor leak and three (12%) had endoscopically proven conduit necrosis. None of the naso-esophageal extraluminal drainage cases (100%) required reintervention or reoperation and all experienced complete cure (100%) during hospitalization. Endoscopic balloon dilatation was performed for four patients after discharge because of anastomotic stricture. Patients with leaks were divided into two groups: current group (n = 32), treated after June 2009, and preceding group (n = 18), treated prior to the introduction of naso-esophageal extraluminal drainage. Significantly more patients in the preceding group suffered respiratory failure (28% vs. 61%, p = 0.024), and higher reoperation rate (0% vs. 17%, p = 0.042) and hospital mortality (0% vs. 22%, p = 0.013). In the current group, 31 (97%) patients experienced complete cure during hospitalization. Naso-esophageal extraluminal drainage and concomitant enteral nutritional support are less invasive, and effective and powerful methods to treat even major leakage after esophagectomy. These methods may be an alternative management to improve mortality for patients with esophageal cancer.

[A Case of Rectal Metastasis from Breast Cancer Diagnosed Two Years after Surgery].

We report a case of rectal metastasis from breast cancer.Colorectal metastasis from breast cancer is sometimes difficult to diagnose before surgery.A transanal needle biopsy was thought to be useful for a diagnosis and selection of treatment method.

A Randomized Clinical Trial of Preoperative Administration of Branched-Chain Amino Acids to Prevent Postoperative Ascites in Patients with Liver Resection for Hepatocellular Carcinoma.

BACKGROUND: Massive postoperative ascites remains a major threat that can lead to liver failure and other fatal complications, especially in patients with poor liver function. Branched-chain amino acid (BCAA) administration increases biosynthesis and secretion of albumin by hepatocytes and increases oncotic pressure by elevating blood albumin concentration, thereby decreasing peripheral edema, ascites, and pleural effusion. METHOD: We randomly allocated consecutive patients undergoing major liver resection for hepatocellular carcinoma to either a group where oral BCAA administration was initiated 3 weeks before liver resection, or a non-BCAA group. The primary study endpoint was development of postoperative ascites. RESULTS: Overall, 39 patients were allocated to the BCAA group, while 38 were assigned to the non-BCAA group. No significant difference in the rate of refractory ascites, considered alone, was evident between the BCAA (5.1 %) and non-BCAA groups (13.2 %; p = 0.263). However, the occurrence of refractory ascites and/or pleural effusion was significantly less frequent in the BCAA group (5.1 %) than in the non-BCAA group (21.1 %; p = 0.047). Furthermore, the postoperative serum concentration of reduced-state albumin was greater immediately after liver resection in the BCAA group than in the non-BCAA group. CONCLUSION: Preoperative administration of BCAA did not significantly improve prevention of refractory ascites, but significant effectiveness in preventing ascites, pleural effusion, or both, as well as improving metabolism of albumin, was demonstrated [University Hospital Medical Information Network (UMIN) reference number 000004244].