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Colorectal neuroendocrine carcinoma（NEC）is extremely rare and has a dismal prognosis. However, no standardized treatment strategy has been established for this lesion. For patients with NEC and distant metastasis, disease stabilization is difficult even after treatment with multidisciplinary strategies including chemotherapy. Here we describe a case of rectal NEC that presented as multiple liver metastases; a favorable prognosis was obtained after treatment with a multidisciplinary strategy that included surgery, irradiation, and chemotherapy. A 66-year-old male presented with diarrhea and constipation. Colonoscopy and a computed tomography（CT）scan revealed a rectal mass involving all of the luminal circumference, after which a diagnosis of NEC was confirmed by pathological examination. A CT scan also revealed several liver metastases in S5, S6, and S8. Abdominoperineal resection with total mesenteric excision and lymphadenectomy, including the lateral area, was performed. After resection, we administered radiation for local disease control in the lateral area. We also administered chemotherapy consisting of cisplatin and irinotecan for the liver metastases because only the endocrine cell component constituted this tumor. After chemotherapy, a CT scan was performed to confirm that the liver metastasis in S5 and S6 had disappeared, and it was shown that the other lesion in S8 had shrunk substantially（it eventually disappeared）. Then, 48 months after resection, all metastatic liver tumors were under good control, and no other recurrent lesion was recognized. In conclusion, a multidisciplinary strategy including optimal chemotherapy seems to be important to achieve a favorable prognosis of NEC of the colorectum with distant metastasis.

The fast-track surgery protocol, including perioperative immunonutritional management, is increasingly gaining attention for the prevention of surgical site infections （SSIs）. To analyze the association between the fast-track surgery protocol employed at a single center and outcomes, including SSIs and the length of hospital stays. This retrospective analysis included 217 patients who underwent hepatectomy at the study department between January 2009 and February 2014. Patients were divided into two groups: those managed by a conventional protocol （group C, n＝75） and those managed by the fast-track surgery protocol （group F, n＝142）. There were no significant differences in patient characteristics or factors between the two groups. However, serum albumin and total cholesterol levels before surgery were significantly higher in group F than in group C, and pre-hepatectomy C-reactive protein （CRP） levels were lower in group F than in group C. Moreover, serum albumin and CRP levels at postoperative day 7 were better in group F than in group C. The operations were longer in group F than in group C （312 vs. 286 min） and blood loss volume was less （385 g in group F vs. 428 g in group C）. SSI rates were significantly lower in group F （4.2％, n＝6） than in group C （13.3％, n＝10）, and the length of hospital stay was significantly shorter in group F （16.7 days） than in group C （25.8 days）. The fast-track surgery protocol as a perioperative management strategy may improve preoperative nutritional status and postoperative inflammation, with subsequent reductions in SSI rates and the length of hospital stay in patients undergoing hepatectomy.

Here we review the prognosis of patients with unsuspected gallbladder carcinoma（GBC）, detected after laparoscopic cholecystectomy（LC）in a single institute. We reviewed the medical records of patients diagnosed with gallbladder stones on admission, who underwent LC. Carcinoma involving the gallbladder was found in 22 of 2,770 patients（0.9％）via postoperative pathological examination. This GBC group spanned 58-87 years of age（mean, 75 years; 13 females and 9 males）. The preoperative diagnosis was gallbladder stones with acute/chronic cholecystitis or adenomyomatosis of the gallbladder in all patients. We performed an additional surgery in 6 of 15 patients with pT2 and T3 disease; of these, 3 patients with pT2 disease and 1 with pT3 experienced bile spillage during the LC. The mean survival of patients with unexpected GBC was 21 months, with bile spillage occurring as a complication of LC identified as a potential risk factor for shorter survival（15.3 vs. 32.5 months）. We identified patients with pT2 and pT3 disease after LC, and two patients with pT2 and 1 with pT3 who had bile spillage during LC died of peritoneal dissemination within 28 months, despite additional surgery. Occasional seeding caused by bile spillage during LC should be carefully avoided to minimize the risk of developing unsuspected GBC after LC.

The most common site of distant metastasis from colorectal cancer is the liver, and hepatectomy presents the best curative treatment for recurrence of colorectal liver metastasis （CRLM）. This study aimed to identify factors of prognostic value for repeat hepatectomy for CRLM and to determine whether a third such procedure could similarly produce favourable outcomes for CRLM. We analyzed data for 161 patients in our department with colorectal metastasis. Of these, 22 patients underwent repeat hepatectomy for recurrent metastasis, with 16 undergoing a second hepatectomy and 6 a third hepatectomy. We analyzed patient characteristics, tumor status, operation-related variables, and short- and long-term outcomes. Univariate analysis for repeat hepatectomy identified the following five prognostic risk factors: T factor （＞SE） of the primary cancer, number of tumors involved in the initial hepatectomy （＞5）, interval from first to second hepatectomy （＜1year）, number of tumors involved in second hepatectomy （＞3）, and post-operation time （＞30days）. By multivariate analysis, T factor （＞SE） of the primary cancer, number of tumors in the initial hepatectomy （＞5）, and number of tumors in the second hepatectomy （＞3） were independently associated with a worse survival after surgery for CRLM. Although surgical outcomes of the third hepatectomy were not compared with those of the first and second hepatectomy, there were no obvious differences, nor did the 1-, 3-, and 5-year survival rates differ significantly among the three groups. Repeat hepatectomy for CRLM could improve long-term survival. In addition, patients undergoing a third hepatectomy showed a similar survival benefit to those having one or two resections.

Various methods, devices, and techniques have been developed to improve safety during laparoscopic hepatectomy procedures. Among these, the Pringle maneuver （PM） is widely used to minimize blood loss during liver transections; however, the risk of ischemic injury associated with this technique is increased by poor hepatic reserve and regeneration dysfunction secondary to liver cirrhosis. This retrospective study evaluated the short-term outcomes and feasibility of precoagulation for endoscopic hepatectomy without PM in patients with liver cirrhosis. Eleven patients with liver cirrhosis who also underwent endoscopic hepatectomy for hepatocellular carcinoma were recruited to undergo either microwave tissue coagulation or radiofrequency ablation for precoagulation before liver transection. A wedge resection without the PM was performed in all patients, with seven patients selected for bipolar radiofrequency ablation and four patients for microwave coagulation therapy. The procedures included video-assisted thoracoscopic hepatectomy in two patients and laparoscopic hepatectomy in nine patients. One patient who underwent radiofrequency ablation developed postoperative bleeding （Clavien-Dindo grade Ⅲ）. In conclusion, precoagulation can help to minimize intraoperative blood loss without the PM, contributing to effective resection of liver tumors. We propose that precoagulation could serve as a standard technique for endoscopic hepatectomy in patients with cirrhosis.

In Japan, amebiasis is typically found in men who have sex with men and in individuals with recent travel to endemic areas. We experienced a patient with fulminant necrotizing amebic colitis and enterocolitis who presented with a severe disorder of the liver and renal function. The patient was a 71-year-old man who had lived in Yokohama City, Japan for 30 years. His stool sample showed no amebic dysentery protozoa and cultured negatively for human immunodeficiency virus. Despite being treated with meropenem, pyrexia of 39-40°C continued for 4 days. On hospital day 8, a colonic abscess and perforation of the transverse colon were detected by computed tomography（CT）. His fever did not improve, suggesting progression of infectious disease. Subsequent emergency laparotomy revealed a perforation in the middle of the transverse colon. Peritoneal lavage and right hemicolectomy were performed; however, a CT scan on hospital day 16 （postoperative day 8） showed re-perforation of the colon and an abscess around the site of anastomosis, prompting emergency intestinal and left hemicolectomy resection. Amebae observed pathologically during the second emergency operation led to a diagnosis of amebic colitis. Endotoxin adsorption therapy was performed, and metronidazole was administered. Despite prompt diagnosis and treatments, the patient’s general conditions became fulminant, and multiple organ failure developed. On hospital day 18 （postoperative day 10）, his C-reactive protein level was 20mg/dl. He was clinically diagnosed as having sepsis and multiple organ failure. The patient died on hospital day 23. Acute colitis is commonly encountered in daily practice, but it is difficult to differentiate between amebic and non-amebic colitis preoperatively and thus, the possibility of amebic colitis should be considered in such clinical presentations.

Herein we report on an extremely rare case of ulcerative colitis （UC） with onset after chemotherapy and colorectal resection, and discuss three previously reported cases. A 61-year-old man presented with fecal occult blood and no subjective symptoms. The diagnosis was rectal cancer with multiple liver metastases. Following chemotherapy, the patient underwent laparoscopy-assisted super-low anterior resection, liver resection. On Day 35 following closure of the ileostomy, the patient was referred to Totsuka Kyoritsu Dai-1 Hospital because of diarrhea, bloody stools. Colonoscopy and pathological examination revealed UC. To the best of our knowledge, only three cases of UC following colorectal cancer resection have been described previously. In conclusion, when encountering intractable diarrhea after chemotherapy or surgery, UC should be one of the bowel diseases considered, with prompt systemic examination recommended.

Controlling Nutritional Status (CONUT) is an efficient tool for early detection of malnutrition, measured using two biochemical parameters (serum albumin and total cholesterol) and one immune indicator (total lymphocyte count). The aim of this study was to define the efficacy of CONUT for predicting postoperative complications in very elderly patients with colorectal cancer. This study enrolled 52 patients aged 85 years or older with colorectal cancer for whom we were able to measure CONUT before surgery, conducted at the Department of Gastroenterological and General Surgery of Showa University Hospital in Japan between January 2010 and December 2014. The patients were subdivided into those with complications (Group C, n=9) and those with no complications (Group NC, n=43), and then were retrospectively compared for clinical characteristics, CONUT, and surgical outcomes. Multivariate analysis was finally performed to identify the risk factors of complications. The percentage of patients with a CONUT score of 5 or more in Group C was significantly greater than that in Group NC (7 vs. 12 patients, 77.8% vs. 27.9%, P=0.0079). No other significant difference was observed in the clinical characteristics between Group C and Group NC. Multivariate analysis identified CONUT score as the only significant predictor of complications in this patient cohort (odds ratio=1.374; 95% confidence interval, 1.019-1.949; P=0.0366). Our study suggests that CONUT score is predictive of postoperative complications in very elderly patients with colorectal cancer.

Glutathione S-transferase (GST) is a major phase II drug-metabolizing enzyme. Several isoforms of human GST as well as different GST genetic polymorphisms are known, but limited data exists concerning the relationship between GST polymorphisms and GST activity using 1-chloro-2,4-dinitrobenzene in human liver. To resolve this query, we analyzed the genetic polymorphisms of four main GST isoforms [GST mu 1 (GSTM1), GST theta 1 (GSTT1), GST alpha 1 (GSTA1), GST pi 1 (GSTP1)] and measured hepatic GST activity isolated from the same patients. We found that GSTM1 null individuals have significantly lower (P=0.0082) GST activity compared with GSTM1 positive individuals. No significant changes in GST activity were observed in individuals with GSTT1, GSTA1, and GSTP1 genotypes. Interestingly, the levels of GST activity exhibited were similar when compared with GSTA1*A/*A and GSTA1*A/*B, and GSTP1*A/*A and GSTP1*A/*B, respectively, if the genotype was GSTM1 null. Therefore, the genotypes of GSTA1*A/*B and GSTP1*A/*B individuals do not significantly affect the level of hepatic GST activity. An examination of the correlation between GST mRNA expression and GST activity subsequently revealed a significant correlation between GSTM1 mRNA levels and GST activity (r=0.626, P=0.007). These data are expected to facilitate research on the prediction of efficacy and safety of GSTM1 null-mediated drug metabolism and may establish whether genetic polymorphisms of the GST gene, specifically GSTM1, can act as a biomarker.

Compared with the conventional open surgery, thoracoscopic esophagectomy results in decreased thorax destruction, fewer postoperative complications, and shorter hospitalisation. However, preoperative fasting causes hyperglycemia, prompting attempts to improve postoperative hyperglycemia by preoperatively administering carbohydrate orally or intravenously. Herein, we examined the effect of preoperative carbohydrate and amino acid infusion on counter-regulatory hormone levels in patients undergoing elective thoracoscopic esophagectomy. The glucose and amino acid (GA) group (n=12) were infused with a low concentration of sugar accelerant and amino acid, and the control (GAF) group (n=12) was infused with a sugar-free extracellular fluid, until entering the operating room. We evaluated plasma catecholamine 3 fractions, cortisol, and glucose, as well as 3-methylhistidine in the urine. Adrenaline levels were significantly higher in the GAF group (263.0±201.8µIU/ml) than in the GA group (114.7±127.0µIU/ml) at the end of the surgery (P=0.042), and at postoperative day (POD) 1 (200.8±137.4 vs. 80.5±64.3µIU/ml; P=0.013). The noradrenalin level was also significantly higher in the GAF group (517.9±523.6µIU/ml) than in the GA group (254.3±205.4µIU/ml) at POD1 (P=0.028), as was the cortisol level (20.0±10.6µIU/ml vs. 10.2±8.0µIU/ml; P=0.015). No significant differences were observed between the two groups in levels of blood glucose or 3-methylhistidine in the urine. Preoperative glucose-amino acid administration improved catabolism suppression in this study.

Esophagectomy for esophageal cancer is one of the most invasive gastrointestinal surgeries. In 1996, we introduced video-assisted thoracic surgery for esophageal cancer (VATS-E) to reduce surgical stress. In 2010, we started employing artificial pneumothorax (AP) using carbon dioxide gas in VATS-E to further reduce surgical stress. In this study, we evaluated interleukin-6 (IL-6) levels in pleural cavity lavage fluid (PLF) of patients undergoing VATS-E with or without AP, and examined the effect of AP on VATS-E-induced stress. This non-randomized study included patients who underwent VATS-E with or without AP at Showa University Hospital between 2009 and 2013 and from whom PLF could be collected. IL-6 concentrations in PLF were examined before and after the thoracic part of the operation. We compared IL-6 variation, defined as the difference between IL-6 concentrations in PLF before and after the thoracic part of the operation, between patients for whom AP was used and those for whom it was not used. A total of 52 patients were included in the study; 26 underwent VATS-E with AP (group AP), and 26 underwent VATS-E without AP (group NP). IL-6 concentrations in PLF were significantly elevated immediately after the thoracic part of the operation in both groups. IL-6 variation in PLF correlated with both thoracic operative time and blood loss, which were considered practical parameters of surgical stress, and was significantly lower in group AP than in group NP. In conclusion, IL-6 variation in PLF is a useful and sensitive maker of surgical stress during VATS-E. VATS-E with AP is less invasive than VATS-E without AP because AP lowers the perioperative systemic inflammatory response to thoracic surgery.

Maintaining a long transnasal ileus tube for a long period can be quite painful for patients such as in those with refractory intestinal obstruction and peritonitis carcinomatosa and it can markedly decrease quality of life (QOL) due to unexpected respiratory complications associated with the tube placement. To mitigate such complications, we undertook a trial insertion of a long ileus tube by gastrostomy in five patients with refractory intestinal obstruction (four cases of peritonitis carcinomatosa and one case of chronic intestinal pseudo-obstruction). We inserted the transgastric ileus tube using a percutaneous gastrostomy catheter kit after puncture with a plastic skin (PS) needle covered with a protective sheath, and then endoscopically placed the tube beyond the ligament of Treitz. Subsequently, we removed the long transnasal ileus tube, and comparable decompression was achieved. In all cases, the entire procedure was easily performed with no complications. Moreover, patients experienced reduced pain and stress and they were able to regain some freedom during activity.

To evaluate prognostic factors for recurrence after tegafur-uracil plus leucovorin (UFT/LV) adjuvant chemotherapy in patients with colorectal cancer (CRC). Consecutive patients with CRC who received UFT/LV as adjuvant chemotherapy at Showa University Hospital between June 2005 and December 2008 were included in the study, 5-year disease-free survival (DFS) and overall survival (OS) rates were estimated, and prognostic factors for recurrence were analyzed using the Cox proportional hazards model for multivariate analysis. Of 92 patients included in the study, 17 (18.5%) had disease recurrence. The 5-year DFS and OS rates were 82.2% and 91.9%, respectively. In the multivariate analysis, preoperative CA19-9 level＞37U/ml, emergency operation, and T4 lesions were independent significant prognostic factors after treatment with UFT/LV adjuvant chemotherapy. The three independent prognostic factors —T4 lesions, emergency operation, and high preoperative CA19-9 levels— may be useful for decision-making regarding whether patients should receive 5-fluouracil-based or L-oxaliplatin-based adjuvant chemotherapy. As this was a single-institution study with a small number of patients, our findings need to be confirmed in larger multicenter studies.

The use of ultrasonically activated devices (USADs) in hepatic resections may be associated with an increased rate of complications, such as postoperative bile leaks. Nonetheless, the safety of USADs for sealing bile ducts during liver surgery has not yet been established. The purpose of this study was to assess the efficacy of a USAD for sealing bile ducts. In animal experiments, the common bile duct of ten anesthetized dogs was individually occluded using a USAD. Additionally, using the prospective liver surgery database from a single institution, we identified 45 consecutive patients who underwent hepatic resection using a USAD (USAD group) and 45 similar patients who underwent hepatic resection without the use of a USAD (NUSAD group). In the occluded and harvested canine bile ducts, the mean burst pressure was 280mmHg, and the lumen of the bile duct was completely sealed morphologically. In the clinical study, there was no significant difference in postoperative mortality or complications between the two groups, and biliary leakage was observed in only one patient (0.7%) in the USAD group. These data demonstrate that the USAD is a safe, efficient, and practical instrument for use during liver surgery to achieve complete hemobiliary stasis.

There is an increasing number of patients with severe liver disease that requires whole organ transplantation or living-related split liver transplantation. This has resulted in a shortage of donor organs, which is particularly problematic and still awaits resolution. Bioartificial liver (BAL) support systems have been developed with the aim of supporting patients with life-threatening liver disease until their liver recovers. Here, we describe a high performance three-dimensional rat hepatocyte culture system using a radial-flow bioreactor (RFB) with a polyvinyl alcohol (PVA) membrane as a small-scale BAL support system. Hepatocytes from male Sprague-Dawley rat livers were isolated and divided into two groups as follows. Group A: isolated hepatocytes were maintained in culture medium as controls; and group B: isolated hepatocytes were injected into the medium chamber of the RFB-PVA culture system. Sampling was carried out every 48 h to analyze the concentrations of ammonia and albumin in the medium. Light and electron microscopic examination of hepatocytes explanted from the PVA membrane was also performed. Albumin production and urea synthesis by cells in group B were both significantly higher than in group A. Hematoxylin-Eosin staining of the cells in group B showed that three-dimensional cell masses were attached to the PVA membrane. It also showed that the cells were stably proliferating in the porous spaces of the PVA. Scanning electron microscopic images of group B also showed clusters of hepatocytes attached to the PVA membrane. Hepatocyte clusters growing in the RFB-PVA culture system retained their biological function and were stable in the porous spaces of the PVA membrane. This cell culture system may be useful for the development of new BAL support systems.

An aneurysm of the abdominal internal organs is relatively rare. Recently, segmental arterial mediolysis (SAM) and median arcuate ligament syndrome (MALS) were identified as specific causes for aneurysms of the pancreaticoduodenal artery arcade. Herein, we report a ruptured anterior superior pancreaticoduodenal artery (ASPDA) aneurysm due to SAM that was misdiagnosed as acute pancreatitis. The patient was a 59-year-old male with acute, severe, and sharp pain in the upper abdomen. He was clinically diagnosed with acute pancreatitis based on abdominal computed tomography (CT). However, a follow-up CT scan revealed an aneurysm of the ASPDA. We therefore diagnosed this case as retroperitoneal hemorrhage due to aneurysm rupture, and we performed an angiogram and transcatheter arterial embolization to prevent aneurysm re-rupture. Based on a subsequent review of all the findings for this patient, we retrospectively determined the cause of the ASPDA aneurysm to be SAM. Such case reports are rare, and further accumulation of similar cases is necessary in the near future to establish proper diagnostic criteria and appropriate treatment protocols.

Transthoracic subtotal esophagectomy for esophageal cancer is a highly invasive procedure, associated with high mortality and morbidity rates. We examined the use of video-assisted thoracoscopic and laparoscopic surgery for esophagectomy (VATS-E). Further, incentive spirometry (IS) is commonly used in perioperative rehabilitation for esophagectomy. We investigated whether pulmonary complications after VATS-E are related to changes in the perioperative IS volumes and whether such changes could be predictive of these complications. This study included 63 patients who underwent VATS-E from June 2008 to December 2009. IS volumes before and after surgery were recorded for all patients. The perioperative IS volumes and clinicopathological factors were correlated with the incidence of postoperative pneumonia and atelectasis. Nine patients (14.5%) had postoperative pneumonia, and thirteen (22.2%) had atelectasis. Univariate analysis showed an increased risk of atelectasis in patients with diabetes and an increased risk of pneumonia in patients with a long operating time and for whom the lung was adhered to the thoracic wall. The vital capacity (VC) correlation coefficient was 0.674. Further, the risk of pneumonia was high in patients with 13% less than the minimum IS volume/preoperative VC ratio and 22% with less than the average IS volume/preoperative VC ratio. Multivariate regression models for pneumonia showed the same results regarding the IS volume/VC ratio. The results indicated that IS volumes could be used to predict the incidence of complications after VATS-E, and thereby facilitate early application of interventions to prevent pulmonary complications.

This study compared results from Gd-EOB-DTPA on two different phases of 3T MRI with those from Tc-99m-GSA hepatic scintigraphy and hepatic function tests. Twenty-four patients with liver tumor were included in this study. All patients underwent Gd-EOB-DTPA-enhanced-MRI and Tc-99m-GSA hepatic scintigraphy. Clearance index (HH15) and receptor index (LHL15) were calculated for the Tc-99m-GSA, while signal intensities (SI) of liver at pre-injection and at 4/20min post-injection, and of spleen at 4 min/20min were measured (SIpre, SI4min, SI20min, SIsp4min, SIsp20min, respectively) for the Gd-EOB-DTPA-MRI. Liver activity at 15min by Tc-99m-GSA scintigraphy or biochemical liver function values were compared with liver spleen contrast at 4min (LSC4min = SI4min/SIsp4min) or 20min post-injection (LSC20min = SI4min/SIsp20min), and the increase in ratio at 4min (IR4min=SI4min/SIsp4min) or 20min (IR20min= SI20min/SIpre). Total bilirubin levels (T-bil), serum albumin levels (Alb), prothrombin activity, and the indocyanine green clearance test (ICG) results were also analyzed. There were statistically significant correlations in all comparisons between Gd-EOB-DTPA and Tc-99m-GSA. The highest coefficient of correlation was obtained in IR4min (LHL15: r = 0.795, P