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Purpose: In recent years, there has been a growing movement in Western countries toward the abolition of gonadal protection during radiography. The reasons for this recommendation are that there are few reports of increased risk of genetic effects, that the ovarian dose is not due to direct X-rays but due to internally scattered X-rays that cannot be shielded, and that the presence of gonadal protection may adversely affect the automatic exposure control mechanism and may mask important findings. In addition, the gonadal protection is a large high absorber of X-rays, and its presence in the irradiation field may have some effect on image quality, but the effect of the gonadal protection on image quality has not been clarified. In addition, after the abolition of gonadal protection, the optimal irradiation field setting is expected to become even more important to avoid unnecessary exposure. In this study, we investigated the effect of gonadal protection on image quality in frontal hip radiographs of adults with different radiation qualities and clarified the image quality under conditions in which the irradiation field is appropriately narrowed., Method: Frontal hip radiographs were taken using a human phantom as the subject, and the image quality of the femoral head was evaluated. Two irradiation fields were used: (a) 14×17 inch field and (b) an appropriate field (11.6×15 inch) that does not impair the reference line and image information necessary for reading hip joint images. The imaging tube voltage was set at 70 kV, and conditions for adding a copper filter were also considered. The incident surface air kerma was set to 1.25 mGy. The incident surface dose at this time was sufficiently lower than the diagnostic reference level (2.5 mGy) in Japan and was judged to be appropriate for imaging using an indirect conversion flat panel detector. The image quality evaluation item was the signal difference to noise ratio (SdNR) including scatterers., Result: The SdNR decreased by 4.6% when a gonadal shield was placed, indicating that the gonadal shield reduced image quality. When the irradiation field size was appropriately narrowed down, SdNR slightly increased or decreased depending on the quality of the imaging material, but the change was small compared to the change in SdNR with and without the gonadal protection shield., Conclusion: The results of this study confirm that the elimination of gonadal protection in hip radiography has significant advantages, such as reducing unnecessary X-ray exposure while ensuring image quality, when the irradiation field is set appropriately.

A 28-year-old female with a history of treatment for small intestinal polyps and characteristic pigmentation of her lip was clinically diagnosed with Peutz-Jeghers syndrome(PJS). Her sister had the pathogenic variant of STK11 upon genetic testing. A 20-mm polyp was identified in the second part the patient's duodenum on routine gastrointestinal surveillance, and biopsy revealed a well-differentiated adenocarcinoma. Laparoscopic partial duodenectomy with endoscopy was planned. After confirming the location of the tumor and Kocherization using a laparoscope, the polyp was resected via submucosal dissection under direct visualization with a small incision. The polyp was diagnosed as well-differentiated adenocarcinoma in situ and was resected without remnants. PJS is characterized by a high incidence of malignant tumors, and lifelong surveillance for gastrointestinal and extra-gastrointestinal tumors is necessary. The incidence of duodenal cancer is not high among patients with PJS. However, surgery for advanced cancer is highly invasive. It is desirable to detect the tumors at an early stage so that they can be resected via a less invasive treatment method such as endoscopic resection or laparoscopic surgery with an endoscope.

Purpose: This retrospective study was performed to investigate the recent trend of occurrence of cancer of the remnant colorectal segment(RCRS)after ileal-pouch anal anastomosis(IPAA)/ileorectal anastomosis(IRA)and to consider the optimal surveillance methods in patients with familial adenomatous polyposis(FAP)undergoing(procto)colectomy., Patients and Methods: The subject was a total of patients with FAP undergoing IPAA or IRA between 2005 and 2022. Clinicopathological data were extracted from medical charts and analyzed. Cumulative incidence of cancer in the RCRS and overall survival after treatment of such tumors were calculated by the Kaplan-Meier method., Results: There were 45 male and 56 female. IPAA was performed in 49 patients(hand-sewn; n=33, stapled; n=16)and IRA was performed in 52 patients. The median age at initial colorectal surgery was 32 years old(range, 13-66 years old). Median postoperative follow-up was 11 years(range, 1-48 years). Eighty-one patients were confirmed to have pathogenic variant of APC by genetic test. The cumulative incidence of cancer of the RCRS did not differ between patients undergoing IPAA and those undergoing IRA(p= 0.73, 4.1% versus 1.9% at 10 years). The cumulative 5-year overall survival rate after additional surgery for the tumor of RCRS was 82%., Conclusion: This study has several limitations due to single institutional retrospective study with small cases and non-standardized postoperative endoscopic surveillance. However, our results seem to show satisfactory oncological outcomes of patients with FAP in terms of the control of cancer of the RCRS under postoperative periodic surveillance, regardless of the type of colorectal resection.

Purpose: We aimed to develop a simulation program for physicians and nurses involved in virtual reality (VR) and augmented reality (AR) treatment and care from the perspective of these professionals and older adults with dementia who developed delirium, and to test the effectiveness of the program., Methods: effectiveness of the program was analyzed through free-response statements from 67 nurses (84.8%) and 12 doctors (15.2%) who participated in the program between February 16 and April 18, 2023., Results: Regarding the experience of delirium from the perspective of older adults with dementia (personal experience), the following statements were extracted "1. I do not understand where I am, the situation, and the treatment/care that is about to be given"; "2. I want the situation to be explained to me so that I can understand the reasons for my hospitalization and the treatment/care I am receiving"; "3. The eerie environment of the hospital and the high pressure of the staff made me feel anxious and fearful"; "4. Please respect my existence as I endure pain, anxiety, and loneliness"; "5. I feel relieved when doctors and nurses deal with me from my point of view"; and "6. I feel relieved when there is a familiar presence, such as a family member or the name I am calling on a daily basis"., Conclusion: Specific categories of self-oriented empathy were extracted from the experience of physical restraint at night using VR and the experience of delirium using AR. This suggests the possibility of objective effects on treatment and care in future practice.

A 2-year-old, male patient presented with an 18-month history of scattered, brown macules and nodules up to 2 cm in size on his trunk and extremities. These macules were accompanied by pruritus and were positive for Darier's sign. A skin biopsy of a brown macule on the left thigh revealed a dense accumulation of CD117-positive, round or oval cells with amphophilic cytoplasm within the upper to middle dermis. The patient was otherwise healthy and had normal laboratory and imaging test results. Sequence analysis of genomic DNA from a skin biopsy demonstrated the presence of an Asp419del mutation in exon 8 of the KIT gene. Based on these findings, maculopapular cutaneous mastocytosis (MPCM) was diagnosed. The patient received H 1-antihistamine. Although the pruritus resolved, the brown macules remained for one year after the initial treatment. To the best of our knowledge, only three cases of cutaneous mastocytosis (CM) with an Asp419del mutation, including the present case, have been reported in the Japanese literature to date; moreover, while the previous two cases were of DCM, the present case was the first instance of MPCM. Normally, the symptoms of childhood-onset MPCM are dormant until puberty. However, a recent study reported that many MPCM patients may experience persistent or exacerbated symptoms. The present study therefore evaluated 53 Japanese cases of childhood onset MPCM with a KIT gene mutation and discussed the patients' clinical outcomes.

Cronkhite-Canada syndrome(CCS)is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities. We report a rare case of CCS associated with gastric cancer and gastric outlet obstruction with a review of the literature. A 75-year-old man was admitted because of frequent vomiting and hypoproteinemia. He was diagnosed with CCS due to typical clinical and laboratory findings including alopecia, nail atrophy, hypoproteinemia, and typical gastrointestinal polyposis. Upper endoscopic examination also pointed out a large gastric cancer mainly located in the antrum and the reversible pyloric obstruction caused by the gastric tumor. Biopsy of the tumor revealed tubular adenocarcinoma. Computed tomography demonstrated the dilated duodenum caused by packing of the gastric tumor. 1.5 months after prednisolone therapy, he underwent total gastrectomy with complete resection of the dilated duodenal bulb. Histological examination revealed gastric cancer(pap>tub1)classified into Stage ⅢC. Postoperative course was uneventful and he moved to another hospital. To our knowledge, including the present case, there were 20 reported cases of CCS associated with gastric cancer from Japan(1979-2022). Also, 7 cases of CCS associated with gastric outlet obstruction was reported.

The patient described herein was diagnosed with left breast, endometrial, and early gastric cancers at 49, 53, and 57 years of age, respectively. Magnetic resonance cholangiopancreatography performed when she was undergoing treatment for cholecystitis at 50 years of age showed local pancreatic duct dilatation in the pancreatic head. She was followed in the Department of Gastroenterology at our hospital for an intraductal papillary mucinous neoplasm(IPMN). An abdominal computed tomography scan obtained at 59 years of age revealed dilation of the main pancreatic duct in the pancreas body and tail, therefore an endoscopic ultrasound-guided fine needle aspiration was performed. She was diagnosed with pancreatic cancer and underwent a laparoscopic distal pancreatectomy. The postoperative course was uneventful; however, the pancreatic cancer recurred and she died approximately 14 months postoperatively. Reports of multiple cancers associated with IPMNs are rare, yet we managed a patient with a pancreatic head IPMN complicated by metachronous quadruple carcinomas( breast, endometrial, gastric, and pancreatic cancers).

Recently, mammography systems equipped with digital breast tomosynthesis (DBT) have become widely used in Japan. Therefore, it is urgently necessary to establish a quality control method for DBTs. So far, we have been studying acceptance tests for DBTs with reference to EUREF. In 2020, IEC 61223-3-6 was published, which provides not only acceptance tests but also constancy test methods. Therefore, we conducted data collection using DBTs sold in Japan and examined the feasibility of conducting constancy tests. Although there were some items that were difficult to implement in each device, we were able to confirm quality control items that could be implemented in many devices. In addition, we were able to confirm routine tests that enable rapid evaluation. Based on these results, we have developed a "Digital Breast Tomosynthesis Quality Control Manual". In this paper, we report an overview of the manual and the results of routine tests.

While open window thoracostomy is used to treat empyema with a high rate of infection control, it is an invasive procedure that leads to a decline in the quality of life. An 80-year-old man who had undergone wedge resection for pulmonary nodules subsequently developed postoperative empyema and underwent open window thoracostomy. After thoracostomy, the patient developed several complications, including bleeding from the lung surface and air leakage. Window closure was planned at this time;however, the plan was scuttled due to his low nutritional status and pulmonary air leakage. After the patient's condition improved with persistent conservative treatment, window closure was performed, and he overcame his complications. Patients with postoperative empyema requiring thoracostomy are at a high risk of developing postoperative complications. Therefore, it is important to manage the patients' condition persistently so that they can receive window closure at an appropriate time.

A 47-year-old woman diagnosed with transverse colon cancer with liver, peritoneal, and lymph node metastases was admitted. Modified FOLFOX6(mFOLFOX6)regimen was given as a first line chemotherapy and was followed by pembrolizumab after 1 cycle of the mFOLFOX6, because microsatellite instability(MSI)test of the tumor showed high-frequency MSI. Because of the transverse colon obstruction after 2 cycles of pembrolizumab, she underwent right hemicolectomy. Histological examination of the resected specimen revealed no residual tumor cells in the primary tumor and reginal lymph nodes. Immunohistochemistry for mismatch repair proteins(IHC-MMR)showed loss of MSH2 and MSH6 expression. Genetic test identified a MSH2 pathogenic variant leading to the diagnosis of Lynch syndrome. The present case shows the importance of MSI test or IHC-MMR before the treatment of metastatic colorectal cancer.

Immune checkpoint inhibitors(ICIs)are widely used for the treatment of unresectable gastric cancer. We treated approximately 70 patients with ICIs. ICI treatment with pembrolizumab was administered for MSI-high cases and nivolumab for MSS cases in the second- or third-line chemotherapy. We observed 5 cases of complete response. Among these, 2 patients presented with liver metastases, 2 with peritoneal disseminations, and 1 with pulmonary metastasis. In 1 patient, the primary tumor invaded the diaphragm and descending aorta; whereas, in another patient the primary tumor invaded the pancreas and liver. All patients had progressive disease after first-line chemotherapy.

In Japan, robot-assisted thoracic surgery (RATS) was introduced in thoracic surgery in 2001, but it did not become widespread. However, surgery for mediastinal tumors and lobectomy for lung cancer with RATS were covered by insurance in 2018 and are currently becoming popular as a general practice, following video-assisted thoracic surgery(VATS). Forty-six patients with mediastinal tumors were treated by RATS from February 2014 to November 2022 in our institution. Theoretically, the RATS approach is performed from one side in a semi-supine position under CO2 insufflation as with the VATS approach of our institution. In the case of extended thymectomy, a bilateral approach is performed by changing the patient's position. The median surgery time was 88 min, and the median surgery time in unilateral and bilateral approaches were 79 and 208 min, respectively. Blood loss during surgery was quite minimum, and no patients required conversion to VATS or thoracotomy. Regarding adverse events, postoperative bleeding was observed in one patient (2.2%). RATS has been successfully introduced and expanded safely for mediastinal tumors. Considering further expansion of RATS indications while conducting verification by comparison with VATS in the future is necessary.

In the present case of a 56-year-old male, hemodialysis was introduced from December 20XX-2 due to chronic renal failure caused by diabetic nephropathy. In February 20XX, a glans penis ulcer was observed. It gradually expanded. Angiography conducted in April revealed complete occlusion of the left internal pudendal artery and poor visualization of the bilateral penile arteries. Given the high risk of obstruction, endovascular treatment was not conducted. The glans penis ulcer continued to expand, and maintenance dialysis became difficult due to intractable pain. Opioids were introduced, but the pain could not be controlled. In May 20XX, the patient was referred to our department for surgical treatment, and partial penile resection was performed. The patient was diagnosed with penile calciphylaxis based on clinical findings and pathological diagnosis. After the surgery, the pain subsided considerably, and the patient is being followed on an out-patient basis.

An 80-year-old woman presented with subacute right lower limb pain and bilateral lower limb weakness. MRI of the spine showed marked cauda equina enlargement with contrast enhancement. Cerebrospinal fluid (CSF) examination showed elevated cell count, decreased glucose, and elevated protein. Cytology of the CSF showed class V, which together with B-cell clonality by flow cytometry, led to the diagnosis of primary central nervous system lymphoma (PCNSL). The patient was treated with steroid, radiation, and chemotherapy. Despite the reduction in lesion size, her neurological symptoms revealed no improvement. PCNSL with cauda equina lesions are rare and often require highly invasive cauda equina biopsy for diagnosis. In recent years, some studies reported useful CSF biomarkers, but they may have some problems. Therefore, as in this case, the combination of cytology, flow cytometry and, CSF biomarkers could be a substitute method for invasive biopsies, and contribute to the early treatment of PCNSL.

The Japanese Pharmacopoeia (JP) is an official normative publication for establishing the authenticity and properties and maintaining the quality of pharmaceutical products in Japan. The JP is revised every five years and partially revised in order to respond to the progress of science and technology, the demand for medical care, and international harmonization. Thus, "Internationalization of the JP" is one of the most important issues to address for the revision of the JP, which is also referred to the basic principles for the preparation of the JP 19th edition. For instance, the incorporation of the test methods that have been used in other pharmacopeias, such as the European Pharmacopoeia (EP) and the United States Pharmacopeia (USP), into the JP is one of promising approaches. From this perspective, we have recently reported changes in test methods, establishment of a quantitative test method for the JP-listed clonidine hydrochloride as well as lorazepam from using a potentiometric titration method to using HPLC method. As our ongoing study to change test methods for internationalization, we selected sodium cromoglicate and trihexyphenidyl hydrochloride. Each pharmaceutical product is analyzed using a potentiometric titration method as listed in the 18th JP; however, both the EP and the USP use HPLC method for quantitative analysis of these drugs. In this study, we synthesized the related impurities of sodium cromoglicate and trihexyphenidyl hydrochloride listed in the EP and determined their purities using quantitative NMR. The separation conditions of these compounds were examined using HPLC and simultaneous analyses were performed.

The treatment of choice for a resectable hilar cholangiocarcinoma is hepatectomy. Alternative treatment for unresectable cases includes liver transplantation;however, curative surgery is hindered by a distal cholangiocarcinoma extension into the intrapancreatic duct. Herein, we present a case of simultaneous living donor liver transplantation and pancreaticoduodenectomy for an extensive cholangiocarcinoma that is associated with primary sclerosing cholangitis, involving the perihilar and intrapancreatic duct. The treatment strategy involved neoadjuvant chemotherapy and radiation therapy, an exploratory laparoscopy and laparotomy for accurate staging, en-bloc whole bile duct and hepatoduodenal ligament resection, portal vein reconstruction with an interposition graft, and arterial reconstruction with the middle colic artery. The patient was discharged 122 days postoperatively although she suffered from postoperative ascites and delayed gastric emptying. Simultaneous living donor liver transplantation and pancreatoduodenectomy should be considered as treatment options for advanced cholangiocarcinoma.

Patient 1 was a female patient in her teens who presented with swelling of the lips and oral discomfort after consuming mung bean sprouts. She had a history of this reaction since the age of 6 years and showed positive on a prick-to-prick test for mung bean sprouts. Patient 2 was a male patient in his twenties who also showed positive for mung bean sprouts as well as soybean sprout. Both patients were positive for IgE specific to birch, Gly m4, and Bet v1.Mung beans belong to the PR-10 family because they contain the allergenic component, Vig r1. A cross reaction to mung bean may occur in a patient with birch allergy as in the present cases. Mung bean sprouts are a cheap and common dietary item in Japan where, however, only a few cases of mung bean sprouts allergy have been reported. Mung bean sprouts allergy should be diagnosed with appropriate testing; if the patient has allergic reactions for this food item, an allergologist should provide detailed dietary guidance for avoiding pollen-food allergy syndrome.

Biopharmaceuticals, including therapeutic genes and proteins, are characterized by highly-targeted, specific action and flexible pharmacological design and have a rapidly growing market share; however, because of high molecular weight and low stability, injection is the most common delivery route of biopharmaceuticals. Thus, pharmaceutical innovations are required to provide alternative delivery routes for biopharmaceuticals. Pulmonary drug delivery via inhalation is a promising approach, particularly for targeting local diseases of the lung, because it can exert therapeutic effects in small doses and can noninvasively and directly deliver drugs to airway surfaces. However, biopharmaceutical inhalers must ensure that the biopharmaceuticals maintain their integrity as they are subjected to several types of physicochemical stress, such as hydrolysis, ultrasound, and heating, at various stages during the process from manufacturing to administration. In this symposium, I present a novel dry powder inhaler (DPI) preparation method without heat-drying, with the goal of developing biopharmaceutical DPIs. Spray-freeze-drying is a nonthermal drying technique that produces a powder with porous shapes; this powder has suitable inhalation characteristics for DPI. A model drug, plasmid DNA (pDNA), was stably prepared as a DPI using the spray-freeze-drying process. Under dry conditions, the powders maintained high inhalation characteristics and maintained pDNA integrity for 12 months. The powder induced pDNA expression in mouse lungs that exceeded at higher levels than the solution did. This novel preparation method is suitable for DPI preparation for various drugs and may help expand the clinical application of DPIs.

Objective: The present study aimed to assess the course of patients with atopic dermatitis (AD) receiving dupilumab treatment., Methods: The present, retrospective survey enrolled 201 patients with AD between May 2018 and May 2022 to examine their previous treatment, skin score, percentage of self-injections, EASI improvement rate, treatment continuation rate, number of treatment interruptions, and reasons for the interruptions., Results: The average EASI severity score was 39.5±18.1, and the self-injection rate was 83%. The percentage of improvement in patients with an EASI-75 was 63% at week 16 and EASI 100 was 15.9% at week 60. At week 16 of treatment, the patients were divided by their improvement rate into an EASI-75, < 50 group. The EASI-75 group maintained their improvement rate until week 60. In the EASI< 50% group achieved 73.4% at week 60. The treatment continuation rate was 82.6%, and 35 patients discontinued the treatment, in most cases shortly after commencement., Conclusion: Dupilumab has revolutionized AD treatment, markedly improving skin symptoms. The present study was the first in Japan to demonstrate a treatment continuation rate of 82.6% at week 60 at a single center. Clear guidelines on long-term, complete maintenance treatment with dupilumab await formulation.

In general, nitrite in food is extracted under slightly alkaline conditions, deproteinized, and analyzed by a colorimetric method using color development by diazotization. However, depending on the sample, the sample solution may become cloudy and difficult to filter by the deproteinization treatment of the analytical method. Recently, an improved analytical method that solves these problems has been reported. Therefore, a validation study was performed on the improved analytical method was performed. The concentrations of sodium nitrite added to cod roe, fish sausage, and ham, which were not labeled with sodium nitrite, were set at the upper limits of the standards for use. We set the target values of 70-120% for trueness, less than 15% for intralaboratory reproducibility, and less than intralaboratory reproducibility for repeatability. As a result, the target values were met for the three samples verified: 88-92% for trueness, 2.0-3.0% for repeatability, and 3.2-4.3% for intralaboratory reproducibility. In addition, an interlaboratory study was conducted by eight institutes on the improved analytical method for nitrite. At each institution, sodium nitrite was added to the same three samples as in the validation study, at concentrations equivalent to twice the lower limit of quantification and the upper limit of the standards for use and analyzed in triplicate. The estimated trueness from the obtained analyses ranged from 82 to 95%, the repeatability ranged from 2.3 to 5.8%, and the inter-room reproducibility ranged from 3.5 to 11%. Thus, the improved analytical method could be useful for determining nitrite in foods.

All-trans retinoic acid (ATRA) is used as standard induction therapy for acute promyelocytic leukemia (APL), but it is contraindicated for patients on hemodialysis. We present a case of a patient with APL on hemodialysis, intubated, and with marked disseminated intravascular coagulation (DIC) who was successfully treated with ATRA. A 49-year-old man was transferred to our hospital and admitted into the intensive care unit due to renal dysfunction, DIC, and pneumonia. Promyelocytes were noted in the peripheral blood, and he was diagnosed with APL after bone-marrow examination. Because of renal dysfunction, only Ara-C was used but with a reduced dose. The patient's condition improved, and he was extubated and withdrawn from dialysis on the 5 th day of hospitalization. The patient suffered from APL syndrome during induction therapy, which necessitated ATRA withdrawal and steroid administration. Remission was achieved after induction therapy, and the patient is currently on maintenance therapy. There are few cases of patients with APL on hemodialysis who were treated with ATRA; hence, it is necessary to review the treatment plan for these patients.

A 55-year-old woman had been admitted to a hospital with abdominal bloating. Retroperitoneal liposarcoma was suspected and diagnosed as not resectable. She was then referred to our hospital with dyspnea and difficulties with movement due to the huge mass. An abdominal CT revealed a large mass originating in the left retroperitoneum. The tumor occupied most of the abdominal cavity, resulting in the displacement of her organs. However, there was no evidence of infiltration of the tumor into the aorta and inferior vena cava. Under a provisional diagnosis of retroperitoneal liposarcoma, a surgical resection was undertaken. The resected specimen had a maximum diameter of 48 cm and weighed 14 kg. Histopathological examination revealed a differentiated liposarcoma. The patient remains alive 6 months after the operation, without recurrence.

A 66-year-old man with severe anemia was diagnosed with gastric cancer. CT examination revealed primary gastric tumor, which involved the pancreas body, with regional lymph nodes that were enlarged(T4b[panc], cN2, cM0, cStage ⅣA). He received three courses of preoperative S-1 plus oxaliplatin therapy. Primary tumor and metastatic lymph nodes were reduced remarkably. We performed a curative distal gastrectomy(D2)without pancreas resection. Histopathological examination revealed Grade 3 pathological complete response in both primary tumor and metastatic lymph nodes.

An 81-year-old female visited a local hospital with complaints of anal pain. A tumor was found on the right side of her anus, and the histopathological diagnosis was a non-epithelial malignant tumor. Therefore, the patient was referred to our hospital. Result of imaging inspection revealed that the tumor had invaded the lower rectum, but had not distantly metastasized. Based on the findings of another biopsy, the patient was diagnosed with a malignant peripheral nerve sheath tumor (MPNST). Robot-assisted abdominoperineal resection(D1)was performed, and the lesion was resected without any pathological remnants. During the postoperative period, the patient developed perineal wound infection. Subsequently, the patient was discharged from the hospital on postoperative day 10. At the 6-month postoperative follow-up, no recurrence was noted. Most MPNSTs occur in the limbs, trunk, and neck. MPNST in the primary gastrointestinal tract or in the vicinity of the gastrointestinal tract is relatively rare, and in principle, combined resection of the intestinal tract is required for surgical treatment. Here, we report a case of MPNST that occurred near the anus and infiltrated to the lower rectum and was completely resected by robot-assisted abdominoperineal resection.

An 82-year-old male with jaundice was referred to our hospital for a detailed examination. The computed tomography (CT) examination detected an enhanced mass lesion of the distal bile duct. Endoscopic retrograde cholangiography showed a filling defect corresponding to the CT findings. Simultaneously, a forceps biopsy and an endoscopic retrograde biliary drainage were performed. We performed pancreatoduodenectomy, and adenocarcinoma was pathologically proven. The histopathological finding of the resected specimen was a mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) composed of large cell neuroendocrine carcinoma and well-differentiated adenocarcinoma. Although pathological R0 resection was achieved, liver metastasis was observed 6 months after the operation. Although neuroendocrine carcinoma (NEC) rarely develops in the bile duct, it manifests a higher degree of malignancy than other ordinary bile duct adenocarcinomas. Further investigation is needed to choose an appropriate treatment.

Mean number of emergency surgery for post infarction ventricular septal perforation( VSP) in Japan from 2001 to 2018 was 235 cases/year, with 35.2% of in hospital mortality. There was no apparent improvement in surgical results in Japan, nor worldwide for this disease during last two decades. In this report, overview of current surgical techniques for VSP was described. Infarction exclusion technique, entire septal patch technique, and sandwich technique through right ventricle incision were summarized. To further improve surgical results for VSP, pre-operative mechanical assist in critically ill patients, or development of new surgical technique using plug device may be necessary.

Objectives　The national database for long-term care insurance (LTCI) of Japan (Kaigo DB) enables researchers to access comprehensive data from its LTCI registry, eligibility assessment records, claims for service usage, and information about service providers. However, studies regarding the death or mortality of beneficiaries cannot be conducted because Kaigo DB does not contain death records, and researchers are not allowed to link Kaigo DB to other databases, such as national death records. Therefore, we aimed to assess the validity of using an insurer's disqualification from an LTCI beneficiary as a proxy of death.Methods　We used 510,751,798 monthly beneficiary records between April 2007 and March 2017 from the LTCI registry, while excluding data for ineligible persons for LTCI benefit or those younger than 65 years. We identified insurer cases disqualified from LTCI beneficiaries and linked them to national death records using deterministic linkage methods by dates of birth and death, sex, and residence. We considered the cases as positive if they were disqualified and their record was linked to a death. We used sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) as validity indices.Results　We identified 5,986,991 (1.17%) disqualified and 5,295,961 death cases. Sensitivity, specificity, PPV, and NPV of disqualification for death were 100%, 99.86%, 88.46%, and 100%, respectively. After stratification, PPV of disqualification was between 85% and 88% before 2012, 91% after 2012, 91.9% in men, and 85.9% in women. PPV increased with age (65-69 years: 80.6%, 70-74 years: 86.7%, 75-79 years: 86.4%, 80-84 years: 86.7%, 85-89 years: 88.0%, 90-94 years: 90.6%, and 95+ years: 93.4%) and level of care needed (support level: 72.2%, care level (CL) 1: 79.7%, CL2: 85.9%, CL3: 89.3%, CL4: 92.3%, and CL5: 94.0%).Conclusions　Disqualification from the LTCI registry is an inappropriate measure to estimate mortality accurately because it has a 10% false-positive rate. However, it appears sufficiently valid to use disqualification as a proxy outcome of death, although the main effect or confounding of a possible predictor of death could be slightly underestimated.

Lung transplantation has become popular in Japan, showing better survival rate than other countries. However, the results are still not satisfactory compared with other solid organ transplantation. One of the reasons for this might be that knowledge on donor-specific antibodies or antibody-related rejection, which has been attracting attention these days, is less than that of kidney or liver transplantation. Our laboratory has continued basic research in this field using rodent lung transplantation model. We have previously shown that type V collagen is associated in chronic rejection as an autoimmune, and that oral administration of type V collagen induces tolerance. The murine chronic rejection model of the minor antigen mismatch was developed, and involvement of the humoral immunity and role of the complement activation were shown. We are now studying the effects of immune checkpoint molecules, which play a central role in the field of cancer therapy, on rejection after lung transplantation. We are also working to verify the effects of anti-complement drugs and molecular targeted drugs in the future treatment on rejection.

A 62-year-old male patient was referred to our hospital for jaundice and bloody feces. He had hyper-IgG4-emia. Computed tomography (CT) showed diffuse pancreatic enlargement, pancreatic pseudocyst, and hematoma of the splenic flexure of the colon. Magnetic resonance imaging (MRI) showed a fistula in the pancreatic pseudocyst and splenic flexure of the colon. Moreover, lower gastrointestinal endoscopy showed a fistula in the same region. Endoscopic retrograde cholangiopancreatography (ERCP) showed narrowing of the main pancreatic duct and stenosis of the lower bile duct. Following this, the patient was diagnosed with autoimmune pancreatitis-induced pancreatic pseudocyst and colonic perforation-induced gastrointestinal bleeding. The pancreatic pseudocyst and fistula were resolved through steroid treatment.

Giant cell carcinoma of the lung is a rare tumor with poor prognosis. A 70-year-old male was referred to our hospital because of chest pain and abnormal shadow on the chest X-ray. He had a lung tumor invading the chest wall. The tumor was surgically removed, and since the diagnosis of giant cell carcinoma with p-N2 was obtained pathologically, adjuvant chemotherapy was performed. However, the local recurrence was found at eight months after surgery and was treated with radiotherapy( total 70 Gy/28 Fr). The patient has been well for over 10 years with no clinically evident recurrence after treatment.

Cutaneous mastocytosis (CM) usually appears in childhood and improves substantially before adolescence. The c-KIT mutation of D816V is present in 36% and 20% of patients with childhood-onset CM and diffuse cutaneous mastocytosis (DCM), respectively. In some cases of childhood-onset DCM, the disease can progress to systemic mastocytosis; in others, it resolves spontaneously. Thus, assessing the prognosis is difficult. Herein, we described a case of DCM in an 11-month-old, male patient without a c-KIT mutation. The patient presented with dark brown macules and sporadic erythema topped by bullous lesions. A skin biopsy of the macule on the abdomen revealed accumulation of mast cells which were round to oval-shaped with amphophilic cytoplasm within the upper dermis. The patient had received H1 inhibitor until age 3 years and continued to experience blisters on the trunk. However, no severe symptoms, such as anaphylaxis, occurred. Included in this manuscript is a review of previous reports of childhood-onset DCM in Japan and cases specifically seen at our dermatology clinic.

Thalidomide was developed as a sedative drug during the 1950s. Unfortunately, it has serious teratogenic properties. When pregnant women ingested thalidomide, their infants developed serious malformations such as short limbs. However, thalidomide is now recognized as a clinically useful drug, with several countries approving it as an anti-myeloma treatment. Although the direct target of thalidomide was largely debated until recently, our groups discovered cereblon (CRBN), a substrate receptor of an E3 ubiquitin ligase as a primary target of thalidomide in 2010. CRBN binds not only to thalidomide, but also to various thalidomide derivatives such as lenalidomide and pomalidomide, as well as compounds containing a thalidomide moiety. These compounds are known as cereblon modulators, which induced specific neosubstrates of CRBN E3 ubiquitin ligase such as Ikaros and Aiolos. Several groups have now joined the CRBN research and have reported the basic mechanism of CRBN and its binding compounds. In this review, we present our findings as well as recent advances in this subject area.

Copper is one of the essential trace elements in humans, and its deficiency causes various diseases. Zinc acetate dihydrate is administered to treat hypozincemia in preterm infants; however, zinc inhibits the gastrointestinal absorption of copper, which may cause copper deficiency. To safely treat hypozincemia in preterm infants, we retrospectively analyzed the factors reducing serum copper concentrations when zinc is administered to preterm infants with hypozincemia. Seventy preterm infants were included in the present study. Serum zinc and copper concentrations, doses, and other clinical characteristics were retrieved from electronic medical records. The administration of zinc acetate dihydrate decreased serum copper concentrations in 21 out of 70 patients. In comparisons between the two groups with and without a decrease in serum copper concentrations, significant differences were observed in postmenstrual age (34.9 and 35.9 weeks, respectively) and serum zinc concentrations (62.0 and 58.0 μg/dL, respectively) at the start of the zinc acetate dihydrate treatment. A logistic regression analysis identified postmenstrual age as a significant factor decreasing serum copper concentrations. In the ROC curve, the cut-off value for postmenstrual age for a decrease in serum copper concentrations was 34.143 weeks. The present results suggest that when zinc acetate dihydrate is administered to preterm infants with a low postmenstrual age who are at higher risk of decreased serum copper concentrations, particularly to those with a postmenstrual age <34 weeks, it is important to consider copper deficiency and periodically measure serum copper concentrations.