Tumor necrosis factor receptor-associated factor 3 (TRAF3) is an anti-inflammatory molecule that negatively regulates the non-canonical nuclear factor-κB pathway. Although TRAF3 haploinsufficiency (TRAF3 HI) can influence innate and adaptive immune cells, its effect on inflammatory bowel disease (IBD) development remains unclear. Here, we report the first case of severe early-onset IBD with a novel TRAF3 variant leading to HI, successfully treated with ustekinumab. A 6-year-old girl with a recurrent parotitis, otitis media, tonsilitis, and atopic dermatitis developed IBD involving the stomach, small intestine, and colon. At diagnosis, the immunoglobulin (Ig)G and IgA levels were relatively high, and lymphocyte subsets showed increased counts of plasmablasts, class-switch recombination B cells, and circulating T-follicular helper cells. Treatment with azathioprine and infliximab failed to maintain remission marked by several relapses accompanied by erythema nodosum and arthritis; however, ustekinumab, an anti-interleukin (IL)-12/23p40 antibody, led to long-term clinical remission, normalizing the Ig level and reducing abnormal lymphocyte counts. Whole-exome sequencing revealed a novel heterozygous mutation in TRAF3 [p.(Pro487Leufs*8)], resulting in TRAF3 under-expression. Our case may highlight the contribution of TRAF3 HI to the development of IBD and provide insights into IBD pathophysiology, suggesting the involvement of the IL-12/23-T-follicular helper cell pathway affected by genetic mutations.

Neoadjuvant chemotherapyeoadjuvant chemoradiotherapy (NAC/NACRT) can be performed in patients with pancreatic cancer to improve survival. We aimed to clarify the clinical outcomes of biliary drainage with a metal stent (MS) or a plastic stent (PS) during NAC/NACRT. Between October 2013 and April 2016, 96 patients with pancreatic cancer were registered for NAC/NACRT. Of these, 29 patients who underwent biliary drainage with MS or PS before NAC/NACRT and a subsequent pancreatoduodenectomy were retrospectively analyzed with regard to patient characteristics, preoperative recurrent biliary obstruction rate, NAC/NACRT delay or discontinuation rate, and operative characteristics. The median age of the patients was 67 years. NAC and NACRT were performed in 14 and 15 patients, respectively, and MS and PS were used in 17 and 12 patients, respectively. Recurrent biliary obstruction occurred in 6% and 83% of the patients in the MS and PS groups, respectively (p<0.001). NAC/NACRT delay was observed in 35% and 50% of the patients in the MS and PS groups, respectively (p=0.680). NAC/NACRT discontinuation was observed in 12% and 17% of the patients in the MS and PS groups, respectively (p=1.000). The operative time in the MS group tended to be longer than that in the PS group (625 minutes vs 497 minutes, p=0.051), and the operative blood loss volumes and postoperative adverse event rates were not different between the two groups. MS was better than PS from the viewpoint of preventing recurrent biliary obstruction, although MS was similar to PS with regards to perioperative outcomes.

　　Case: A 62-year-old woman underwent high anterior resection and partial lobectomy for colon cancer and lung metastasis, respectively, and postoperative chemotherapy. During the follow-up period, she visited the Department of Otolaryngology at our hospital, complaining of expectoration of a mass. Laryngeal fiberscopy showed no abnormality, but thoracic computed tomography revealed nodular lesions protruding into the bronchial lumen. Bronchoscopy confirmed the presence of multiple granular nodules protruding from the bronchial wall. The nodules had a polyp-like appearance and were easily dissected or detached. Anti-cancer drug therapy was initiated for endobronchial metastases from colorectal cancer diagnosed in transbronchial biopsy. Conclusion: This was a rare case of endobronchial metastases that were discovered after expectoration of tumor masses. Bronchoscopic findings were extremely unusual, showing multiple tumors that were easily detached because of their extremely weak connection to the bronchial wall. The findings suggest that it is important to consider endobronchial metastasis from colorectal cancer and perform early diagnostic imaging and bronchoscopy when patients present with recurrent expectoration of masses after surgery for colon cancer.

Pancreatic cancer is the fifth leading cause of cancer-related death in Japan. Surgical treatment is the effective way to achieve a long survival. Because of the development of surgical procedure and perioperative management, pancreatic surgery becomes safer. However, it still includes a certain number of morbidities and mortalities. It is important to perform safe operation for long survival. We herein introduce our operative procedure for pancreatic surgery including pancreaticoduodenectomy (PD) and distal pancreatectomy. In patients undergoing PD, leakage from the pancreatic anastomosis remains an important cause of morbidity and contributes to prolonged hospitalization and mortality. Recently, a new end-to-end pancreatojejunostomy technique without the use of any stitches through the pancreatic texture or pancreatic duct has been developed. In this novel anastomosis technique, the pancreatic stump is first sunk into deeply and tightened with a purse string in the bowel serosa. We modified this method in an end-to-side manner to complete the insertion of the pancreatic stump into the jejunum, independent of the size of the pancreas or the jejunum. Since April 2013, we have performed this new anastomosis technique in 36 patients. The breakdown of preoperative diagnosis of 36 patients were 13 pancreatic cancers, 8 extrahepatic bile duct cancers, 7 intraductal papillary mucinous neoplasms and so on. Of 36 PD, 32 were subtotal stomach preserving PD (SSPPD), and the rest were SSPPD combined with left hemihepatectomy or distal pancreatectomy, and middle pancreatectomy. The concentration of amylase in discharged fluid through an abdominal drain decreased day by day. According to the ISGPF definition, pancreatic fistula (PF) was observed in 4 patients (11%). Of 4, only 1 case had grade C PF. This case had a hemorrhage from pancreatic cut end. This occurred probably because the pancreatic cut end was not compressed by the intestinal wall with this technique. This case had reoperation and the hemostasis of pancreatic cut end was secured. The other severe complications were not observed. This new method can be performed safely and is expected to reduce the occurrence of leakage from PD. The development of PF following distal pancreatectomy is an unsolved problem. We introduce a simple technique, the parallel suturing technique, which prevents severe PF by hand-sewn closure of the pancreatic stump. After standard distal pancreatectomy in the described cases, the main pancreatic duct was secured. The stump of the pancreatic remnant was closed with three nonabsorbable monofilament sutures. The three sutures were positioned about 3 mm proximal to the cut end of the pancreas and tied parallel to the pancreatic stump. Ascites fluid was collected through a drain tube, and its concentration of amylase was measured on days 1, 2, 3, and 4 postoperatively. PF was diagnosed according to the ISGPF classification. On postoperative day 4, three patients were categorized as having grade A PF, six were diagnosed with no PF, and the drain tubes of the remaining three were removed on day 3. This simple technique may effectively lighten the severity of PF following distal pancreatectomy. It may have a particular advantage in patients with a wide pancreatic stump.

Branching morphogenesis of the fetal mouse submandibular gland (SMG) is regulated by signaling through the ErbB and FGF families of tyrosine kinase receptors, whose members activate the ERK-1/2 pathway. The four Sprouty (Spry) proteins are inhibitory modulators of ERK-1/2. There is little information on their expression during pre- and postnatal development of the SMG. Qualitative RT-PCR detected mRNAs for Spry1, 2, and 4 from embryonic day 13 (E13) through postnatal day 7 (P7), but only trace amounts of Spry1 and 2 in adult SMGs. More sensitive quantitative RT-PCR revealed that transcripts for all four Spry isoforms are expressed, and each shows individual patterns of variation across fetal and early postnatal stages, and that there are very low levels of Spry1 and 2, but no Spry3 and 4, in adult glands. EGF, FGF7 and FGF10 upregulate expression of mRNA for Spry1, but only FGF7 upregulates Spry2 mRNA. EGF strongly induces an activating phosphorylation of all four Spry isoforms, but both FGFs do so only minimally. Quantitative RT-PCR of samples collected by laser capture microdissection showed that transcripts for Spry1 are confined to the epithelium of E13 SMG rudiments. The isoform-specific temporal variation in the patterns of expression of Spry1, 2, 3 and 4 suggests a potentially important role for these negative modulators of growth-factor driven ras/ERK-1/2 signaling at stages when the SMG is most actively undergoing branching morphogenesis.

Purpose: We examined the safety and efficacy of cataract surgery and postoperative management in our hospital and at the homes of the patients who live on medically underserved remote.
Patients and methods: A total of 27 patients (54 eyes), who were followed in our hospital or at their homes were enrolled in this study. Cataract surgery was performed on them between January 2009 and January 2010 and we could follow up six months postoperatively. We divided these patients into two groups:group I (GI) consisted of 13 patients who could come to our hospital regularly during both preoperative and postoperative periods, and group II (GII) consisted of 14 patients who could not come to our hospital regularly during either preoperative or postoperative periods. Cataract surgeries were performed on all the patients in GI and GII in our hospital. The patients in GI were hospitalized for three days and those in GII were for seven days. After cataract surgery, the patients in GI had their eyes checked regularly in our hospital and those in GII were in their homes where the doctor visited. Postoperative ophthalmic clinical tests were conducted to examine visual acuity, intraocular pressure and fundus.
Results: GI comprised three males and 10 females. Their age averaged 79.3. GII comprised four males and 10 females. Their age averaged 82.6. Preoperative ophthalmic examinations found that preoperative average visual acuity (LogMAR and decimal visual acuity in parentheses) and spherical equivalent in GI and GII were 0.69 (0.41), 0.80 (0.33) and -0.43 dioptors, -0.42 dioptors respectively, showing no significant differences between the two groups. Postoperative ophthalmic examinations found that, best corrected visual acuity (LogMAR) was significantly increased to 0.36 (0.66) and 0.44 (0.53) in GI and GII respectively, showing no significant differences either.
Conclusions: We concluded that we could get safe and efficient cataract surgery and postoperative management combined with prolonged hospitalization and house calls on the patients who live in the isolated islands.

A19-year-old man was admitted to the hospital because of severe congestive heart failure on 7 April 2000. In the previous year his case had been diagnosed as Churg-Strauss syndrome (allergic granulomatous angiitis, AGA) with bronchial asthma and mononeuritis multiplex. Echocardiography revealed the dilatation of the left ventricle (LVDd 74 mm) and impaired left ventricular systolic function (LVEF 20%). On the 21st hospital day, the irregularity of peripheral branches of left and right coronary arteries was detected by coronary arteriography. Right ventricular endomyocardial biopsy yielded little fibrosis and no infiltration of eosinophil. Although all the laboratory tests showed lower activity of AGA, steroid pulse therapy was tried and the use of steroids was tapered at intervals of two weeks. Left ventricular function was slowly improved (LVDd 60 mm, LVEF 36%). He was discharged on foot on the 71st hospital day.

We performed a retrospective study on the clinical data of 13 remission failure cases in 53 patients who had received remission induction therapy for acute leukemia (AL) in our hospital over the past seven years.
The outstanding clinical manifestations of the remission failure cases, as compared with the successful cases, included (a) disseminated intravascular coagulation (DIC) syndrome (b) complex chromosomal abnormalities (c) leukocytosis over 100, 000/μl and (d) markedly elevated seum LDH level and thymidine kinase activitis at the time of initial admission.
The greater majority of these cases (10 out of 13) resulted in death within 90 days after the start of induction therapy.
The causes of death were predominantly hemorrhagic events associated with DIC syndrome, cerebral hemorrhage and severe infectious diseases such as sepsis and pneumonia.
Earlier death within 14 days after therapy was caused from hemorrhagic events and later one was severe infections.
In the G-CSF treated group, the febril term of over 38°C was shorter and the number of days taken for the neutrophil counts to be restored to the 1, 000/μl level was fewer than in the non G-CSF treated group.
Thus, it was suggested that G-CSF was expected to be one of the useful supporting agents to prevent infections in remission induction therapy for acute leukemia.