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Background We previously reported the good feasibility and favorable efficacy of perioperative capecitabine plus oxaliplatin (CapeOx) in patients (pts) with clinical T3(SS)/T4a(SE) N1-3 M0 gastric cancer (GC) in a phase II study in which the pathological response rate, the primary endpoint, of 54.1% was demonstrated. Here, we report 3-year follow-up data. Methods The eligibility criteria included clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of Gastric Carcinoma-3rd English Edition (JCGC). Three cycles of neoadjuvant CapeOx (capecitabine, 2000mg/m2 for 14 days; oxaliplatin, 130mg/m2 on day 1, every 3 weeks) were administered, followed by 5 cycles of adjuvant CapeOx after D2 gastrectomy. Three-year overall survival and relapse-free survival are presented here, and analyzed by cohorts based on pathologic response rate (pRR). Results Thirty-seven pts were enrolled from July 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of neoadjuvant CapeOx and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29). The overall survival (OS) rate and relapse-free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Further, the 3-year OS rate in pts with pathological response of grade 1a (n = 13) and grade 1b or higher (n = 20) was 69.2% (95% CI: 48.2-99.5%) and 100.0%, respectively, based on JCGC. Pathological response rate was classified according to JCGC as follows: grade 0, the tumor was not affected; grade 1a, less than one-third of the tumor was affected; grade 1b, one to two thirds of the tumor was affected; grade 2, greater than or equal to two thirds was affected; and grade 3, no residual tumor. A pathological response was defined as grade 1b or greater. Conclusion Perioperative CapeOx showed good feasibility and favorable prognosis, especially in pts with pathological response of grade 1b or higher and was found to be useful in predicting prognosis. The data obtained using this novel approach warrant further investigation (Trial ID: UMIN000021641, jRCTs051180109).

Many surgeons in Japan use 1-day nasogastric tube (NGT) decompression after gastrectomy as a standard procedure. This prospective randomized study aimed to define whether 1-day NGT decompression is necessary after distal gastrectomy. The subjects were 233 patients with gastric cancer, randomized into two groups immediately after distal gastrectomy: one group received 1-day NGT decompression (NGT group, n = 119) and the other did not (no-NGT group, n = 114). The primary outcome measure was postoperative surgery-related and respiratory complications, whereas secondary measures were the postoperative course to recovery and patient complaints. The incidence of surgery-related complications did not differ significantly between the NGT and no-NGT groups (21.0 and 19.2%, respectively; p = 0.87). The rate of respiratory complications was 6.7% in the NGT group and 7.0% in the no-NGT group (p > 0.99). The time to passage of first flatus and the postoperative hospital stay did not differ between the groups. Twenty-five patients in the NGT group and none in the no-NGT group complained of nasopharyngeal discomfort (p

We report a case of advanced sigmoid colon cancer that was resected after chemoradiation therapy(CRT)following ineffective chemotherapy. A 59-year-old woman harbored a lower abdominal tumor the size of an infant's head and was diagnosed with a huge sigmoid colon cancer with invasion to the urinary bladder and metastases to the para-aortic lymph nodes. The patient received 2 courses of modified FOLFOX6(mFOLFOX6)plus cetuximab therapy, which was assessed as ineffective; She then received CRTwith 50.4 Gy in 28 fractions plus concurrent oral S-1(100mg/day for 28 days). Tumor shrinkage in the primary lesion was achieved after CRT; total pelvic exenteration with the removal of metastatic para-aortic lymph nodes was then performed 5 months after the first diagnosis. This case of locally distant advanced colon cancer in the pelvic cavity coexisting with resectable metastatic lesions suggested that CRTmight contribute to successful local treatment after the failure of preoperative chemotherapy.

An 81-year-old woman underwent preoperative chemoradiotherapy(CRT)for advanced lower rectal cancer with vaginal invasion. However, she refused surgery and received additional radiotherapy. We detected a rectal-vaginal leak, so we performed ileostomy with double orifices and chemotherapy. As the tumor and vaginal leak increased, we performed laparoscopy- assisted abdominoperineal resection and vaginal posterior wall resection after 16 months of CRT. Although adhesion occurred due to inflammation and tumor invasion after the CRT, surgery could be performed safely. Despite the advanced age of the patient, complications did not occur, and no recurrence was observed for 66 month after the surgery. In rectal cancer, operation is usually performed until 6 to 8 weeks after CRT, but in our case, the surgery was performed after a long interval, with good results. Thus, we report the case herein.

A 63-year-old man was followed-up for diabetes mellitus. During follow-up, computed tomography(CT)showed dilatation of the main pancreatic duct in the tail of the pancreas. Abdominal enhanced CT revealed a 25 mm tumor in the body of the pancreas. Endoscopic ultrasound-fine needle aspiration(EUS-FNA)was performed, and the pathological diagnosis was adenocarcinoma. Therefore, based on the diagnosis of pancreatic body carcinoma, distal pancreatectomy with splenectomy was performed. The postoperative course was uneventful. Histological and immunohistochemical examination revealed that the tumor consisted of a ductal carcinoma and a neuroendocrine component. Therefore, combined pancreatic tumor (fT3N1M0, StageⅡB)was diagnosed. The patient subsequently received postoperative adjuvant chemotherapy(S-1 100mg/ day), and survived without recurrence 6 months after the operation. We report this case of combined pancreatic tumors with a review of the literature.

203 Background: D2 gastrectomy followed by adjuvant S-1 is one of the standard therapy for the patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with clinical SS/SE N1-3 M0 GC. Methods: The eligibility criteria included histopathologically confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of GC (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to JCGC ( ≥Grade 1b). Results: Thirty-seven pts were enrolled from April 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of NAC and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4–68.2) were demonstrated. The relative dose intensity (RDI) of capecitabine and oxaliplatin were 90.5% and 91.9%, respectively. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment, and the RDI of capecitabine and oxaliplatin were 80.9% and 65.1%, respectively. Grade 3–4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%), but no treatment-related death was reported. The overall survival (OS) rate and relapse free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Subgroup analyses according to residual tumor after surgery (R status) showed a 3-year OS and RFS rate of 86.2% (95% CI, 74.5-99.7%) and 75.7% (95% CI, 63.0-90.8%) for R0. Conclusions: Perioperative CapeOx showed good feasibility and favorable prognosis with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations. Clinical trial information: 000021641.

A 70-year-old man was referred because of suspected gallbladder cancer and gallstones. Contrast-enhanced CT, EOB-MRI and PET-CT could not completely rule out gallbladder cancer. The patient preferred follow-up without surgery. At 4 months after initial examination, the gallbladder wall thickening showed improvement, but appeared worse at 9 months after initial examination. Therefore, we decided to perform surgery. Since malignant findings were not observed on rapid intraoperative pathology, we performed a cholecystectomy and right hemicolectomy because of inflammation in the transverse colon. Pathological examination diagnosed xanthogranulomatous cholecystitis. The imaging appearance of xanthogranulomatous cholecystitis varies, and also changes over time, making it difficult to distinguish from advanced gallbladder cancer. We experienced a case of xanthogranulomatous cholecystitis that changed over time, and report this case with a review of the literature.

A 60-year-old man was admitted for a liver mass(S3), which rapidly increased in size during intraductal papillary mucinous neoplasm(IPMN)follow-up. Although EOB-MRIwas performed, the mass could not be accurately diagnosed as hepatic cancer. Thus, we performed a lateral segmentectomy. In the resected specimen, a solid tumor mass was clearly bound in segment 3 of the liver. Since histopathology revealed no malignant cells and many IgG4-positive cells, we confirmed the diagnosis as IgG4-related inflammatory pseudotumor of the liver. IgG4-related diseases occur in various organs in the body, and they are known to associate with autoimmune pancreatitis and sclerosing cholangitis, but an IgG4-related inflammatory pseudotumor of the liver is a rare disease. It is often difficult to distinguish from hepatic cancer and surgical resection is performed.

We report a case of advanced sigmoid colon cancer resected via laparoscopic surgery after preoperative chemotherapy. A- 55-year-old man visited our hospital with diarrhea. CTrevealed a giant tumor in the sigmoid colon, and surrounding lymph node enlargement was also noted. The tumor appeared to be locally advanced; thus, preoperative chemotherapy was started. Due to the possibility of obstruction, we constructed an ileostomy laparoscopically. The tumor was found to be RAS wild, and 4 courses of mFOLFOX6 plus panitumumab were given. Follow-up CTshowed remarkable tumor reduction allowing laparoscopic resection; as such, laparoscopic sigmoidectomy was performed successfully. Chemotherapy with molecular-targeted drugs is a promising method to make laparoscopic surgery possible for advanced colorectal cancer.

To elucidate ideal strategy of treatment for advanced lower rectal cancer, we investigated 11 patients with clinically suspected lateral pelvic node(LPN)metastasis among 36 patients who received neoadjuvant chemoradiation therapy(NCRT). Nodal metastasis was diagnosed as positive when the major axis of a lymph node was over 7mm in computed tomography(CT). Both tumor and nodal downstaging were observed in CT after NCRT; pathological complete response and ypN0 was obtained in 2(18.2%)and 6(54.5%)cases, respectively, and positive LPN was observed only in 2 cases. All of 4 cases who were diagnosed as ycN0 in CT after chemoradiation were confirmed as ypN0. Extended examination with 36 patients who underwent NCRT showed that 85% of 21 ycN0-cases were confirmed to be ypN0. As a conclusion, NCRT for lower rectal cancer with suspected LPN metastasis was highly effective, and omitting lateral node dissection when all nodes turned to be less than 7mm on CT, can be a hopeful option.

The patient was a 79-year-old woman, who had undergone pancreaticoduodenectomy(PD)for lower bile duct carcinoma in our hospital(pT3N0H0P0M0, fStage III ). Four years 6 months after the initial operation, abdominal CT revealed left bile duct expansion and hilar bile duct thickening. Therefore, based on the diagnosis of perihilar cholangiocarcinoma originating from the left hilar duct, we performed left lobectomy with caudate lobectomy and biliary tract reconstruction. The surgical specimen showed a tumor in the left hilar bile duct. Histopathological diagnosis of the tumor was a moderately differentiated adenocarcinoma(pT2aN0H0P0M0, fStage II ). Surgical margins were histologically negative. Since the tumor was located away from the anastomosed site of the cholangiojejunostomy, we determined that the tumor was not a recurrence but a metachronous cholangiocarcinoma. The postoperative course was uneventful. The patient survived without recurrence 2 years after the second operation. The possibility of heterochronic biliary carcinomas should be considered during follow-up evaluation. We report this case of metachronous cholangiocarcinoma that occurred 4 years 6 months after PD, with a review of the literature.

A therapeutic guideline for sigmoid volvulus (SV) has not been established, and the most recommended surgical procedure for SV has not been determined. Our objective is to assess the usability of elective laparoscopic sigmoidectomy and the feasibility of single-incision laparoscopic surgery for SV following endoscopic reduction. SV typically affects the elderly and accounts for 1% to 7% of intestinal obstructions in Western countries. We report on 3 patients with SV who underwent elective laparoscopic sigmoidectomy following endoscopic reduction, and we first describe single-port surgery for SV. We discuss the 3 patients (a 79-year-old male, an 88-year-old female, and a 67-year-old female) with SV who underwent elective laparoscopic sigmoidectomy following endoscopic reduction. All 3 patients underwent laparoscopic sigmoidectomy, and 2 patients underwent single-port laparoscopic surgery without complications. Recurrence of volvulus was not seen during the course of 12 to 24 months. In experienced hands, elective laparoscopic sigmoidectomy after colonoscopic detorsion is a valuable alternative, and single-port surgery is also feasible.

Lessons Learned Perioperative capecitabine and oxaliplatin (CapeOx) therapy showed favorable efficacy with sufficient pathological response. Small sample size limited the statistical power of this result. Perioperative CapeOx therapy showed good feasibility. Further studies with larger sample size are required to validate this novel approach. Background D2 gastrectomy followed by adjuvant S-1 is the standard therapy for patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with GC. Methods The eligibility criteria included confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification (JCGC; 3rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m2 for 14 days; oxaliplatin, 130 mg/m2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx (AC) after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to the JCGC (≥grade 1b). Results Thirty-seven pts were enrolled on CapeOx. An R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4–68.2) were demonstrated. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment. Grade 3–4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%). Conclusion Perioperative CapeOx showed good feasibility and favorable efficacy with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations.

Some patients with unresectable colorectal cancer can be treated by chemotherapy leaving the primary tumor unresected, but indications and implications of a later resection of the primary tumor (RPT) are often controversial. We investigated 5 patients whose primary tumors were resected during chemotherapy, either panitumumab or bevacizumab. The median age of these patients was 63 years and all were men. The unresectable disease was liver metastases in 4 patients and a primary tumor in 2 patients. A diverting stoma was constructed before initiation of chemotherapy in 2 patients. The median interval until RPT was 8.3 months and the reasons for resection were the appearance of obstructive symptoms in 3 patients and a desire for stoma closure in 2 patients. The size of the primary tumor had decreased until RPT in all patients. RPT was performed successfully in all patients, but 2 of the 3 operations that were initiated laparoscopically had to be converted to open surgery. Intensive chemotherapy was resumed in all patients and median survival after RPT was 19 months, including a patient whose liver metastasis was also resected later. RPT can relieve obstructive symptoms and close stomas. Because intensive chemotherapy is still possible and a lengthy survival can be expected after RPT, it should be considered not merely as a palliative option but also as a treatment strategy.

We report a case of a 62-year-old woman with a growing liver tumor that was difficult to differentiate from hepatocellular carcinoma (HCC). Abdominal CT revealed a hypervascular tumor (36 mm in diameter) in segment 3 of the liver that showed early enhancement and which had grown from 30 mm to 36 mm over the previous year. A fatty liver and gallstones were also detected. Magnetic resonance imaging (MRI) showed high intensity staining of the tumor on both T1- and T2-weighted images, and EOB-MRI revealed a mass that showed high signal intensity in the hepatobiliary phase. The imaging findings were not typical for HCC; however, the possibility of malignancy could not be ruled out due to the enlargement of the mass. Therefore, in February 2015, we performed a laparoscopic left lateral segmentectomy with cholecystectomy. After a good postoperative course, the patient was discharged from the hospital 11 days after surgery. Histological assessment revealed the tumor was focal nodular hyperplasia (FNH).

Barrett潰瘍は，食道腺癌の前癌病変として知られるBarrett食道の24％にみられるとされている．今回われわれは逆流性食道炎経過中に完全閉塞をきたし切除したBarrett潰瘍の1例を経験したので報告する．症例は82歳，女性．主訴は食思不振と嘔吐．平成20年10月頃より嘔吐を繰り返すため11月当院を受診した．上部消化管造影で下部食道に閉塞性病変を認め，造影剤の肛門側への流出は全く認めなかった．上部消化管内視鏡検査にて門歯列より30cmに全周性のびらん・狭窄を認めた．胸部CTでは下部食道に全周性の壁肥厚を認め，MRI拡散強調像では高信号を示さなかった．閉塞部はガイドワイヤーが通過せず，拡張術やステント留置が困難であり，悪性疾患の否定ができないため，右開胸開腹胸部食道切除術を施行した．病理組織像では狭窄部に一致して潰瘍形成が認められ，粘膜表面は炎症細胞浸潤を伴う肉芽層に覆われていた．また閉塞部位の肛門側粘膜表面はspecialized columnar epitheliumに覆われていた．

The first measurements of (63)Ni produced by A-bomb fast neutrons (above approximately 1 MeV) in copper samples from Hiroshima encompassed distances from approximately 380 to 5062 m from the hypocenter (the point on the ground directly under the bomb). They included the region of interest to survivor studies (approximately 900 to 1500 m) and provided the first direct validation of fast neutrons in that range. However, a significant measurement gap remained between the hypocenter and 380 m. Measurements close to the hypocenter are important as a high-value anchor for the slope of the curve for neutron activation as a function of distance. Here we report measurements of (63)Ni in copper samples from the historic Hiroshima Atomic Bomb Dome, which is located approximately 150 m from the hypocenter. These measurements extend the range of our previously published data for (63)Ni providing a more comprehensive and consistent A-bomb activation curve. The results are also in good agreement with calculations based on the current dosimetry system (DS02) and give further experimental support to the accuracy of this system that forms the basis for radiation risk estimates worldwide.

Those inhabitants of Hiroshima and Nagasaki who were affected by the A-bomb explosions, were exposed to a mixed neutron and gamma radiation field. Few years later about 120,000 survivors of both cities were selected, and since then radiation-induced late effects such as leukemia and solid tumors are being investigated in this cohort. When the present study was initiated, the fast neutron fluences that caused the neutron doses of these survivors had never been determined experimentally. In principle, this would have been possible if radioisotopes produced by fast neutrons from the A-bomb explosions had been detected in samples from Hiroshima and Nagasaki at distances where the inhabitants survived. However, no suitable radioisotope had so far been identified. As a contribution to a large international effort to re-evaluate the A-bomb dosimetry, the concentration of the radionuclide 63Ni (half-life 100.1 years) has been measured in copper samples from Hiroshima and Nagasaki. These measurements were mainly performed at the Maier-Leibnitz-Laboratory in Munich, Germany, by means of accelerator mass spectrometry. Because the 63Ni had been produced in these samples by fast A-bomb neutrons via the reaction 63Cu(n,p)63Ni, these measurements allow direct experimental validation of calculated neutron doses to the members of the LSS cohort, for the first time. The results of these efforts have already been published in a compact form. A more detailed discussion of the methodical aspects of these measurements and their results are given in the present paper. Eight copper samples that had been significantly exposed to fast neutrons from the Hiroshima A-bomb explosion were investigated. In general, measured 63Ni concentrations decreased in these samples with increasing distance to the hypocenter, from 4 × 106 63Ni nuclei per gram copper at 391 m, to about 1 × 105 63Ni nuclei per gram copper at about 1,400 m. Additional measurements performed on three large-distant copper samples from Hiroshima (distance to the hypocenter 1,880–7,500 m) and on three large-distant copper samples from Nagasaki (distance to the hypocenter 3,931–4,428 m) that were not exposed significantly to A-bomb neutrons, suggest a typical background concentration of about 8 × 104 63Ni nuclei per gram copper. If the observed background is accounted for, the results are consistent with state-of-the-art neutron transport calculations for Hiroshima, in particular for those distances where the victims survived and were included in the life span study cohort.

— In order to resolve the discrepancy between the measured and calculated 152Eu activity induced by the atomic bomb at Hiroshima, extremely low background gamma-ray spectrometry was performed for 17 granite samples collected from 134 m to more than 3 km from the hypocenter. Measurements agreed well with theoretical calculations based on DS02 up to 1.4 km from hypocenter.

A 67-year-old-man came to our hospital for further evaluation of a liver tumor detected by abdominal ultrasonography at another hospital. Abdominal computed tomography showed a tumor (8 cm in diameter)in the left lobe of the liver, with invasion of the left and middle hepatic veins, and multiple lymph node metastases. Liver biopsy examination revealed intrahepatic cholangiocellular carcinoma (cStage IVB). Therefore, chemotherapy with gemcitabine(GEM)was administered. The hepatic tumor and multiple lymph nodes were reduced in size after eight courses of GEM chemotherapy. In May 2013, we performed an extended left hepatectomy with biliary tract reconstruction and extended lymph node dissection. The histological diagnosis was intrahepatic cholangiocellular carcinoma, pT3N0H0P0M (-), fStage III. The patient's postoperative recovery was good, and 1 month after surgery, the patient received 6 course of postoperative adjuvant GEM chemotherapy. No serious adverse events occurred during the postoperative adjuvant therapy period. The patient is alive without recurrence 14 months after surgery and 23 months after diagnosis.

A 64-year-old man presented with a chief complaint of abdominal pain. An abdominal computed tomography (CT) scan showed a mass 30-mm in diameter at the splenic flexure, and we diagnosed a retroperitoneal abscess. Conservative therapy was successful, and the patient was discharged. However, 1 month later, he again experienced abdominal pain. To reassess the abscess, contrast-enhanced abdominal CT was performed. In addition to the retroperitoneal abscess, the CT scan showed an approximate 30-mm mass in the head of the pancreas with no contrast uptake. The abscess was also detected by endoscopic retrograde pancreatography. We suspected but could not confirm pancreatic cancer. Two months later, the patient developed obstructive jaundice. At this time, we diagnosed pancreatic cancer, and subtotal stomach-preserving pancreaticoduodenectomy was performed. The histopathologic diagnosis was pancreatic cancer, T4, N0, M0, Stage IVa. The postoperative course was favorable, and the patient received postoperative adjuvant chemotherapy. He remains alive without recurrence 15 months after surgery.

When a carbenoid species generated from a tosylhydrazone is reacted with a cyclobutanol in the presence of a chiral rhodium catalyst, a C–C single bond of the cyclobutanol is cleaved, and the carbenoid carbon is inserted therein to furnish a ring-expanded cyclopentanol in an enantioselective manner.

The Radiation Effects Research Foundation has recently implemented a new dosimetry system, DS02, to replace the previous system, DS86. This paper assesses the effect of the change on risk estimates for radiation-related solid cancer and leukemia mortality. The changes in dose estimates were smaller than many had anticipated, with the primary systematic change being an increase of about 10% in gamma-ray estimates for both cities. In particular, an anticipated large increase of the neutron component in Hiroshima for low-dose survivors did not materialize. However, DS02 improves on DS86 in many details, including the specifics of the radiation released by the bombs and the effects of shielding by structures and terrain. The data used here extend the last reported follow-up for solid cancers by 3 years, with a total of 10,085 deaths, and extends the follow-up for leukemia by 10 years, with a total of 296 deaths. For both solid cancer and leukemia, estimated age-time patterns and sex difference are virtually unchanged by the dosimetry revision. The estimates of solid-cancer radiation risk per sievert and the curvilinear dose response for leukemia are both decreased by about 8% by the dosimetry revision, due to the increase in the gamma-ray dose estimates. The apparent shape of the dose response is virtually unchanged by the dosimetry revision, but for solid cancers, the additional 3 years of follow-up has some effect. In particular, there is for the first time a statistically significant upward curvature for solid cancer on the restricted dose range 0-2 Sv. However, the low-dose slope of a linear-quadratic fit to that dose range should probably not be relied on for risk estimation, since that is substantially smaller than the linear slopes on ranges 0-1 Sv, 0-0.5 Sv, and 0- 0.25 Sv. Although it was anticipated that the new dosimetry system might reduce some apparent dose overestimates for Nagasaki factory workers, this did not materialize, and factory workers have significantly lower risk estimates. Whether or not one makes allowance for this, there is no statistically significant city difference in the estimated cancer risk.

Purpose: Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its expression in this type of cancer and its immunogenicity in esophageal cancer patients have not yet been fully elucidated. We report here the frequency of NY-ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO-1-specific immune response in patients. Experimental Design: One hundred twenty three esophageal squamous cell carcinoma specimens were analyzed for the expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription-PCR and the expression of protein by immunohistochemistry and Western blot. Sera and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1 antibody production by enzyme-linked immunosorbent assay and NY-ESO-1 T cell response by enzyme-linked immunospot assay. Survival analyses were also performed. Results: NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal squamous cell carcinoma specimens, and its expression was found at higher frequency in well-differentiated and moderately differentiated type of cancer. No mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24 (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression and the degree of immunohistochemistry positivity was observed. Antibody production was observed in 2 patients with tumors that showed protein expression. Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2 seropositive patients. Conclusions: The high expression frequency of NY-ESO-1 mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal cancer.

36Cl is a long-lived radioisotope, which, because it is created mainly through a thermal neutron capture process by 35Cl, may be used to estimate the strength of thermal neutron flux from A-bombs or nuclear fuel facilities. The 36Cl contents in granite samples from the Hiroshima A-bomb site have been measured by the Cl-36 accelerator mass spectrometry (AMS) system at the University of Tsukuba. The 36Cl/Cl ratios deduced from the 36Cl measurements are compared with independent evaluations based upon the Dosimetry System 2002 (DS02) of the radiation doses received by the survivors of the Hiroshima A-bomb. The measurements corresponded well up to a ground distance of 1100 m, which proved the effectiveness of the DS02. Measurements of the 36Cl/Cl ratio of unexposed granite samples were 1.92 × 10−13 on average, and because the measured ratio for samples at a ground distance of 1163 m was 2.50 × 10−13, the assessment of the neutron flux by the 36Cl measurements of samples beyond about 1100 m is not practical. This limitation arises from the inability to distinguish bomb-induced Cl-36 from activation due to ambient sources.

NY-ESO-1 is a cancer/testis antigen expressed in normal adult tissues solely in the testicular germ cells of normal adults and in various cancers. It induces specific humoral and cellular immunity in patients with NY-ESO-1-expressing cancer. The aim of this study was to determine the frequency of NY-ESO-1 mRNA and protein expression in malignant and benign breast tumors. NY-ESO-1 mRNA expression was detected by conventional reverse transcription-PCR and real-time PCR, and that of the protein expression by immunohistochemistry and Western blot analysis. Expression of NY-ESO-1 mRNA was detected in 37 of 88 (42%) cancer specimens, whereas that of the NY-ESO-1 protein was detected only in 1 mRNA-positive specimen. In the latter case, expression level of NY-ESO-1 mRNA relative to that in the testis was relatively high (75% of testicular expression) and to the other among breast cancer specimens. In benign breast lesions, 21 of 31 (68%) specimens expressed low levels of NY-ESO-1 mRNA. In 1 case of fibroadenoma, NY-ESO-1 mRNA was 8% of the testicular level, and protein was detected by Western blot analysis. Only 1 breast cancer patient had detectable antibody at time of surgery, which disappeared within 2 years. Tumor specimen from this patient was both NY-ESO-1 mRNA and protein positive, and NY-ESO-1-specific CD8 T cells were detected in this patient by IFN-γ enzyme-linked immunospot assay using NY-ESO-1 recombinant adeno and vaccinia virus. A higher rate of NY-ESO-1 expression was noted in breast cancer with high histological grade and negative hormone receptor status, suggesting NY-ESO-1 as a potential tumor antigen for immunotherapy in patients with breast cancer and poor prognosis.

60 Co / Specific activity / Atomic bomb / DS86 / Neutrons Residual 60 Co activity in five steel samples induced by neutrons from the Nagasaki atomic bomb has been measured within about 1000 m from the hypocenter. The chemical separation of cobalt and nickel from steel samples was performed, and cobalt-enriched samples were prepared for all samples. Gamma-ray measurements were carried out with a low-background well-type germanium detector. The gamma-ray spectra for five samples were compared with the spectrum of a control sample to ensure that the observed 60 Co was actually induced by A-bomb neutrons. The activation of cobalt by environmental neutrons was also investigated. It has been shown that the present 60 Co data are consistent with earlier Hashizume’s data.

A 66-year-old woman was diagnosed with pancreatic tail cancer, and she was referred to our hospital. Abdominal computed tomography(CT)revealed a tumor(2.5 cm in diameter)in the pancreatic tail, with invasion to the spleen and splenic vein. In February 2013, we performed distal pancreatectomy with splenectomy, left adrenal gland resection, and D2 lymph node dissection. Diagnostic peritoneal lavage cytology during surgery was positive; however, we performed curative resection because there were no signs of peritoneal dissemination and distant metastasis. The patient was discharged from the hospital 23 days after the operation, with good postoperative course. Histological diagnosis was pancreatic tail cancer, pT4N0H0P0M(-) fStage IVa. Subsequently, the patient received postoperative adjuvant chemotherapy(TS-1: 100mg/day, 4 courses)combined with Wilms'tumor 1(WT1)peptide-pulsed dendritic cell therapy. No serious adverse events occurred during the postoperative adjuvant therapy. The patient remains alive without recurrence 16 months after the operation.

When a carbenoid species generated from a tosylhydrazone is reacted with a cyclobutanol in the presence of a chiral rhodium catalyst, a C–C single bond of the cyclobutanol is cleaved, and the carbenoid carbon is inserted therein to furnish a ring-expanded cyclopentanol in an enantioselective manner.

In this retrospective study, we investigated the clinical outcomes of endoscopic gastroduodenal stenting (EGDS) for gastric outlet obstruction( GOO) caused by unresectable gastric cancer( UGC).A retrospective study was performed on 20 UGC patients with GOO between 2007 and 2012. We compared the clinical outcomes of EGDS using the WallFlex stent( GDS group, n=8) and palliative Roux-en-Y gastrojejunostomy( RYGJ group, n=12).The numbers of patients with a poor performance status and prior use of chemotherapy were higher in the GDS group than in the RYGJ group. No postoperative complications were observed, and the GOO score improved in both groups. The median days taken to resume oral food intake, the median duration of oral food intake, and the median survival time in the RYGJ and GDS groups were 4 and 3 days( p=0.0008), 301 and 151 days( p=0.0698), and 345 and 161 days (p=0.0070), respectively.EGDS for GOO caused by UGC can be performed safely even after chemotherapy and is beneficial in terms of improvement of oral food intake.

Twenty patients( 30 nodules) with metastatic liver cancer( MLC) and 10 cases with hepatocellular carcinoma( HCC) treated by stereotactic radiotherapy (SRT) were analyzed. SRT was administered at 48.0 or 52.8 Gy/4 Fr/1 wk. The response rate (RR) in MLC patients was 78%, and 11 patients survived longer than 1 year and 9 patients survived as long as 2 years. Clinical analysis suggests that the ideal indications for SRT in MLC are solitary nodules in patients without extrahepatic disease who have undergone systemic chemotherapy. Although RR of SRT for HCC was as high as 85%, intrahepatic recurrence was observed in all patients and 6 patients died within 1 year. Further analysis is needed to determine the indication for SRT in HCC patients.

The technique of laparoscopy-assisted colectomy (LAC) was developed for benign and malignant diseases of the colon and rectum; however, its feasibility and the associated clinical outcome remain unclear. We reviewed 45 patients who underwent LAC (LAC group) and 62 patients who underwent traditional open surgery (Open group) for colorectal carcinoma in our hospital, and compared the clinical data between the two groups in an effort to determine whether LAC is really minimally invasive and if it enhances the quality of life. So that the backgrounds of the patients in both groups were almost the same, we only compared data of patients with colorectal carcinoma of stages 0, I, and II. The duration of surgery in the Open group was significantly shorter for all procedures except sigmoid resection, but the blood loss was not significantly different between any of the procedures except for right colectomy. The time to the first passing of flatus and restarting oral intake, length of hospital stay, and duration of epidural analgesia were significantly shorter in the LAC group. The morbidity and mortality rates in the LAC group were almost the same as those in the Open group at 29.5% and 3.3% versus 22.6% and 1.6%, respectively. However, five major complications of LAC for advanced colorectal carcinomas might be prevented by performing an open procedure. In conclusion, LAC is a safe and minimally invasive surgical technique following which we can expect a faster recovery; however, patients with advanced colorectal carcinomas must be carefully selected for this operation.

Crack model/Hiroshima atomic bomb/Neutron/Neutron discrepancy/DS86 There has been a large discrepancy between the Dosimetry system 1986 (DS86) 1) and measured data, some of which data in Hiroshima at about 1.5 km ground distance from the hypocenter are about 10 times larger than the calculation. Therefore its causes have long been discussed 2‐10) , since it will change the estimated radiation risks obtained based on the Hiroshima and Nagasaki data. In this study the contradiction was explained by a bare-fission-neutron leakage model through a crack formed at the time of neutron emission. According to the present calculation, the crack has a 3 cm parallel spacing, which is symmetric with respect to the polar axis from the hypocenter to the epicenter of the atomic bomb. We made also an asymmetric opening closing 3/4 of this symmetric geometry, because there are some data which shows asymmetry 5,12,13) . In addition, the height of the neutron emission point was elevated 90 m. By using the asymmetric calculation, especially for long distant data located more than 1 km, it was verified that all of the activity data induced by thermal and fast neutrons, were simultaneously explained within the data scattering. The neutron kerma at a typical 1.5 km ground distance increases 3 and 8 times more than DS86 based on the symmetric and asymmetric model, respectively.

An experimental system was established to study in vivo T-cell receptor αβ (TCR) mutations in murine CD4 + T-lymphocytes. The frequency of TCR-defective mutant T-cells that have the CD3 − 4 + surface phenotype, was measured using two-color flow cytometry of splenic T-cells passed through nylon wool. The spontaneous TCR mutant frequency (MF) in BALB/c mice (2.3×10 −4 ) was significantly lower than the frequencies of C57BL/6 (4.0×10 −4 ) and C3H/He (4.2×10 −4 ) mice. The general trend of the TCR MF started to increase at 3 days after whole-body X-irradiation, reached a peak level at 2–3 weeks, and then gradually decreased with a half-life of about 2 weeks. To analyze how the dose responses for each strain of mouse differed 2 weeks after X-irradiation, the TCR MF dose responses were fitted to a linear–quadratic or a quadratic curve. The coefficients of the quadratic terms in both models for BALB/c mice were significantly higher than those for the other two strains. These findings suggest that some genetic factor(s) may control the susceptibility of somatic genes to both spontaneous and radiation-induced mutagenesis. Establishing an animal model for in vivo TCR mutations will contribute to the clarification of certain unresolved aspects of TCR mutagenesis in humans and will further advance knowledge of screening for environmental mutagens.

The Japanese gastric cancer treatment guidelines(published as a web supplement for version 3)recommend the implementation of HER2 testing prior to the selection of chemotherapy. Since we had not yet implemented HER2 immunohistochemistry(IHC)methods for gastric cancer, we tried to compare the HER2 testing results from a reference laboratory(ref lab) and our hospital(in-house). The HER2 concordance rates were calculated between the results from in-house and ref lab using 26 cases(31 samples)which were from patients with advanced, metastatic unresectable, or Stage IV resectable gastric cancer. The HER2 expression(in-house/ref lab)was distributed as follows: negative/negative, 18 cases; negative/equivocal, 2 cases; negative/positive, 1 case;equivocal/equivocal, 2 cases; and positive/positive, 3 cases. The concordance rate was 88. 4%(23/26), and the mismatch rate was 11. 6%(3/26)between in-house and ref lab. Although IHC test results with in-house and ref lab had been generally consistent, it is still necessary to improve and standardize diagnostic accuracy in the near future.

To clarify the complications associated with subcutaneous central venous access port devices, we investigated the patients who underwent placement of central venous access port devices in our hospital.Overall, 171 cancer patients who underwent placement of subcutaneous central venous access port devices (119 for chemotherapy and 52 for home parenteral nutrition) between February 2006 and December 2011 and who were followed up for 1 month, were retrospectively analyzed in this study. Univariate analysis was performed on complications related to clinical factors, including age, gender, insertion sites, intended purposes, duration of catheterization, surgeons, catheter materials, and use of bevacizumab.The mean follow-up time was 213 days (range, 31-1,873), and 35 patients (20.5%) required the port device to be extracted due to complications, including infection in 24(14.0%), wound dehiscence at the port site in 2 (1.2%), obstruction of the catheter in 6 (3.5%), catheter-induced venous thrombosis in 1 (0.6%), and catheter fracture in 2(1.2%). No statistically significant differences were observed between the frequency of complications and age, gender, insertion sites, intended purposes, duration of catheterization, surgeons, catheter materials, or use of bevacizumab.The incidences of complications related to implantation and management of these devices are relatively high and early. Patients should be followed carefully by chest radiography at regular intervals.

Twenty cases (27 therapeutic sites/30 nodules) of metastatic liver cancer treated with stereotactic radiotherapy (SRT)were analyzed. The original sites of cancer were colorectal(8 cases), breast(4 cases), stomach(3 cases), esophagus(2 cases), and other organs (3 cases). SRT was performed with 52.8 Gy·4 fr·-1·wk-1. The response rate was 78%, including complete response (CR) at 8 sites, partial response (PR) at 10 sites, stable disease (SD) at 2 sites, progressive disease(PD) at 3 sites, and not detected(ND) at 4 sites, thus demonstrating a potent local therapeutic effect. Ten patients survived for more than 1 year, 8 patients survived for 2 years, and 4 died before 6 months. Clinical analysis suggests that the ideal indications for SRT are patients with a solitary nodule and without extrahepatic disease who have undergone systemic chemotherapy.

We report a case of recurrent gastric cancer with paraaortic lymph nodes (No.16LNs) that was effectively controlled with chemoradiation therapy. A 63-year-old man underwent distal gastrectomy, cholecystectomy, and D2 dissection in July 2004 for advanced gastric cancer in the lower third area that was diagnosed as moderately differentiated stage II adenocarcinoma [T1(SM), N2, H0, P0, CY0, M0]. He suffered from No.16LNs metastasis with serum CEA elevation in October 2007, and therefore, 4 courses of S-1, followed by 3 courses of CPT-11 as second-line treatment, 14 courses of docetaxel as third-line treatment, and 15 courses of paclitaxel+cisplatin as fourth-line chemotherapy, were administrated. Enlargement of No.16LNs with serum CEA elevation was observed in October 2010. Other metastases were not observed, and hence, chemoradiotherapy (CRT; S-1: 80 mg/body+total of 65 Gy per 26 Fr) for No.16LNs was performed. A partial response and reduction of serum CEA level were noted, and the patient is alive with no sign of progression 18 months after CRT. Grade 1 adverse events including anemia, fatigue, and anorexia were recognized. It is thought that chemoradiation therapy is an effective treatment for localized LN metastasis originating from gastric cancer resistant to chemotherapy.

Abdominal ultrasonographic screening for cancer was performed in 6001 Hiroshima and Nagasaki A-bomb exposed and comparison subjects, all members of the Adult Health Study of the Radiation Effects Research Foundation, formerly the Atomic Bomb Casualty Commission. This study yielded 20 cancers, including 7 hepatocellular, 3 gastric, 3 renal and 2 urinary bladder cancers; one cancer each of the ovary, pancreas, colon and ureter; and one cancer metastatic to the liver, whose primary was unknown. Seventeen of these 20 subjects manifested no symptoms or signs of their disease. A variety of additional tumors, unproven and probably benign, including uterine myomata, and other abnormalities were also detected. Abdominal ultrasonographic screening greatly assisted in the detection of cancers, most of which neither the patients nor their physicians were aware. In this screened fixed population sample the cancer detection rate was 0.33%, exceeding any such rates previously reported in the medical literature.

The frequency of mutant T lymphocytes defective in T-cell receptor gene (alpha or beta) expression was measured using the 2-color flow cytometric technique. Results for a total of 203 atomic bomb survivors, 78 of whom were proximally exposed (DS86 doses of greater than or equal to 1.5 Gy) and 125 of whom were distally exposed (DS86 dose of less than 0.005 Gy), showed that the mutant frequency was significantly higher in males than in females. No significant dose effects were observed. In contrast, a significant increase of mutant frequency was observed for 6 patients treated with Thorotrast, a contrast medium containing thorium-232 formerly used for radioligands. In addition, thyroid disease patients treated with 131I showed a dose-related increase of mutant frequency. It was suggested that the present T-cell receptor mutation assay has a unique characteristic as a biological dosimeter for measurement of recent exposures to genotoxic agents.

This study aimed to test whether scored biologic functions can predict individual life expectancies and to investigate the disease-related and time-related differences in evaluated associations. A biologic score was defined as the first principal component score of the five physiological tests. Study participants were 4,871 people aged 35-74 years at baseline examination in 1970-1972 and followed until the end of 1999. We evaluated the prognostic value of the biologic score by Cox proportional hazard analysis. In all age and sex groups, increasing trends of mortality for all diseases by increment of biologic score were observed after adjustment for potential risk factors. The validity of the biologic score was significant throughout the entire study period. Each disease except cancer showed a significant association with biologic score at baseline examination. In conclusion, the biologic score is a valid predictor of life span in this large-scale prospective study of middle-aged and elderly Japanese.

We reported a case of super-elderly colon cancer with peritoneal dissemination effectively treated with modified FOLFOX6 chemotherapy. A 80-year-old woman was referred to our hospital for abdominal distension in January 2007. Abdominal CT showed peritoneal dissemination and colonoscopy revealed transverse colon cancer. The patient's performance status (PS) score was 3. She had pleural effusion on the left side and massive acsites. After the general condition was improved, operation was performed for sub-ileus in March, but it became a probe laparotomy for severe peritoneal dissemination. We tried modified FOLFOX6 chemotherapy from April. The patient's pleural effusion decreased after 3 courses of chemotherapy and we could remove the thoracic tube. Massive acsites observed in abdominal CT disappeared after 5 courses of chemotherapy. The patient did not suffer from sub-ileus after around 8 courses of chemotherapy and she could then take food. The patient's PS score became 1, and she was discharged in September. Two more courses of chemotherapy were given on as an outpatient basis. The chemotherapy was changed to S-1 on the patient's request in November. As of February 2008, the patient's PS score was 0, and she has been under treatment as an outpatient.

A substantial discrepancy exists between the measured values for thermal neutron activation and the values calculated using the new A-bomb dosimetry system, DS86. As part of a joint US-Japan effort aimed at resolving this discrepancy, we have shown that 36Cl/Cl in mineral samples (i.e., concrete, granite, tiles) can be measured with sufficient precision using accelerator mass spectrometry (AMS) to quantify the very low thermal neutron activation levels at distances between 1000 and 2000 m from the hypocenter in Hiroshima. Our initial measurement results show that activation of Cl by the bomb neutrons disagree with calculations based on the new DS86 dosimetry system (measurements of 36Cl at 1450 m from the hypocenter indicate thermal neutron activation that is ∼15 times higher than obtained from DS86 calculations; discrepancies are even larger at 1606 m). This is a preliminary report of work in progress. The principal objectives of this work are to reconstruct the thermal neutron fluence as a function of distance from the hypocenters in both Hiroshima and Nagasaki using 36Cl/Cl and obtain information about fast neutron fluence.

In the decade after the bombings of Hiroshima and Nagasaki, several large cohorts of survivors were organized for studies of radiation health effects. The U.S. Atomic Bomb Casualty Commission (ABCC) and its U.S./Japan successor, the Radiation Effects Research Foundation (RERF), have performed continuous studies since then, with extensive efforts to collect data on survivor locations and shielding and to create systems to estimate individual doses from the bombs' neutrons and gamma rays. Several successive systems have been developed by extramural working groups and collaboratively implemented by ABCC and RERF investigators. We describe the cohorts and the history and evolution of dose estimation from early efforts through the newest system, DS02, emphasizing the technical development and use of DS02. We describe procedures and data developed at RERF to implement successive systems, including revised rosters of survivors, development of methods to calculate doses for some classes of persons not fitting criteria of the basic systems, and methods to correct for bias arising from errors in calculated doses. We summarize calculated doses and illustrate their change and elaboration through the various systems for a hypothetical example case in each city. We conclude with a description of current efforts and plans for further improvements.

The present paper presents the {sup 36}Cl measurement effort in the US. A large number of {sup 36}Cl measurements have been made in both granite and concrete samples obtained from various locations and distances in Hiroshima and Nagasaki. These measurements employed accelerator mass spectrometry (AMS) to quantify the number of atoms of {sup 36}Cl per atom of total Cl in the sample. Results from these measurements are presented here and discussed in the context of the DS02 dosimetry reevaluation effort for Hiroshima and Nagasaki atomic-bomb survivors. The production of {sup 36}Cl by bomb neutrons in mineral samples from Hiroshima and Nagasaki was primarily via the reaction {sup 35}Cl(n,{gamma}){sup 36}Cl. This reaction has a substantial thermal neutron cross-section (43.6 b at 0.025 eV) and the product has a long half-life (301,000 y). hence, it is well suited for neutron-activation detection in Hiroshima and Nagasaki using AMS more than 50 years after the bombings. A less important reaction for bomb neutrons, {sup 39}K(n,{alpha}){sup 36}Cl, typically produces less than 10% of the {sup 36}Cl in mineral samples such as granite and concrete, which contain {approx} 2% potassium. In 1988, only a year after the publication of the DS86 final report (Roesch 1987), itmore » was demonstrated experimentally that {sup 36}Cl measured using AMS should be able to detect the thermal neutron fluences at the large distances most relevant to the A-bomb survivor dosimetry. Subsequent measurements in mineral samples from both Hiroshima and Nagasaki validated the experimental findings. The potential utility of {sup 36}Cl as a thermal neutron detector in Hiroshima was first presented by Haberstock et al. who employed the Munich AMS facility to measure {sup 36}Cl/Cl ratios in a gravestone from near the hypocenter. That work subsequently resulted in an expanded {sup 36}Cl effort in Germany that paralleled the US work. More recently, there have also been {sup 36}Cl measurements made by a Japanese group. The impetus for the extensive {sup 36}Cl and other neutron activation measurements was the recognized need to validate the neutron component of the dose in Hiroshima. Although this was suggested at the time of the DS86 Final Report, where it was stated that the calculated neutron doses for survivors could possibly be wrong, the paucity of neutron validation measurements available at that time prevented adequate resolution of this matter. It was not until additional measurements and data evaluations were made that it became clear that more work was required to better understand the discrepancies observed for thermal neutrons in Hiroshima. This resulted in a large number of additional neutron activation measurements in Hiroshima and Nagasaki by scientists in the US, Japan, and Germany. The results presented here for {sup 36}Cl, together with measurements made by other scientists and for other isotopes, now provide a much improved measurement basis for the validation of neutrons in Hiroshima.« less