Association Between Workplace Social Support and Use of Health-Promoting Wearable Devices: A Prospective Cohort Study of Japanese Employees.

We examined the relationship between workplace environmental factors, including support from supervisors and colleagues, and the continued use of a wearable device meant to promote occupational health. One hundred employees at a Japanese manufacturing company participated in a 3-month study, and information related to their physical health status was recorded by a wearable device. We analyzed the results using the χ2 test and logistic regression analysis. We found that men aged 40-49 years and employees reporting low support from supervisors and colleagues were significantly more likely to be continuing device users. Participants with low workplace support had adjusted odds ratios approximately two to three times higher than those with high levels of support, which was significant. Employees with low workplace support were able to communicate at work, access appropriate support, and enthusiastically participate in occupational health promotion with little psychological difficulty in using the device. Occupational health promotion using wearable devices can complement traditional face-to-face occupational health promotion.

Successful percutaneous transhepatic lymphangiography and embolization for intractable hepatic lymphorrhea after laparoscopic distal gastrectomy: a case report.

BACKGROUND: Hepatic lymphorrhea is a rare and serious complication of surgery for digestive tract cancers and is thought to occur as a result of lymph node dissection of the hepatoduodenal ligament. This complication results in the accumulation of lymphatic fluid, which may in turn lead to nutritional disorders, immune deficiency, and circulation insufficiency. However, there is currently no standard strategy for treating this condition. CASE PRESENTATION: A 49-year-old woman with alcoholic liver damage underwent laparoscopic distal gastrectomy with lymph node dissection for early gastric cancer. Abundant ascites persisted postoperatively, and the fluid was suspected to indicate hepatic lymphorrhea. The patient was re-admitted on postoperative day 26 due to the onset of a brain infarction caused by dehydration. Various conservative treatments for hepatic lymphorrhea were ineffective. She underwent percutaneous transhepatic lymphangiography and embolization on postoperative day 81, with obvious effect. Computed tomography images demonstrated complete disappearance of ascites. CONCLUSIONS: Postoperative hepatic lymphorrhea is a rare and serious complication of radical surgery for digestive tract cancers. The current case suggests that percutaneous transhepatic lymphangiography and embolization may be a rational treatment option when conservative treatments fail.

[Distal Gastrectomy under Management of Intra-Aortic Balloon Pumping Therapy for an Elderly Patient with Carcinomatous Pyloric Stenosis Complicated by Severe Coronary Stenosis].

This case involved an 82-year-old man with a history of diabetes mellitus and myocardial infarction. He was undergoing treatment with 2 oral antiplatelet agents. The patient presented to our hospital for carcinomatous pyloric stenosis caused by type 4 advanced gastric cancer. Although distal gastrectomy was planned, preoperative coronary angiography revealed triple- vessel coronary artery disease. Therefore, surgery was performed under management of intra-aortic balloon pumping (IABP)therapy. The patient's hemodynamics at the time of the operation were stable, and no perioperative cardiovascular complications occurred. However, the patient was not able to start an oral diet because of impaired swallowing function. Although he underwent daily swallowing rehabilitation, he died of aspiration pneumonia 40 days postoperatively. There are many reports of cancer resection under IABP management for patients with severe heart disease. Because the perioperative hemodynamics were stable in all 21 reported cases of digestive malignant tumor resections in Japan, an IABP is suggested to be very effective for patients with severe heart disease. However, early death has also occurred, as in the present case. Close attention to the indications for IABP therapy is needed, especially in elderly patients, in consideration of not only cancer and heart disease but also preoperative activities of daily living.

Using Computed Tomography Lymphography for Mapping of Sentinel Lymph Nodes in Patients with Breast Cancer.

OBJECTIVES: In breast cancer surgery, the combined use of the dye method and radioisotope (RI) method is recommended for identifying sentinel lymph nodes. However, the RI method is difficult to license, expensive, and difficult to introduce. Thus, we introduced computed tomography lymphography (CTLG) and investigated the characteristics and usefulness of CTLG. MATERIAL AND METHODS: Among breast cancer patients who underwent surgery during a 6-year period from January 2013 to December 2018, CTLG was performed on 141 patients with clinically negative lymph node metastasis. These cases were then retrospectively investigated. The number and location of lymph vessel, true sentinel lymph nodes, and the positional relationships with surrounding muscles and blood vessels were confirmed from the constructed 3D images. The actual surgeries were then performed using a dye method with indigo carmine based on images obtained using CTLG. RESULTS: CTLG was able to identify lymph vessels and true sentinel lymph nodes in 131 of the 141 cases (92.91%). There were 97 patients in whom the first true sentinel lymph node reached from the breast was one node, 30 with two nodes, and 4 with three nodes. Moreover, there were three cases in which sentinel lymph nodes were present at Level II. During surgery, sentinel lymph nodes were identified in 131 patients (92.91%) using dye. CONCLUSION: CTLG has a high identification rate in sentinel lymph nodes, and it is considered a convenient and useful examination method because a lot of information, such as the number and position of sentinel lymph nodes, can be obtained.

[Long-Term Follow-Up of Patients Who Received Chemotherapy with S-1 and Docetaxel after Relatively Curative Surgery for Advanced Gastric Cancer Including Non-Curative Factors].

There is no known recommended chemotherapy after radical surgery for gastric cancer for patients who have non-curative disease. We defined positive peritoneal cytology(CY1), resection margin involvement, pathological peritoneal metastasis (pP1)and pN3b as clinical non-curative factors and administered adjuvant chemotherapy with S-1 and docetaxel(DOC) (80 mg/m2 day 1-14 of S-1 for 2 weeks with 40 mg/m2 of DOC on day 1, every 3 weeks). This regimen lasted for 1 year; however, if chemotherapy could be continued after this period, we used S-1 only. We reported the results of 11 cases who received this treatment. PATIENTS: There were 6 total gastrectomies and 5 distal gastrectomies. Clinical non-curative factors were 5 pP1, 5 pN3b, 3 CY1 and 1 resection margin involvement. RESULTS: At the end of adjuvant therapy there were 6 completions, 4 recurrences, and 1 patient with side effects. The main adverse event of Grade 3 or greater was neutropenia (46%). The recurrence rate was 63.6%. Types of relapse included 6 disseminations and 1 patient with lymph node involvement. One-, 3-, and 5-year survival rates were 100%, 72.7% and 72.7%, respectively, and the RFS was 64.0 months. CONCLUSION: S-1 and DOC adjuvant chemotherapy produced good results and may serve as a therapy of choice for patients with advanced gastric cancer with non-curative factors after a relatively curative resection.

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 and docetaxel/cisplatin/S-1 as neoadjuvant chemotherapy for advanced gastric cancer.

AIM: Neoadjuvant chemotherapy (NAC) is promising to improve the survival of resectable gastric cancer. However, suitable regimen and treatment duration for NAC have not yet been established. METHODS: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and S-1/cisplatin/docetaxel(DCS) using a two-by-two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous-type cancer received two or four courses of SC or DCS. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 eligible patients. RESULTS: Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). The 3-year OS was 58.1% in CS and 60.0% in DCS with hazard ratio of 0.80 (95% CI, 0.48-1.34), while it was 53.1% in the two courses and 65.0% in the four courses with hazard ratio of 0.72 (95% CI, 0.43-1.22). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% for both two and four courses in CS, while it was 48.5% for two courses of DCS and 71.9% for four courses of DCS. CONCLUSIONS: Considering high 3-year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer.

A randomised phase II trial of capecitabine plus cisplatin versus S-1 plus cisplatin as a first-line treatment for advanced gastric cancer: Capecitabine plus cisplatin ascertainment versus S-1 plus cisplatin randomised PII trial (XParTS II).

BACKGROUND: Capecitabine plus cisplatin (XP) is a standard global regimen, while S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP for patients with AGC to confirm whether these regimens can be used as controls in a phase III study and to explore whether histological subtypes favour XP or SP. PATIENTS AND METHODS: Eligible patients were randomised to receive either S-1 40 mg/m2 for 21 days plus cisplatin 60 mg/m2 (q5w) or capecitabine 1000 mg/m2 for 14 days plus cisplatin 80 mg/m2 (q3w). The primary end-point was progression-free survival (PFS). The secondary end-points were overall survival (OS), overall response rate (ORR) and safety. RESULTS: In 110 eligible patients, 24-week PFS was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p = 0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most common grade ≥3 adverse events with SP/XP were anaemia (16%/20%), neutropenia (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification showed no statistical difference between treatments. CONCLUSIONS: XP and SP are comparable and can be recommended as control arms in a phase III study for AGC. Histological subtypes were not sensitive markers for the selection of XP or SP. CLINICAL TRIAL REGISTRATION: NCT00140624.

Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701).

BACKGROUND: Lentinan (LNT) is a purified ß-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment. RESULTS: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group. CONCLUSIONS: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer. CLINICAL TRIAL REGISTRATION ID NUMBER: UMIN 000000574.

qAC2, a novel QTL that interacts with Wx and controls the low amylose content in rice (Oryza sativa L.).

KEY MESSAGE: This manuscript reports the fine mapping of a novel QTL, qAC2 controlling the low amylose in rice. The action mechanism of the qAC2 is also investigated by the analysis of genetic interactions to Wx (a), Wx (b), du1, du2 and du3. Amylose content of the rice (Oryza sativa L.) endosperm greatly affects starch properties and eating quality of cooked rice. Seeds of japonica rice cultivar Kuiku162 have low amylose content (AC) and good eating quality. Our analysis revealed a novel QTL, designated as qAC2 that contributed to the low AC of Kuiku162. qAC2 was fine mapped within a 74.9-kb region between two insertion and deletion markers, KID3001 and KID5101, on the long arm of chromosome 2. Seven genes are predicted in this region, but none of them is known to be related to the regulation of AC. The AC of a near-isogenic line (NIL110) carrying qAC2 (Kuiku), the Kuiku162 allele of qAC2, in the genetic background of japonica cultivar Itadaki was lower by 1.1% points than that of Itadaki. The chain length distributions of amylopectin were similar in NIL110 and Itadaki; therefore, the low AC of NIL110 was caused by a decrease in the actual AC, but not by a difference in the amylopectin structure. The interaction analyses revealed that qAC2 (Kuiku) has epistatic interaction with Wx (a). The qAC2 (Kuiku) has epistatic interactions with two loci, du1 and du2, on Wx (b), whereas the genetic effect of qAC2 (Kuiku) has additive to that of du3 on Wx (b). Thus, similar to du1 and du2, qAC2 may have a function related to Wx (b) mRNA splicing.

[A case of esophageal squamous cell carcinoma with an adenocarcinoma component that dedifferentiated after chemotherapy].

CASE: A 69-year-old man was diagnosed with advanced esophageal cancer(well-differentiated squamous cell carcinoma). Neoadjuvant chemotherapy consisting of nedaplatin and 5-fluorouracil(5-FU)was initiated. After two courses of chemotherapy, the patient was judged to have achieved a clinical complete response. The patient then decided against undergoing surgery and opted instead to continue with the chemotherapy, receiving five courses in total. However, the esophageal cancer recurred, and subtotal esophagectomy was performed in January 2011. Squamous cell carcinoma with an adenocarcinoma component, which consisted of poorly differentiated squamous cell carcinoma and tubular adenocarcinoma cells, was observed at the primary site. Metastasis of the cancer to the liver was detected 2 months after surgery. The subsequent administration of four courses of docetaxel to the patient did not result in any beneficial effects, and the patient developed carcinomatous pleurisy and died of this complication in November 2011. The patient survived for a total of 21 months after starting chemotherapy. In this case, the chemotherapy itself may have resulted in the dedifferentiation of a well differentiated squamous cell carcinoma to result in a poorly differentiated squamous cell carcinoma with an adenocarcinoma component.

Gastric mixed adenoneuroendocrine carcinoma occurring 50 years after a gastroenterostomy with braun anastomosis.

A 75-year-old man was diagnosed with gastric cancer. Fifty years previously, he had undergone gastroenterostomy with a Braun enteroenterostomy. At present, a distal gastrectomy and small intestinal partial resection were performed. Intraoperatively, the tumor was localized to the previous stomal site. HE staining showed that the tumor comprised two elements: a tubular adenocarcinoma on the gastric side and a neuroendocrine carcinoma (NEC) on the jejunal side. The final pathologic diagnosis was mixed adenoneuroendocrine carcinoma based on an immunohistochemical analysis of endocrine markers and an elevated Ki-67 labeling index. The risk of later cancer development cancer recurrence near the gastrojejunostomy site is well known. Potentially, chronic enterogastric bile reflux may irritate the gastric mucosa and act as a promoter. Gastric NEC has a strong malignant potential. We suspect that, in the present case, the constant exposure to secondary bile may have induced a gastric mucosal adenocarcinoma, which finally differentiated into a NEC.

p16 Methylation is frequently detected in the serum of metastatic colorectal cancer patients.

For the purpose of detection of colorectal cancers, we tried to detect p16 methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). Out of 211 serum samples derived from colorectal cancer patients, 14 (7%) exhibited p16 methylation in their serum DNA by qMSP. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis. Interestingly, a significant difference was observed in the presence of distant metastasis (P = 0.0420). Moreover, a trend was shown toward preferentially developing lymph node metastasis (P = 0.0547), thus suggesting that p16 methylation in serum could be detected more frequently in metastatic colorectal cancer patients. High sensitivity of qMSP makes it possible to detect smaller amounts of tumor DNA in the serum. In principle, the methylation status of a primary tumor is not required in advance to detect circulating tumor DNA, suggesting that qMSP can be used as a screening method for cancer.

[Efficacy and safety of cetuximab+irinotecan for unresectable advanced or recurrent colorectal cancer].

BACKGROUND: In July 2008, cetuximab treatment for unresectable advanced or recurrent colorectal cancer was approved in Japan, but there have been few reports on this therapy in Japan. PURPOSE: We retrospectively analyzed the efficacy and safety of cetuximab(Cmab)+irinotecan(CPT-11)for unresectable advanced or recurrent colorectal cancer from October 2008 to April 2010 at 5 centers in the Kanagawa region. PATIENTS AND METHODS: The number of patients enrolled was 38, all of whom were treated after second-line therapy. RESULTS: The RR was 24%. DCR was 68%. TTF was 105 days and OS was 242 days. CONCLUSION: At 5 centers, Cmab+CPT-11 was an effective and safe treatment after second-line therapy.

Methylation of the HACE1 gene is frequently detected in hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that HACE1, the E3 ubiquitin ligase, is epigenetically inactivated in human Wilms' tumors and HACE 1 expression was also down-regulated in colorectal and gastric carcinomas. METHODOLOGY: In this study, methylation status of the HACE1 gene was examined in primary carcinomas and the corresponding normal tissues derived from 27 patients with HCC using quantitative methylation-specific PCR (qMSP). RESULTS: Methylation of the HACE1 gene was detected in 18 out of the 27 (67%) HCCs, suggesting that the methylation of HACE1 was frequently observed in HCC. The clinicopathological data were then correlated with these results. In the value of serum AFP (α-fetoprotein), a significant difference was observed (p=0.0025). CONCLUSIONS: All stages of HCCs presented HACE1 methylation, indicating that the HACE1 gene has been methylated from the early stages of HCCs.

[A case of progressive gastric carcinoma accompanied by disseminated carcinomatosis of bone marrow (DCBM)due to bone metastasis, with DIC recovery by administration of S-1 and docetaxel].

A 63-year-old- female was admitted to our hospital complaining of cough. Based on CT, bone centigram and peripheral blood findings, a diagnosis of gastric carcinoma accompanied by bone marrow metastasis was made. As DIC developed following hospital admission, S-1 and docetaxel(DOC)therapy was initiated(daily oral administration of 80 mg/m(2) S-1 for 14 days and DOC at 40 mg/m(2) on day 1, q3w). Recovery from DIC was achieved. S-1 and DOC therapy is considered to be effective for DIC due to bone marrow metastasis of gastric carcinoma. S-1/DOC is thought to be an effective chemotherapy against progressive gastric carcinoma accompanied by disseminated carcinomatosis bone marrow with DIC.

Methylation of the UNC5C gene is frequently detected in hepatocellular carcinoma.

BACKGROUND/AIMS: Recently, we detected that UNC5C expression was downregulated in colon and gastric cancer. METHODOLOGY: In the present study, the methylation status of the UNC5C gene was examined in primary carcinomas and the corresponding normal tissues derived from 42 patients with HCC. RESULTS: Methylation of the UNC5C gene was detected in 11 out of the 42 (26%) HCCs, suggesting that the methylation of UNC5C was frequently observed in HCCs. The clinicopathological data were correlated with the methylation results. CONCLUSIONS: TNM stage 1 HCC presented UNC5C methylation, indicating that the UNC5C gene has been methylated from the early stages of HCC.

Methylation of the WNT5A gene is frequently detected in early gastric carcinoma.

BACKGROUND/AIMS: Recently, it has been reported that WNT5A methylation was frequently detected in colorectal cancers. However, the relationship between the WNT5A methylation and the characteristics of gastric cancer remains unknown. METHODOLOGY: Methylation status of the WNT5A gene was examined in primary carcinomas and the corresponding normal tissues derived from 38 patients with gastric cancer using quantitative methylation-specific PCR (qMSP) and the correlation between the methylation status and the clinicopathological findings was evaluated. RESULTS: Aberrant methylation of the WNT5A gene was detected in 7 out of the 38 (18%) primary gastric carcinomas, suggesting that the methylation of WNT5A is observed in gastric carcinomas as well as colorectal ones. The clinicopathological data were correlated with the methylation results. A significant difference was observed in the extent of tumor (p=0.0226). Moreover, a trend was shown towards early TNM stages in methylated tumors (p=0.209). CONCLUSIONS: WNT5A was more frequently methylated in early gastric carcinomas.

Heterozygous loss of NF2 is an early molecular alteration in well-differentiated papillary mesothelioma of the peritoneum.

Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare disease, and many cases are either benign neoplasms or low-graded malignancies; however, a few cases show rapid progressive clinical courses. No effective therapy has yet been established for WDPMP, and the molecular basis of WDPMP tumorigenesis has never been reported. This study shows the malignant transformation of WDPMP in a Japanese female patient, who was alive for 54 months after the initial diagnosis by a laparoscopic biopsy. A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene. Furthermore, SNP analyses determined that LOH was observed in the IL17RA (22q11.1), CHECK2 (22q12.1), and SHANK3 (22q13.3) genes, thus suggesting that NF2 loss occurred through 22q deletions or monosomy 22. The LOH of the NF2 gene was observed in an early stage of WDPMP, thus indicating that LOH of the NF2 gene is an early molecular alteration, and NF2 loss is a molecular mechanism associated not only with malignant pleural mesothelioma, but also with WDPMP.

FBN2 methylation is detected in the serum of colorectal cancer patients with hepatic metastasis.

BACKGROUND, MATERIALS AND METHODS: For the purpose of colorectal cancer detection, we investigated fibrillin-2 (FBN2) methylation in the serum of colorectal cancer patients using quantitative methylation-specific polymerase chain reaction (qMSP). RESULTS: Out of 78 patients with colorectal cancer, 49 (63%) exhibited methylation of FBN2 in their tumor tissue DNA, suggesting that FBN2 methylation frequently exists in colorectal cancer. We next examined the methylation status of FBN2 in the serum DNA of patients with colorectal cancer. Out of 49 serum samples, four (8%) exhibited FBN2 methylation in their serum DNA by qMSP, suggesting that FBN2 methylation exists in the serum of colorectal cancer patients. After completion of qMSP analysis in all specimens, clinicopathological data were correlated with the molecular analysis findings. Interestingly, methylation of FBN2 was found in the serum DNA of male (p=0.0167) patients, and in those with hepatic metastasis (p<0.0001). CONCLUSIONS: The clinical sensitivity of this assay can be potentially improved by incorporating other common genetic targets such as p53 and KRAS. Advances in technology which will permit for rapid detection of an array of specific mutations and methylation would enhance the utility of this approach.

Expression levels of thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase in patients with colorectal cancer.

BACKGROUND: Predictors of the response of colorectal cancer to chemotherapy remain poorly understood. We analyzed the mRNA expression levels of enzymes related to sensitivity to 5-fluorouracil derivatives in patients with colorectal cancer. PATIENTS AND METHODS: Danenberg tumor profile method (DTP) was used in order to measure mRNA expression levels of thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), and thymidine phosphorylase (TYMP) from 180 patients with colorectal cancer. The relations of expression levels with clinicopathological factors and outcomes were studied. RESULTS: Higher TYMS expression was associated with greater age, DPYD expression with greater age, poorer differentiation and low invasion, and TYMP expression with poorer differentiation and lack of peritoneal metastasis. DPYD expression positively correlated with TYMP expression. In patients with stage IV disease, high DPYD or TYMP expression was associated with poor outcomes. CONCLUSION: mRNA expression of TYMS, DPYD, and TYMP is associated with distinct characteristics and may be useful for predicting survival in patients with stage IV colorectal cancer.