Questionnaire-Based Survey on Management of Ulcerative Colitis-Associated Cancer in East Asian Countries.

BACKGROUND/AIMS: To elucidate the current management of ulcerative colitis (UC)-associated cancer, a questionnaire-based survey was conducted to gather current opinions on colitis-associated cancer in different East Asian countries. METHODS: The questionnaire, based on physicians, contains 9 questions focused on UC management and cancer surveillance. In addition, the questionnaire based on neoplastic cases, which contains 17 questions, was collected and analyzed. RESULTS: With regard to the diagnosis of UC-associated cancer, most respondents started surveillance colonoscopy within 10 years from onset, favored targeted biopsies, and thought advanced imaging was useful. As for morphology, the frequency of elevated lesion and type 4 lesions was most common in early and advanced cancer, respectively. Peritoneal metastasis was frequently observed, and undifferentiated tumor was frequently developed. Laparoscopic surgery was widely used because it is less invasive. The prognostic outcome was poor, particularly in stage III and undifferentiated type. CONCLUSIONS: The current survey elucidated the current management in Asian countries and characteristics of colitis-associated cancer in these countries.

Correction to: Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC­06).

The correct name of the twelfth author should be ''Yasuhiro Yuasa", and not ''Yasuhiko Yuasa'' as given in the original publication of the article.

Multicenter phase II study of trastuzumab plus S-1 alone in elderly patients with HER2-positive advanced gastric cancer (JACCRO GC-06).

BACKGROUND: S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. METHODS: Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. RESULTS: A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. CONCLUSIONS: Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. CLINICAL TRIALS REGISTRATION: UMIN000007368.

Minimally Invasive Salvage Operations for Esophageal Cancer after Definitive Chemoradiotherapy.

BACKGROUND/AIMS: Because salvage surgery after definitive chemoradiotherapy for esophageal cancer is associated with high postoperative mortality and morbidity, minimally invasive methods are desirable. We analyzed the validity of minimally invasive salvage operations (MISO). METHODS: Twenty-five patients underwent salvage operation between 2010 and 2016 in our institution, 10 having undergone right transthoracic salvage esophagectomy (TTSE group), 6 transhiatal salvage esophagectomy (THSE), 6 salvage lymphadenectomy (SLA), and 3 salvage endoscopic submucosal dissection (SESD). Patients who had undergone THSE, SLA, or SESD were categorized as the MISO group. Short- and long-term outcomes were assessed. RESULTS: The mean duration of surgery was significantly shorter in the SLA groups than in the TTSE group (p = 0.0248). Blood loss was significantly less in the SLA than the TTSE group (p = 0.0340). Intensive care unit stay was shorter in the THSE than the TTSE group (p = 0.0412). There was no significant difference in postoperative mortality between the MISO and THSE groups. Postoperative hospital stay was significantly shorter in the SLA than the TTSE group (p = 0.0061). Patients' survivals did not differ significantly between the MISO and TTSE groups (p = 0.752). Multivariate analysis revealed that residual disease (R0; HR 4.872, 95% CI 1.387-17.110, p = 0.013) was the only independent factor influencing overall survival. CONCLUSION: MISO is preferable because short-term outcomes are better and long-term outcomes do not differ from those of TTSE.

[A Case of Advanced Gastric Cancer with Multiple Bone Metastases, Virchow Lymph Node and Para-Aortic Lymph Node Metastases That Responded to Combined Modality Therapy and Underwent Conversion Surgery].

A 41-year-old woman with type 3 advanced gastric cancer and Virchow lymph node, para-aortic lymph node, and multiple bone metastases was diagnosed with U-less cType 3 cT4aN3M1, cStage IV. We administered docetaxel, cisplatin, and S-1 (DCS)therapy for unresectable gastric cancer. After 11 courses of DCS, we confirmed that the distant lymph node metasta- ses were significantly reduced. We performed radiotherapy(30 Gy/10 Fr)on the thoracic lumber vertebrae. Because the patient was successfully downstaged, we performed total gastrectomy with Roux-en-Y reconstruction. The histopathological diagnosis was ypT3N2M0, ypStage III A. In this case, DCS therapy successfully treated gastric cancer with distant metastases, including multiple bone metastases.

Long-term comparison of boomerang-shaped jejunal interposition and Billroth-I reconstruction after distal gastrectomy.

BACKGROUND: Billroth-I (BI) is a simple, physiological method of reconstruction following distal gastrectomy. In actuality, postoperative QOL is by no means favorable due to the high incidence of post-gastrectomy syndrome. The aim of this study is to assess the safety and efficacy of boomerang-shaped jejunal interposition (BJI) after distal gastrectomy. METHODS: Sixty-six patients with early gastric cancer underwent the BI procedure (n = 33) or BJI (n = 33) after distal gastrectomy, following which they were compared for 5 years. Tumor characteristics, operative details, postoperative complications and complaints, number of meals, and body weight were analyzed. Patients were followed up by endoscopy every 12 months. RESULTS: There were no significant differences in the incidence of postoperative complications. The incidence of heartburn (30 vs. 0 %, P = 0.0009) and oral bitterness (33 vs. 6 %, P = 0.0112) were significantly lower in the BJI cases. Endoscopic findings revealed significantly lower incidences of reflux esophagitis (24 vs. 0 %, P = 0.0051) and remnant gastritis (70 vs. 3 %, P < 0.0001) in the BJI group. The incidence of food stasis was low in both groups (12 vs. 15 %). In the BJI group, 30 patients (90 %) were eating 3 meals/day within 12 months, whereas in the BI group, 16 patients (48 %) were still eating 5 meals/day at 12 months or later. CONCLUSIONS: BJI is as safe as BI, but is better in terms of improvement in bile reflux and food intake without stasis. This procedure, therefore, appears to be a useful method for reconstruction after distal gastrectomy.

MUTYH-associated colorectal cancer and adenomatous polyposis.

MUTYH-associated polyposis (MAP) was first described in 2002. MUTYH is a component of a base excision repair system that protects the genomic information from oxidative damage. When the MUTYH gene product is impaired by bi-allelic germline mutation, it leads to the mutation of cancer-related genes, such as the APC and/or the KRAS genes, via G to T transversion. MAP is a hereditary colorectal cancer syndrome inherited in an autosomal-recessive fashion. The clinical features of MAP include the presence of 10-100 adenomatous polyps in the colon, and early onset of colorectal cancer. Ethnic and geographical differences in the pattern of the MUTYH gene mutations have been suggested. In Caucasian patients, c.536A>G (Y179C) and c.1187G>A (G396D) mutations are frequently detected. In the Asian population, Y179C and G396D are uncommon, whereas other variants are suggested to be the major causes of MAP. We herein review the literature on MUTYH-associated colorectal cancer and adenomatous polyposis.

CD24 expression is associated with progression of gastric cancer.

BACKGROUND/AIMS: Mortality rates due to gastric cancer are high in Japan. To improve patient prognosis, new biomarkers for diagnosis and treatment are urgently required. In this study we investigated the role of CD24, a cell adhesion glycoprotein implicated in tumor cell proliferation, which is used as a prognostic marker in various cancers. METHODOLOGY: We analyzed CD24 expression in 173 gastric adenocarcinomas by immunohistochemistry and compared the data with clinicopathological parameters and patient overall survival. Furthermore, we performed Western blotting analysis of CD24 in six human gastric adenocarcinoma cell lines, Kato III, MKN1, MKN28, MKN45, MKN74, and HGC-27. RESULTS: CD24 up-regulation was significantly correlated with depth of invasion (p=0.005) and pathological high stages (p=0.043). We observed a relationship between high CD24 expression and lymph node metastasis, venous invasion and lymphatic invasion. CD24 expression tended to be higher in cell lines derived from differentiated gastric carcinoma, including those derived from lymph node metastasis. CONCLUSIONS: Our study suggests that gastric cancer patients with high CD24 expression should be closely monitored for recurrence following resections. CD24 expression is a potential biomarker for gastric cancer prognosis and provides a new molecular target for therapeutic strategies.

[Esophageal cancer].

Esophageal cancer is the 6th most common cancer in Japan. For the early cancer without lymph node metastasis, endoscopic resection is commonly performed. Esophagectomy with 3-field lymphadenectomy is the standard therapy for resectable esophageal cancer (stage I - IV). Chemoradiotherapy (CRT) is the standard therapy for unresectable esophageal cancer and could also be considered as an option for resectable esophageal cancer. The complications of endoscopic resection are stenosis, perforation, pneumomediastinum, and so on. Major surgical complication are anastomotic leakage, recurrent nerve paralysis, heart failure, respiratory insufficiency. The rates of complications increase after salvage operation, therefore, hospital mortality rate is 7-15%. The serious complications of chemoradiotherapy are late pericardial effusion and pleural effusion.

Treatment strategy for brain metastases from esophageal cancer.

BACKGROUND: This study aimed to examine the treatment outcomes of patients with brain metastases from esophageal cancer. Brain metastases from esophageal cancer are rare and have a poorer prognosis than brain metastases from lung and breast cancer. METHODS: This study included patients who were diagnosed with and treated for esophageal cancer in our department and subsequently developed brain metastases between April 2010 and December 2014. We examined the differences in survival in patients based on receiving chemotherapy. RESULTS: In total, 8 patients (7 men and 1 woman) with a mean age of 65 years (range 51-73) were included. Seven presented with neurologic symptoms. Two were diagnosed via computed tomography (CT), 5 via magnetic resonance imaging, and 1 via positron emission tomography/CT. They were treated using whole-brain irradiation or with a gamma knife. In 5 patients, chemotherapy was administered after treatment of the brain metastases. The mean survival from the start of treatment was 358 days (range 31-1196). CONCLUSION: The relatively successful local control of brain metastases in these patients indicates that long-term survival may be attainable via concomitant chemotherapy.

Nutritional status predicts adjuvant chemotherapy outcomes for stage III colorectal cancer.

OBJECTIVES: Previously, adjuvant chemotherapy using oxaliplatin was a standard treatment for patients with node-positive colorectal cancer (CRC) who underwent curative surgery. The factor predicting adverse events and therapeutic effect have not yet been established. METHODS: A retrospective cohort of 42 patients diagnosed with stage III CRC between April 2009 and March 2013 in our institution were included in this study. The indicators of host nutritional status were body weight (BW), body mass index (BMI), serum albumin, Onodera's prognostic nutritional index (OPNI), and Glasgow Prognostic Score (GPS). The indicators of host immunocompetence was total lymphocyte counts, total neutrophil counts, granulocytes/lymphocytes ratio (G/L ratio). RESULTS: The overall recurrence rate was 26.1%. Patients who had a recurrence were more likely to be older. The recurrence was not associated with type of regimen or adverse events. The cases with a few cumulative doses and relative dose intensity of oxaliplatin experienced significantly more recurrence. Nutritional status indicators, such as the serum albumin level, OPNI, and the modified Glasgow prognostic score (mGPS) were associated with the adjuvant chemotherapy outcome. Our study results indicated worse nutritional status induced worse disease-free survival (DFS) and more recurrence. CONCLUSION: The host's nutritional status associated with outcomes in stage III CRC patients.

18 F-Fluorodeoxyglucose positron emission tomography can be used to determine the indication for endoscopic resection of superficial esophageal cancer.

18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET) is a useful imaging modality that reflects the tumor activity. However, FDG-PET is mainly used for advanced cancer, not superficial cancer. In this study, we investigated the relationship between the superficial tumor depth of esophageal cancer and the FDG uptake to determine the indications for endoscopic resection (ER). From 2009 to 2017, 444 patients with esophageal cancer underwent esophagectomy or endoscopic submucosal dissection (ESD), and 195 patients were pathologically diagnosed with superficial cancer. Among them, 146 patients were examined by FDG-PET before esophagectomy or ESD. In these 146 patients, the relationship between the pathological tumor depth and FDG uptake was analyzed. The mean maximum standardized uptake value in pT1a-EP/LPM tumors was 1.362 ± 0.890, that in pT1a-MM/pT1b-SM1 tumors was 2.453 ± 1.872, and that in pT1b-SM2/SM3 tumors was 4.265 ± 3.233 (P < .0001). Among 51 pT1a-EP/LPM tumors, 10 (19.6%) showed positive detection of FDG. For pT1a-MM/pT1b-SM1 and pT1b-SM2/SM3 tumors, the detection rate was 52.9% (18/34) and 82.0% (50/61), respectively. The detection rate of pT1a-EP/LPM was significantly lower than in the other two groups (P < .0001). Among 10 FDG-PET-positive lesions, only 1 had no apparent reason for PET positivity; however, 9 of 10 had a suitable reason for detectability by PET and inadequacy for ER. Negative detection of superficial esophageal squamous cell carcinoma by FDG-PET is useful to determine the indication for ER when the tumor depth cannot be diagnosed even after performing magnifying endoscopy with narrow band imaging and endoscopic ultrasonography. When FDG uptake is recognized, a therapeutic modality other than ER should be considered.

Adverse Prognostic Factors of Advanced Esophageal Cancer in Patients Undergoing Induction Therapy with Docetaxel, Cisplatin and 5-Fluorouracil.

BACKGROUND/AIM: The purpose of this study was to identify adverse prognostic factors for patients with advanced esophageal cancer undergoing chemotherapy with docetaxel, cisplatin and 5-fluorouracil (DCF). PATIENTS AND METHODS: The study cohort comprised of 45 patients with advanced esophageal cancer who underwent induction DCF therapy followed by esophagectomy or chemoradiotherapy. Treatment outcomes and factors affecting early recurrence and death were analyzed. RESULTS: Overall 3-year survival was 61.4%, and 3-year disease-free survival was 44.7%. Clinically evident lymph node metastasis and clinical stage were associated with recurrence within 1 year and death within 2 years. Low maximum standardized uptake value (SUVmax) after induction DCF therapy and small decreases in SUVmax from pre- to post-DCF therapy were also predictors of recurrence and poor prognosis. CONCLUSION: Induction DCF therapy may be ineffective for advanced-stage esophageal cancer and clinical lymph node metastasis (≥N2, ≥stage IIIB). Moreover, small decreases in SUVmax DCF therapy are associated with early disease relapse and death.

Waardenburg syndrome with isolated deficiency of myenteric ganglion cells at the sigmoid colon and rectum.

Waardenburg syndrome (WS) has the characteristic clinical features caused by the embryologic abnormality of neural crest cells. WS patients sometimes suffer from functional intestinal obstruction. When it is Hirschsprung disease (HD), the WS is diagnosed as type 4 WS. We report a case of WS which did not have myenteric ganglion cells in the sigmoid colon and rectum. Whether to diagnosis this case as type 1 or 4 WS is controversial. Moreover, this is the third report which has peristalsis failure caused by abnormal myenteric plexus. In all three cases, the eosinophils had aggregated in the myenteric layer of the transition zone. During embryonic life, enteric ganglion cells migrate to the myenteric layer from the proximal to the distal side sequentially and, subsequently, to the submucosal layer through the circular muscle. Therefore, we hypothesize that myenteric ganglion cells that had already migrated were eliminated by an eosinophil-mediated mechanism in these three cases. We believe this report may be helpful to elucidate the pathogenesis of some types of HD.

Laparoscopic surgery for a Bochdalek hernia triggered by pregnancy in an adult woman: A case report.

INTRODUCTION: A Bochdalek hernia (BH) is a type of congenital diaphragmatic hernia. We herein describe an adult woman with a BH triggered by pregnancy and treated by laparoscopic surgery. PRESENTATION OF CASE: A 26-year-old woman was referred to our hospital because of abdominal pain and dyspnea resulting from a left diaphragmatic hernia. She was diagnosed with a BH and underwent laparoscopic surgery. Her postoperative progress was satisfactory, and no recurrence was found at follow-up approximately 1 year later. DISCUSSION: A recently published study reviewing detailed cases of laparoscopic and/or thoracoscopic repair of adult BH from 1999 to 2016 identified 30 cases. A laparoscopic approach for treatment of BH has recently attracted increasing interest. CONCLUSION: Laparoscopic surgery can be safely performed on adults with BH without complications.

Salvage esophagectomy combined with partial aortic wall resection following thoracic endovascular aortic repair.

OBJECTIVE: Definitive chemoradiotherapy is useful for locally advanced esophageal cancer. However, salvage esophagectomy is required when residual or recurrent tumor is evident after chemoradiotherapy. We performed salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair for aortic invasion, and we evaluated the results. METHODS: Four patients underwent esophagectomy combined with aortic wall resection after thoracic endovascular aortic repair because the lesion was diagnosed as stage T4b. We evaluated short-term outcomes, including duration of thoracic surgery, blood loss, duration of intubation, intensive care unit stay, and postoperative morbidity, as well as survival after salvage surgery. RESULTS: Lesions were resected with no intraoperative procedural adverse events. Mean thoracic operation time was 444 min, and mean thoracic blood loss was 506 g. In all patients, complete resection of the lesion was possible with no intraoperative adverse events. All patients were extubated on postoperative day 0, and all were discharged from the intensive care unit on postoperative day 1. One patient experienced grade II wound pain (bilateral chest pain), and another patient experienced difficult sputum expectoration (grade IIIA). The mean follow-up time was 19.8 months, and two patients were alive with no disease recurrence at the time of this report. However, the remaining two patients had died secondary to lymph node metastasis. CONCLUSIONS: Salvage esophagectomy combined with partial aortic wall resection after thoracic endovascular aortic repair provides acceptable short-term outcomes. Future studies are needed to evaluate long-term survival and patient selection criteria.

Validity of neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 for resectable locally advanced gastric cancer.

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.

Prospective trial of radiotherapy for patients 80 years of age or older with squamous cell carcinoma of the thoracic esophagus.

PURPOSE: To assess the safety and efficacy of external beam radiotherapy for elderly patients with esophageal cancer. METHODS AND MATERIALS: A trial testing external beam radiotherapy (66 Gy within 6.5 weeks) as a single-modality treatment was performed for biopsy-proven squamous cell carcinoma of the thoracic esophagus clinically staged as Stage I and IIA (T1-T3N0M0, International Union Against Cancer, 1987) in patients aged > or =80 years. RESULTS: From January 1999 through December 2002, 51 evaluable patients (35 men and 16 women) with a median age of 83 years (range, 80-91 years) were enrolled from 22 institutions. Of the 51 patients, 18 (35%) had Stage T1 and 33 (65%) had Stage T2-T3 disease. Radiotherapy could be completed in 47 patients (92%) within 43-58 days (median, 49). The actuarial incidence of Grade 3 or worse cardiopulmonary complications at 3 years was 26%, with 3 early deaths, and correlated significantly with the size of the anteroposterior radiotherapy portals. The median survival time and overall survival rate at 3 years was 30 months and 39% (95% confidence interval, 25-52%), respectively. CONCLUSION: The results of high-dose radiotherapy in octogenarians are comparable to those in younger patients, but meticulous treatment planning and quality control is required.

The suppressant effect of GEA3162 on spontaneous serotonin release from human colonic mucosa in vitro.

The effect of a lipophilic nitric oxide (NO)-releasing compound 5-amino-3-(3,4-dichlorophenyl) 1,2,3,4-oxatriazolium (GEA3162) on the spontaneous release of 5-hydroxytryptamine (5-HT) from human colonic mucosa was investigated in vitro. In the presence of tetrodotoxin, spontaneous outflow of 5-HT from the human colonic mucosa was measured by high-performance liquid chromatography with electrochemical detection. GEA3162 concentration-dependently suppressed the 5-HT outflow, but neither the NO-activated soluble guanylate cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) nor peroxynitrite scavenger ebselen affected the suppressant effect of GEA3162. Moreover, neither the L-type calcium channel blocker nicardipine, NO synthase inhibitor l-N(G)-nitroarginine methyl ester nor guanylate cyclase activator guanylin affected the spontaneous 5-HT outflow. These results indicate that human colonic mucosa is capable of eliciting tetrodotoxin-resistant and nicardipine-insensitive 5-HT release, and that GEA3162 can suppress the 5-HT release via an action on colonic mucosa through mechanism independent of ODQ-sensitive cyclic GMP system or peroxynitrite generation.