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Subjects: We first reviewed surgical outcomes and pathological findings of 32 patients(laparoscopic group: LDP n=11, open group: ODP n=21)who underwent distal pancreatectomy for pancreatic cancer from January 2018 to October 2022. Then we reviewed long-term outcomes, and recurrence type for 20 patients(LDP: n=5, ODP: n=15)from January 2018 to February 2021., Results: LDP group had significantly longer operation time and less blood loss. There was no difference in length of hospital stay, postoperative complications, number of dissected lymph nodes, positive lymph node metastasis rate, and adjuvant chemotherapy rate. Because of high rate of pancreatic stump closure by hand sewing in ODP, postoperative pancreatic fistula rate was higher in ODP than in LDP. The 2-year relapse-free survival rate was 60% in LDP, 33% in ODP, and the 2-year overall survival rate was 60% in LDP, 71% in ODP, and there were no significant differences. As for the type of recurrence, in LDP group, 2 cases of distant metastases and no local recurrence was observed, and in ODP group, 6 cases each of local recurrences and distant metastases were observed., Conclusion: LDP was not inferior to ODP in short and long- term outcomes, safety, curability, and local control ability.

Obinutuzumab frequently triggers an infusion reaction(IR). In the GALLIUM study, despite the use of corticosteroids, antipyretic analgesics, and antihistamines to prevent IR, IR occurred at a high frequency of 68.2% for all Grades and 12.4% for Grades 3 or higher. The dose of methylprednisolone was increased from 80 mg administered in the GALLIUM study to 125 mg, and the development of IR was investigated in 30 patients with follicular lymphoma who received the initial dose of obinutuzumab. The incidence of IR was 43.3% for all Grades and 0% for Grades 3 or higher, and no serious IR was observed. It also had no effect on infectious diseases. Increased doses of corticosteroids were well tolerated and suggested as an effective method for reducing the frequency of IR.

Granulocyte colony-stimulating factor(G-CSF)is useful for preventing febrile neutropenia induced by chemotherapy. Recently, some cases of aortitis have been reported following administration of G-CSF. Here, we present a case of aortitis induced by pegfilgrastim(peg-G)use during neoadjuvant chemotherapy for treating breast cancer. A 61-year-old woman with breast cancer(cT2N1M0, stage ⅡB, triple negative)started neoadjuvant chemotherapy FEC(100). Eleven days after the third course of peg-G administration, the patient developed a fever and general malaise. Blood test results showed an increase in inflammatory markers and severe anemia. The symptoms were not controlled with antibiotics. Blood and urine culture test results were negative. Computed tomography revealed remarkable wall thickening of the aorta. Therefore, we suspected aortitis induced by peg-G. The symptoms rapidly improved with prednisolone therapy. The possibility of aortitis should be considered for those with fever or raised inflammatory markers following the use of G-CSF. Steroids can be used for the treatment of G-CSF-induced aortitis.

In the pharmaceutical ingredients contamination testing of 702 commercial dietary supplement products, during fiscal years 2014-2021, 14 pharmaceutical ingredients, barrenwort, leaf axils of senna, and small leaf of senna were detected in 28 products. Screening and confirmation of the pharmaceutical ingredients in the products were performed by ultra-high performance liquid chromatography with photodiode array detector and ultra-high performance liquid chromatography-quadrupole-kingdon trap mass spectrometry, respectively. In particular, leaf axils and small leaf of senna were identified by stereomicroscopy and scanning electron microscopy. Furthermore, we found several pharmaceutical ingredients that exceeded the daily medicated dosage; therefore, it is important to prevent the distribution of such products to prevent the occurrence of health hazard. For that reason, it is necessary to continue the sample purchasing and testing systems to monitor the distribution of products containing pharmaceutical ingredients.

This study determined the configuration of the isomers of tadalafil, nortadalafil, and homotadalafil in dietary supplements. The products purchased over the Internet studied included a honey product and a tablet, which contained tadalafil, and a candy, which contained nortadalafil and homotadalafil. Each of the pharmaceutical ingredients isolated from the products was measured with circular dichroism (CD).As a result, the CD spectrum of each isolated pharmaceutical ingredient was found to align with the standard CD spectrum of the 6R,12aR isomer, confirmed that each isolated tadalafil or tadalafil analogue included in a 6R,12aR isomer. According to a report, among the stereoisomers of tadalafil, the 6R,12aR isomers have the most potent inhibitory activities of phosphodiesterase-type-5. From the report, the potential strength of the inhibitory activity of the 6R,12aR isomers of nortadalafil and homotadalafil was suggested. Therefore, it seemed that the 6R,12aR isomer often used in the product.

From May 2006 to March 2018, a total of 30 patients with multiple ground glass opacities( GGO) lessor equal to 2.0 cm underwent percutaneous preoperative computed tomography (CT)-guided Lipiodolmarking and subsequent video-assisted thoracic surgery( VATS). There were 22 patients with 2 GGOs,6 patients with 3 GGOs, 1 patient with 4 GGOs, and 1 patient with 5 GGOs. Of the 71 CT-guided Lipiodolmarking procedures were successfully completed. All 71 Lipiodol spots were detected with C-armshapedfluoroscopy and completely resected. Pneumothorax was the most common complication andoccurred in 22 (73.3%) of 30 cases. There were severe complications in two (6.7%) cases of pneumothoraxrequiring chest tube placement and three( 10.0%) cases of bloody sputum. Of 30 cases multipleGGOs revealed 24 synchronous lung cancer (19 patients with double lung cancer, 3 patients with triplelung cancer, 1 patient with quadruple lung cancer, and 1 patient with quintuple lung cancer). PreoperativeCT-guided lipiodol marking and VATS resection is a safe and reliable method for synchronous multiplelung cancer showing GGO.

A 69-year-old woman underwent a pancreaticoduodenectomy at the age of 41 years for a submucosal tumor of duodenum, which was diagnosed as leiomyoma at that time. Twenty eight years later, a liver tumor, which is 10 cm in a diameter, was identified on an abdominal ultrasonography. The left hepatectomy was undertaken. Immunohistochemical examination indicated that the tumor was positive for c-kit and diagnosed as a gastrointestinal stromal tumor(GIST). The pathological reexamination revealed the primary tumor was also positive for c-kit and diagnosed as GIST. Therefore, the liver tumor was considered as a metastasis of the duodenal GIST, which was resected 28 years earlier.

Among gastric submucosal tumors, neurogenic tumors are considered to be rare diseases. We experienced a case of laparoscopic local gastrectomy of gastric schwannoma coexisting with extramurally developed gastric GIST found accidentally during surgery. A 61-year-old man was pointed out a gastric submucosal tumor with a diameter of 15 mm in a medical checkup. Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)was performed, and immunostaining showed that c-kit(-), CD34(-), S-100(+), SMA(-), MIB-1<2%. Diagnosis was gastric schwannoma. We performed laparoscopic local gastrectomy. During the surgery another extramural nodule was accidentally found with a diameter of 8 mm at the anterior wall of the gastric body near lesser curvature. Immunostaining showed c-kit(+), CD34(+)and was diagnosed GIST. Because a gastric schwannoma coexisting with GIST is a rare case, we decided to report it by adding discussion with some literatures.

A 60-year-old woman was referred to our hospital due to pancreatic head cancer with right ureter invasion. We considered that it was difficult to achieve R0 resection for the patient by operation because of a wide range of retroperitoneal invasions involving the right ureter. She was treated with chemotherapy(gemcitabine plus nab-paclitaxel: GnP). GnP therapy was administered 3-weeks on/1-week off for 1 course. After 3 courses, we performed pancreaticoduodenectomy, right nephrectomy and partial transverse colectomy. We achieved R0 resection and considered the GnP therapy to be effective.

A 78-year-old woman with a chief complaint of mammary tumor was referred to our hospital and was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma using needle biopsies. She presented with MALT lymphoma lesions in the stomach, duodenum, and intraperitoneal lymph nodes. Abdominal ultrasonography revealed thickened internal layer of the bile duct. Cholangiocarcinoma, immunoglobulin G4-related sclerosing cholangitis, and MALT lymphoma were suspected. She did not report any abdominal pain, and did not have jaundice. Endoscopic retrograde cholangiopancreatography and intraductal ultrasonography indicated diffuse, irregular wall thickening with the formation of nodule lesions in the extrahepatic bile duct. Transpapillary cytology indicated CD20-positive atypical lymphocytes. MALT lymphoma of the bile duct was diagnosed. CVP with rituximab therapy was performed. After treatment, computed tomography, gastrointestinal endoscopy, endoscopic retrograde cholangiopancreatography, intraductal ultrasonography, and transpapillary cytology revealed that the tumor and the biliary wall thickening had disappeared. It is difficult to diagnose MALT lymphoma of the bile duct. We report a case in which intraductal ultrasound and transpapillary cytology were useful for establishing a diagnosis and evaluating the therapy for MALT lymphoma of the bile duct.

Introduction: Primary small-cell carcinomas occur commonly in the lungs but rarely in the other organs. We studied the treatment outcomes in 6 cases of primary small-cell carcinoma of the digestive tract at our hospital., Patients: Six patients were diagnosed with small-cell carcinoma of the digestive tract histopathologically and treated at our hospital from September 2000 to December 2018., Results: The average age of the patients was 61.5 years(range: 40-80 years). Patients were 3 men and 3 women. The occurrence sites were the esophagus, stomach, and colon in 1, 2, and 3 patients, respectively. The patient with esophageal cancer underwent chemoradiotherapy without surgery. Other patients, except for 1 patient with colon cancer, underwent adjuvant chemotherapy after the surgery. Two of the 6 patients survived for over 5 years., Discussion: For small-cell carcinomas of the digestive tract with poor prognosis, long-term survival can be expected using multidisciplinary treatments depending on the case.

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that has cytoreductive effects on subependymal giant cell astrocytoma and renal angiomyolipoma in tuberous sclerosis complex (TSC). Recent studies have also shown its efficacy against refractory seizures in TSC. We investigated the efficacy of everolimus in nine patients with TSC, who were admitted to the TSC clinic in Seirei Hamamatsu General Hospital and who suffered from refractory seizures. At the start of treatment, patients ranged from 1 month to 23 years of age, and were refractory to a mean of 5.4 antiepileptic agents. Main seizures were focal in six patients and generalized in three patients. After 0.5 to 4.0 years (mean=2.4 years), three patients (33%) were seizure-free and two patients (22%) experienced >90% reduction in seizures. Everolimus may therefore be effective in the treatment of refractory seizures in TSC. (Received February 20, 2019; Accepted April 2, 2019; Published June 1, 2019).

A 50-year-old man underwent low anterior resection for rectal cancer. The final diagnosis was rectal cancer of pT3N0M0, fStage Ⅱ. CT performed for examination of obstructive jaundice at 17 months after surgery revealed metastatic lesions of the pancreatic head and right lung. By core needle biopsies, the lesions were pathologically diagnosed as metachronous metastases of rectal cancer. Chemotherapy was carried out but was discontinued at 5 courses due to severe side effects. The pancreatic metastasis disappeared after 11 months. As the lung metastasis remained, a right upper lobectomy was performed 1 month later. The patient remains alive without recurrence 6 months after the partial lung resection.

Background: Oral mucositis and body weight loss are the most critical conditions known to lead to the discontinuation of chemoradiotherapy for head and neck cancer. We investigated the effect of a nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)on body weight loss, oral mucositis, and the completion rate of chemoradiotherapy in patients with oropharyngeal and hypopharyngeal cancer., Patients and Methods: The study group comprised patients with oropharyngeal and hypopharyngeal cancer who were treated with concomitant cisplatin and 70 Gy of radiotherapy. These patients received 2 packs of Prosure®per day during chemoradiotherapy., Results: A total of 17 patients were included in this study. The reduction in body weight was significantly improved compared with that in the historical control group that did not receive Prosure®(7.3% vs 10.3%, p<0.01), and the rate of Grade 3-4 oral mucositis was significantly reduced for the patient groups that received Prosure®(CTCAE v3.0 GradeB3; 24% vs 58%, p<0.05). The completion rate of chemoradiotherapy was not significantly different between both groups(77% vs 60%, NS)., Conclusions: A nutritional supplement with a high blend ratio of w-3 fatty acids(Prosure®)had effects on oral mucositis and body weight loss in head and neck cancer patients treated with chemoradiotherapy.

Were port a caseof an 82-year-old man who presented with vomiting. Computed tomography(CT)revealed a jejunum tumor and small bowel obstruction. Enteroscopy revealed a protruded lesion and biopsy indicated adenocarcinoma. PET-CT revealed nothing without jejunal tumor. Therefore, with a preoperative diagnosis of primary small bowel cancer, we performed operation. Surgery indicated peritoneal disseminations and a jejunal tumor 40 cm distal from the ligament of Treitz, and we performed small bowel partial resection. Pathological examination revealed adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Ectopic pancreatic cancer in the jejunum is rare, and we review case reports in the literature.

Since acinar cell carcinoma(ACC)of pancreas is rare, we sometimes meet a case hard to make diagnosis before surgery. We here reported a case of ACC of pancreas with extensive intraductal growth to the main pancreatic duct and the branch of the pancreatic duct. A 43-year-old man visit a clinic with a concern of uncomfortable feeling on left side abdomen. CT/MRI examination showed a ischemic tumor, 38×25 mm, in the body-tail of the pancreas, and the tumor infiltrated to left renal capsule. ERCP showed the interruption and stenosis of the pancreatic duct at the point adjacent to tumor. Cytological diagnosis of the pancreatic juice was performed, but malignant cells were not detected(Class III ). The tumor abnormally accumulated FDGin PET-CT examination(SUVmax 3.3). We diagnosed the tumor PDAC with infiltrating to the left renal capsule, and the distal pancreatectomy was performed. The pathological examination of the resected specimen showed that the tumor progressed into main pancreatic duct and the branch of the pancreatic duct accompanying with fibrosis around pancreatic duct. The tumor was diagnosed ACC with immunohistochemistry; positive to ACC phenotype(a1-antitrypsin, a1-antichymotrypsin, BCL10). The patient is alive without any recurrence findings 3 years 2 months after surgery.

Regorafenib is an oral multikinase inhibitor; the CORRECTtrial evaluated its efficacy in patients with metastatic colorectal cancer following disease progression with standard therapies. However, regorafenib has toxicities that develop quickly. Few studies have reported the safe dose and usage of regorafenib to avoid these adverse events in Japanese patients. We examined the side effects and safe administration technique of regorafenib in this study. We administered regorafenib to 15 patients with metastatic colorectal cancer following disease progression with standard therapies. Between August 2013 and January 2014, 5 patients received 160 mg oral regorafenib once daily on days 1-21 of a 28 day course(group A). Between February 2014 and July 2015, 10 patients received initiating therapy with 120 mg regorafenib, with the intention of increasing the dose(group B). We retrospectively assessed side effects, number of dose courses, and total dose of regorafenib in both groups. The median dosing course was 5 coureses in group B, which was more than the 1 course in group A. The median total dose was 10,800 mg in group B, which is about 4 times as much as the 2,400 mg in group A. In group B, 7 out of 10 patients (70%)were successful in the dose escalation of regorafenib from 120 to 160 mg daily over 3-5 courses. The disease control rate was 40% in both groups. The rate of adverse events of Grade 3 or higher was 60% in group A, compared to 40% in group B within 2 courses. The overall survival time was 308 days in group B, which was significantly longer than the 168 days in group A. Initiating therapy with 120 mg regorafenib with the intention of increasing the dose improves safety and allows an increase in dosing courses, as well as in the total dose of regorafenib and overall survival time.

A 75-year-old man was admitted to our hospital for further examination of swollen lymph nodes and a possible gastric submucosal tumor. He had persistent fever and anorexia. Blood examination showed anemia, thrombocytopenia, and elevated lactate dehydrogenase and soluble interleukin 2 receptor levels. Swollen lymph nodes and splenomegaly were evident on computed tomography, and the submucosal tumor was revealed by esophagogastric endoscopy. Cervical lymph node biopsy and endoscopic biopsy were performed, which revealed a diagnosis of intravascular lymphoma. In Asian countries, patients with intravascular lymphoma often have hemophagocytic syndrome without lesions of the central nervous system or skin, which is called the Asian variant of intravascular lymphoma. In this case, the patient had no indicative lesions and had no evidence of the hemophagocytic syndrome. He also had lymph node swelling and a gastric submucosal tumor, which are rare in intravascular lymphoma. The patient was treated with chemotherapy (R-CHOP;rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisolone), and complete response was demonstrated (based on the Response Evaluation Criteria for Solid Tumours [RECIST] guideline). In cases of possible intravascular lymphoma, gastrointestinal endoscopy and biopsy should be considered because they are a useful diagnostic strategy.

Hokkaido COPD cohort study is a carefully-designed, well-conducted, prospective observational 10 year-long study, which ended early in 2015. We have obtained a number of clinically-relevant novel findings, some of which are as follows. Severity of emphysema was highly varied even in those individuals whose airflow limitation is comparable. The annual change in forced expiratory volume in 1 second (FEV1) over 5 years was also widely varied with normal distribution among the subjects under appropriate treatment. Some patients maintained their pulmonary function for a long time, and others showed a rapid decline. Emphysema severity, but not pulmonary function, was independently associated with such an inter-subject variation in the annual decline in FEV1. When we explored any biomarkers for predicting the FEV1 decline, a lower leptin/adiponectin ratio alone emerged as an explanatory parameter for the rapid decline, and this was also confirmed in an independent Danish cohort study of different ethnicity. Monitoring of quality of life (QOL), using SGRQ scores, also provided interesting observations. The annual change in total score reflected that of FEV1 decline during the follow-up period. However, activity component in QOL deteriorated in almost all the subjects, while symptom component rather improved in many of the patients under appropriate treatment.

Background: Long-acting β 2 -agonists (LABA) and leukotriene receptor antagonists (LTRA) are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. In our previous study, the Gly16Arg genotype of the β 2 -adrenergic receptor (ADRB2) gene did not influence the differential bronchodilator effect of salmeterol versus montelukast as an add-on therapy to ICS within 16 weeks of follow-up (the J-Blossom study)., Methods: We examined if genes encoding CYSLTR1, CYSLTR2, PTGER2 or PTGER4 could explain differential responses to salmeterol versus montelukast using the participants of the J-Blossom study. This study included 76 patients with mild-to-moderate asthma. The difference in peak expiratory flow (PEF) (ΔPEF, l/min) after 16 weeks of treatment with salmeterol (ΔPEFsal) versus montelukast (ΔPEFmon) was associated with the genotypes at each of 4 genes. In addition, multivariate analyses were used to identify a gene-gene interaction between ADRB2 gene and each of these 4 genes., Results: Although none of 4 genes were associated with ΔPEFsal-ΔPEFmon in the univariate analyses, multivariate analysis showed that PTGER4 gene, interacting with ADRB2 Gly16Arg, was associated with ΔPEFsal-ΔPEFmon (p=0.0032)., Conclusion: Our findings suggested that the interactions between two genetic loci at ADRB2 and PTGER4 is important in determining the differential response to salmeterol versus montelukast in patients with chronic adult asthma.

The prognosis of esophageal cancer patients who undergo non-curative resection is very poor. Here, we retrospectively analyzed the factors associated with non-curative resection. Thirty-five patients with cT3 or T4 thoracic esophageal cancer treated with neoadjuvant chemotherapy or chemoradiotherapy followed by esophageal resection were included in this study. Among the 35 patients, 27 underwent curative resection (R0 group), while 8 underwent non-curative resection (R1R2 group). A comparison of the clinicopathological factors between groups revealed no significant differences in presurgical factors. The pathological T factor was significantly deeper in the R1R2 group than in the R0 group (p=0.0086). Histopathological response tended to be higher in the R0 group (p=0.055). An accurate preoperative diagnosis of T factor is important.

We report the cases of 2 patients with advanced rectal cancer who achieved pathological complete response to treatment with preoperative therapy. Case 1 was a 72-year-old man diagnosed with cT3N1M0 advanced rectal cancer. Neoadjuvant chemoradiotherapy with S-1 (120 mg/day) and radiation (50 Gy/25 Fr) was administered. Eight weeks after the last chemoradiation therapy, we performed laparoscopic Hartmann's operation. Case 2 was a 59-year-old man diagnosed with cT4aN0M0 advanced rectal cancer. He was treated with XELOX plus bevacizumab as neoadjuvant chemotherapy. Four weeks after 4 courses of treatment, he underwent laparoscopic Mile's operation. Neoadjuvant therapy was performed without any complications, and a pathological complete response was achieved in both patients. These cases demonstrated that neoadjuvant therapy can be a promising option for locally advanced rectal cancer.

A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma.

It is sometimes difficult to differentiate between metastatic and primary liver tumors, when the liver tumor occurs simultaneously with a gastric cancer. We encountered a case of resected gastric cancer, which occurred concomitantly with intrahepatic cholangiocarcinoma after S-1 plus cisplatin chemotherapy, in a patient who was previously diagnosed with metastatic liver tumor before treatment. An 80-year-old man was admitted to our hospital because of epigastralgia. Endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper body of the stomach. A plain CT scan showed an irregular, low-density area, which was enhanced by contrast medium in the lateral segment of the liver. We performed an ultrasound- guided needle biopsy, because it was impossible to make a definitive diagnosis by dynamic CT, contrast-enhanced ultrasonography, and MRI. Immunohistochemical analysis for cytokeratin 7/20 resulted in 7 (+)/20 (-) for both the gastric cancer and the liver tumor. Therefore, we diagnosed the patient with gastric cancer, which occurred concomitantly with the metastatic liver tumor, and administered chemotherapy with S-1 plus cisplatin. After 3 courses of the regimen, a reduction in the size of mass was observed in the stomach and the liver. We subsequently performed left hepatectomy and total gastrectomy with lymph node dissection. Microscopic examination revealed the gastric cancer, which occurred simultaneously with the intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and the patient remains well without recurrences.

The diagnosis of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas includes radiographic (CT, MRI) and endoscopic evaluation (ERCP, EUS). The treatment strategy is outlined in the 2012 International Consensus Guidelines (ICG). Herein, we report a case initially not indicated for surgery. Four months after the initial diagnosis, the cystic lesion transformed into a solid mass-like lesion visible on CT. FDG-PET showed abnormal FDG uptake at the same location. Surgical resection was performed immediately, and the tumor was diagnosed as IPMN with inflammation. FDG-PET showed a false-positive diagnosis for the malignancy in this case of IPMN.

Alternative splicing is an important mechanism that links to transcription and contributes to protein diversity. Disturbed alternative splicing is frequently observed in cancers, but its precise mechanism remains largely unknown. FUSE-binding protein (FBP) -interacting repressor (FIR) is a transcriptional repressor of the c-myc gene. Previous studies indicated that a splice variant of FIR, FIRΔexon2, that lacks exon2 in the transcriptional repressor domain, was increased in colorectal cancers, hepatocellular carcinomas, and leukemia cells. Furthermore, FIRΔexon2 activated c-myc transcription by disabling wild-type FIR as a dominant-negative form of FIR. Recently, somatic mutations of the SF3B1 (SAP155) gene, a subunit of the SF3B spliceosome complex, were found in myelodysplastic leukemia. In this study, FIR heterozygous knockout (FIR(+/-)) was established as a dominant-negative model of FIR in the C57BL/6 mouse. FIR(+/-) mice showed an increased c-myc mRNA expression level, particularly in peripheral blood, although FIR(+/-) mice had no apparent pathogenic phenotype. Therefore, an increased c-myc mRNA expression level alone is not enough for leukemogenesis. Nevertheless, FIR(+/-)TP53(-/-) mice generated acute T-cell lymphoblastic leukemia (T-ALL) with increased organ and/or bone marrow invasion. In conclusion, alternative splicing of FIR, generating FIRΔexon2, contributes to not only colorectal carcinogenesis but also leukemogenesis independent of the c-Myc activation pathway. Finally, we will discuss our hypothesis that FIRΔexon2 interferes with FBW7, that FIRΔexon2 inhibits PP1 in the EGFR pathway, and that FIR haploinsufficiency is potentially associated with protein expression through transcriptional and post-transcriptional mechanisms.

Aim: To elucidate the characteristics of patients with asthma who have specific IgE responses to inhaled allergens detected by ImmunoCAP, which is not detectable by MAST-26., Methods: A total of 168 patients with adult asthma who reside in the Kanto region were recruited. Levels of total serum IgE and allergen specific IgE antibodies towards 14 common inhaled allergens (MAST-26) were measured. Among these samples, 48 patients with no detectable allergen-specific IgE (group A) and 44 patients with strong sensitization to Dermatophagoides farinae (group B) were selected for further assessment of their sensitization to inhaled allergens such as cockroach and moth using ImmunoCAP., Results: In group A, ImmunoCAP detected specific IgE responses to some inhaled allergens in 27.1% of the patients. The strongest predictive factor for the presence of allergen-specific IgE responses detected by ImmunoCAP was elevated levels of total serum IgE (p=0.0007). In group B, the presence of IgE responses specific to cockroach or moth by ImmunoCAP were found in 27.8% or 52.3% of the patients, respectively. The predictive factor for the presence of these positive IgE responses was also elevated levels of total serum IgE (p=0.0003)., Conclusion: Asthma patients with no detectable specific IgE responses to any inhaled allergens by MAST-26 may be still sensitized to common inhaled allergens, including cockroach and moth. Thus, the presence of allergen-specific IgE responses may be re-assessed by ImmunoCAP in patients with asthma, especially when patients have higher levels of total serum IgE.

Aneurysms of the sinus of Valsalva are rare. We report a case of extra-cardiac unruptured aneurysm of the sinus of Valsalva with moderate aortic regurgitation (AR). A 57-year-old woman was referred to our institution because of AR. Echocardiography showed moderate AR and computed tomographic scanning demonstrated an extra-cardiac aneurysm of the unruptured sinus of Valsalva, which extended from the right sinus of Valsalva to the non-coronary sinus of Valsalva. She underwent aortic root reimplantation procedure with a Valsalva graft. Although mild AR was observed postoperatively, her postoperative course was uneventful.

In the field of laboratory medicine, sex differences are found in many clinical tests. Human sex-determination system is at least doubly driven: by sex-chromosomes and by sex-hormones. Karyogram and sex-hormones are typical clinical tests that show sexual dimorphism. Cases of Androgen-Insensitive Syndromes imply sex hormones exert great influences on sex differences found in clinical tests. While childhood, sex steroids secretions from sex-specific organs are inhibited in both sexes. After puberty onset, differences in sex steroids enlarge. In case of females, estrogen secretion decreases in postmenopausal periods. In some of clinical tests, sex differences enlarge after puberty onset, and decrease in postmenopausal periods. Some clinical tests in the field of bone metabolism and lipid metabolism show this kind of sex difference, which seem to be influenced by estrogen.

Vitamin D is pro-hormone that has important roles in calcium metabolism in the intestine, kidneys, and bone. Many studies have indicated that vitamin D deficiency causes not only rickets and osteomalacia, but also increases the risk of various diseases such as cancer and autoimmune disease. Of the many vitamin D metabolites, 25-hydroxyvitamin D[25OH-D], 1α,25-dihydroxyvitamin D[1,25(OH)2-D], and 24,25-dihydroxyvitamin D [24,25 (OH) 2-D] are important for assessing vitamin D metabolism. They are circulating, biologically active, and major inactive forms of vitamin D metabolite, respectively. Immunoassays are widely used for the measurement of serum/plasma vitamin D metabolites. With such an assay, however, the accurate quantification of these metabolites is difficult because of cross-reactivity. Liquid chromatography-tandem mass spectrometry [LC-MS/MS] is the gold standard method for analyzing these metabolites due to its high sensitivity and selectivity. Derivatization with a Cookson-type reagent is a key technique for robust and sensitive analysis by LC-MS/MS. A Cookson-type reagent rapidly and quantitatively reacts with the s-cis-diene structure of vitamin D metabolites, and markedly enhances the ionization efficiency. Using a recently developed Cookson-type reagent (DAPTAD), we successfully established an LC-MS/MS-based method for analyzing serum vitamin D metabolites including 250H-D, 1,25 (OH) 2-D, and 24,25 (OH) 2-D. Thus, LC-MS/MS can be a powerful tool for the accurate determination of vitamin D metabolism. In this review, we describe the advantages of LC-MS/MS for the determination of vitamin D metabolites.

Alternative splicing is a fundamental process of gene regulation that contributes to protein diversity, a common phenomenon in the mammalian genome. Alternative splicing events not only happen in the normal gene regulation process, but are also closely related to certain diseases, including cancer. In this review, we briefly demonstrate the proof of concept (POC) of the relationship between alternative splicing and DNA damage, and describe the associations among alternative splicing and cancer pathogenesis, DNA damage, and gastrointestinal cancers. We discuss whether alternative splicing leads to genetic instability, which is considered to be a driving force for tumorigenesis. FUSE-binding protein (FBP) -interacting repressor (FIR) is a c-myc transcriptional suppressor. A splice variant of FIR that lacks exon 2 in the transcriptional repressor domain (FIRΔexon2), upregulates c-myc transcription by inactivating wild-type FIR. FIR+/- mice exhibited marked c-myc mRNA upregulation, particularly in the peripheral blood (PB), without any significant pathogenic phenotype. Because the single knockout of TP53 generates thymic lymphoma, FIR+/-TP53-/- mice developed T-cell type acute lymphocytic/lymphoblastic leukemia (T-ALL) with increased organ or bone marrow invasion and showed a poor prognosis. After describing the POC of alternative splicing of FIR in DNA damage and carcinogenesis, clinical application for cancer diagnosis and treatment by FIR/FIRΔexon2 was briefly summarized. Chiba University has prepared a biobank to support studies to develop biomarker detection, molecular diagnosis, and "Omics" research. In conclusion, alternative splicing of FIR, generating FIRΔexon2, potentially contributes to not only colorectal carcinogenesis, but also leukemogenesis, and a better understanding of the role and mechanism of alternative splicing in tumorigenesis may reveal new directions for cancer biomarker detection.

Duchenne muscular dystrophy (DMD) is an X-linked disease, but female carriers infrequently have some symptoms, who are called manifesting carriers. Here we report a case of a manifesting carrier of DMD with skeletal muscle weakness and cardiac abnormalities such as deterioration of cardiac function and left ventricular dilatation, who successfully underwent cardiac surgery. A 79-year-old female with acute heart failure for severe mitral regurgitation was admitted to our hospital. Surgical replacement of the mitral valve was performed under general anesthesia with intravenous anesthetics and non-depolarizing muscle relaxant. Cardiac surgery on a manifesting carrier of DMD is rare and requires a careful preoperative assessment of the heart function and anesthetic management.

5-aminolevulinic acid (5-ALA) is widely used in clinical practice because it shows tumor-selective accumulation of protoporphyrin IX, a fluorescent substance and a metabolite of 5-ALA. In addition, some studies have reported that 5-ALA increases the radiation sensitivity of glioma and melanoma. In this study, we investigated the radiosensitization effect of 5-ALA on colon cancer. Mice implanted with the human colon cancer cell line HT29 were administered 5-ALA and subsequently X-ray irradiated. These mice were compared with those not administered 5-ALA. Following multiple irradiations, the tumor volume of the 5-ALA group was significantly lower than that of the non-5-ALA group (day 5: p value=0.0489, day 8: p value= 0.0318, day 12: p value=0.0394). Tumor growth was inhibited by multiple irradiations in the 5-ALA group compared with the non-5-ALA group. These results suggest that 5-ALA also exhibits a radiosensitization effect on colon cancer.

Purpose: The efficacy of chemotherapy for advanced or recurrent gastric cancer in patients who were aged over 75 years was investigated., Materials and Methods: Progression free survival (PFS) and overall survival (OS) of advanced gastric cancer patients who received first-line chemotherapy with TS-1 plus cisplatin or TS-1 in our hospital from 2009 to 2013 were determined. The patients were divided into two groups: H and L. H group patients were aged over 75 years, and L group patients were aged less than 75 years., Results: Median PFS and median OS of patients in the H and L groups who received TS-1 plus cisplatin chemotherapy were not significantly different. PFS was 77[range, 13-211] days and 139[range, 53-211]days for the H and L groups, respectively(p=0.141), while OS was 523[range, 22-1,030] days and 402 [range, 322-623] days, respectively (p=0.620). Similarly, median PFS and median OS of patients who received TS-1 chemotherapy were not significantly different between the H and L groups. PFS was 103[range, 51-156]days and 152.5[range, 85-278]days for the H and L groups, respectively (p=0.230), while OS was 414 [range, 224-714]days and 605[range, 452-1,077] days, respectively ( p=0.1337)., Conclusion: PFS and OS were not significantly different in younger patients with advanced gastric cancer who received TS-1 plus cisplatin or TS-1 chemotherapy compared to that in similarly treated elderly patients with advanced gastric cancer.

Distal anterior choroidal artery aneurysms are quite rare, and appropriate treatment timing and methods remain unclear. Direct surgery of these aneurysms is difficult due to their deep location, small size, and angioarchitecture;however, pseudoaneurysms might disappear spontaneously with conservative treatment. A 65-year-old man with a history of hypertension was admitted to our hospital with a 5-day history of sudden headache and nausea. Computed tomography revealed an intraventricular hematoma located mainly in the right lateral ventricle. Cerebral angiography 7 days after onset revealed a right distal anterior choroidal artery aneurysm and proximal right middle cerebral artery occlusion caused by atherosclerotic changes. Endovascular coil embolization was performed under general anesthesia 14 days after onset. Preoperative angiography demonstrated definite enlargement of the aneurysm and stasis of the contrast agent in the aneurysm in the venous phase. Detachable platinum coils were delivered into the aneurysm and parent artery. The patient was discharged neurologically intact after the procedure. Follow-up angiography 3 months after coil embolization showed complete occlusion of the aneurysm. In recent years, endovascular surgery has emerged as a less invasive treatment option. Early treatment should be considered for patients with ruptured distal anterior choroidal artery aneurysm because these aneurysms might grow and re-rupture in the short term.

Background: Delayed discharge from ICU to the general ward can exert an adverse effect. We researched whether patients are discharged smoothly from our ICU to the general ward., Methods: We defined that patients were eligible for discharge if they are without administration of catecholamine, being assisted by mechanical ventilation and having blood purification therapy., Results: Average time from actual discharge to the time patient was considered eligible for discharge was fifteen hours. This study was retrospective., Conclusions: We need to investigate further the reasons why delayed discharge occurred. It is im portant that patients are discharged from the ICU to the general ward properly. Delayed discharge can delay the recovery and expose the patient to multi-resistant microorganisms. We studied whether patients are discharged smoothly from the ICU to the general ward.

Objectives: In order to improve the appropriateness of contact examinations, we investigated the characteristics of secondary tuberculosis cases., Subjects and Methods: We included tuberculosis patients that were located in Kawasaki City between 2008 and 2011. The patients were considered as 2 separate groups: those with tuberculosis following contact with index cases registered in Kawasaki City and those with tuberculosis who were located in Kawasaki City. Secondary cases were defined as subjects who underwent a contact examination and developed active tuberculosis within 2 years from the last contact with the index case. The secondary cases were classified by diagnostic method, time, and sputum smear test results, followed by consideration of improvement measures., Results: There were 1196 tuberculosis patients and 6157 subjects who underwent a contact examination. Of these, 35 patients developed tuberculosis secondary to index cases registered in Kawasaki City. These 35 cases were classified by diagnostic methods. Diagnosis occurred during a contact examination in 31 cases and during a symptomatic visit in 4 cases. There were 2 sputum smear-positive patients detected in a contact examination that was conducted > or = 6 months after contact. These 2 cases had a symptomatic cough, but did not visit a medical institution. There were 39 patients with secondary tuberculosis who were located in Kawasaki City. These 39 cases were also classified by diagnostic methods. Diagnosis occurred during a contact examination in 33 cases and during a symptomatic visit in 6 cases. There were 4 sputum smear-positive patients detected in a contact examination that was conducted > or = 6 months after contact. These 4 cases had a symptomatic cough, but did not visit a medical institution., Discussion: Of the secondary cases, a sputum smear-positive state was detected in some of the patients at the time of a contact examination that was conducted > or = 6 months after contact. However, secondary cases should be discovered at a sputum smear-negative stage. Appropriate education regarding the importance of a medical visit at the onset of symptoms could decrease the number of patients that are identified in the sputum smear-positive state during a contact examination that occurs at least 6 months after contact.

Purpose: To investigate changes in the prevalence of adult asthma and allergic rhinitis from 2006 to 2011 in Kamishihoro, a town in Hokkaido, Japan., Methods: The Japanese edition of the European Community Respiratory Health Survey questionnaire was completed by 1472 residents aged from 20 to 81 years old. (718 men, 749 women). The age and gender distribution of respondents matched that of respondents in 2006., Results: Response rates were 98.1% in 2011 and 95.8% in 2006. Wheezing in the last 12 months was reported by 10.7% of men and 8.3% of women in 2011, compared to 12.9% and 9.8%, respectively, in 2006. The questions "Have you ever had asthma?" followed by "Was this confirmed by a doctor?" both received positive answers from 7.9% of men and 7.5% of women in 2011, compared to 5.7% and 6.3%, respectively, in 2006. The rate of current smoking was 34.8% in men and 14.7% in women in 2011, compared to 42.8% and 17.2%, respectively, in 2006. A "Yes" answer to the questionnaire item, "Do you have any nasal allergies, including hay fever?" (defining allergic rhinitis) was given by 23.2% of men and 25.4% of women in 2011, compared to 17.6% and 23.0%, respectively, in 2006. The prevalence of allergic rhinitis was increased, particularly among younger respondents., Conclusion: Rates of current asthma and allergic rhinitis increased, whereas the rate of wheezing in the past 12 months decreased from 2006 to 2011. Optimal treatment of asthma might be related to these trends.

Introduction: We have previously reported that a distinct sensitization pattern was associated with thymic stromal lymphopoietin (TSLP) genotype. The aim of this study is to identify the characteristics of asthma phenotypes determined by a cluster analysis of IgE responsiveness and the relationship between these phenotypes and TSLP genotypes., Patients and Methods: We studied 297 patients of adult asthma and 1571 non-asthmatic healthy adults from Ibaraki, a prefecture in central Japan and Kamishihoro, a cedar-free, birch-dominant town in northern Japan. Levels of total serum IgE and specific IgE antibodies towards 14 major inhaled allergens were measured. With the use of these measures, cluster analysis was applied to classify the phenotypes of adult asthma. We also examined the genetic effects of 2 TSLP functional single nucleotide polymorphism (SNPs) on the development of each asthma phenotype using multinomial logistic regression analysis., Results: The cluster analysis identified four distinct clinical phenotypes of asthma, including "Dust mite dominant" (A, N=82), "Multiple pollen" (B, N=14), "Cedar dominant" (C, N=44), and "Low reactivity" (D, N=154). Asthma phenotype A consisted of younger patients with elevated IgE levels and decreased pulmonary function. Asthma phenotype B was characterized by sensitization by many pollen allergens. Asthma phenotype C was not formed in Kamishihoro. Asthma phenotype D was a group of older women who are less atopic. In current or past smokers, both TSLP SNPs (rs2289276 and rs3860933) were associated with the asthma phenotype D (odds ratio 2.11 [1.36-3.30] and 2.11 [1.34-3.33], respectively)., Conclusion: In patients with adult asthma who are less atopic, the genetic polymorphisms of TSLP may have some important roles in the development of the disease in smokers.

A 44-year-old man (ASA-PS 1) underwent right lobectomy of the liver under total intravenous anesthesia with propofol, remifentanil, ketamine and rocuronium. In order to evade allogeneic blood transfusion, 1,200 g of the patient's blood was taken and hemodilution was induced for autologous blood transfusion (HAT) after the induction of anesthesia. As intraoperative blood loss amounted to about 4,000 g, Hb level decreased from 13.6 to 6.2 g x dl(-1). However, as intraoperative hemodynamics was relatively stable with crystalloidal and colloidal transfusion with no ischemic change on ECG and no metabolic acidosis, autologous blood transfusion was withheld. After returning the autologous blood, Hb increased to 9.8 g x dl(-1). Any postoperative complications related to the low Hb level were not recognized. HAT is a useful method to evade or at least decrease the amount of allogeneic blood transfusion by anesthesiologists.

Purpose: Public knowledge-based application for paclitaxe(l PAC) has been approved for advanced or recurrent esophageal cancer. We investigated the feasibility of weekly PAC chemotherapy as a second-line or subsequent regimen for metastatic or recurrent esophageal cancer., Materials and Methods: Patients received PAC( 100 mg/m2 intravenously) on days 1, 8, 15, 22, 29, and 36 of each 8-week period. We analyzed the toxicity and efficacy in 6 patients treated with the weekly PAC chemotherapy., Results: Grade 3-4 toxicities were neutropenia, leukopenia, and anemia. Two patients had stable disease and 2 had progressive disease., Conclusion: By managing the side effects, weekly PAC therapy is considered a feasible regimen that can be administered on an outpatient basis.