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Lactoferrin (LF) is a multifunctional protein abundant in breast milk that modulates the functions of neural stem cells. Recent studies have demonstrated the efficacy of bovine LF (bLF) in mitigating behavioral changes; however, the molecular mechanisms on the nervous system have not yet been elucidated. The presented study aimed to characterize the molecular mechanisms of bLF on nerve extension in PC12 cells. PC12 cells were treated with 0.01-1000 µg/mL of bLF, and cell viability was determined using the cell counting kit-8 assay after treatment for 24 h. Morphometric evaluation was performed after 24 or 72 h of treatment with 50 ng/mL nerve growth factor (NGF) or 100-500 µg/mL bLF. The molecular mechanisms were investigated using Western blotting and real-time quantitative PCR. Cell viability was significantly decreased after treatment with 600-1000 µg/mL bLF for 24 h compared with the control group. Morphometric evaluation revealed neurite outgrowth after 72 h of NGF treatment, with a significant increase in neurite outgrowth after treatment with 250 µg/mL bLF. The phosphorylated p44/42 expression ratio peaked at 5 min and persisted for up to 10 min. Quantitative real-time PCR revealed a significant decrease in MAP2 expression. Our findings suggested that bLF enhanced PC12 cell neurite outgrowth to a similar extent as NGF. These effects are thought to be mediated via the TrkA receptor and activated by the phosphorylated ERK signaling pathway. Therefore, this study demonstrates that bLF promotes neurite outgrowth via a pathway similar to that of NGF.

Fluctuations in estradiol levels at each stage of life in women are considered one of the causes of mental diseases through their effects on the central nervous system. During menopause, a decrease in estradiol levels has been reported to affect the serotonin nervous system and induce depression-like and anxiety symptoms. However, the regulation of brain and behaviour during childhood and adolescence is poorly understood. Moreover, the role of oestrogen receptors α and β in the regulation of the serotonergic nervous system has been reported, but little is known about the involvement of G protein-coupled receptor 30. Therefore, in this study, we used an ovariectomized childhood mouse model to analyse behaviour and investigate the effects on the serotonin nervous system. We showed that ovariectomy surgery at 4 weeks of age, which is the weaning period, induced a decrease in spontaneous locomotor activity during the active period and a preference for novel mice over familiar mice in the three-chamber social test at 10 weeks of age. In addition, the administration of G-1, a protein-coupled receptor 30 agonist, to ovariectomized mice suppressed spontaneous locomotor activity and the preference for novel mice. Furthermore, we demonstrated that childhood ovariectomy induces increased tryptophan hydroxylase gene expression in the raphe nucleus and increased serotonin release in the amygdaloid nucleus, and administration of G-1 ameliorated these effects. Our study suggests that G protein-coupled receptor 30-mediated regulation of serotonin synthesis is involved in changes in activity and social-cognitive behaviour due to decreased estradiol levels during childhood., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Background: Extrahepatic cholangiocarcinoma (eCCA) is a rare and aggressive disease and consisted of conventional eCCA and intraductal papillary neoplasm of the bile duct (IPNB). Intraepithelial spread (IES) of cancer cells beyond the invasive area is often observed in IPNBs; however, the prevalence of IES remains to be examined in conventional eCCAs. Here, we evaluated the clinicopathological features of eCCAs according to tumor location, with a focus on the presence of IES. The IES extension was also compared among biliary tract cancers (BTCs)., Methods: We examined the prevalence and clinicopathological significance of IES in eCCAs (n=382) and the IES extension of BTCs, including gallbladder (n=172), cystic duct (n=20), and ampullary cancers (n=102)., Results: Among the invasive eCCAs, IPNB had a higher rate of IES (89.2%) than conventional eCCAs (57.0%). Among conventional eCCAs, distal eCCAs (75.4%) had a significantly higher prevalence of IES than perihilar eCCAs (41.3%). The presence of IES was associated with a significantly higher survival rate in patients with distal eCCAs ( P =0.030). Extension of the IES into the cystic duct (CyD) in distal eCCAs that cancer cells reached the junction of the CyD was a favorable prognostic factor ( P <0.001). The association of survival with IES, either on the extrahepatic bile duct or on the CyD, differed depending on the tumor location and type of eCCA. The extension properties of IES were also dependent on different types of tumors among BTCs; usually, the IES incidence became higher than 50% in the tissues that the tumor developed, whereas IES extension to other tissues decreased the incidence., Conclusion: Thus, eCCAs have different clinicopathological characteristics depending on the tumor location and type., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nagashima, Esaki, Nara, Ban, Takamoto, Mizui, Shimada and Hiraoka.)

Lactoferrin (LF), known to be present in mammalian milk, has been reported to promote the proliferation of osteoblasts and suppress bone resorption by affecting osteoclasts. However, the mechanisms underlying the effects of human sources LF on osteoblast differentiation have not yet been elucidated, and almost studies have used LF from bovine sources. The presented study aimed to characterize the molecular mechanisms of bovine lactoferrin (IF-I) and human recombinant lactoferrin (LF-II) on MC3T3-E1 pre-osteoblast cells. MC3T3-E1 cells were treated with LF, ascorbic acid, and β-glycerophosphate (β-GP). Cell proliferation was analyzed using the MTT assay. Alkaline phosphatase activation and osteopontin expression levels were evaluated via cell staining and immunocytochemistry. The differentiation markers were examined using quantitative real-time PCR. The cell viability assay showed the treatment of 100 μg/mL LF significantly increased; however, it was suppressed by the simultaneous treatment of ascorbic acid and β-GP. Alizarin red staining showed that the 100 μg/mL treatment of LF enhanced calcification. Quantitative real-time PCR showed a significant increase in osterix expression. The results suggest that treatment with both LFs enhanced MC3T3-E1 cell differentiation and promoted calcification. The mechanisms of calcification suggest that LFs are affected by an increase in osterix and osteocalcin mRNA levels.

Objective: To validate the newly developed artificial intelligence (AI)-assisted simulation by evaluating the speed of three-dimensional (3D) reconstruction and accuracy of segmental volumetry among patients with liver tumors., Background: AI with a deep learning algorithm based on healthy liver computer tomography images has been developed to assist three-dimensional liver reconstruction in virtual hepatectomy., Methods: 3D reconstruction using hepatic computed tomography scans of 144 patients with liver tumors was performed using two different versions of Synapse 3D (Fujifilm, Tokyo, Japan): the manual method based on the tracking algorithm and the AI-assisted method. Processing time to 3D reconstruction and volumetry of whole liver, tumor-containing and tumor-free segments were compared., Results: The median total liver volume and the volume ratio of a tumor-containing and a tumor-free segment were calculated as 1035 mL, 9.4%, and 9.8% by the AI-assisted reconstruction, whereas 1120 mL, 9.9%, and 9.3% by the manual reconstruction method. The mean absolute deviations were 16.7 mL and 1.0% in the tumor-containing segment and 15.5 mL and 1.0% in the tumor-free segment. The processing time was shorter in the AI-assisted (2.1 vs. 35.0 min; p < 0.001)., Conclusions: The virtual hepatectomy, including functional liver volumetric analysis, using the 3D liver models reconstructed by the AI-assisted methods, was reliable for the practical planning of liver tumor resections., (© 2022. The Society for Surgery of the Alimentary Tract.)

Background: Applicability of the albumin-bilirubin (ALBI) grade in preoperative decision-making criteria based on the indocyanine green retention (ICG) test remains unclear. This study aimed to predict abnormal ICG values using standard blood tests and evaluate the impact on postoperative outcomes among patients undergoing hepatectomy for hepatocellular carcinoma (HCC)., Methods: Data on 949 consecutive HCC patients undergoing curative-intent hepatectomy between 1996 and 2014 were retrospectively assessed. A nomogram using preoperative standard blood tests was created to predict abnormal ICGR15 (>15%)., Results: Three-hundred nine patients had abnormal ICGR15. Predictors of abnormal ICGR15 included in the nomogram were: ALBI grade >1 (hazard ratio [HR]: 2.16, 95% confidence interval [CI]: 1.59-2.94), platelet count <130 000/mm 3 (HR: 2.27, 95% CI: 1.68-3.08), aspartate aminotransferase >50 (IU/L) (HR: 1.90, 95% CI: 1.29-2.81), and viral hepatitis infection (HR: 1.46, 95% CI: 1.03-2.07). The nomogram named the PLT-ALBI score was discriminative [C-statistics: 0.719 (0.684-0.754)], and reliable (Hosmer-Lemeshow Chi-Square: 9.05, p = 0.338). The higher PLT-ALBI score was associated with a more frequent incidence of clinically relevant posthepatectomy liver failure and poor overall survival., Conclusions: The PLT-ALBI score is applicable in distinguishing HCC patients with abnormal ICGR15. Patients with higher PLT-ALBI score require more careful postoperative care, despite following the ICG criteria., (© 2022 Wiley Periodicals LLC.)

Purpose: Mohs' paste, which is composed of zinc chloride and zinc oxide starch, is used for hemostasis of superficial malignancy in the clinical setting. We investigated the concentration of intramuscular zinc in mice after Mohs' paste application and evaluated its relationship with angiogenesis from the perspective of blood flow levels within 24 h., Methods: Male C57BL/6JJmsSlc mice were administered single dose of Mohs' paste at 25%, 50%, and 75% after unilateral hind limb surgery, and glycerin, a viscosity modifier, was administered to the control group (0%). Hind limb blood flow levels were measured with a laser Doppler perfusion imaging system (n = 6). The amounts of intramuscular zinc and vascular endothelial growth factor-A (VEGF-A) expression were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) and western blotting, respectively (n = 5 or 3)., Results: Blood flow levels were significantly decreased in the 50% group after 8 h, and significantly decreased in the 25% and 50% groups after 24 h. Intramuscular zinc was significantly increased in the 50% and 75% groups after 8 h. Western blotting showed that VEGF-A levels were significantly increased in the 25% and 50% groups after 8 h. Based on analytical experiments and biological investigation, we predicated the pharmacological effect of Mohs' paste and found over 50% of it is critical in the blood flow and angiogenesis suppression after more than 8 h of its application., Conclusions: The results suggest that the mechanism of blood flow suppression is independent of VEGF-A levels and might suppress future angiogenesis. Our findings support that of previous studies, in which Mohs' paste was expected to induce hemostasis and suppress angiogenesis. It is an excellent ointment that facilitates hemostasis by suppressing blood flow regardless of angiogenesis, and may be apt for situations where hemostasis is required in the clinical setting., (© 2021. Springer Nature Switzerland AG.)

Objectives: In this study, we aimed to establish a method for quantifying bromide ions (Br - ) in blood and urine using gas chromatograph-mass spectrometer (GC-MS) equipped with a headspace sampler, for biological monitoring of workers exposed to methyl bromide., Methods: Samples were mixed with dimethyl sulfate, and Br - ions were detected using GC-MS with a headspace sampler. The validity of the proposed method was evaluated based on most of the US FDA guidance. The values obtained were compared with reference values by analysis using Seronorm TM Trace Elements Whole Blood L-1 RUO., Results: The calibration curve showed good linearity in the Br - concentration range of 0.1-20.0 mg/L, and the coefficient of determination R 2 value was >.999. Intraday and interday accuracy values were 99.3%-103.1% and 97.4%-101.8%, respectively. The measured and reference values of Seronorm were concordant. Herein, eight urine and serum samples of workers were analyzed; the samples' Br - concentrations were known. The correlation coefficients of urine and serum samples were 0.97 and 0.96, respectively, and results were consistent., Conclusions: This study established a simple and rapid method for the determination of Br - concentration in biological samples using GC-MS with a headspace sampler. Moreover, it can be used for biological monitoring of occupational exposure to methyl bromide and for the determination of Br - concentration in a wide range of biological samples., (© 2021 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Hyperammonemia is a rare adverse event of 5-FU. Here, we report a case of hyperammonemia with disturbance of consciousness during 5-FU plus nedaplatin therapy for esophageal cancer and present a literature review. A 69-year-old man was diagnosed with cT2N2M0, cStage Ⅲ esophageal cancer. He was administered with DCF therapy as the first-line neoadjuvant chemotherapy. After the first course, he showed renal dysfunction. Therefore, as the second-line neoadjuvant chemotherapy, he was administered with 5-FU plus nedaplatin. He vomited on treatment day 5 and suddenly presented with disturbance of consciousness on treatment day 6. Blood tests showed hyperammonemia(114 μg/dL). He was treated with rehydration and branched-chain amino acid solutions, resulting in a gradual improvement of symptoms. Hyperammonemia has been reported in patients with colorectal cancer but rarely in patients with esophageal cancer. A case of hyperammonemia during the 5-FU plus nedaplatin therapy has never been reported in Japan. We should be aware that 5-FU may cause hyperammonemia and resultant disturbance of consciousness during chemotherapy with 5-FU.

Desmoid tumor is one kind of fibromatosis, and much occurs the abdominal wall and outside the abdominal wall. Intra- abdominal desmoid tumor is rare at about 8%. We experienced a case of intra-abdominal desmoid tumors occurring 4 years after open radical prostatectomy with some literature review. A 72-year-old man had undergone open radical prostatectomy for prostate cancer. Four years after that resection, multiple intra-abdominal tumors measuring 56 mm in maximum diameter was identified on follow-up computed tomography, and he was referred to our department for management. We performed laparotomy and investigation of the biopsy. Immunohistochemistry of the resected specimen indicated the tumor cells were positive for vimentin and β-catenin, and the diagnosis was desmoid. We performed partial resection of the small intestine and ileocecal resection. His postoperative course was uneventful and he was discharged on the 12th postoperative day. He has shown no sign of recurrence in the 4 months follow-up since surgery. In the past, an operation was the best treatment for intra-abdominal desmoid tumor. But it is reported that watchful waiting is also possible by the case which has no symptom and dysfunction in NCCN guidelines 2019. Further research is needed.

A 77-year-old man with rectal cancer was admitted to our hospital. After neoadjuvant chemotherapy, laparoscopic abdominoperineal resection of rectum with D3 dissection was performed. The pathological diagnosis was poorly differentiated carcinoma, pT3, N1a, M0, pStage Ⅲa. Adjuvant chemotherapy was not performed. Fifteen months after operation, his chief complaint was fatigue. Thrombocytopenia and elevation of tumor maker was detected by blood test and disseminated intravascular coagulation(DIC)was suspected. He was admitted to our hospital and we started anti DIC therapy immediately. Bone scintigraphy revealed multiple bone metastases, then we diagnosed disseminated carcinomatosis of the bone marrow. He died 10 days after hospitalization. Disseminated carcinomatosis of the bone marrow with colon cancer is rare and prognosis is very poor. It is important to diagnose and start treatment as early as possible.

An 81-year-old man underwent laparoscopic right hemicolectomy for ascending colon cancer. The postoperative diagnosis was tub1>tub2, pT4apN1bM0, pStage Ⅲb, ascending colon cancer. At 1 year 4 months after operation, abdominal CT showed dissemination around anastomosis. The patient has been treated with first-line systematic chemotherapy(capecitabine, oxaliplatin and bevacizumab). Epigastralgia and grade 4 anemia were observed at 5 years 7 months after initiation of chemotherapy when he was treated with second-line chemotherapy(capecitabine, irinotecan and bevacizumab). As abdominal CT showed that the dissemination progressed rapidly in size 30 mm to 100 mm, we diagnosed tumor bleeding in the dissemination. Palliative radiotherapy(30 Gy/10 Fr)for the dissemination was performed. Hemostasis and tumor shrinkage were achieved, and epigastralgia improved after receiving the radiation therapy. The patient discharged our hospital on 31 days form admission. We believe that palliative radiotherapy is effective to recurrent colon cancer with tumor bleeding.

A 61-year-old male was referred to our department after decompression of the transanal ileus tube due to a rectal cancer obstruction. Colonoscopy revealed a circumferential type 2 tumor, 4 cm from the anal verge. The tumor was diagnosed as rectal cancer tub1-2, Group 5 on biopsy analysis. Longitudinal ulcers descending to the sigmoid colon were present and obstructive colitis was suspected. Enhanced computed tomography showed wall thickness in the Ra, Rb rectum and swelling of the mesorectum lymph node, but distant metastases were not identified. We diagnosed the patient with Ra, Rb rectal cancer cT4aN1aM0, cStage Ⅲb. Because of the risk of anastomotic leakage with obstructive colitis, we planned neoadjuvant chemotherapy(SOX therapy)after laparoscopic transverse colostomy. After neoadjuvant chemotherapy, colonoscopy revealed improvements in the obstructive colitis. The tumor was reduced in size and the chemotherapy appeared effective. We performed laparoscopic rectal super low anterior resection with resection of the D3 lymph node. Histopathological examination revealed tub1, ypT3, ypN0, and the chemotherapeutic outcome was rated as Grade 1a. The final diagnosis was Ra, Rb rectal cancer with ypT3ypN0M0, ypStage Ⅱa.

1,2-Dichloropropane (1,2-DCP) is recognized as the causative agent for cholangiocarcinoma among offset color proof-printing workers in Japan. The aim of the present study was to characterize the molecular mechanisms of 1,2-DCP-induced hepatotoxic effects by proteomic analysis. We analyzed quantitatively the differential expression of proteins in the mouse liver and investigated the role of P450 in mediating the effects of 1,2-DCP. Male C57BL/6JJcl mice were exposed to 0, 50, 250, or 1250 ppm 1,2-DCP and treated with either 1-aminobenzotriazole (1-ABT), a nonselective P450 inhibitor, or saline, for 8 h/day for 4 weeks. Two-dimensional difference in gel electrophoresis (2D-DIGE) combined with matrix-assisted laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF/MS) was used to detect and identify proteins affected by the treatment. PANTHER overrepresentation test on the identified proteins was conducted. 2D-DIGE detected 61 spots with significantly different intensity between 0 and 250 ppm 1,2-DCP groups. Among them, 25 spots were identified by MALDI-TOF/TOF/MS. Linear regression analysis showed significant trend with 1,2-DCP level in 17 proteins in mice co-treated with 1-ABT. 1-ABT mitigated the differential expression of these proteins. The gene ontology enrichment analysis showed overrepresentation of proteins functionally related to nickel cation binding, carboxylic ester hydrolase activity, and catalytic activity. The results demonstrated that exposure to 1,2-DCP altered the expression of proteins related with catalytic and carboxylic ester hydrolase activities, and that such effect was mediated by P450 enzymatic activity.

Purpose: Acrylamide is known to induce disorders in the central nervous system in humans and experimental animals. The present study investigated effects of exposure to acrylamide on adult neurogenesis, noradrenergic axons and the level of norepinephrine in the brain of male rats., Method: Four groups of 12 male Wistar rats each were exposed to acrylamide at 0, 0.2, 2 and 20 mg/kg body weight by gavage for 5 weeks. Six rats of each groups were injected with 5-bromo-2'-deoxy-uridine (BrdU) after five-week exposure to acrylamide to examine proliferative cells in the dentate gyrus using immunostaining. Density of noradrenergic and serotonergic axons in the prefrontal cortex, hippocampus and cortex behind the bregma was quantified. Remaining 6 rats were decapitated after the last exposure and brains were dissected out to measure monoamine level in the hippocampus and prefrontal cortex using high performance liquid chromatography., Result: Exposure to acrylamide dose-dependently decreased the density of noradrenergic axons in the prefrontal cortex with a significant change at 20 mg/kg. Norepinephrine level decreased in the hippocampus at 20 mg/kg. Exposure to acrylamide at 20 mg/kg or less did not change the number of BrdU positive cells, but the result should be considered preliminary., Conclusion: The results show that oral exposure to acrylamide induces decrease in noradrenergic axons and norepinephrine level in the brain of rats. Given the similar effects are observed in 1-bromopropane-exposed rats, there may be the common mechanism in the toxicity of soft electrophiles to the central nervous system., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Acrylamide, a soft electrophile, is widely used in the industry and laboratories, and also contaminates certain foods. Neurotoxicity and neurodegenerative effects of acrylamide have been reported in humans and experimental animals, although the underlying mechanism remains obscure. Activation of microglia and neuroinflammation has been demonstrated in various neurodegenerative diseases as well as other pathologies of the brain. The present study aimed to investigate the role of microglial activation and neuroinflammation in acrylamide neurotoxicity. Male 10-week-old Wistar rats were exposed to acrylamide by gavage at 0, 0.2, 2, or 20 mg/kg BW, once per day for 5 weeks. The results showed that 5-week exposure to acrylamide induced inflammatory responses in the cerebral cortex, evident by upregulated mRNA and protein expression of pro-inflammatory cytokines IL-1β, IL-6, and IL-18. Acrylamide also induced activation of microglia, indicated by increased expression of microglial markers, CD11b and CD40, and increased CD11b/c-positive microglial area and microglial process length. In vitro studies using BV-2 microglial cells confirmed microglial inflammatory response, as evident by time- (0-36 h; 50 μM) and dose- (0-500 μM; 24 h) dependent increase in mRNA expression of IL-1β and IL-18, as well as the inflammatory marker iNOS. Furthermore, acrylamide-induced upregulation of pro-inflammatory cytokines was mediated through the NLRP3 inflammasome pathway, as evident by increased expression of NLRP3, caspase 1, and ASC in the rat cerebral cortex, and by the inhibitory effects of NLRP3 inflammasome inhibitor on the acrylamide-induced upregulation of NLRP3, caspase 1, IL-1β, and IL-18 in BV-2 microglia.

Acrylamide has been used industrially and also found in certain foods cooked at high temperatures. Previous reports described acrylamide-related human intoxication who presented with ataxia, memory impairment, and/or illusion. The aim of this study was to characterize the molecular mechanisms of neurotoxicity of acrylamide by analyzing the expression levels of various proteins in the hippocampus of rats exposed to acrylamide. Male Wistar rats were administered acrylamide by gavage at 0, 2, and 20 mg/kg for 1 week or 0, 0.2, 2, and 20 mg/kg for 5 weeks. At the end of the experiment, the hippocampus was dissected out and proteins were extracted for two-dimensional difference gel electrophoresis combined with matrix-assisted laser-desorption ionization time-of-flight/time-of-flight mass spectrometry (MALDI-TOF/TOF/MS). MALDI-TOF/TOF/MS identified significant changes in two proteins in the 1-week and 22 proteins in the 5-week exposure groups. These changes were up-regulation in 9 and down-regulation in 13 proteins in the hippocampus of rats exposed to acrylamide at 20 mg/kg for 5 weeks. PANTHER overrepresentation test based on the GO of biological process showed significant overrepresentation in proteins annotated to nicotinamide nucleotide metabolic process, coenzyme biosynthetic process, pyruvate metabolic process, and carbohydrate metabolic process. The test also showed significant overrepresentation in proteins annotated to creatinine kinase activity for the GO of molecular function as well as myelin sheath, cytoplasmic part, and cell body for the GO of cellular component. Comparison with a previous proteomic study on hippocampal proteins in rats exposed to 1-bromopropane identified triosephosphate isomerase, mitochondrial creatine kinase U-type, creatine kinase β-type and proteasome subunit α type-1 as proteins affected by exposure to acrylamide and 1-bromopropane, suggesting a common mechanism of neurotoxicity for soft electrophiles.

Background: Little epidemiological evidence exists regarding the chronic respiratory effects of inhaled powdered toner exposure in humans, although several case reports have suggested the existence of lung disorders that might be related to exposure to toner dust., Objective: We aimed to estimate the chronic health risk to humans associated with routine toner dust exposure in copier industry workers under current actual work conditions., Design: A prospective observational cohort study of occupational population., Methods: Changes in chest radiogram, spirometry measurements and serum and urine biomarkers of biomedical responses to extrinsic stress, as well as subjective symptoms were longitudinally observed for up to 10 years in Japanese copier industry workers responsible for the manufacturing, maintenance or recycling of powdered toner or toner-using machines. A total of 694 subjects who did not change their work category during the follow-up and were free from chronic respiratory diseases at the baseline survey provided reliable results on at least three survey occasions during 3 years or more of follow-up., Results: Typical fibrosis findings associated with pneumoconiosis was not observed on chest radiograms. No significant differences associated with toner exposure were noted in the frequency of new incidence of either non-specific findings on chest radiogram or serum fibrosis biomarkers (sialylated carbohydrate antigen KL-6 and surfactant protein D). However, the exposed subjects tended to show increases in the frequency of respiratory symptoms and reduced spirometry results during the follow-up compared with the control group, although significant differences were only seen in chronic cough., Conclusions: Under the current reasonably controlled work environmental conditions, lung fibrotic changes caused by inhaled dust exposure, including powdered toner, appear to be relatively uncommon; however, non-specific temporal irritation causing subjective symptoms and inflammatory responses might exist., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

An asymptomatic mediastinal abscess was incidentally found in a 68-year-old male patient with a long history of hemodialysis. He had never had any symptoms but complained of chest pain only after the abscess ruptured into the right thoracic cavity. The abscess was discovered incidentally, when computed tomography was performed to determine the cause of his increasing ascites. Video-assisted thoracic surgery was performed to facilitate sufficient drainage and safe debridement. After the operation, we administered adequate antibiotics and continued irrigation of the thoracic cavity. The origin of his abscess was still unknown, but we have to consider that immunocompromised patients including those undergoing hemodialysis can develop severe infectious conditions even with minor causes. This case is clinically suggestive of the need to focus on the immunocompromised condition of hemodialysis patients. Furthermore, our case reveals video-assisted thoracic surgery to be a safe and less invasive procedure for patients in poor general condition.

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.

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 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.

It is important in the clinical setting to integrate all of the findings when diagnosing and making treatment decisions. We report a case of particular interest for managing cancer patients. A 69-year-old man underwent endoscopic resection for an Rb rectal tumor. The tumor showed a positive vertical margin and required laparoscopy-assisted super low anterior resection with ileostomy for histopathological stage Ⅰrectal cancer. His postoperative course was uneventful. The follow-up computed tomography (CT) scan revealed a tumor locating close to the left common iliac artery. Although positron emission tomography (PET) showed 18F-fluorodeoxyglucose (FDG) accumulation in the tumor, none of the other clinical findings indicated a recurrence of rectal cancer. FDG is not specific to malignant neoplasias, but the location of the tumor and the FDG uptake suggested the possibility of malignancy. No other tests found any evidence of a recurrence. Tumor resection was performed concurrently with ileostomy closure. Histopathology demonstrated it was an asymptomatic abscess in a lymph node. Tumor recurrence and metastases have to be kept in mind even if the primary lesion is in an early stage. This case shows the difficulty in deciding how to manage patients when clinical results are not consistent, especially in cases needing surgical procedures.

Background: Enhanced recovery programs (ERPs) have been developed in various surgical fields and have been shown to accelerate postoperative recovery without increasing the incidence of adverse events. Whether ERP can be safely applied to patients undergoing complex liver surgery with a risk of liver failure remains unclear., Methods: We created an ERP by rearranging our conventional postoperative treatments and applied this program to patients undergoing major hepatectomy between 2008 and 2013. The ERP elements included greater perioperative education, individualized postoperative fluid therapy, and early mobilization. The success of the ERP was evaluated on postoperative day (POD) 6 based on the criterion of independence from continuous medical intervention with the exception of an abdominal drainage tube. Adherence to each item in the ERP was evaluated, and risk factors for delayed accomplishment were analyzed., Results: Altogether, 200 patients were included, and 165 patients (82.5 %) completed the ERP. Multivariate analyses showed that (1) an age of 65 years or older and (2) a red blood cell transfusion were independent risk factors for delayed accomplishment. The performance of thoracotomy or choledocojejunostomy did not significantly affect accomplishment of the ERP. Oral intake starting on POD 1 was achieved in 179 patients (89.5 %), and termination of intravenous drip infusions on POD 5 was feasible in 72.5 %., Conclusions: An ERP for major hepatectomy was completed in more than 80 % of the patients. Earlier bowel movement can be challenged. The liquid in-out balance should be adjusted on an individual basis, rather than uniformly, especially for patients over 65 years of age or who required a red blood cell transfusion.

Introduction: Skeletal muscle metastases from carcinomas, especially to intercostal muscles, are rare. Most metastatic chest wall tumors from hepatocellular carcinoma (HCC) result from disseminations through needle tracts of intrahepatic HCC treatments., Presentation of Case: We report the case of a 65-year-old man with chronic viral hepatitis B whose intrahepatic lesions were stabilized by repeated radiofrequency ablations and transcatheter arterial chemoembolization. Follow-up computed tomography demonstrated a well-enhanced mass in the right chest wall. Because α-fetoprotein and des-γ-carboxy prothrombin levels were elevated and no other tumors were detected, we diagnosed the mass as an extrahepatic metastasis from the HCC and resected it along with the surrounding ribs. There was no involvement of the bone, pleura, and lung., Discussion: The tumor was microscopically diagnosed as an intercostal muscle tumor metastasized from HCC, which has not been documented previously. The resection rate of extrahepatic tumors of HCC is low in literature. No other apparent extrahepatic recurrence has been observed for more than 20 months after the surgery., Conclusion: We report the case of HCC patient who underwent surgical resection of an intercostal muscle tumor that had metastasized from HCC. Pathological examination of the tumor revealed the tumor cells in the blood vessels, and we speculate it hematogeneous metastasis., (Copyright © 2012 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

We report a patient with unresectable remnant gastric cancer with common bile duct stricture, whose quality of life(QOL) was improved by switching to cholecystojejunostomy from percutaneous transhepatic gallbladder drainage(PTGBD). He was a 69-year-old man who underwent distal gastrectomy(Billroth I reconstruction)3 years previously, and he vomited many times due to cancer at the anastomosis. It could not be resected because of its involvement with the hepatoduodenal ligament, and therefore, gastrojejunostomy was performed. Four days later, abdominal pain occurred and gallbladder swelling was observed, resulting from common bile duct obstruction. PTGBD relieved the pain, and four courses of S-1/cisplatin (CDDP)treatment were performed. The bile duct stenosis was still so severe that the chemotherapy regimen was changed to weekly paclitaxel(PTX). The bile amount of PTGBD decreased after its four courses and the tube, which was a great burden for the patient, was removed. Because abdominal pain recurred in 2 weeks, the tube needed to be reinserted. An endoscopic stent was not inserted successfully. We performed cholecystojejunostomy and he was finally free from the PTGBD tube. The spread of cancer to the cystic duct was controlled by continuing the PTX for more than 20 courses. Thus, this case highlights PTX's contribution toward improving the patient's QOL.