Background: Immune checkpoint inhibitors (ICIs) including anti-CTLA-4, anti-PD-1, and anti-PD-L1 antibodies have been increasingly used for various malignancies. These ICIs activate immune functions to treat malignant tumors; however, this causes characteristic complications called immune-related adverse events (irAE). In the gastrointestinal tract, ICIs cause adverse events such as diarrhea and enterocolitis, thus warranting treatment discontinuation. These irAEs require treatment that suppresses immunity; however, no treatment strategies based on approved guidelines have been reported. This review aimed to investigate the current treatment status for refractory cases of ICI-induced colitis in accordance with their diagnosis, therapy, and prognosis.

Summary: We systematically reviewed studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) checklist. Two investigators searched PubMed and Scopus in January 2019. We extracted data, including the number of ICI-treated patients developing colitis and diarrhea. The number of cases classified as severe per the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) definitions and the progress of corticosteroid-treated and anti-TNF-α- antibody-treated cases (e.g., infliximab) were recorded. Details of further treatment were also recorded for cases that did not improve with antiTNF-α- antibody. Among patients receiving anti-CTLA-4 antibody, corticosteroids were administered to 14.6% of patients, and infliximab was administered to 5.7% of patients. Among patients receiving anti-PD-1/PD-L1 antibody, corticosteroids were administered to 2.37% of patients. For refractory cases unsuccessful with infliximab, the continuation of infliximab every 2 weeks, tacrolimus administration, prolonged corticosteroid treatment, colectomy, or vedolizumab administration were reported.

Key Messages: Treatment of ICI-induced colitis is important to avoid the need to discontinue cancer treatment. Many therapeutic agents for inflammatory bowel disease are reportedly effective in treating refractory ICI-induced colitis.

Summary: The superficial musculoaponeurotic system (SMAS) was advocated by Mitz and Peyronie in 1976. The concept of this superficial fascia was established by surgical findings of facelift surgery and is familiar to plastic surgeons and anatomists. However, detailed characteristics of this fascia are still not widely known among head and neck surgeons. Moreover, the SMAS is generally located at the parotid and cheek regions and divides facial fat into superficial and deep layers. The SMAS connects to the superficial temporal fascia cranially and to the platysma caudally. The frontal muscle and the peripheral part of the orbicularis oculi are also in the same plane. The exact expanse of the SMAS in the face is controversial. Some authors claimed that the SMAS exists in the upper lip, whereas others denied the continuity of the SMAS to the superficial temporal fascia in a histological study. There are various other opinions regarding SMAS aside from those mentioned above. The concept of the SMAS is very important for facial soft tissue surgeries because the SMAS is a good surgical landmark to avoid facial nerve injuries. Therefore, this article summarized SMAS from an anatomical point of view.

Summary: A variety of Candida spp. can be found as a natural commensal fungus in various parts of the human body. This fungus may be associated with various diseases such as celiac disease (CD). Gliadin, a component of the gluten protein complex that is mostly found in wheat, is the main inducer of CD. A number of studies have demonstrated that patients infected with Candida can develop CD, and vice versa. C. albicansis presumed to induce CD because it has a protein homologous to gliadin in its cell wall called Hwp1. Despite the non-specificity of the anti-gliadin test, the detection of antibodies against anti-gliadin (AGA) and anti-tissue transglutaminase (anti-tTG) are important in the diagnosis of CD. Some evidence is now available to support the hypothetical correlation between Candida spp. and CD, as high levels of AGA have been found in patients infected with candidiasis without CD. Further study is needed to confirm this relationship.

Summary: This study interviewed 39 mother-doctors from two university hospitals in Japan to investigate how certain stages in their lives influenced their working motivation. We conceptualized a Motivational Drive Chart to track changes of work motivation from enrollment in medical courses to the present day, recording changes in motivational values, age, and life events. It was found that the average value of motivation increased from the beginning of medical school enrollment until graduation; however, a sudden drop was noted in the age group 25 to 29 due to childcare and work-life conflicts. Motivational values were found to gradually increase in the 30 to 34 age group, owing to professional accomplishments, such as obtaining a specialist license. In Japanese society, social roles have traditionally been divided between men and women. The present study found that Japanese female doctors faced a decrease in work motivation during childrearing stages. The finding suggests that new avenues should be explored to support mother-doctors.

Summary: Background: Our goal was to revisit the innervation of the adductor muscles of the thigh and add new evidence to currently existing knowledge.

Methods: Ten thighs from five fresh frozen cadavers were dissected. Obturator nerve innervation to the pectineus, obturator externus, adductor brevis, adductor magnus, adductor longus, and gracilis was documented.

Results: The adductor longus and gracilis were innervated by the anterior branch in 100%, and the adductor magnus was innervated by the posterior branch in 100%. The adductor brevis was supplied by both the anterior and posterior branches in 90%. The obturator externus was innervated by the posterior branch in 60% and a direct branch from the main trunk in 10%. No innervation of the obturator externus by the obturator nerve was found in 30%.

Conclusions: The obturator externus and adductor brevis need to be explored further to clarify their innervation.

Summary: Background: Distal bile duct carcinoma continues to be one of the most difficult cancers to manage in terms of staging and radical resection. Pancreaticoduodenectomy (PD) with regional lymph node dissection has become the standard treatment of distal bile duct carcinoma. We evaluated treatment outcomes and histological factors in patients with distal bile duct carcinoma.

Methods: Seventy-four cases of resection of carcinoma of the distal bile ducts treated at our department during the period from January 2002 and December 2016 using PD and regional lymph node dissection as the standard surgical procedure were investigated. Survival rates of factors were analyzed using uni- and multivariate analyses.

Results: The median survival time was 47.8 months. On univariate analysis, age of 70 years or older, histologically pap, pPanc2,3, pN1, pEM0, v2,3, ly2,3, ne2,3 and postoperative adjuvant chemotherapy were statistically significant factors. On multivariate analysis, histologically pap was identified as a significant independent prognostic factor. The multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as showing a significant trend towards independent prognostic relevance.

Conclusion: The good news about resected distal bile duct carcinoma is that the percentage of those who achieved R0 resection has risen to 89.1%. Our multivariate analysis identified age of 70 years or older, pEM0, ne2,3 and postoperative adjuvant chemotherapy as prognostic factors. In order to improve the outcome of treatment, it is necessary to improve preoperative diagnostic imaging of pancreatic invasion and lymph node metastasis, establish the optimal operation range and clarify whether aortic lymph node dissection is needed to control lymph node metastasis, and establish effective regimens of chemotherapy.

Summary: Reflux esophagitis and gastric tube ulcer sometimes cause severe clinical problems in patients undergoing esophagectomy with gastric tube reconstruction. We previously reported that acidity in the gastric tube was decreased for 1 year after esophagectomy, and that lower acidity levels were associated with Helicobacter pylori (H. pylori) infection. However, the long-term changes in gastric acidity remain unknown. We aimed to investigate the long-term changes in gastric acidity after surgery. Eighty-nine patients who underwent esophagectomy with gastric tube reconstruction for esophageal cancer were analyzed. They underwent 24-hour pH monitoring, serum gastrin measurement, and H. pylori infection examination before surgery, at 1 month, 1 year, and 2 years after surgery. The gastric acidity at 1 month and 1 year after surgery was significantly lower than that before surgery (p=0.003, p=0.003). However, there was no difference in gastric acidity before and 2 years after surgery. The gas tric acidity in H. pylori-infected patients was significantly lower in comparison to non-infected patients at each time point (p=0.0003, p<0.0001, p<0.0001, p<0.0001, respectively). In H. pylori-infected patients, gastric acid ity was decreased for 1 year after surgery, and recovered within 2 years after surgery. However, no significant differences were observed in the acidity levels of non-infected patients during the 2-year follow-up period. The serum gastrin level increased after esophagectomy. The acidity levels in the gastric tube recovered within 2 years after surgery. Periodic endoscopy examination is recommended for early detection of acid-related disease, such as reflux esophagitis or gastric tube ulcer, after esophagectomy with gastric tube reconstruction.

Summary: Background: The combination of dual antiplatelet therapy (DAPT) plus warfarin in atrial fibrillation (AF) patients after coronary stenting has been reported to confer a significant risk of bleeding complications. Direct oral anticoagulants (DOAC) reduce the risk of stroke and bleeding complications in AF patients compared to warfarin. The optimal anticoagulation strategy for Japanese non-valvular AF patients after coronary stenting remains unclear.

Methods: A total of 3230 patients who underwent coronary stenting were retrospectively reviewed. Of these, 284 cases (8.8%) were complicated by AF. Following coronary stenting, 222 patients received triple antithrombotic therapy (TAT) by DAPT plus oral anticoagulants; 121 patients received DAPT plus warfarin, and 101 patients received DAPT plus DOAC. We compared the clinical data between the two groups.

Results: The median International normalized ratio (INR) in the DAPT plus warfarin group was 1.61. Bleeding complications occurred in both groups. No cerebral infarction occurred in the DAPT plus DOAC group, while 4.1% of the DAPT plus warfarin group experienced cerebral infarction during follow-up (P=0.04). Twelve-month freedom from cerebral infarction, myocardial infarction, and cardiovascular death was significantly higher in the DAPT plus DOAC group than in the DAPT plus warfarin group [100% vs. 93.4%, P=0.009].

Conclusions: DOAC might be an optimal selection as an oral anticoagulant for Japanese AF patients who are receiving DAPT after PCI. A larger, longitudinal follow-up should be performed to clarify the clinical advantage of DOAC over warfarin, including among patients who receive single antiplatelet after coronary stent implantation.

Summary: Background: Hepcidin is an antimicrobial peptide and a key hormone involved in iron homeostasis. Hepcidin level is elevated in the serum during the course of Helicobacter pylori infection and hepcidin is considered to contribute to iron deficiency anemia. However, it is unclear whether H. pylori infection influences hepcidin expression in the gastric mucosa.

Method: In this study, 15 patients with H. pylori-infected nodular gastritis, 43 patients with H. pylori-infected chronic gastritis, and 33 patients without H. pylori infection were enrolled. Endoscopic biopsy, and histological and immunohistochemical analysis were performed to evaluate the expression of hepcidin and its distribution in the gastric mucosa.

Result: Hepcidin was strongly expressed in the lymph follicles of patients with nodular gastritis. The detection rates of gastric hepcidin-positive lymphocytes in patients with nodular gastritis and chronic gastritis were significantly higher than that without H. pylori infection. Moreover, regardless of the H. pylori infection status, hepcidin was expressed in the cytoplasm and intracellular canaliculi of gastric parietal cells.

Conclusion: Hepcidin is expressed at a steady state in gastric parietal cells, and H. pylori infection may induce hepcidin expression in lymphocytes present in the gastric mucosal lymphoid follicles. This phenomenon may be associated with systemic hepcidin overexpression and iron deficiency anemia in patients with H. pylori-infected nodular gastritis.

Summary: Background: The purpose of this study was to investigate the structure of the incisive canal using dry maxillae harvested from human cadavers.

Methods: Seven dry maxillae were harvested from adult Caucasian human cadavers. The incisive canals in all specimens were observed from an intraoral viewpoint with the naked eye and under a surgical microscope with 20× magnification.

Results: All specimens had a single incisive foramen leading to different numbers of canals. Two specimens had a single canal (Type I), two were double (Type II), and three had triple canals (Type III). In both type I specimens, the canal was centered in the incisive foramen. Type II had a septum between the two canals. This septum was irregular in shape near the entrance of the canal but smooth inside the canal. The canals were positioned asymmetrically within the foramen. Type III had two septa between the three canals. Again, those located near the entrance of the canal were irregular while those inside the canal were smooth. The orientation of the lumina differed from one another in the type III canals.

Conclusion: The study identified morphological variations in the anatomy of the incisive canal, underscoring the importance of pre-surgical planning in the administration of local anesthesia, placement of dental implants, or removal of impacted teeth in the anterior maxillary region.

Summary: Background: Parity is related to breast cancer in various ways. Its effects on the development of breast cancer are not independent and should be investigated at the same time as other reproductive factors. The association between parity and stage and type of breast cancer receptor was studied.

Methods: Parity was established for 75 patients with estrogen receptor (ER) positive breast cancer and 45 patients with ER-negative breast cancer. The stages of breast cancer were also determined.

Results: Breast cancer was found to have an association with high parity (≥ 3 parities). Significantly, most patients were diagnosed with stage II breast cancer, and this was especially frequent in patients with high parity. Stage IIB was most common, particularly among those 40-49 years old. ER-positive and ER-negative stage II breast cancer were both common among patients with high parity.

Conclusion: Breast cancer, particularly at stage II, is associated with high parity. Parity is also associated with type of breast cancer, based on estrogen receptor category. This finding supports the recommendation that breast cancer should be screened in women with a high parity. Increased births should be considered a risk factor particularly for stage II breast cancer independent of cancer type.

Summary: Ivabradine has been shown to improve heart failure with sinus tachycardia by reducing the heart rate without affecting left ventricular systolic function or blood pressure. Here we report a case of a catecholaminedependent patient, New York Heart Association (NYHA) class IV, LVEF of 18%, and low cardiac output, who was able to discontinue intravenous catecholamine by oral administration of ivabradine.

Summary: Vanishing tumor of the lung, also known as phantom tumor, is uncommonly observed in congestive heart failure. We report a case of a vanishing tumor that rapidly disappeared and reappeared in just a few minutes due to repositioning in a patient after open-heart surgery.

Summary: Open surgery for the treatment of focal infrarenal aortic stenosis in high-risk patients may result in complications and mortality. Endovascular aortic repair may be used to treat these lesions. Here, we present the case of a 78-year-old woman with severe, highly calcified stenosis of the infrarenal abdominal aorta, which was successfully treated with the GORE VIABAHN VBX (Gore Medical; Flagstaff, AZ) balloon-expandable covered stent. Long-term and randomized controlled studies comparing open surgery with EVAR are necessary to evaluate the usefulness of this novel device.

Summary: A man in his seventies was referred to our hospital for radical therapy for advanced rectal cancer with multiple liver metastases. A colonic stent had already been placed in his rectum at the previous hospital because of malignant colorectal obstruction, so our therapeutic strategy was to perform systematic chemotherapy after resection of the primary tumor. Laparoscopic low anterior resection with a covering stoma was performed under general anesthesia. At about one hour after the surgery, the patient had sudden abdominal pain with watery diarrhea, and a similar discharge from his drainage tube. We suspected peritonitis caused by bowel perforation and emergency surgery was performed. The operative findings showed that his peritonitis was caused by anastomotic leakage from the rectum. Radical lavage of the abdominal space and reconstruction of colostomy was performed. The patient gradually recovered and we were able to start systematic chemotherapy at one month after the surgery. Anastomotic leakage immediately after anterior resection caused by watery diarrhea is rare, and it may be concerned with several issues. The covering stoma is intended to stop anastomotic leakage but it cannot prevent all cases of leakage especially when obstruction is present. We recommend that preventive measures be taken against anastomotic leakage, including intraoperative leakage tests or anal decompression tube placement.

Summary: The management of medication overuse headache (MOH) is sometimes challenging, particularly for patients with a long disease duration. We observed that patients who used goshuyuto, a traditional Japanese medicine, exhibited a favorable clinical course. Two women who had a history of MOH for over 20 years were treated using 5.0–7.5 g/day goshuyuto in an outpatient setting. The treatment reduced their use of habitual drugs, including triptan (33–55%) and non-steroidal anti-inflammatory drugs (75–82%), as well as the headache impact test score-6 (16–23%) over 24 weeks. As goshuyuto has a protective effect on chronic headache and is reported not to lead to MOH, it is a good candidate for the treatment of patients with MOH in an outpatient setting, even for those with an over 20-year history of MOH.

Summary: This case series aimed to evaluate the peptide-specific immunoglobulin G (IgG) response, clinical effectiveness, and the safety of a personalized peptide vaccine (PPV) in four children with refractory solid cancer. Although the pre-vaccination IgG responses were suppressed, IgG levels against the vaccinated peptides after 12 vaccinations were increased in all three cases who received at least 12 vaccinations. Vaccination-related adverse effects were grade 1 injection-site local skin lesions. One patient, whose diagnosis was relapsed rhabdomyosarcoma, remains in sustained remission after 37 months. Although the pre-vaccination immune response in this patient was low, IgG levels against 2 of the 4 peptide vaccines were increased after the sixth vaccination, followed by a strong increase at the eighteenth vaccination against all 4 peptides, with a >100-fold increase vs. 2 peptides. The remaining three patients exhibited progressive disease and eventually died of their original cancer. The results of the current case series suggest that in cases of childhood solid tumors, when the tumor is controlled at the time of entry PPV may have some consolidation effect. Therefore, PPV could be a new immunotherapy modality for refractory childhood solid tumors.

Summary: A 36-year-old woman diagnosed with Silver-Russell syndrome during childhood presented to our department after a primary care physician suspected renal dysfunction. At birth, she had an extremely low weight (1210 g), and in childhood, she was diagnosed with Silver-Russell syndrome. At the age of 14 she was found to have proteinuria; however, the condition was never further examined. One month prior to her presentation to our department, the following were noted: 3+ urinary protein, 3.9 urinary protein/creatinine ratio, and 48 mL/min/1.73 m² estimated glomerular filtration rate. Abdominal computed tomography revealed small kidneys difficult to visualize using ultrasound. Therefore, an open renal biopsy was performed. The renal biopsy revealed no significant findings in the glomerulus except glomerular hypertrophy, and the glomerular density in the cortical area was low (0.6/mm²). The patient was diagnosed with oligomeganephronia. Proteinuria and renal dysfunction were likely due to glomerular hyperfiltration resulting from a low nephron count caused by low birth weight. Silver-Russell syndrome is characterized by intrauterine growth retardation and additional developmental disorders after birth. Here, we detected oligomeganephronia following kidney biopsy in a patient with Silver-Russell syndrome. We suspect that a reduced number of nephrons due to low birth weight caused proteinuria and renal dysfunction.