Strangulated bowel obstruction caused by an ileo-ileal knot: a rare case report.

BACKGROUND: Intestinal knot formation is a condition wherein two segments of the intestine are knotted together; however, reports of small-intestinal ileo-ileal knot formation are rare. CASE PRESENTATION: The patient was a 62-year-old Asian male with a history of endoscopic colorectal adenoma resection and a spontaneous pneumothorax. The patient had no history of a laparotomy. He consulted his local doctor with the chief complaint of abdominal pain and was admitted to our hospital with suspicion of an acute abdomen. The abdomen had muscular guarding with tenderness and rebound tenderness. Contrast-enhanced computed tomography (CT) showed torsion of the mesentery of the small intestine with poor contrast filling. The patient was referred to our department with strangulated bowel obstruction and underwent an emergency laparotomy. Intraoperative findings revealed that two segments of the ileum were wrapped around each other to form a knot, and the strangulated small bowel was necrotic. After the release of the knot, partial resection of the small intestine was performed from 220 cm distal to the ligament of Treitz to 80 cm proximal to the cecum. The patient had a good postoperative course and was discharged on the 11th postoperative day. CONCLUSION: Ileo-ileal knots should be considered as part of the differential diagnosis when treating strangulated bowel obstruction.

[A Case of Stage â £ Gastric Cancer Treated with Conversion Surgery after Chemotherapy].

A case is a female of 61-year-old. She visited her local doctor with a chief complaint of frequent burping. She was hospitalized for gastric cancer with pyloric stenosis. Although open gastrectomy was planned the gastric cancer was unresectable due to pancreatic invasion and peritoneal dissemination. Cytology with abdominal lavage was CY0. She underwent gastrojejunostomy. She was treated by 19 courses of chemotherapy with SOX therapy for 2 years. The tumor reduced, and she underwent distal gastrectomy as conversion surgery. Pathological findings were por2>muc>tub2>tub1, ypT2(ypMP), INF c, int, Ly1a, V0, pPM0, pDM0, pN0(0/43), ypStage ⅠB, R0, Grade 2b. Adjuvant chemotherapy(S-1 and docetaxel)was administered after conversion surgery. She is alive without recurrence for 1 year and 6 months after gastrectomy. We report a case of Stage Ⅳ gastric cancer treated with conversion surgery after chemotherapy.

[Three Cases of Conversion Surgery for Unresectable Advanced Gallbladder Cancer with Distant Metastasis Treated with Gemcitabine plus CDDP].

All three patients were female, one in her 50s, and the other two in their 60s. The one in her 50s had liver metastasis and the other two had unresectable advanced cholecystic carcinomas with peritoneal dissemination. All three received 8-12 courses of gemcitabine plus CDDP(GC). After GC, all three were deemed to be candidates for R0 resection and underwent resection of two central liver segments. In addition, the second patient required an extrahepatic cholangiectomy; an extended cholecystectomy, plus an extrahepatic cholangiectomy, plus a complete omental resection; and the third needed an extended cholecystectomy, plus an extrahepatic cholangiectomy with a partial transverse colon resection, plus a partial duodenectomy. The pathologic response to chemotherapy was moderate in the patient with liver metastases, mild in the one who underwent the omental resection, and moderate in the patient who had the partial resection of the digestive tract. All three patients continued with postoperative chemotherapy. The patient with liver metastases and the one with the partial gastrointestinal tract resection have survived without recurrence for 52 months and 43 months, respectively, after the initial treatment. The patient with the omental resection has survived 44 months after the initial treatment with recurrent peritoneal dissemination and is continuing chemotherapy as an outpatient. Although further study is needed to accumulate more cases, the results suggest the usefulness of multidisciplinary treatment including conversion surgery in cases such as these.

Diabetes in Humans Activates Pancreatic Stellate Cells via RAGE in Pancreatic Ductal Adenocarcinoma.

Pancreatic stellate cells (PSCs) mainly consist of cancer-associating fibroblasts in pancreatic ductal adenocarcinoma (PDAC). The receptor for advanced glycation end products (RAGE) is implicated in the pathophysiology of diabetic complications. Here, we studied the implication of RAGE in PSC activation in PDAC. The activation of cultured mouse PSCs was evaluated by qPCR. The induction of epithelial mesenchymal transition (EMT) in PDAC cell lines was assessed under stimulation with culture supernatant from activated PSCs. A total of 155 surgically resected PDAC subjects (83 nondiabetic, 18 with ≦3-years and 54 with >3-years history of diabetes) were clinicopathologically evaluated. A high-fat diet increased the expression of activated markers in cultured PSCs, which was abrogated by RAGE deletion. Culture supernatant from activated PSCs facilitated EMT of PDAC cells with elevation of TGF-ß and IL-6, but not from RAGE-deleted PSCs. Diabetic subjects complicated with metabolic syndrome, divided by cluster analysis, showed higher PSC activation and RAGE expression. In such groups, PDAC cells exhibited an EMT nature. The complication of metabolic syndrome with diabetes significantly worsened disease-free survival of PDAC subjects. Thus, RAGE in PSCs can be viewed as a new promoter and a future therapeutic target of PDAC in diabetic subjects with metabolic syndrome.

Characterization of 2 Neisseria gonorrhoeae Strains With High-Level Azithromycin Resistance Isolated in 2015 and 2018 in Japan.

ABSTRACT: We identified and characterized the first 2 Neisseria gonorrhoeae strains with high-level azithromycin resistance isolated in Japan. These were in the clade of ceftriaxone- and azithromycin-resistant strains isolated in Australia and the United Kingdom. The multilocus sequence typing, N. gonorrhoeae multiantigen sequence typing, and N. gonorrhoeae sequence typing for antimicrobial resistance types of these strains were found in gonococci from eastern Asia.

Corrigendum: Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

[This corrects the article DOI: 10.3389/fendo.2019.00651.].

Diabetes, an independent poor prognostic factor of non-B non-C hepatocellular carcinoma, correlates with dihydropyrimidinase-like 3 promoter methylation.

A concurrent increase in the prevalence of hepatocellular carcinoma (HCC) with that of type 2 diabetes (T2D) and obesity has been reported in the absence of hepatitis B virus surface antigen-negative/hepatitis C virus antibody-negative HCC (NBNC-HCC). However, the prognostic relevance of this association remains unclear. Promoter methylation (PM) of the dihydropyrimidinase-like 3 gene (DPYSL3) has been implicated in virus-related HCC. However, it remains unclear whether T2D influences PM in NBNC-HCC. We determined the influence of T2D on clinicopathological profile and PM of DPYSL3 and CDK2NA in patients with NBNC-HCC who were divided into two groups: non-diabetes (non-DM; n = 46) and diabetes (DM; n = 47). DM was associated with a higher Union for International Cancer Control grade, marginal vascular invasion and tumour cell proliferation irrespective of the duration of T2D as well as higher rates of PM of DPYSL3 than non-DM; however, PM of CDK2NA was similar between both groups. PM of DPYSL3 reduced its expression which inversely correlated with reduced patient survival. In conclusion, T2D is associated with poor prognosis of NBNC-HCC in which a high frequency of PM of DPYSL3 may play a pivotal role in its pathogenesis.

Normal High HbA1c a Risk Factor for Abnormal Pain Threshold in the Japanese Population.

Purpose: Small fiber dysfunction is common in subjects with diabetic polyneuropathy (DPN). It is unsettled, however, whether marginal glucose intolerance is implicated in the onset and progression of small fiber dysfunction. Herein, we explored the relationship between glycated hemoglobin levels (HbA1c) and pain sensation in the Japanese population. Methods: A population-based study of 894 individuals (352 men, 542 women; average age 53.8 ± 0.5 years) and 55 subjects with impaired fasting glucose (IFG) in the 2017 Iwaki project were enrolled in this study. Individuals with diabetes were excluded. Relationships between pain threshold for intraepidermal electrical stimulation (P-IES) and parameters associated with metabolic syndrome were examined. Results: P-IES was elevated with increasing of age in women but not in men. Average P-IES (mA) was increased in IFG subjects (n = 55, 0.20 ± 0.03) compared with normoglycemic/non-IFG individuals (n = 894, 0.15 ± 0.11) (p < 0.01). It was comparable between IFG and a group of normal high HbA1c (5.9-6.4%). Univariate linear regression analyses showed no influence of sex, triglyceride, or cholesterol on the value of P-IES. In contrast, there were significant correlations between P-IES and serum HbA1c level (ß = 0.120, p < 0.001) Adjustments for the multiple clinical measurements confirmed positive correlation of P-IES with HbA1c (ß = 0.077, p = 0.046). Conclusion: Individuals with normal high HbA1c exhibited an elevated P-IES in a healthy Japanese population which may be useful for the screening of subclinical DPN.

Improvement of PTSD-like behavior by the forgetting effect of hippocampal neurogenesis enhancer memantine in a social defeat stress paradigm.

Post-traumatic stress disorder (PTSD) is a psychiatric disorder associated with memories of traumatic experiences. Recent studies have shown that the forgetting of contextual fear memory is promoted via increased adult hippocampal neurogenesis induced by neurogenesis enhancers, such as memantine (MEM) and exercise, raising the possibility that neurogenesis enhancers improve PTSD by facilitating the forgetting of traumatic memory. On the other hand, repeated exposure to social defeat (SD) stress by aggressor mice induces social avoidance behavior to the aggressor and chronic anxiety-like behavior. In this study, we assumed this SD stress paradigm as a PTSD-like model and examined the effects of treatment with neurogenesis enhancer MEM on SD stress-induced PTSD-like behavior. Male C57BL/6 mice received SD stress for 10 consecutive days and were assessed for social avoidance memory to the aggressor (memory of aggressor mice) and anxiety-like behavior using social interaction and elevated zero maze tasks. Consistent with previous studies, SD mice formed social avoidance memory and exhibited increased anxiety-like behavior. Importantly, subsequent MEM treatment (once a week for 4 weeks) significantly reduced social avoidance behavior, suggesting that MEM-treated SD mice showed forgetting of social avoidance memory. Interestingly, MEM-treated SD mice showed comparable anxiety-like behavior with control mice that were not exposed to SD stress. Moreover, MEM-treated SD mice showed no reinstatement of social avoidance memory following single re-exposure to the aggressor. Our findings suggest that neurogenesis enhancer not only enhanced the forgetting of traumatic memory but also improved PTSD (anxiety)-like behavior.

Surveillance of the prevalence of macrolide and/or fluoroquinolone resistance-associated mutations in Mycoplasma genitalium in Japan.

To clarify the status of macrolide and fluoroquinolone resistance of clinical strains of Mycoplasma genitalium in Japan, we amplified portions of the gyrA, parC, and 23S rRNA genes from DNAs in 627 first-voided urine specimens collected from men with M. genitalium-positive urethritis who visited clinics mainly in Sendai, Tokyo, and Osaka, Japan, from 2013 to 2017, by PCR and sequenced. The incidence of single amino acid changes at Met95 or Asp99 in GyrA increased chronologically and was approximately 10% from 2015 onward. The incidence of amino acid changes at Ser83 or Asp87 in ParC was approximately 50% in 2013 but increased to 60-70% from 2014 to 2017. The incidence of mutations at A2071 or A2072 in the 23S rRNA gene increased chronologically and reached over 70% in 2017. The prevalence of M. genitalium harboring alterations in ParC and mutations in the 23S rRNA gene increased and was approximately 50% in 2016 and 2017. The prevalence of M. genitalium with alterations in both GyrA and ParC and mutations in the 23S rRNA gene, which could be associated with treatment failures with the sitafloxacin and azithromycin regimens, were approximately 15% and 10% in 2016 and 2017, respectively. The prevalence of M. genitalium with genetic alterations associated with resistance to fluoroquinolones and/or macrolides is increasing rapidly in Japan. We must prevent the further selection of multi-drug-resistant M. genitalium so that M. genitalium infections will not become untreatable.

Smoking cessation contributes to weight gain in patients with hepatobiliopancreatic malignancy.

BACKGROUND & AIMS: The relationship between smoking cessation and weight gain is well recognized. However, there is no data currently available on the effect of smoking cessation on weight gain in patients with malignancy. The aim of this study was to clarify the body weight (BW) change after smoking cessation in patients with malignancy. METHODS: We retrospectively analyzed 159 subjects who underwent hepatobiliopancreatic surgery. The smoking status was determined using questionnaires administered at the initial presentation, and the candidates were divided into two groups: recent quitters and nonsmokers. The change in the BW was compared between these two groups. RESULTS: There were 134 subjects with malignant disease (84.3%), with a median age of 68 (range: 26-84) years. In the nonsmoker group, 28 of 116 subjects (24.1%) gained weight between the initial presentation and admission. In the recent quitter group, 12 of 18 subjects (66.7%) gained weight in the same period (P < 0.01). Regarding the change in the BW from the initial presentation, recent quitters gained more weight than nonsmokers (+1.7 kg [+2.7%] vs. -1.0 kg [-2.0%], P < 0.01). Furthermore, the improvement from the initial presentation was seen in a higher percentage of recent quitters than nonsmokers with respect to Onodera's prognostic nutritional index (61.1% vs. 36.2%, P = 0.04) and the controlling nutritional status score (38.9% vs. 19.3%, P = 0.07). CONCLUSIONS: Weight gain due to smoking cessation was observed even in patients with hepatobiliopancreatic malignancy.

[Outcomes of Total Mesorectal Excision and Lateral Lymph Node Dissection following Neoadjuvant Chemotherapy for Lower Rectal Cancer with Lateral Lymph Node Metastasis].

INTRODUCTION: Progressive lower rectal cancer with metastasis to the lateral lymph nodes has poor prognosis, requiring systemic chemotherapy. In addition, because laparoscopic lateral lymph node dissection(LLND)in positive cases of metastasis to the lateral lymph nodes is difficult, it has not been commonly used. Here, we report the treatment results of neoadjuvant chemotherapy(NAC)and subsequent laparoscopic total mesorectal excision(TME)plus LLND in cases of lower rectal cancer with metastasis to the lateral lymph nodes. SUBJECTS AND METHODS: The subjects were 4 patients with metastasis to the lateral lymph nodes who underwent LLND after NAC. The surgical outcomes were investigated retrospectively. RESULTS: The mean surgical time was 398 minutes, and the mean bleeding amount was 150 g. In total, 33.5 lymph nodes were dissected, including 15.3 lateral lymph nodes. There was no switch to laparotomy, and no postoperative complications of Grade Ⅲ or higher according to the Clavien-Dindo classification were observed. CONCLUSION: Laparoscopic TME plus LLND after NAC is considered safe and useful as radical surgery for positive cases of metastasis to the lymph nodes.

Worsened outcome in patients with pancreatic ductal carcinoma on long-term diabetes: association with E-cadherin1 (CDH1) promoter methylation.

Prevalence of pancreatic ductal carcinoma (PDC) is nearly twice in patients with diabetes mellitus, but the reason for this close association remains obscure. Recently promoter methylation of E-cadherin1 (CDH1) and CDKN2A genes, encoding E-cadherin and P16 respectively, are invoked in development of PDC. It is still unclear whether diabetes affects such epigenetic changes and malignant behavior in PDC. In this study, we studied whether diabetes influences the clinico-pathological profile and methylation status of CDH1 and CDKN2A genes in patients with PDC. PDC subjects were divided into 3 groups; 59 cases without diabetes (non-DM), 17 cases with short-term diabetes (short-DM)(diabetes duration 3 yrs>) and 33 cases with long-term diabetes (long-DM)(≧3 yrs). Compared to non-DM or short-DM, long-DM was associated with a higher histological grade of malignancy and a higher tumor stage. Promoter methylation of both CDH1 and CDKN2A was encountered more frequently in PDC patients with long-DM than non-DM or short DM. Cases with CDH1 promoter methylation showed reduced E-cadherin expression and worsened survival. We consider that the presence of long-DM has a negative impact on the prognosis of PDC patients which may be relevant to a high frequency of promoter methylation of CDH1.

Living donor liver transplantation in a pediatric patient with preexisting yolk sac tumor.

There is ongoing discussion regarding the indications and timing of LT for patients with a preexisting extrahepatic malignancy. We herein report a pediatric case that underwent LDLT after therapy for YST. The patient, a 13-year-old female with biliary atresia, had undergone portoenterostomy at 2 months of age. She developed a left ovarian tumor with a high serum alpha-fetoprotein concentration at 10 years of age. She underwent left oophorectomy and was diagnosed with ovarian YST (Stage I). After surgery, hepatopulmonary syndrome progressed gradually. She was examined carefully and exhibited no findings to suggest the recurrence of YST. We decided to perform LDLT at 3 years and 6 months of age after the surgery for YST. The patient is currently alive and doing well without recurrence of YST at approximately 2 years after transplantation. There is no significant difference between the recurrence rate of preexisting extrahepatic malignancy and the incidence of de novo malignancy if specific cases are selected. The indications and period from surgery for preexisting extrahepatic malignancy to LT should thus be determined according to the type and stage of cancer.

[A Case of Long-Term Survival after Surgeries for Gastric Cancer and Metachronous Ovarian Metastasis].

The patient was a 57-year-old woman. In October 2011, she underwent distal gastrectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for gastric cancer (pT4a, pN3b, Stage ⅢC [JCGC 14th Edition]). She then received S-1 plus CDDP combination therapy and S-1 monotherapy as postoperative adjuvant chemotherapies for 1 year, and was followed up as an outpatient. In April 2013, a significant increase in the CA19-9 level was noted, and CT indicated a right ovarian tumor. Ovarian metastasis from the gastric cancer was diagnosed, and the response to 3 courses of weekly PTX was stable disease. No findings indicated metastasis to other organs. In July 2013, a salpingo-oophorectomy was performed, after which her CA19-9 level returned to the normal range. Follow-up was adopted as the postoperative strategy in part due to the desires of the patient. Presently, 3 years and 6 months after the initial surgery and 1 year and 9 months after the last surgery, no recurrence has been detected. Generally, ovarian metastasis from gastric cancer is considered to be associated with a poor prognosis. However, our patient showed long-term survival after surgeries for gastric cancer and asynchronous ovarian metastasis. Here, we report the details of our case and review the relevant literature.