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The need for closure (NFC), a desire for a firm answer and less ambiguity, has a key role in cognitive flexibility in typical development (TD) populations. This study investigated this motivational construct and its relation to cognitive inflexibility in autism spectrum disorder (ASD). Compared with individuals with TD, those with ASD reported higher levels in preference for predictability and closed-mindedness and lower levels in decisiveness. These NFC facets were significantly associated with cognitive flexibility in ASD as well as TD groups. The study findings provide further insights into the motivational underpinnings of flexible behavior in ASD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The sunk cost effect is the tendency to continue an investment, or take an action, even though it has higher future costs than benefits, if costs of time, money, or effort were previously incurred. This type of decision bias is pervasive in real life and has been studied in various disciplines. Previous studies and clinical observations suggest that decision-making under sunk costs is altered in gambling disorder (GD). However, the neural mechanisms of decision-making under sunk costs in GD remain largely unknown, and so is their association with the clinical characteristics of this patient group. Here, by combining functional magnetic resonance imaging and the task that demonstrated a clear example of the sunk cost effect, we investigated the neural correlates during decision-making under sunk costs in GD. We found no significant differences in the strength of the sunk cost effect between the GD and healthy control (HC) groups. However, the strength of the sunk cost effect in patients with GD showed a significant negative correlation with abstinence period and a marginally significant positive correlation with the duration of illness. We also found a reduction in the neural activation in the dorsal medial prefrontal cortex during decision-making under sunk costs for the GD group compared with the HC group. Furthermore, in patients with GD, the levels of activation in this area negatively correlated with the duration of illness. These findings have important clinical implications. This study will contribute to a better understanding of the mechanisms underlying altered decision-making abilities in GD., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

The terrestrial forest ecosystems in the northern high latitude region have been experiencing significant warming rates over several decades. These forests are considered crucial to the climate system and global carbon cycle and are particularly vulnerable to climate change. To obtain an improved estimate of the response of vegetation activity, e.g., forest greenness and tree growth, to climate change, we investigated spatiotemporal variations in two independent data sets containing the dendroecological information for this region over the past 30 years. These indices are the normalized difference vegetation index (NDVI3g) and the tree-ring width index (RWI), both of which showed significant spatial variability in past trends and responses to climate changes. These trends and responses to climate change differed significantly in the ecosystems of the circumarctic (latitude higher than 67°N) and the circumboreal forests (latitude higher and lower than 50°N and 67°N, respectively), but the way in which they differed was relatively similar in the NDVI3g and the RWI. In the circumarctic ecosystem, the climate variables of the current summer were the main climatic drivers for the positive response to the increase in temperatures showed by both the NDVI3g and the RWI indices. On the other hand, in the circumboreal forest ecosystem, the climate variables of the previous year (from summer to winter) were also important climatic drivers for both the NDVI3g and the RWI. Importantly, both indices showed that the temperatures in the previous year negatively affected the ecosystem. Although such negative responses to warming did not necessarily lead to a past negative linear trend in the NDVI3g and the RWI over the past 30 years, future climate warming could potentially cause severe reduction in forest greenness and tree growth in the circumboreal forest ecosystem., (© 2018 John Wiley & Sons Ltd.)

Sister chromatid cohesion, mediated by cohesin, is required for accurate chromosome segregation [1, 2]. This process requires acetylation of cohesin subunit SMC3 by evolutionarily conserved cohesin acetyltransferases: Eco1 in budding yeast; XEco1 and XEco2 in Xenopus; and ESCO1 and ESCO2 in human [3-10]. Eco1 is recruited to chromatin through physical interaction with PCNA [11] and is degraded by the Skp1/Cul1/F-box protein complex after DNA replication to prevent ectopic cohesion formation [12]. In contrast, XEco2 recruitment to chromatin requires prereplication complex formation [13] and is degraded by the anaphase-promoting complex (APC) [14]. In human, whereas ESCO1 is expressed throughout the cell cycle, ESCO2 is detectable in S phase and is degraded after DNA replication [6, 15]. Although PDS5, a cohesin regulator, preferentially promotes ESCO1-dependent SMC3 acetylation [16], little is known about the molecular basis of the temporal regulation of ESCO2. Here, we show that ESCO2 is recruited to chromatin before PCNA accumulation. Whereas no interaction between PCNA and ESCO proteins is observed, ESCO2, but not ESCO1, interacts with the MCM complex through a unique ESCO2 domain. Interestingly, the interaction is required to protect ESCO2 from proteasomal degradation and is attenuated in late S phase. We also found that ESCO2 physically interacts with the CUL4-DDB1-VPRBP E3 ubiquitin ligase complex in late S phase and that post-replicative ESCO2 degradation requires the complex as well as APC. Thus, we propose that the MCM complex couples ESCO2 with DNA replication and that the CUL4-DDB1-VPRBP complex promotes post-replicative ESCO2 degradation, presumably to suppress cohesion formation during mitosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Inflexible behaviours in people with autism spectrum disorder (ASD) broadly obstruct social communication. Meanwhile, flexibility implicates cognitive control to resolve socially conflicting situations; however, it remains unclear how people with ASD behave in the face of these conflicts in this respect. We used the ultimatum game (UG) and the implicit-association test (IAT) to examine goal-directed/economic flexibility, both of which involve conflict and cognitive control. In addition, we used the Detail and Flexibility Questionnaire (DFlex) to measure inflexible everyday behaviour with diminished cognitive control and attention shifting. We observed the decreased flexibility in participants with ASD (DFlex and IAT); further, their IAT scores positively correlated with DFlex. However, in the UG, contrary to our prediction, participants with ASD accepted unfair offers more frequently than TD. These results suggest that assessing the automatic/attention processing level with the IAT could be a useful approach to study behavioural flexibility among ASD compared with the UG, which might comprise multiple response strategies besides economic rationality. Overall, the severity of inflexible daily behaviours in people with ASD may be associated with a reduced flexible attitude at an automatic level, altered attention processing and decreased cognitive control.

Background/aim: Nab-paclitaxel (nab-PTX) is an albumin-bound paclitaxel formulation. Although nab-PTX has shown superior efficacy compared to conventional paclitaxel (PTX) in metastatic breast cancer (MBC), chemotherapy-induced peripheral neuropathy (CIPN) was more frequently observed in nab-PTX. In this study, we aimed to estimate the feasibility of the nab-PTX 175 mg/m 2 /3weeks regimen., Patients and Methods: Patients having metastatic or inoperable HER2-negative breast cancer received 175 mg/m 2 of nab-PTX every three weeks. The primary endpoint was safety and the secondary endpoints were response and survival., Results: Seventeen patients were enrolled with a median age of 64 years. Ten patients had estrogen receptor positive disease and seven had triple-negative disease. CIPN was observed in seven patients (41%) however, grade 3 CIPN was only seen in one patient (6%). Objective response rate was 41% and progression-free survival was 23 weeks., Conclusion: Nab-PTX 175 mg/m 2 /3wks regimen has a good safety profile and less frequent CIPN. This regimen can contribute to the strategy of MBC treatment., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A 52-year-old woman presented with sudden left lower abdominal pain, fever, and vomiting. As the symptom got improved immediately she went home then. She consulted our hospital with chief complaint of the left lower abdominal mass. Abdominal computed tomography revealed sigmoid colon cancer with abscess. She was diagnosed with sigmoid colon cancer via colonoscopy. Sigmoidectomy including partial resection of the abdominal wall was performed(D3 lymphadenectomy). Surgical specimen showed penetration of diverticulum on mucous membrane of the lesion which had been thought of a abdominal wall permeation and a tumor of I sp type at anal side. Pathological examination showed diverticulitis with penetration and the tumor was tubular adenocarcinoma(tub1, pT1bpN0, pStage I ). We had doubted penetration of sigmoid colon cancer most, but the cause of penetration turned out to be diverticulitis. We experienced a case in which we could performed surgery of sigmoid colon cancer and penetration of diverticulum at the same time.

We are constantly exposed to socially conflicting situations in everyday life, and cognitive flexibility is essential for adaptively coping with such difficulties. Flexible goal choice and pursuit are not exclusively conscious, and therefore cognitive flexibility involves both explicit and implicit forms of processing. However, it is unclear how individual differences in explicit and implicit aspects of flexibility are associated with neural activity in a resting state. Here, we measured intrinsic fractional amplitude of low-frequency fluctuations (fALFF) by resting-state functional magnetic resonance imaging (RS-fMRI) as an indicator of regional brain spontaneous activity, together with explicit and implicit aspects of cognitive flexibility using the Cognitive Flexibility Scale (CFS) and Implicit Association Test (IAT). Consistent with the dual processing theory, there was a strong association between explicit aspects of flexibility (CFS score) and "rationalism" thinking style and between implicit aspects (IAT effect) and "experientialism." The level of explicit flexibility was also correlated with fALFF values in the left lateral prefrontal cortex, whereas the level of implicit flexibility was correlated with fALFF values in the right cerebellum. Furthermore, the fALFF values in both regions predicted individual preference for flexible decision-making strategy in a vignettes simulation task. These results add to our understanding of the neural mechanisms underlying flexible decision-making for solving social conflicts. More generally, our findings highlight the utility of RS-fMRI combined with both explicit and implicit psychometric measures for better understanding individual differences in social cognition., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Circumboreal forest ecosystems are exposed to a larger magnitude of warming in comparison with the global average, as a result of warming-induced environmental changes. However, it is not clear how tree growth in these ecosystems responds to these changes. In this study, we investigated the sensitivity of forest productivity to climate change using ring width indices (RWI) from a tree-ring width dataset accessed from the International Tree-Ring Data Bank and gridded climate datasets from the Climate Research Unit. A negative relationship of RWI with summer temperature and recent reductions in RWI were typically observed in continental dry regions, such as inner Alaska and Canada, southern Europe, and the southern part of eastern Siberia. We then developed a multiple regression model with regional meteorological parameters to predict RWI, and then applied to these models to predict how tree growth will respond to twenty-first-century climate change (RCP8.5 scenario). The projections showed a spatial variation and future continuous reduction in tree growth in those continental dry regions. The spatial variation, however, could not be reproduced by a dynamic global vegetation model (DGVM). The DGVM projected a generally positive trend in future tree growth all over the circumboreal region. These results indicate that DGVMs may overestimate future wood net primary productivity (NPP) in continental dry regions such as these; this seems to be common feature of current DGVMs. DGVMs should be able to express the negative effect of warming on tree growth, so that they simulate the observed recent reduction in tree growth in continental dry regions., (© 2017 John Wiley & Sons Ltd.)

The patient, 49-year-old woman, who was referred to our hospital in August 2016 because of left abdominal pain. The abdominal CT scan showed a large tumor, over 10 cm dimeter at splenic flexure of the transverse colon, and colonoscopy detected transvers colon cancer(por, cT4b, cN1, M0, cStage III A). There was no distant metastasis, although invasion to the retroperitoneum and the abdominal wall. Left hemicolectomy was successfully performed with D3 lymph node dissection. Pathological diagnosis was endocrine cell carcinoma, pT4a(SE), pN0, M0, pStage II . The Surgical margin was completely free of carcinoma(R0). The postoperative course was uneventful, and she has been in good health with no recurrence for 8 months after surgery. Neuroendocrine cell carcinoma is recommended for adjuvant treatment based on small cell lung cancer, but there are not effective clinical trials nor established treatment methods because it is rare disease.

A 63-year-old man presented with abdominal pain in the lower right quadrant and high fever. An abdominal CT scan on admission revealed ileocecal wall thickening and inflammation of the terminal ileum. No foreign body was observed on CT scan. He received antibiotic therapy, but no improvement was noticed. Colonoscopy showed a sporadic type 0- I s+ II c lesion in the sigmoid colon. Histological examination showed well differentiated adenocarcinoma. We diagnosed the patient as having inflammation of the terminal ileum and sigmoid colon cancer. Laparoscopic surgery was performed. Inflammation was present in the terminal ileum, and local resection and sigmoidectomy were performed. A foreign body that appeared to be a fish bone was present in the resected specimen, and this led to the diagnosis of granulomatous inflammation of the ileum caused by fish bone. In the sigmoid colon, the pathological diagnosis was pT1b(sm), pN0, ly1, v1, pDM0, pPM0, R0, pStage I . He was discharged without any complication and has not shown any evidence of recurrence more than 1 year after surgery.

A 46-year old man presented with lower right quadrant abdominal pain caused by abdominal trauma. Abscess drainage was performed after the diagnosis of retroperitoneal abscess in the ileocecal portion of the colon. Type 2 advanced cancer was found in the cecum and ascending colon. Surgery was performed after improvement of inflammation. Considering the difficulty of curative resection for retroperitoneal invasion, we first performed ileo-transverse colon anastomosis. After surgery, the patient received FOLFOX with panitumumab(Pmab)as neoadjuvant chemotherapy. After 6 courses of this regimen, contrast enhanced computed tomography revealed shrinkage of the tumor. We performed a second surgery but the tumor was unresectable because of retroperitoneal invasion. After 47 courses of chemotherapy(5-FU plus LV with Pmab), the tumor was stable and we observed no distant metastasis. A third surgery was performed, and we were able to perform ileocecal resection including the retroperitoneum. The pathological diagnosis was pT4b(SI), pN1, ly2, V2, pPM0, pDM0, R0, pStage III a. On histological examination, the efficacy of chemotherapy was evaluated as Grade 1a. The patient received adjuvant chemotherapy with capecitabine and remains healthy without any evidence of recurrence more than 10 months after surgery.

Although the ability to make optimal decisions under uncertainty is an integral part of everyday life, individuals with autism spectrum disorder (ASD) frequently report that they experience difficulties with this skill. In behavioral economics, researchers distinguish two types of uncertainty to understand decision-making in this setting: risk (known probabilities) and ambiguity (unknown probabilities). However, it remains unclear how individuals with ASD behave under risk and ambiguity, despite growing evidence of their altered decision-making under uncertainty. We therefore extended previous research by studying the attitudes of those with ASD toward risk and ambiguity in both positive and negative contexts (i.e., gain and loss). In gain contexts, no significant difference was observed between the groups in risk attitudes, but ambiguity aversion was attenuated in ASD. In loss contexts, ambiguity attitudes did not significantly differ between the groups, but the ASD participants were less risk-seeking compared with the controls. In addition, insensitivity to the context change under risk and ambiguity in ASD was both significantly associated with poor social skills. These results improve our understanding of altered decision-making under uncertainty by disentangling the attitudes toward risk and ambiguity in ASD individuals. Applying behavioral economic tools may provide insights into the mechanisms underlying behavioral disturbances in ASD.

Behavioural flexibility is essential for everyday life. This involves shifting attention between different perspectives. Previous studies suggest that flexibility is mainly subserved by the dorsolateral prefrontal cortex (DLPFC). However, although rarely emphasized, the temporoparietal junction (TPJ) is frequently recruited during flexible behaviour. A crucial question is whether TPJ plays a role in different types of flexibility, compared to its limited role in perceptual flexibility. We hypothesized that TPJ activity during diverse flexibility tasks plays a common role in stimulus-driven attention-shifting, thereby contributing to different types of flexibility, and thus the collaboration between DLPFC and TPJ might serve as a more appropriate mechanism than DLPFC alone. We used fMRI to measure DLPFC/TPJ activity recruited during moral flexibility, and examined its effect on other domains of flexibility (economic/perceptual). Here, we show the additional, yet crucial role of TPJ: a combined DLPFC/TPJ activity predicted flexibility, regardless of domain. Different types of flexibility might rely on more basic attention-shifting, which highlights the behavioural significance of alternatives.

Although the concurrent use of anthracycline-containing chemotherapy and taxane with trastuzumab are considered the treatment of choice for the primary systemic therapy of human epidermal growth factor receptor 2 (HER2)-overexpressing early breast cancer, non-anthracycline regimens, such as concurrent administration of docetaxel and carboplatin with trastuzumab, exhibited similar efficacies in a previous study. In addition, tri-weekly treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) resulted in significantly higher response rates and a favorable safety profile compared with standard paclitaxel for metastatic breast cancer patients in another phase III study. Based on these results, a phase I study of combination therapy with nab-paclitaxel, carboplatin and trastuzumab was planned, in order to estimate its efficacy and safety for HER2-overexpressing locally advanced breast cancer. The present study was designed to determine the dose-limiting toxicity (DLT), maximum tolerated dose and recommended dose of this combination treatment in women with HER2-overexpressing locally advanced breast cancer. The starting dose of nab-paclitaxel was 220 mg/m 2 (level 1), and the dose was escalated to 260 mg/m 2 (level 2). Nab-paclitaxel was administered with carboplatin (area under the curve, 6 mg/ml/min) and trastuzumab tri-weekly. A total of 6 patients were enrolled. Although no DLT was observed during the first cycle, 4 patients developed grade 4 thrombocytopenia, 2 had grade 4 neutropenia and 3 exhibited a grade 4 decrease in hemoglobin levels. In the present phase I study, although no patients experienced DLTs, this regimen was associated with severe hematological toxicities and it was not well tolerated. However, considering the high efficacy and lower risk of cardiotoxicity and secondary carcinogenesis with taxane, platinum and trastuzumab combination therapy, further evaluation of another regimen including weekly administration or a more accurate dose setting should be conducted.

A 71-year-old male was referred to our hospital with right scrotal swelling. The ultrasonography and magnetic resonance imaging revealed a 6.5 cm mass adjacent to the right testicle. Under the preoperative diagnosis of benign intrascrotal lipoma, local tumor excision through scrotal skin incision was performed. The histopathological examination revealed atypical lipomatous tumor/well-differentiated liposarcoma. With the evidence of malignancy, two-stage surgery was mandatory. Thus, radical orchiectomy with high cord ligation and wide excision of surrounding soft tissue structures through inguinal skin incision was performed. However, there were no tumor cells remaining in the resected samples. Neither adjuvant radiation therapy nor chemotherapy has been performed since contrast computed tomography showed no evidence of metastasis. He is free of disease at 1 year postoperatively.

When making decisions in everyday life, we often have to choose between uncertain outcomes. Economic studies have demonstrated that healthy people tend to prefer options with known probabilities (risk) than those with unknown probabilities (ambiguity), which is referred to as "ambiguity aversion." However, it remains unclear how patients with schizophrenia behave under ambiguity, despite growing evidence of their altered decision-making under uncertainty. In this study, combining economic tools and functional magnetic resonance imaging (fMRI), we assessed the attitudes toward risk/ambiguity and investigated the neural correlates during decision-making under risk/ambiguity in schizophrenia. Although no significant difference in attitudes under risk was observed, patients with schizophrenia chose ambiguity significantly more often than the healthy controls. Attitudes under risk and ambiguity did not correlate across patients with schizophrenia. Furthermore, unlike in the healthy controls, activation of the left lateral orbitofrontal cortex was not increased during decision-making under ambiguity compared to under risk in schizophrenia. These results suggest that ambiguity aversion, a well-established subjective bias, is attenuated in patients with schizophrenia, highlighting the need to distinguish between risk and ambiguity when assessing decision-making under these situations. Our findings, comprising important clinical implications, contribute to improved understanding of the mechanisms underlying altered decision-making in patients with schizophrenia., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A 75-year-old woman was diagnosed with aplastic anemia 6 months ago and was under follow-up at our hospital. She had originallypresented to our hospital because of ongoing diarrhea and abdominal pain. Her blood tests showed a rise in inflammatorymarkers (WBC count was 6,900/mL[eosinophil was 1.3%]and CRP was 8.60mg/dL). Her abdominal computed tomography(CT)scan showed gastric wall and small intestine edema as well as ascites. There was no evidence of free air. We diagnosed her with generalized peritonitis and performed an emergencyoperation . Intra-operatively, moderate amounts of yellowish ascitic fluid were noted, as was a diffuse reddening of the small intestine. We performed a partial resection of the small intestine. Histopathological examination showed transmural infiltration of inflammatorycells mainly comprising eosinophilic leukocytes. Eosinophils were also present in the ascitic fluid. Post-operative blood tests confirmed eosinophilic, and we diagnosed her with eosinophilic enteritis. She was started on corticosteroids and her symptoms improved immediately. We report a rare case of eosinophilic enteritis with a review of the pertinent literature.

It has now been more than 20 years since laparoscopic gastrectomy was introduced in Japan, and the 2014 guidelines recommend laparoscopic distal gastrectomy as a treatment for cStage I gastric cancers. This operation facilitates minute lymphadenectomy via the option of enlarging the image, but there are some difficulties associated with limited range of motion. A hallmark of gastrectomy for gastric cancer is the widespread dissection of lymph nodes, and the limits imposed by laparoscopic forceps can complicate the operation. In this study, we subdivided regional lymph nodes, examined distal gastrectomy cases in our hospital, and compared the contents of lymphadenectomy.

A 59-year-old woman presented to our hospital with a mass in her left breast. Mammography and ultrasound showed a 9 ×11×12mm mass in her left breast, and left axillary lymph adenopathy. Core needle biopsy and pathological examination confirmed the diagnosis of ER-negative, PgR-negative, HER2-positive invasive ductal carcinoma with axillary lymph metastasis. Dynamic computed tomography(CT)and bone scintigraphy showed no metastasis. A diagnosis ofbreast cancer with stage II A(T1N1M0)was made, and we started neoadjuvant chemotherapy. After 4 cycles of chemotherapy with 5-fluorouracil/ epirubicin/cyclophosphamide in 3-weekly cycles, we administered combination chemotherapy ofnab -paclitaxel and trastuzumab in 3-weekly cycles. After 7 months, the tumor disappeared and the axillary lymph node got significantly smaller. We performed nipple-sparing mastectomy/axillary lymph nodes dissection/tissue-expander placement. The pathological examination ofthe resected tumor confirmed a pathological complete response(pCR). The patient was treated with implant reconstruction and adjuvant therapy. One year has passed after the surgery, and no significant problem has been observed.

We reviewed 21 patients with locally advanced breast cancer with distant metastasis.The median age was 61 years.The median time to presentation at hospital was 13 months, and the median neoplasm diameter on the first visit was 10 cm.The main histological type was scirrhous carcinoma.Sixteen cases tested positive for hormone receptor(76%), 4 tested positive for HER2(19%), and 3 were triple negative(14%).Four patients underwent surgery.The techniques performed included mastectomy and axillary lymph node dissection.Three patients experienced local recurrence.The first-line treatment was surgery for 1 patient, chemotherapy for 12 patients, hormonal therapy for 7 patients, and trastuzumab for the HER2 positive patients.The median follow-up period was 49 months.The patients for where an operation was performed were 49 months and the operation not- enforcement patients were 54 months.If treatment is possible for patients with locally advanced breast cancer with distant metastasis, multidisciplinary treatment according to individual patient characteristics is recommended. In the case of surgical treatment, careful consideration must also be given to these characteristics.

A 50-year-old post-menopausal woman with sudden lower abdominal pain was transported to hospital by ambulance. Abdominal symptoms and computed tomography(CT)suggested a diagnosis of acute pan-peritonitis due to gastrointestinal perforation, and emergency surgery was performed. The intraoperative findings led to a diagnosis of a ruptured cyst in the left ovary, a portion of which was observed to be partially solid, and therefore, ovarian cancer was suspected. Accordingly, a unilateral(left)salpingo-oophorectomy and intraperitoneal drainage were performed with assistance from a gynecologist. Following a diagnosis of ovarian clear cell adenocarcinoma based on histopathological examination, the patient underwent further debulking surgery at a later date, followed by postoperative chemotherapy. In acute pan-peritonitis associated with a large quantity of ascites in women, the rupture of ovarian tumors should be considered as a possible etiology. The therapeutic strategy for ovarian cancer is determined according to post-operative staging, even during emergency surgery. It is therefore important not only to repair the rupture, but also, if possible, to perform a diagnosticbiopsy or resection.

There is controversy as to whether immediate autologous breast reconstruction followed by postoperative radiotherapy has acceptable complications and aesthetic outcomes., Purpose: To evaluate the interval between surgery and adjuvant chemotherapy and radiation in patients treated with mastectomy and immediate expander-implant reconstruction, and to evaluate locoregional and distant control and cosmesis in these patients., Methods and Materials: Between 2011 and 2015, 9 patients with breast cancer were treated at our institution with definitive mastectomy and axillary lymph node dissection followed by immediate tissue expander placement and postreconstruction radiotherapy. We reviewed the complications of implant-based breast reconstruction followed by postreconstruction radiotherapy., Results: The timing of irradiation was after implant insertion for 8 patients and after tissue expander insertion for 1 patient. The mean follow-up was 601 days. There were no unacceptable complications or local recurrences., Conclusions: For the majority of patients, overall symmetry, aesthetic results, and patient satisfaction were high. Breast reconstruction using tissue expansion and implants is an acceptable option for the subset of patients who may undergo postreconstruction radiotherapy.

A 90-year-old woman was referred to our hospital because of abdominal distension and pretibial edema. No tumors were palpable in either breast. Her abdomen was distended and palpitation was noticed. Laboratory examination revealed hypercalcemia and elevated levels of tumor markers(PIVKA- II , CEA, CA19-9, SCC). Contrast-enhanced computed tomography(CT) showed pleural effusion and ascites, an approximately 17-mm high-contrast mass in the D area of the left breast, and osteolysis of the dorsal lumber spine. We initiated treatment for pleural effusion, ascites, and hypercalcemia. However, on her 11th day in the hospital, hematemesis was observed and the patient died. We suspected metastasis of a malignant tumor, but a primary lesion had not been identified; therefore, an autopsy was performed. Autopsy showed a 17-mm mass in the D area of the left breast. Histopathological examination showed the growth of a signet-ring cell tumor that was immunohistochemically ER-positive, PgR-positive, and E-cadherin-negative. The patient was diagnosed with primary signet-ring cell carcinoma of the breast derived from lobular carcinoma. We reported a rare case of primary signet-ring cell carcinoma of the breast with a review of literature.

We report a case of resection of a paraaortic lymph node recurrence, wherein complete response to bevacizumab was observed. Our patient was a 50-year-old woman who had a paraaortic lymph node recurrence during adjuvant chemotherapy with FOLFOX 6 months after surgery for sigmoid colon cancer. She was treated with chemotherapy consisting of FOLFOX plus bevacizumab/FOLFIRI plus bevacizumab, which suppressed progression of the periaortic lymph node recurrence. She underwent surgery for the paraaortic lymph node recurrence, and the pathologic result was complete response. We report that bevacizumab was effective for her paraaortic lymph node recurrence.

We report 2 cases of metastatic rectal cancer patients who received chemotherapy with FOLFOXIRI plus bevacizumab(Bev). Case 1: A 54-year-old woman diagnosed with advanced rectal cancer with synchronous liver metastasis underwent a laparoscopic low anterior resection. After the operation, she received FOLFOXIRI plus Bev treatment, and experienced Grade 4 adverse events, including dyspnea and ventricular fibrillation(Vf). After chemotherapy, no other metastasis was detected except a liver metastasis, and partial resection of the liver was performed. Histopathological evaluation revealed that the effect of the chemotherapy was Grade 1a. After liver resection, FOLFOXIRI plus Bev was administered, and a recurrence of the rectal cancer was not detected. Case 2: A 44-year-old woman was diagnosed with advanced rectal cancer with synchronous liver metastasis, distant lymph nodes metastasis, and vaginal invasion. First a colostomy was performed and FOLFOXIRI plus Bev treatment was administered. Grade 3 adverse events, including tremor, neuralgia, and anemia occurred, and chemotherapy was stopped for 3 months. Her adverse events were not under control when progression of the disease was detected, and her treatment was changed to another chemotherapy regimen.

An 85-year-old man presented to the emergency department with vomiting. He had tenderness in the left abdomen and under the umbilicus. Laboratory data showed an increase in the inflammatory response. Enhanced abdominal computed tomography showed thickening ofthe small intestinal wall in the lower left abdomen with a small amount ofadjacent free air. The fat tissue around the small intestine also revealed a high density area suggestive of inflammation. A diagnosis of peritonitis caused by intestinal perforation was made and an emergency operation was performed. We resected part of the ileum about 90 cm from the ileum end. The resected specimen showed a 1 by 1 cm mass with an ulcer and perforation at the base of the tumor. Histopathological findings revealed densely increased numbers of monomorphic medium-sized lymphoma cells infiltrating into all layers ofthe intestine. Immunohistochemically, the lymphocytes were positive for CD3, CD20, CD30, and CD79a. We diagnosed diffuse large B-cell lymphoma. Two cycles ofchemotherapy were given post-operatively. A recurrence was not observed. After chemotherapy he was transferred to rehabilitation.

The sunk cost effect, an interesting and well-known maladaptive behavior, is pervasive in real life, and thus has been studied in various disciplines, including economics, psychology, organizational behavior, politics, and biology. However, the neural mechanisms underlying the sunk cost effect have not been clearly established, nor have their association with differences in individual susceptibility to the effect. Using functional magnetic resonance imaging, we investigated neural responses induced by sunk costs along with measures of core human personality. We found that individuals who tend to adhere to social rules and regulations (who are high in measured agreeableness and conscientiousness) are more susceptible to the sunk cost effect. Furthermore, this behavioral observation was strongly mediated by insula activity during sunk cost decision-making. Tight coupling between the insula and lateral prefrontal cortex was also observed during decision-making under sunk costs. Our findings reveal how individual differences can affect decision-making under sunk costs, thereby contributing to a better understanding of the psychological and neural mechanisms of the sunk cost effect.

This data article tested whether polymorphisms within the dopamine D4 receptor (DRD4) gene promoter can lead to differences in the promoter activity. The variants, a 120-bp variable number tandem repeat (VNTR), -906 T/C, -809 G/A, -616G/C, and -521C/T, were introduced into the DRD4 promoter and the promoter activity was measured in a neural cell line using the luciferase assay. However, no differences were detected among the haplotypes investigated, and the in vitro data obtained from our protocol could not support the involvement of DRD4 promoter polymorphisms in heritable human traits.

The treatment goals for metastatic breast cancer (MBC) are prolonging survival and improving the quality of life. Eribulin, a non-taxane tubulin inhibitor, demonstrated improved survival in previous studies and also showed mild toxicity when used in late-line therapy for MBC. We conducted a phase II study to investigate the efficacy of eribulin mesylate as the first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative MBC. This was a phase II, open-label, single-arm, multicenter trial conducted in Japan. Patients with HER2-negative MBC received intravenous eribulin (1.4 mg/m(2) on days 1 and 8 of each 21-day cycle). The primary efficacy outcome was overall response rate (ORR). Secondary outcomes included time to treatment failure, progression-free survival (PFS), overall survival (OS), and safety. A total of 35 patients were enrolled and received a median of 8 (range 1-21) cycles of eribulin therapy. ORR and clinical benefit rate were 54.3 and 62.9 %, respectively. Median PFS was 5.8 months and median OS was 35.9 months. Grade 3 or 4 neutropenia was observed in 63 % of patients. The majority of non-hematological adverse events were mild in severity. The present trial demonstrated that eribulin has antitumor activity comparable with other key established cytotoxic agents with acceptable safety and tolerability. Thus, eribulin as first-line chemotherapy might be beneficial for patients with HER2-negative MBC.

We experienced a case of locally advanced breast cancer treated with modified radical mastectomy with immediate reconstruction using a tissue expander after endocrine therapy. A 64-year-old postmenopausal woman had a 50 mm tumor in her right breast with extensive reddening of the skin. She had axillary lymph node metastasis. Core needle biopsy showed invasive ductal carcinoma with positive hormone receptor (ER+, PgR+) and negative HER2 status. The patient was diagnosed with locally-advanced breast cancer (cT4bN1M0, stage ⅢB). She was treated with anastrozole at a dose of 1 mg per day. The tumor decreased in size gradually and became operable after 7 months of anastrozole monotherapy. She underwent modified radical mastectomy with immediate reconstruction using a tissue expander. The resected specimen was a 30 mm tumor; adverse effects due to endocrine therapy were of Grade 1a severity. Seven months after adjuvant chemotherapy (FEC→DTX), the tissue expander was removed, and the right breast was reconstructed using an implant. No complications were noted, and the patient was treated with radiation therapy. Ten months have passed since surgery, and no local recurrence or distant metastasis has been noted.

Background: The effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery is unclear. In this study, we investigated the effectiveness of intraoperative histologic assessment of surgical margins for breast-conserving surgery., Methods: Sixty-six patients who underwent breast-conserving surgery for breast cancer at our hospital between January 2007 and December 2013 were retrospectively examined for an association between the surgical margin status and locoregional recurrence. The surgical margins were then evaluated by intraoperative histologic assessment., Results: The median observation period was 52 months. Positive margins were found in 14 patients (21%). A total mastectomy was performed in 9 patients, and additional resection in 5 patients. In the permanent tissue sample, the intraoperative assessment was found to be false negative in 2 patients (3.8%), who received boost irradiation postoperatively. No locoregional recurrence was observed in all patients who underwent additional resection or total mastectomy due to positive margins. The rate of margin positivity was significantly higher in invasive lobular carcinomas and in cancers with intraductal extension., Conclusions: Intraoperative histologic assessment of the surgical margin was useful for reducing the rate of local recurrence.

CHRNA1 encodes the α subunit of nicotinic acetylcholine receptors (nAChRs) and is expressed at the neuromuscular junction. Moreover, it is one of the causative genes of Congenital Myasthenic Syndromes (CMS). CHRNA1 undergoes alternative splicing to produce two splice variants: P3A(-), without exon P3A, and P3A(+), with the exon P3A. Only P3A(-) forms functional nAChR. Aberrant alternative splicing caused by intronic or exonic point mutations in patients leads to an extraordinary increase in P3A(+) and a concomitant decrease in P3A(-). Consequently this resulted in a shortage of functional receptors. Aiming to restore the imbalance between the two splice products, antisense oligonucleotides (AONs) were employed to induce exon P3A skipping. Three AON sequences were designed to sterically block the putative binding sequences for splicing factors necessary for exon recognition. Herein, we show that AON complementary to the 5' splice site of the exon was the most effective at exon skipping of the minigene with causative mutations, as well as endogenous wild-type CHRNA1. We conclude that single administration of the AON against the 5' splice site is a promising therapeutic approach for patients based on the dose-dependent effect of the AON and the additive effect of combined AONs. This conclusion is favorable to patients with inherited diseases of uncertain etiology that arise from aberrant splicing leading to a subsequent loss of functional translation products because our findings encourage the option of AON treatment as a therapeutic for these prospectively identified diseases., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Cognitive behavioral therapy (CBT) is widely used to treat major depressive disorder (MDD). Although improved response prediction could facilitate the development of individualized treatment plans, few studies have investigated whether underlying brain structure is related to CBT response in MDD., Methods: Ten MDD patients who received individual CBT were studied in this study. We investigated the relationship between the regional gray matter (GM) volume and subsequent responses to CBT using voxel-based morphometry., Results: The degree of improvement in depressive symptoms was positively correlated with GM volume in the caudal portion of the anterior cingulate cortex., Limitations: The sample size was small, and the effects of medication on the results could not be excluded., Conclusions: Our results, although preliminary, suggest that the anterior cingulate cortex is a key structure whose volume can be used to predict responses to CBT and is thus a potential prognostic marker in MDD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

A case of successful chemotherapy for a metachronous liver metastasis following resection for sigmoid colon cancer is presented. A 51-year-old man underwent sigmoidectomy, ileocecal resection, and descending colon colostomy for sigmoid colon cancer with ileum invasion. Six courses of FOLFOX4 were performed as adjuvant chemotherapy. One year after sigmoidectomy, a liver metastasis was detected on computed tomography (CT) examination. Chemotherapy with FOLFOX+bevacizumab was restarted. Three courses were administered, but hepatic dysfunction occurred after the second and third courses, and FOLFOX was discontinued. Subsequent chemotherapy was reinitiated with FOLFIRI+bevacizumab. After 9 courses, the carcinoembryonic antigen level was normalized and appeared to be decreased by imaging studies. Upon the patient's request, only oral S-1 was administered. After 2 courses, CT revealed that the diameter of the tumor had increased by 2 cm. Therefore, right lobectomy of the liver, colostomy closure, and anastomosis were performed. During these procedures, a nodule was found in the omentum and was removed. Rapid intra-operative diagnosis revealed peritoneal dissemination. The pathological diagnosis was liver metastasis of sigmoid colon cancer, with necrosis and fibrosis seen in approximately one-half of specimens. The surgical margins were negative. Neither metastatic cancer nor dissemination were found in the resected greater omentum.

A 61-year-old man was diagnosed with rectal cancer with multiple liver metastases in December 2009, and low anterior resection of the rectum was performed. Postoperative adjuvant chemotherapy with 6 courses of oxaliplatin, Leucovorin, and 5-FU (FOLFOX4) and bevacizumab was initiated, followed by 5 courses of fluorouracil, Leucovorin, and irinotecan (FOLFIRI) and bevacizumab. Right posterior segment (S6, S7) hepatectomy with enucleation of S2, S3 and S5 was performed, and chemotherapy with FOLFOX4 (11 courses) was administered. New metastases in the S5 segment were observed in August 2011 and right hepatic lobectomy was performed. The patient then underwent 8 courses of adjuvant chemotherapy with FOLFOX4. However, left hepatic lobe lateral segment and caudate lobe metastases then appeared. Subsequent repeated chemotherapy with FOLFIRI plus cetuximab (3 courses) and irinotecan plus cetuximab was interrupted in August 2013 owing to adverse events resulting in rapid growth of hepatic metastases. The patient underwent hepatic left lateral segmentectomy and left caudate lobectomy. The postoperative course was uneventful and the patient has currently survived 4 years and 7 months after the initial surgery.

Stage IV gastric cancer has poor prognosis, and median survival time (MST) is reported to range from 6 to 13 months. We report a case of long-term survival in a Stage IV gastric cancer patient who was successfully treated with multi combination chemotherapy with S-1. A 73-year-old woman presenting with gastric cancer with pyloric stenosis and peritoneal dissemination at the sigmoid colon underwent distal gastrectomy with D2 lymphadenectomy and sigmoidectomy. She received adjuvant chemotherapy with S-1 and CDDP after surgery. During the twelfth administration of S-1 and CDDP, she developed an anaphylactic reaction against CDDP; therefore, only S-1 was administered for the next 6 courses. Thirty one months postgastrectomy, a left ovarian metastasis (about 4 cm) was detected by computed tomography. Two courses of S-1 and CPT-11 were administered; however, the ovarian metastasis grew to twice its initial size. She underwent hysterectomy and bilateral ovariectomy. The pathological diagnosis was metastatic tumors in the uterus and ovary(Krukenberg tumor). After the second surgery, S-1 and docetaxel therapy was initiated. A metastasis (S2, 5mm diameter) appeared in the right lung around 65 months after the gastrectomy. The patient received a total of 28 courses, up until 69 months post-gastrectomy. At present, she hopes to finish the chemotherapy and is consulting a palliative care facility. At 80 months post-gastrectomy, she has no symptoms because the lung metastasis exhibits slow growth (15 mm diameter), and is maintaining her quality of life (QOL).

Background: A standard treatment for primary peritoneal carcinoma has not been established to date. We describe a case in which this cancer was successfully treated by use of paclitaxel and carboplatin chemotherapy., Case: An 80-year-old woman who presented with abdominal distension and right upper abdominal pain was diagnosed with massive ascites and an omentum tumor via abdominal computed tomography and magnetic resonance imaging (MRI); her ovaries were normal-sized. Serum levels of the tumor marker CA125 were above normal (170 U/mL), and aspiration cytology showed the presence of adenocarcinoma cells. Despite several examinations, the primary tumor was not detected. The patient underwent exploratory laparotomy and was diagnosed with primary peritoneal carcinoma. She received combination chemotherapy consisting of paclitaxel and carboplatin. Serum CA125 levels returned to normal, and an MRI showed no evidence ofa tumor., Conclusion: Paclitaxel and carboplatin combination chemotherapy is effective for treatment of primary peritoneal adenocarcinomas.

A 78-year-old man presented to our hospital with lung abnormality on his chest radiograph. Computed tomography (CT) showed a mass and obstructive pneumonia in the right upper lobe of the lung. The mass was diagnosed as a pulmonary adenocarcinoma with a bronchoscopy (cT4N2M0, Stage IIIB). CT also revealed multiple hepatic tumors, which were diagnosed as hepatocellular carcinoma (HCC) by dynamic CT and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging(EOB-MRI). First, we treated the lung cancer with a combination of cisplatin and pemetrexed (PEM), but it caused renal dysfunction. Carboplatin (CBDCA) and PEM combination chemotherapy was administered, and not only the lung cancer but also the HCCs decreased in size. There are few reports of synchronous double cancers of HCC and primary lung cancer, and the treatment is not established. We report that platinum-containing anticancer drugs such as CBDCA may be effective against synchronous double cancers of HCC and lung cancer.

There is insufficient evidence for the pre-operative use of chemoradiotherapy (CRT) in treatment of advanced rectal cancers, and its efficiency and safety are unclear. However, it has recently been suggested that a new class of carcinostatic agents are more effective during preoperative CRT. Under the National Comprehensive Cancer Network (NCCN) guidelines, 5-FU and capecitabine have been recommended as the standard drugs for use during combination chemoradiotherapy. The Japanese Society for Cancer of Colon and Rectum (JSCCR) guidelines for 2014 also recommend the use of both drugs during preoperative CRT. We report a case of rectal cancer, which was successfully treated with radical resection and neoadjuvant chemoradiotherapy.

Background: Empathy has a central role in successful interpersonal engagement. Several studies have reported altered empathy in major depressive disorder (MDD), which could lead to interpersonal difficulties. However, the neural basis of altered empathy in the disorder is still largely unknown. To address this, we performed functional magnetic resonance imaging that tested empathy for others׳ pain in MDD patients., Methods: Eleven patients with MDD and 11 age-, gender-, handedness-, and education level-matched healthy control subjects were studied. We compared MDD patients and healthy controls for their regional hemodynamic responses to visual perception of videos showing human hands in painful situations. We also assessed subjective pain ratings of the videos in each group., Results: The MDD patients showed lower pain ratings for the painful videos compared with the healthy controls. In addition, the MDD patients showed reduced cerebral activation in the left middle cingulate cortex, and the right somatosensory-related cortices, whereas they showed greater cerebral activation in the left inferior frontal gyrus., Limitations: We relied on a relatively small sample size and could not exclude effects of medications., Conclusions: These results suggest that in MDD patients the altered neural activations in these regions may be associated with a deficit in the identification of pain in others. This study adds to our understanding of the neural mechanism involved in empathy in MDD., (Copyright © 2014 Elsevier B.V. All rights reserved.)

XELOX plus bevacizumab is an effective treatment strategy and has a manageable tolerability profile when administered to Japanese patients with metastatic colorectal cancer (mCRC). In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efficacy and safety in clinical practice. In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a first-line treatment between September, 2009 and April, 2012. Eligible patients had histologically confirmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m 2 on day 1 plus oral capecitabine 1,000 mg/m 2 twice daily for 2 weeks of a 3-week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. The median progression-free survival (PFS) was 290 days [95% confidence interval (CI): 222-409 days] and the median OS was 816 days (95% CI: 490 days-not calculated). The response rate (RR; complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. The most common adverse events observed following administration of XELOX plus bevacizumab were neurosensory toxicity (82.5%), anorexia (50%), hypertension (45%) and a decrease in the platelet count (40%). The most common grade 3/4 adverse events were neurosensory toxicity (15%) and fatigue (15%). In conclusion, XELOX plus bevacizumab may be considered a routine first-line treatment option for patients with mCRC. Notably, the combination of capecitabine and bevacizumab was safe with an acceptable toxicity profile and induced a significant rate of disease control.

We report a case of gastric cancer accompanied by disseminated carcinomatosis of the bone marrow treated with S-1 and cisplatin( CDDP) combination chemotherapy. The patient was a 68-year-old woman who was detected as having disseminated intravascular coagulation( DIC) during an examination for gastric cancer and she was diagnosed as having disseminated carcinomatosis of the bone marrow by lumbar puncture. She was immediately treated with S-1 and CDDP combination chemotherapy( S-1, 80 mg/body orally administered[ po] on days 1-21 and CDDP, 60 mg/body intravenously [iv] administered on day 8) and her DIC improved on the fourth day. Subsequently, the patient was treated with 3 courses of combination chemotherapy and she survived for 184 days from the initiation of the treatment. Although disseminated carcinomatosis of the bone marrow is associated with a poor prognosis, we believe that the duration of survival of our patient was extended due to initiation of chemotherapy at an early stage.

A 63-year-old man presented with a tumor in his left supraclavicular fossa. Aspiration biopsy of the tumor revealed metastasis of an adenocarcinoma. Further examination indicated the presence of advanced sigmoid colon cancer with metastases to Virchow's lymph nodes and the para-aortic lymph nodes. Sigmoidectomy with D3 lymph node dissection was performed. Histological examination revealed moderately and well differentiated adenocarcinomas( double cancers) that had invaded the subserosa as well as metastases of the para-aortic lymph nodes. Twelve days after the operation, systemic chemotherapy with FOLFOX4 (8 courses), followed by FOLFIRI (8 courses) was administered. Six months later, CT examination determined that the metastases of Virchow's lymph nodes and the para-aortic lymph nodes had completely disappeared. Capecitabine was administered for approximately 1 year, and complete response was achieved. However, a pancreatic tumor measuring 2×3 cm was detected 44 months after the operation. Distal pancreatectomy was performed and pathological examination that included immunohistochemical staining (CK7 and CK20) of the tumor indicated the primary pancreatic cancer. The patient was treated with chemoradiotherapy after the operation and survived for 5 years and 9 months after the initial operation.

In cases of advanced rectal cancer, preoperative chemoradiotherapy( CRT) serves to improve the local control rate, survival rate, radical resection rate, and/or probability of sphincter muscle preservation. According to the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2010 for the treatment of colorectal cancer, preoperative CRT is the standard treatment for rectal cancer in Europe and the United States. However, there is insufficient evidence in support of its efficacy and safety in Japan, and therefore, CRT needs to be evaluated in properly designed clinical trials. Recently, several studies have reported on the efficacy of preoperative CRT in Japan. Herein, we report a case of rectal cancer in which radical resection was successfully performed with neo-adjuvant CRT.

A 67-year-old woman with complaints of cough and dyspnea was admitted; her chest radiographs and computed tomography (CT) scans revealed pulmonary carcinomatous lymphangitis. Endoscopic examination revealed advanced gastric cancer and the patient was treated with a combination of 40 mg/m2 docetaxel, administered on day 1, and S-1 100 mg/body/day, administered for 14 days followed by a 7-day interval, as 1 course despite her performance status( PS) being grade 3. After 2 courses of chemotherapy, CT showed that the carcinomatous lymphangitis had improved, and the patient was discharged with PS of grade 0. We report that combination chemotherapy with docetaxel and S-1 might be effective for the treatment of advanced gastric cancer with carcinomatous lymphangitis of the lung in patients with a poor systemic condition.

In the present study, we evaluated the outcome of preoperative treatment with S-1 and CDDP for the treatment of advanced gastric cancer. Fifty-five cases of advanced gastric cancer received pre-operative treatment with S-1 and CDDP. The tumor control rate( PR and CR according to RECIST criteria) was 55%. The clinical response and histological response to the treatment and curative resection were closely related to favorable postoperative survival. We noted that patients who demonstrated CR or PR received S-1 as postoperative treatment, whereas those with SD or PD were more likely to receive paclitaxel as postoperative treatment. Preoperative treatment with S-1 and CDDP was not only an effective initial treatment, but also demonstrated favorable results in a S-1 in vivo sensitivity test.

It is common to use systemic chemotherapy, instead of hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) or other cytotoxic agents, for unresectable hepatic metastases in colorectal cancer patients. Nevertheless, systemic administration of anticancer agents such as FOLFOX or FOLFIRI is sometimes difficult to continue for infirm patients. A 71-year-old female who had undergone sigmoidectomy for sigmoid colon cancer received HAI for 12 months because of big bilobar hepatic metastases and poor performance status. Thereafter, a two-stage hepatectomy(first, left lobe: second, S7+8 and S5) was performed successfully. She has been alive for 2.5 years after the first operation but with two small lung metastases in the left lobe. Because of bad performance status and her weak social and familial conditions, treatment with standard systemic chemotherapy could not be continued. In such cases, HAI should be performed if the metastases are limited to the liver.

Frontofacial monobloc advancement is one of the most rewarding techniques for correcting aesthetic and functional problems of patients with severe craniofacial synostosis, which can advance the upper and middle third of the face simultaneously. Application of gradual distraction technique has been reported to reduce notorious risks after a frontofacial monobloc advancement. The so-called "bibloc advancement" is a derivative of the frontofacial monobloc advancement. "Facial bloc" is horizontally divided into 2 different components: fronto-orbital component and maxillozygomatic component. From a different angle, it can be described as a combination of fronto-orbital advancement and Le Fort III advancement. Two pairs of distracters (1 internal for the supraorbital area and 1 external for the maxillozygomatic area with a pair of cross-facial pinning) were applied after the so-called bibloc osteotomy. Advancement of the upper and middle third of the face was done individually. This technique can be a good option for treating infants with severe syndromic craniofacial synostosis.