Verification of the Usefulness of an Assessment and Risk Control Sheet that Promotes Management of Cancer Drug Therapy.

Background: Proper management of adverse events is crucial for the safe and effective implementation of anticancer drug treatment. Showa University Hospital uses our interview sheet (assessment and risk control [ARC] sheet) for the accurate evaluation of adverse events. On the day of anticancer drug treatment, a nurse conducts a face-to-face interview. As a feature of the ARC sheet, by separately describing the symptoms the day before treatment and the day of treatment and sharing the information on the medical record, it is possible to clearly determine the status of adverse events. In this study, we hypothesized that the usefulness and points for improvement of the ARC sheet would be clarified by using and evaluating a patient questionnaire. Methods: This study included 174 patients (144 at Showa University Hospital (Hatanodai Hospital) and 30 at Showa University Koto Toyosu Hospital (Toyosu Hospital) who underwent pre-examination interviews by nurses and received cancer chemotherapy at the outpatient center of Hatanodai and Toyosu Hospital. In the questionnaire survey, the ARC sheet's content and quality, respondents' satisfaction, structural strengths, and points for improvement were evaluated on a five-point scale. Results: The patient questionnaire received responses from 160 participants, including the ARC sheet use group (132 people) and the non-use group (28 people). Unlike the ARC sheet non-use group, the ARC sheet use group recognized that the sheet was useful to understand the adverse events of aphthous ulcers (p = 0.017) and dysgeusia (p = 0.006). In the satisfaction survey questionnaire, there was a high sense of security in the pre-examination interviews by nurses using the ARC sheet. Conclusions: The ARC sheet is considered an effective tool for comprehensively evaluating adverse events. Pre-examination interviews by nurses using ARC sheets accurately determined the adverse events experienced by patients with anxiety and tension due to confrontation with physicians.

The utility of patent ductus arteriosus closure with hemostatic clip in dogs.

This study investigated the utility of patent ductus arteriosus (PDA) closure with hemostatic clip by comparing with traditional PDA closure. Medical records of 51 dogs with surgical closure of PDA were reviewed and retrospective study was conducted. 29 dogs were treated by procedure with hemostatic clip (Group HC), and 22 dogs were treated by surgical ligation (Group SL). Data pertaining to breed, sex, age and body weight at the time of surgery, echocardiographic minimal ductal diameter, duration of surgery, hemostatic clip size, echocardiographic findings, hemor-rhage, residual ductal flow and recanalization were collected from records. The results showed that procedure with hemostatic clip had been selected in lighter dogs than traditional PDA closure. Duration of surgery performed only hemostatic clip technique was significantly shorter than that in group SL. Preoperative LVIDd, E-wave and FS were significantly lower than postoperative ones. As regard all parameters, the differences between pre- and postoperative periods were not significantly different between group HC and group SL. Hemorrhage, residual ductal flow, and recanalization were not significantly different in both groups. The present study showed that procedure with hemostatic clip is beneficial in that it is available in smaller dogs and can make shorter operation duration than traditional PDA closure. Moreover, the procedure is effective for the resolution of volume overload of the left atrium and ventricle in short-term outcome. Complications including hemorrhage, residual ductal flow and recanaliza-tion were not significantly different with both techniques.

Arthroscopic release for the severely stiff elbow.

BACKGROUND: Arthroscopic release for the stiff elbow has been widely used, but there are no reports limited to severe stiffness. The purpose of this study was to investigate the outcomes of severe cases. MATERIALS AND METHODS: Ten patients with 10 severely stiff elbows defined by a limited arc of ≤ 60° underwent this arthroscopic release. Causes of stiffness were post-traumatic stiffness (one patient), osteoarthritis (three patients), and rheumatoid arthritis (six patients). Using arthroscopy, the capsule contracture and the intra-articular fibrosis were removed and the impinging osteophyte and part of the radial head were resected. For four patients with preoperative ulnar nerve symptoms or contracture of the posterior oblique ligament of the medial collateral ligament, mini-open ulnar nerve neurolysis and release of the posterior oblique ligament were performed. Patients were followed up for an average of 24 months. RESULTS: Arthroscopic release could be performed without any intraoperative complications. Range of motion for the elbow significantly improved from 95° of flexion and - 55° of extension to 109° of flexion and - 32° of extension. The Mayo Elbow Performance Score also improved from 56 points to 80 points. Two patients underwent a second arthroscopic surgery and gained further arc of motion. One patient showed osteophyte reformation and needed revision open surgery 1 year after the initial surgery. CONCLUSIONS: Arthroscopic release for the severely stiff elbow could improve range of motion. Careful attention should be given during surgery to avoid complications such as intramuscular bleeding or nerve damage.

Feasibility of resecting the portal vein only when necessary during pancreatoduodenectomy for pancreatic cancer.

Background: Whether the portal/superior mesenteric vein (PV) should be resected during pancreatoduodenectomy for pancreatic ductal adenocarcinoma (PDAC) based on preoperative CT or intraoperative findings is controversial. Methods: This was a retrospective study with data of patients who had undergone pancreatoduodenectomy for PDAC between 2002 and 2016 in a tertiary referral centre. Based on the extent of contact between the PV and tumour on CT, patients were categorized into: group 1, no contact; group 2, contact 180° or less; group 3, contact greater than 180°. Extent of pathological PV invasion (pPV) (no invasion, pv0; invasion to tunica adventitia, pv1; invasion to media, pv2; invasion to intima, pv3) was compared with patient survival. To assess the feasibility of performing PV resection (PVR) based on intraoperative findings, the prognosis of patients in groups 1 and 2 with pv0 and no PVR (PVR(-)pv0) was compared with that of patients who had PVR (PVR(+)pv0), selected using propensity score matching. Results: Groups 1, 2 and 3 comprised 230, 232 and 38 patients respectively, and PVR was performed in 10·9, 73·3 and 95 per cent of them (P < 0·001). Extent of pPV differed significantly (P < 0·001). The positive predictive value of radiological tumour contact with PV in predicting positive pPV was 42·6 per cent. In 64 patients with PVR(-)pv0 and 64 matched patients with PVR(+)pv0, the R0 resection rate (66 versus 73 per cent respectively; P = 0·337) and survival (median 32·4 versus 32·1 months; P = 0·780) were not significantly different. Conclusion: PVR is needed only when the tumour is in clear contact with the PV and cannot be detached during surgery.

Dirac gap opening and Dirac-fermion-mediated magnetic coupling in antiferromagnetic Gd-doped topological insulators and their manipulation by synchrotron radiation.

A new kind of magnetically-doped antiferromagnetic (AFM) topological insulators (TIs) with stoichiometry Bi1.09Gd0.06Sb0.85Te3 has been studied by angle-resolved photoemission spectroscopy (ARPES), superconducting magnetometry (SQUID) and X-ray magnetic circular dichroism (XMCD) with analysis of its electronic structure and surface-derived magnetic properties at different temperatures. This TI is characterized by the location of the Dirac gap at the Fermi level (EF) and a bulk AFM coupling below the Neel temperature (4-8 K). At temperatures higher than the bulk AFM/PM transition, a surface magnetic layer is proposed to develop, where the coupling between the magnetic moments located at magnetic impurities (Gd) is mediated by the Topological Surface State (TSS) via surface Dirac-fermion-mediated magnetic coupling. This hypothesis is supported by a gap opening at the Dirac point (DP) indicated by the surface-sensitive ARPES, a weak hysteresis loop measured by SQUID at temperatures between 30 and 100 K, XMCD measurements demonstrating a surface magnetic moment at 70 K and a temperature dependence of the electrical resistance exhibiting a mid-gap semiconducting behavior up to temperatures of 100-130 K, which correlates with the temperature dependence of the surface magnetization and confirms the conclusion that only TSS are located at the EF. The increase of the TSS's spectral weight during resonant ARPES at a photon energy corresponding to the Gd 4d-4f edge support the hypothesis of a magnetic coupling between the Gd ions via the TSS and corresponding magnetic moment transfer at elevated temperatures. Finally, the observed out-of-plane and in-plane magnetization induced by synchrotron radiation (SR) due to non-equal depopulation of the TSS with opposite momentum, as seen through change in the Dirac gap value and the k∥-shift of the Dirac cone (DC) states, can be an indicator of the modification of the surface magnetic coupling mediated by the TSS.

Acquired undescended testis and possibly associated testicular torsion in children with cerebral palsy or neuromuscular disease.

INTRODUCTION: Torsion of an undescended testis (UDT) associated with cerebral palsy (CP) and neuromuscular disease (NMD) is an uncommon condition that is not well recognized by primary care physicians or healthcare providers. OBJECTIVE: The objective of this study was to highlight the clinical importance of torsion of a UDT in children with CP and NMD. MATERIALS AND METHODS: Eleven children with testicular torsion of a UDT operated on at the study institute between 1991 and 2015 were identified. The records of seven children (63.6%) associated with CP or NMD were retrospectively reviewed. Clinical findings of testicular torsion were assessed along with the treatment outcome and testicular salvageability. RESULTS: All seven children were not identified with a UDT by public health checkup for infant and young children. No children with CP or NMD had torsion of a descended testis during the present study period. Median age at surgery was 15 years (range, 1-20 years). The testis location was at the external inguinal ring in five patients, in the inguinal canal in one, and in the superficial inguinal pouch in one. Of the contralateral testes, four were a UDT, one was a retractile testis, and two were descended testes. Orchiectomy was performed in six patients (85.7%). In the remaining patients, the testis was preserved but became atrophic. DISCUSSION: This study demonstrated that children with CP or NMD may be affected with torsion of a UDT with peak at around puberty with the poor salvage rate, even if the testes appear descended in infancy and young children. Shortcomings of this study were the retrospective design and a small series of children undergoing surgery for torsion of a UDT. CONCLUSION: Pediatric urologists need to educate primary care physicians and healthcare providers in the recognition of acquired UDTs and possibly associated testicular torsion in children with CP and NMD. Genital examination should be continued regularly until adolescence in these children to detect acquired UDT. These children should be referred to pediatric urologists to promote surgery as soon as the diagnosis of acquired UDT is carried out. It is believed that it is perhaps the best approach to prevent loss of the testis in children with CP and NMD.

Extent of lymph node dissection in patients with gallbladder cancer.

BACKGROUND: Definitions of regional lymph nodes for gallbladder cancer differ according to staging system. Hence, the appropriate extent of lymph node dissection has not yet been standardized. METHODS: Pathological stages and disease-specific survival (DSS) of patients who had undergone surgical resection of gallbladder cancer between 1990 and 2016 were reviewed. Patients with nodal metastases limited to the hepatoduodenal ligament or common hepatic artery, extending to the posterosuperior pancreatic head lymph nodes (PSPLNs), or in nodes along the coeliac axis or superior mesenteric vessels were grouped as having Na, Nb and Nc disease respectively. Metastases beyond these regions were defined as distant metastases (M1). Absence of distant metastasis was expressed as M0. RESULTS: A total of 259 patients were evaluated. There were 74, 31 and nine patients respectively in the Na, Nb and Nc groups. Twenty-five, nine and four patients in the respective groups had M1 disease (P = 0·682). The 5-year DSS rate was comparable between patients with Na M0 and those with Nb M0 disease (36 versus 34 per cent respectively; P = 0·950), whereas the rate in patients with Nc M0 status (0 per cent) was worse than that of patients with Nb M0 (P = 0·017) and comparable to that of patients with M1 disease (14 per cent; P = 0·590). Among 22 patients with Nb M0 disease, the 5-year DSS rate did not differ between those who had undergone pancreatoduodenectomy and those who had had dissection of PSPLNs without pancreatoduodenectomy (50 versus 30 per cent respectively; P = 0·499). CONCLUSION: PSPLNs and nodes along the hepatoduodenal ligament and hepatic artery should be considered regional nodes for gallbladder cancer, and should be resected.

S-1 and irinotecan plus bevacizumab versus mFOLFOX6 or CapeOX plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer (TRICOLORE): a randomized, open-label, phase III, noninferiority trial.

Background: Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS). Patients and methods: Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin. Result: Between June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6-11.6) in the control group and 14.0 months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P < 0.0001 for noninferiority, P = 0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher. Conclusion: S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment. Clinical trials number: UMIN000007834.

Salvage hepatectomy for local recurrence of hepatocellular carcinomas offers survival comparable to that of matched patients who undergo primary hepatectomies.

BACKGROUND: The feasibility of salvage hepatectomy for locally recurrent hepatocellular carcinomas (HCCs) is unclear, especially for patients with viable parts of previously multinodular tumors. METHODS: We reviewed charts of patients who underwent initial hepatectomies between 2000 and 2014 to select those with local recurrences (LR) after non-surgical treatments. Their postoperative outcomes, including morbidity, recurrence-free survival (RFS), and overall survival (OS) were compared with matched patients who underwent initial hepatectomies for primary HCCs (PR). Their local recurrence patterns were divided into recurrent solitary tumors (Subgroup A); and recurrent parts of multinodular tumors (Subgroup B). RESULTS: Among 664 patients, hepatectomy for LR was performed in 62 patients. Matched 59 patients were selected as PR. Clinicopathologic profiles at initial surgery were comparable between the LR and PR groups. Incidence of major morbidity (LR vs. PR, 7% vs. 5%, P = 1.00), 5-year RFS (21% vs. 37%, P = 0.28), and 5-year OS (69% vs. 69%, P = 0.62) were comparable. In the LR group, Subgroup B showed worse 5-year RFS (A vs. B, 29% vs. 0%, P < 0.01) and 5-year-OS (80% vs. 53%, P = 0.01). Postoperative recurrence occurred in 46 patients, but local and extrahepatic recurrence was seen only in 2 patients and 2 patients, respectively. CONCLUSION: Salvage hepatectomy for locally recurrent HCCs is feasible, and results in prognosis comparable with hepatectomy for primary HCCs. Although the risk of postoperative recurrence was high in Subgroup B, rare local recurrence suggests the usefulness of salvaging uncontrolled tumor by nonsurgical treatment.

Estrogen receptor-beta genetic variations and overall survival in patients with locally advanced gastric cancer.

Estrogen has been shown not only to reduce the incidence of colorectal cancer but also gastric cancer (GC). Polymorphisms in estrogen receptor ß gene, ESR2, correlate with colorectal cancer survival. To better understand the role of ESR2 in GC, genomic DNA extracted from 169 Japanese patients and 172 patients from Los Angeles County (LAC) was analyzed for association of overall survival (OS) with three ESR2 polymorphisms, which are of biological significance using multivariable Cox proportional hazard regression. ESR2 rs1271572 (C>A) and rs3020443 (T>G) had univariate and multivariable associations with OS in the Japanese cohort, whereas the C allele of ESR2 rs2978381 (T>C) predicted favorable OS in the Japanese cohort but worse OS in the LAC cohort. The interaction term of the ESR2 rs2978381 and cohort group reached statistical significance. Our study provides evidence that genetic variations in ESR2 gene are significantly associated with survival in patients with locally advanced GC.

Development and analysis of patient-derived xenograft mouse models in intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBCL) is a distinct disease entity with the peculiar characteristic that tumor cells proliferate within vessels. Despite recent advances in understanding the disease from clinical aspects, the underlying pathogenesis remains unknown. Here we demonstrate analyses of IVLBCL biology using four xenograft mouse models established from primary IVLBCL samples. In all four models, the main characteristic of IVLBCL tumor cell proliferation within vessels was retained. Time-lapse engraftment analyses revealed that the tumor cells initially engrafted and proliferated in the sinusoids and vessels in the liver and then engrafted and proliferated in multiple organs. Intriguingly, serial passage of tumor cells from the adrenal gland of a transplanted mouse developed from primary patient bone marrow cells into a second mouse showed that the tumor cells mainly distributed into the adrenal gland in the second mouse, implying the existence of clonal selection and/or evolution at engraftment of a specific organ. Gene expression profiling analyses demonstrated that the gene set associated with cell migration was enriched for normal peripheral blood B cells, indicating that inhibition of cell migration might be involved in IVLBCL pathogenesis. In conclusion, the mouse xenograft models described here are essential tools for uncovering IVLBCL biology.

Randomized clinical trial comparing long-term quality of life for Billroth I versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND: Patients' quality of life (QoL) deteriorates remarkably after gastrectomy. Billroth I reconstruction following distal gastrectomy has the physiological advantage of allowing food to pass through the duodenum. It was hypothesized that Billroth I reconstruction would be superior to Roux-en-Y reconstruction in terms of long-term QoL after distal gastrectomy. This study compared two reconstructions in a multicentre prospective randomized clinical trial to identify the optimal reconstruction procedure. METHODS: Between January 2009 and September 2010, patients who underwent gastrectomy for gastric cancer were randomized during surgery to Billroth I or Roux-en-Y reconstruction. The primary endpoint was assessment of QoL using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) questionnaire 36 months after surgery. RESULTS: A total of 122 patients were enrolled in the study, 60 to Billroth I and 62 to Roux-en-Y reconstruction. There were no differences between the two groups in terms of postoperative complications or mortality, and no significant differences in FACT-Ga total score (P = 0·496). Symptom scales such as epigastric fullness (heaviness), diarrhoea and fatigue were significantly better in the Billroth I group at 36 months after gastrectomy (heaviness, P = 0·040; diarrhoea, P = 0·046; fatigue, P = 0·029). The rate of weight loss in the third year was lower for patients in the Billroth I group (P = 0·046). CONCLUSION: The choice of anastomotic reconstruction after distal gastrectomy resulted in no difference in long-term QoL in patients with gastric cancer. REGISTRATION NUMBER: NCT01065688 (http://www.clinicaltrials.gov).

The use of muscle biopsy in the diagnosis of systemic vasculitis affecting small to medium-sized vessels: a prospective evaluation in Japan.

OBJECTIVES: The aim of this study was to assess the use of muscle biopsy for histopathological confirmation of small vessel vasculitis (SVV) or medium vessel vasculitis (MVV). METHOD: Muscle biopsies were performed for all consecutive cases of suspected SVV or MVV seen at Tokyo Metropolitan Tama Medical Centre between February 2012 and May 2014 except those for which a skin or renal biopsy was indicated. RESULTS: Forty-nine patients underwent muscle biopsies. All patients were followed for a minimum of 6 months. Diagnosis of SVV or MVV was made in 35 patients. An unrelated condition was diagnosed in 11 patients and no diagnoses were made in three patients. Of the 35 patients in whom SVV or MVV was diagnosed, positive muscle biopsies were obtained in 20 patients [15 microscopic polyangiitis (MPA), three polyarteritis nodosa (PAN), and two eosinophilic granulomatosis with polyangiitis (EGPA)], while other findings led to the same diagnosis in 15 (seven MPA, four GPA, three PAN, and one rheumatoid vasculitis). The sensitivity of the muscle biopsy was 57% [20/35; 95% confidence interval (CI) 50-57]. Of 13 patients presenting with peripheral neuropathy, the muscle biopsy demonstrated vasculitis in nine patients, with 75% sensitivity (9/12; 95% CI 69-75). There were no complications in the procedure apart from delayed wound healing in one patient. CONCLUSIONS: Muscle biopsy is a safe method that offers a high diagnostic yield for SVV or MVV, especially in patients with vasculitic neuropathy.

A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer.

BACKGROUND: We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). PATIENTS AND METHODS: Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). RESULTS: Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37-0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54-1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47-1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. CONCLUSION: The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. CLINICAL TRIALS NUMBER: Japan Pharmaceutical Information Center: JapicCTI-111554.

Calculating disability-adjusted life years (DALY) as a measure of excess cancer risk following radiation exposure.

This paper has proposed that disability-adjusted life year (DALY) can be used as a measure of radiation health risk. DALY is calculated as the sum of years of life lost (YLL) and years lived with disability (YLD). This multidimensional concept can be expressed as a risk index without a probability measure to avoid the misuse of the current radiation detriment at low doses. In this study, we calculated YLL and YLD using Japanese population data by gender. DALY for all cancers in Japan per 1 Gy per person was 0.84 year in men and 1.34 year in women. The DALY for all cancers in the Japanese baseline was 4.8 in men and 3.5 in women. When we calculated the ICRP detriment from the same data, DALYs for the cancer sites were similar to the radiation detriment in the cancer sites, excluding leukemia, breast and thyroid cancer. These results suggested that the ICRP detriment overestimate the weighting fraction of leukemia risk and underestimate the weighting fraction of breast and thyroid cancer. A big advantage over the ICRP detriment is that DALY can calculate the risk components for non-fatal diseases without the data of lethality. This study showed that DALY is a practical tool that can compare many types of diseases encountered in public health.

Intratumoral tertiary lymphoid organ is a favourable prognosticator in patients with pancreatic cancer.

BACKGROUND: Host immunity has critical roles in tumour surveillance. Tertiary lymphoid organs (TLOs) are induced in various inflamed tissues. The aim of this study was to investigate the clinicopathological and pathobiological characteristics of tumour microenvironment in pancreatic ductal carcinoma (PDC) with TLOs. METHODS: We examined 534 PDCs to investigate the clinicopathological impact of TLOs and their association with tumour-infiltrating immune cells, the cytokine milieu, and tissue characteristics. RESULTS: There were two different localisations of PDC-associated TLOs, intratumoral and peritumoral. A better outcome was observed in patients with intratumoral TLOs, and this was independent of other survival factors. The PDC tissues with intratumoral TLOs showed significantly higher infiltration of T and B cells and lower infiltration of immunosuppressive cells, as well as significantly higher expression of Th1- and Th17-related genes. Tertiary lymphoid organs developed with an association with arterioles, venules, and nerves. These structures were reduced in an association with cancer invasion in PDC tissues, except for those with intratumoral TLOs. The PDC tissues with intratumoral TLOs had capillaries consisting of mature endothelial cells covered by pericytes. CONCLUSIONS: Our results suggest that the presence of intratumoral TLOs represents a microenvironment that has an active immune reaction, and shows a relatively intact vascular network retained.

Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer.

BACKGROUND: We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC). PATIENTS AND METHODS: In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease. RESULTS: Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%). CONCLUSION: SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS. CLINICAL TRIAL NUMBER: JapicCTI-101021.

Outcomes of immediate perforator flap reconstruction after skin-sparing mastectomy following neoadjuvant chemotherapy.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.

Comprehensive data on ionising radiation from Fukushima Daiichi nuclear power plant in the town of Miharu, Fukushima Prefecture: The Misho Project.

Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.