Association of polydoctoring and mortality among very old persons with multimorbidity: a prospective cohort study in Japan.

BACKGROUND: Polydoctoring is a crucial aspect of care fragmentation among patients with multimorbidity, but its impact on health outcomes remains unclear. AIM: To determine the effects of polydoctoring, as measured by the Regularly Visited Facility (RVF) indicator, on patient outcomes among older individuals with multimorbidity. DESIGN & SETTING: Data from the ongoing prospective cohort study, Kawasaki Aging and Wellbeing Project (KAWP), was utilized in this study. Among the 1,026 KAWP participants aged 85-89 years, those with two or more chronic conditions were enrolled in this study. METHOD: Care fragmentation or polydoctoring, was evaluated using the RVF, a new indicator that measures the number of medical facilities consistently involved in a patient's care. Based on RVF, mortality was analysed using the Cox-hazards model, with adjustments for age, sex, frailty, and number of comorbidities. RESULTS: A significant reduction in mortality rates was observed in participants with an RVF of ≥3 and 2-4 comorbidities (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.18-0.99). However, no significant difference in mortality based on RVF was observed for those with ≥5 comorbidities. Notably, individuals with ≥5 comorbidities and an RVF of 0 had a significantly higher HR for death (HR 2.68, 95% CI 1.05-6.84). CONCLUSIONS: In older patients with multimorbidity, polydoctoring reduces mortality in patients with ≤4 coexisting conditions, but it does not significantly impact mortality in those with ≥5 conditions. These findings provide insights for healthcare decision-making in managing older patients with multimorbidity.

The association between surgical site infection and postoperative colorectal cancer recurrence and the effect of laparoscopic surgery on prognosis.

PURPOSE: Studies have shown that surgical site infection (SSI) incidence is lower in patients undergoing laparoscopic surgery. Therefore, we reported the SSI countermeasures adopted by our institution and aimed to evaluate the association between SSI occurrence and postoperative colorectal cancer recurrence and the usefulness of laparoscopic surgery for prognosis. METHODS: Among the patients with colorectal cancer who underwent radical surgery at our hospital between January 2015 and December 2017, 197 with stage I-III cancer without distant metastases were included. We retrospectively analyzed patients' electronic medical records and classified them into the non-SSI (without SSI, n = 159) and SSI (with SSI, n = 38) groups. We calculated and compared the 5-year relapse-free survival (RFS) and overall survival (OS) rates. Additionally, we assessed the relationship between prognosis in the non-SSI, incisional SSI, and organ/space SSI groups and the usefulness of laparoscopic surgery. RESULTS: The 5-year RFS and OS were 80.5% versus 63.2% (P = 0.024; hazard ratio [HR], 2.065; 95% confidence interval [CI], 1.099-3.883) and 88.7% versus 84.2% (P = 0.443; HR, 1.436; 95% CI, 0.570-3.617), respectively. The SSI group had a significantly worse 5-year RFS prognosis. Regarding the relationship with laparoscopic surgery, the SSI incidence was 45.0% (9/20 cases) and 16.4% (29/177 cases) with laparotomy and laparoscopic surgery, respectively, indicating a significantly reduced SSI occurrence with laparoscopic surgery (P = 0.005). CONCLUSION: Patients with SSI were at high risk for colorectal cancer recurrence, and laparoscopic surgery may be useful for reducing SSI.

Plasma amino acid signature for sarcopenic phenotypes in community-dwelling octogenarians: Results from the Kawasaki Aging Wellbeing Project.

Sarcopenia is one of the primary risk factors for various adverse health events in later life. However, its pathophysiology in the very old population remains unclear. Hence, this study aimed to examine whether plasma free amino acids (PFAAs) correlate with major sarcopenic phenotypes (i.e., muscle mass, muscle strength, and physical performance) in community-dwelling adults aged 85-89 years living in Japan. Cross-sectional data from the Kawasaki Aging Well-being Project were used. We included 133 adults aged 85-89 years. In this study, fasting blood was collected to measure 20 plasma PFAAs. Measures for the three major sarcopenic phenotypes included appendicular lean mass assessed by multifrequency bioimpedance, isometric handgrip strength, and gait speed from a 5 m walk at a usual pace. Furthermore, we used phenotype-specific elastic net regression models adjusted for age centered at 85 years, sex, body mass index, education level, smoking status, and drinking habit to identify significant PFAAs for each sarcopenic phenotype. Higher histidine and lower alanine levels were associated with poor gait speed, but no PFAAs correlated with muscle strength or mass. In conclusion, PFAAs such as plasma histidine and alanine are novel blood biomarkers associated with physical performance in community-dwelling adults aged 85 years or older.

A single-center retrospective analysis of the efficacy and safety of a modified regimen of irinotecan plus S-1 (IRIS) with molecular targeting agents as second-line chemotherapy in Japanese patients with recurrent or nonresectable colorectal cancer.

Background: As the second-line chemotherapy for stage IV recurrent or nonresectable colorectal cancer, our hospital started a modified treatment regimen comprising of irinotecan plus S-1 (IRIS) [tegafur/gimeracil/oteracil (S-1)] plus molecular targeting agents (MTAs), i.e., an epidermal growth factor receptor (EGFR) inhibitor such as panitumumab (P-mab) or cetuximab (C-mab) or vascular endothelial growth factor (VEGF) inhibitor such as bevacizumab (B-mab) since October 2012. The purpose of this study is to evaluate the efficacy and safety of this modified regimen. Methods: This retrospective study included 41 patients with advanced recurrent colorectal cancer at our hospital whom at least 3 courses of chemotherapy were conducted from January 2015 to December 2021. Based on the location of the primary tumor, patients were classified into two group (right-sided group, proximal to the splenic curve, and left-sided, distal to the splenic curve). We assessed archived data on RAS and BRAF status and UGT1A1 polymorphisms and use of the VEGF inhibitor bevacizumab (B-mab) and the EGFR inhibitors panitumumab (P-mab) and cetuximab (C-mab). In addition, progression-free survival rate (36M-PFS) and the overall survival rate (36M-OS) were calculated. Furthermore, the respective median survival time (MST), the median number of treatment courses; the objective response rate (ORR) and clinical benefit rate (CBR) and the incidence of adverse events (AEs) were assessed as well. Results: There were 11 patients (26.8%) in the right-sided group, and 30 patients (73.2%) in the left-sided group. There were 19 patients with RAS wild type (46.3%) (1 in the right sided group and 18 in the left sided group). P-mab was used for 16 of these patients (84.2%), C-mab for 2 (10.5%), and B-mab for 1 (5.3%); the remaining 22 patients (53.7%). Ten patients in the right group and 12 patients in the left group were a mutated type and received B-mab. BRAF testing was performed in 17 patients (41.5%); as more than 50% of patients (58.5%) were included before the assay's introduction. Five patients in the right-sided group and 12 patients in the left-sided group had wild type. There was no mutated type. UGT1A1 polymorphism was tested in 16/41 patients: Eight were wild type (8/41 patients, 19.5%) and 8, mutated type. Regarding the *6/*28 double heterozygous type, there was only 1 patient in the right-sided group and the remaining 7 patients were in the left-sided group. The total number of chemotherapy courses was 299, and the median number, 6.0 (range, 3-20). PFS, OS, and MST were as follows: 36M-PFS (total/Rt/Lt), 6.2%/0.0%/8.5% (MST; 7.6/6.3/8.9 months); and 36M-OS (total/Rt/Lt), 32.1%/0.0%/44.0% (MST; 22.1/18.8/28.6 months). The ORR and CBR were 24.4% and 75.6%, respectively. The majority of AEs were grades 1 or 2 and were improved with conservative treatment. Grade 3 leukopenia was observed in 2 cases (4.9%), neutropenia in 4 cases (9.8%), and malaise/nausea/diarrhea/perforation in 1 case each (2.4%). Grade 3 leukopenia (2 patients) and neutropenia (3 patients) were more commonly observed in the left-sided group. Diarrhea and perforation were also common in the left-sided group. Conclusions: This second-line modified IRIS regimen with MTAs is safe and effective and results in good PFS and OS.

Does health literacy moderate the psychological pathways of physical activity from guideline awareness to behavior? A multi-group structural equation modeling.

BACKGROUND: Awareness, knowledge, beliefs, and behavioral intentions of physical activity (PA) guidelines may be important mediating factors for promoting PA. However, these pathways of the psychological process to PA behavior have not been examined. These pathways may differ depending on health literacy levels. This study investigated the pathways to PA, from guideline awareness to behavior, and further examined whether they differed by health literacy. METHODS: A cross-sectional study was conducted with 7,000 Japanese participants aged 20-69 years. The participants were registered with an Internet survey company. Participants' awareness, knowledge, beliefs, and behavioral intentions regarding the PA guidelines of Japan, the volume of moderate-to-vigorous intensity PA, activity level, and health literacy were examined through a questionnaire. The PA pathways, from guideline awareness to behavior, were examined by structural equation modeling (SEM), with PA behavior as the dependent variable. Multi-group SEM was conducted to examine the moderating effect of health literacy on PA pathways. Health literacy scores were dichotomized into high and low groups in multi-group modeling by the median split. RESULTS: SEM revealed that PA guideline awareness directly affects PA behavior and has certain indirect effects through the mediation of knowledge, beliefs, and behavioral intentions. Furthermore, the multi-group SEM showed that the proportion of indirect effects (path coefficient [PC]: 0.11, 95% confidence interval [CI]: 0.10-0.13) was higher than direct effects (PC: 0.07, 95%CI: 0.03-0.11) in the high-health literacy group. In contrast, the proportion of direct effects (PC: 0.22, 95%CI: 0.15-0.30) was higher than indirect effects (PC: 0.06, 95%CI: 0.05-0.07) in the low-health literacy group. CONCLUSIONS: PA guideline awareness is both directly and indirectly associated with PA behavior, mediated by psychological pathways of knowledge, beliefs, and behavioral intentions, and influenced by health literacy. These results suggest that health literacy should be considered when implementing PA guideline-based interventions.

Osteoporosis and sarcopenia are associated with each other and reduced IGF1 levels are a risk for both diseases in the very old elderly.

It is mandatory to manage musculoskeletal disorders in the elderly to prevent their becoming bed-ridden or requiring long-term care. However, the prevalence of musculoskeletal disorders such as osteoporosis and sarcopenia in otherwise healthy people over 85 years old is not completely known. Here we enrolled 1026 healthy subjects between 85 and 89 years old and evaluated them for the presence of osteoporosis, sarcopenia and fragility fracture(s), and how those conditions were related. We also evaluated biomarkers such as serum levels of insulin-like growth factor 1 (IGF1) and vitamin D status. The prevalence of osteoporosis, sarcopenia or fragility fracture(s) in these subjects was 22.4, 10.2 or 15.0 %, respectively. Serum IGF1 and 25(OH)D were significantly and negatively correlated with osteoporosis or sarcopenia. Osteoporosis and either sarcopenia or fragility fracture(s) were significantly related and shown to be risk factors for each other, even after adjustment for gender and BMI, while sarcopenia and fragility fracture(s) were not associated. Our data may provide a health platform for the very elderly and suggest strategies to prevent musculoskeletal disorders in this population.

Conversion surgery by hand-assisted laparoscopic surgery following chemotherapy for rectal cancer with H3 liver metastases: a case report.

Background: Recent advancements in molecularly targeted chemotherapy for stage IV colorectal cancer have enabled the possibility of complete resection in primary colorectal cancer, which often involves distant liver or lung metastases, by aggressive surgical resection followed by multi-combination chemotherapy. Case description: A 73-year-old man treated previously for hyperuricemia, hypertension, and a dissecting abdominal aortic aneurysm was referred to us after an incidental finding of multiple liver masses on abdominal ultrasound during follow-up for the aneurysm. A detailed examination by contrast-enhanced computed tomography revealed a ring-enhancing mass larger than 5 cm in diameter in segment 3 of the liver and more than 6 low-density areas with total diameter of 1 to 2 cm in both lobes. A barium enema examination revealed a Borrmann type 2 lesion covering two-thirds of the circumference of the colon, with a 5-cm major axis in the rectosigmoid colon. Biopsy revealed a well-differentiated adenocarcinoma. The patient was diagnosed with stage IV rectal cancer. Because there was no intestinal obstruction, we administered 9 cycles of bevacizumab with capecitabine and oxaliplatin as chemotherapy. Subsequent diagnostic imaging revealed the metastatic lesions in liver segment 3 had reduced to 2 low-density areas with a diameter of 8 mm, and the other hepatic metastases had disappeared; the main tumor had flattened and shrunk. Therefore, we used hand-assisted laparoscopic surgery (HALS) to perform anterior resection of the rectosigmoid colon and partial resection of liver segment 3 as conversion therapy. The patient was discharged 10 days after surgery. The rectal lesion was a well-differentiated adenocarcinoma with a depth of invasion of p-MP and a spread of L0, V0, and pN0. The partial hepatectomy did not indicate viable cancer cells; only necrotic, lysed tissue was observed. Postoperative chemotherapy involved 4 cycles of bevacizumab with capecitabine and oxaliplatin. At more than 42 months postoperatively, no metastasis or recurrence has been observed. Conclusions: This rare case demonstrates that conversion surgery can be a viable option following systemic chemotherapy in patients with advanced colon cancer and H3 liver metastases.

Long-term outcome of metachronous, multiple, early Epstein-Barr virus-associated gastric carcinoma: a case report.

Background: Epstein-Barr virus is associated with various malignancies. Epstein-Barr virus-associated gastric carcinoma (EBVaGC) was reported in 1990. While gastric carcinoma with lymphoid stroma (GCLS) is a rare gastric cancer, 80% to 90% of these tumors are associated with Epstein-Barr virus infection. Case Description: The patient was a 67-year-old male in 2004, when he underwent laparoscopy-assisted distal gastrectomy with Billroth I reconstruction to treat early stage 0-IIc gastric cancer; the pathological diagnosis was moderately differentiated adenocarcinoma, pT1b, pN0, stage IA with a negative margin. In 2009, endoscopic submucosal dissection (ESD) was performed on reoccurring stage 0-IIc gastric cancer; pathology results identified well-differentiated adenocarcinoma, pT1b, Ly0, V0, pHM0, pVM0. Although further gastric resection was recommended, the patient declined the procedure and opted to receive only follow-up evaluation. During the follow-up period, upper gastrointestinal (GI) endoscopy revealed a protruding mass on the remaining gastric fundus; biopsy indicated a poorly differentiated adenocarcinoma. Approximately 15 years after the initial treatment, the patient underwent total resection of the remnant stomach and Roux-en-Y reconstruction. The histopathological diagnosis was gastric cancer, pT1b, N0, no lymphatic and venous invasion, stage IA with lymphoid stroma and lymphocyte infiltration associated with formation of lymphoid follicles. Immunohistochemistry with EBV-encoded RNA in situ hybridization (EBER-ISH) was positive, resulting in diagnosis of EBVaGC. Retrospective EBER-ISH performed on resected specimens from the 2 prior surgeries yielded similar results. Furthermore, immunohistochemistry using anti-programmed death ligand 1 (PD-L1) antibody demonstrated an increase in the combined positive score (CPS) over time. Conclusions: This report describes the rare case of a patient who experienced 3 occurrences of EBVaGC at different times and locations over 15 years and discusses the clinical relevance in the context of a literature review. It aims to increase awareness among clinicians and pathologists of the necessity of considering EBVaGC when deciding on the treatment strategy after reoccurrence of gastric cancer.

A 73-Year-Old Woman Treated for Rheumatoid Arthritis with Lower Rectal Carcinoma Who Underwent Abdominoperineal Resection, Lateral Regional Lymph Node Resection, and Partial Hepatectomy by Hand-Assisted Laparoscopic Surgery (HALS): A Case Report.

BACKGROUND This report describes the case of a 73-year-old woman treated for rheumatoid arthritis with lower rectal carcinoma who underwent abdominoperineal resection, lateral regional lymph node resection, and partial hepatectomy by hand-assisted laparoscopic surgery (HALS). More recently, HALS has proven to be useful in multiple organ resections. CASE REPORT A 73-year-old woman who presented with hematochezia was diagnosed with lower rectal cancer and referred to our hospital. The patient had a history of rheumatoid arthritis and was taking oral nonsteroidal anti-inflammatory drugs. After further evaluation, the patient was diagnosed with stage IV rectal cancer with a metastatic liver lesion and a right lateral lymph node metastasis. All lesions were resected using HALS. A 50-mm longitudinal umbilical incision was created for use as a hand access site, and 3 ports with a diameter of 5 mm each were inserted into the lower abdomen to perform right lateral lymph node dissection and abdominoperineal resection. HALS was performed in the upper abdomen, where the liver was used to partially resect segment S6. The patient was discharged without complications 13 days after the operation. CONCLUSIONS In this complex case of advanced rectal carcinoma with liver metastases, use of the HALS surgical method was shown to be possible. Immunomodulatory treatment for rheumatoid arthritis may have influenced the outcome for this patient.

Efficacy of hand-assisted laparoscopic surgery (HALS) in older adult patients (≥80 years) with primary colorectal cancer.

Background: From 2004 to 2014, 821 colorectal cancer primary resections were conducted at our institution. Of these, 102 patients (12.4%) were older adults over 80 years old. underwent either the conventional laparotomy group (72 patients) or the hand-assisted laparoscopic surgery (HALS) group (30 patients). Methods: Data were extracted for 102 patients over 80 years old who underwent primary resection for colorectal cancer and were divided into two groups: conventional laparotomy (CL) (n=72) and hand-assisted laparoscopy (n=30). Pre-operative characteristics and outcomes were compared. Results: Baseline characteristics were similar between groups, except for age: CL group median 83.5 years old (range, 80-92 years old) and hand-assisted laparoscopy (HALS) group median 81.5 years old (range, 80-88 years old) (P=0.027). Pre-operative cardiac and lung function risk, performance status, and pathological classification stage (pStage) were almost similar between groups (P=0.668, P=0.176, P>0.999, P=0.217). No significant differences were found for operation time. The HALS group resulted in less blood loss (median 204 mL in the CL group and median 68 mL in the HALS group, P=0.003), shorter postoperative hospital stay (median was 18 days in the CL group and median was 12 days in the HALS group, P<0.001), and fewer postoperative wound infections (18 cases in the CL group and 2 cases in the HALS group, P=0.034). Five-year relapse-free survival (5Y-RFS) was 48.1% in the CL group and 73.3% in the HALS group (P=0.028). Five-year overall survival (5Y-OS) was 48.2% in the CL group and 73.3% in the HALS group (P=0.027). Conclusions: Approximately 70% of surgical treatment for patients over 80 years old with colorectal carcinoma were performed by CL. However, HALS had significant advantages including less blood loss, fewer wound infections, and shorter hospital stays. Therefore, HALS could proactively be considered to older adult patients with colorectal cancer.

[Current status of awareness, knowledge, beliefs, and behavioral intentions regarding the Japanese physical activity guidelines and their relationship with physical activity and sedentary behavior].

Objective　This study clarified the current status of awareness, knowledge, beliefs, and behavioral intentions regarding the Japanese physical activity guidelines (Active Guide) and their relationship with physical activity, sedentary behavior, and the participants' characteristics.Methods　A cross-sectional study was conducted with 7,000 participants aged 20-69 years registered with an online survey company. Awareness, knowledge, beliefs, and behavioral intentions regarding the Active Guide were examined. Awareness was assessed by unprompted and prompted recall. Knowledge was assessed by numerical responses to "the recommended daily activity time (18-64 years/65 years and older)" and "physical activity time to be increased (plus-ten)," respectively. To survey the beliefs and behavioral intentions, we created a 5-point scale for the Active Guide. For physical activity, the amount of moderate-to-vigorous intensity physical activity was calculated from the Japan Public Health Center-based prospective Study (JPHC study) questionnaire. Physical activity level was calculated from the standard specific medical checkup and health guidance questionnaire. For sedentary behavior, the Japanese version of the International Physical Activity Questionnaire (IPAQ) was used. The dependent variables were awareness, knowledge, beliefs, and behavioral intentions. The independent variables were physical activity, sedentary behavior, and the participants' characteristics (gender, age, body mass index, marital status, educational background, work status, and household income). After descriptive statistics were measured, a logistic regression analysis was performed to examine the associations.Results　Unprompted and prompted recall of the Active Guide were 1.7% and 5.3-13.4%, respectively. Those with knowledge of it scored 37.2%, 7.0%, 24.8%, and 2.6% for recommended daily activity time (18-64 years), daily physical activity time (65 years and older), plus-ten, and all three items answered correctly, respectively. The median (interquartile range) score of the beliefs was 21 (16-25) points (32-point scale). Those with behavioral intentions scored 51.4% for "recommended daily activity" and 66.9% for "plus-ten." Logistic regression analysis showed that awareness, knowledge, beliefs, and behavioral intentions were positively associated with moderate-to-vigorous intensity physical activity and level. The results were inconsistent for sedentary behavior. Although personal characteristics differed based on assessment item, they were mainly associated with age, education level, employment, and household income.Conclusions　This study revealed that the number of people who had awareness and knowledge of the Active Guide remained low. Those with awareness, knowledge, beliefs, and behavioral intentions were more physically active. However, the results for sedentary behavior were not consistent. Hence, further research is required to understand this tendency. A future longitudinal study is also required.

Scatter patterns in lymph node metastases as a novel prognostic indicator in patients with stage III/N2 colorectal cancer.

To classify patients with stage III/N2 colorectal cancer into high- and low-risk groups for recurrence, the present study compared clinicopathological features by immunohistochemical staining. The single-center analysis included 53/668 patients (7.9%) with stage III/N2 colorectal cancer who underwent radical resection between January 2006 and December 2014. The present study examined cancer cell distribution in metastatic lymph nodes and classified patients into a group with circumferential localization patterns like a cystic mass (CLP) and a group with scatter patterns like fireworks (SPF). Subsequently, 5-year relapse-free survival (5Y-RFS) and 5-year overall survival (5Y-OS) rates were compared and the histological type (differentiation degree) of the primary adenocarcinoma was included. The CLP group included 16 patients (30.2%) and the SPF group included 37 patients (69.8%). The 5Y-RFS rates in these groups were 75.0 vs. 37.8%, respectively (P=0.021), and the 5Y-OS rates were 81.3 vs. 48.6% (P=0.033). Patient clinicopathological characteristics exhibited no significant differences between groups. The adenocarcinoma was well differentiated in 14 patients (Well; 26.4%) and moderately (Mod; n=37) or poorly (Por; n=2) differentiated in 39 patients (Mod+Por; 73.6%). Patients were further classified into four groups: Well/CLP (n=6), Well/SPF (n=8), Mod+Por/CLP (n=10) and Mod+Por/SPF (n=29). For Well/CLP vs. Well/SPF, the 5Y-RFS rates were 66.7 vs. 25.0%, respectively (P=0.293), and for Mod+Por/CLP vs. Mod+Por/SPF (80.0 vs. 41.4%; P=0.052), the respective values for 5Y-OS were 66.7 vs. 50.0% (P=0.552) and 90.0 vs. 48.3% (P=0.059). Based on the aforementioned results, the CLP group was considered a low-risk group for recurrence with a relatively good prognosis; however, the SPF group was considered a high-risk group for recurrence with a poor prognosis, suggesting a need for more potent multi-combination chemotherapy in these patients from the early postoperative period.

A community-wide intervention to promote physical activity: A five-year quasi-experimental study.

Evidence on the effects of a community-wide intervention (CWI) on population-level physical activity (PA), especially in the long term, is limited. Therefore, we evaluated the five-year effect of CWI on promoting PA through information dissemination, education, and community support primarily targeting older adults, by incorporating Japanese guidelines, in Fujisawa City, from 2013. To assess the effect of the whole-city intervention, we distributed questionnaires in 2013, 2015, and 2018 to three independent random samples of 3,000 community-dwelling adults (aged ≥ 20 years) using a quasi-experimental study design. Three separate samples responded to the survey (41% at baseline, 46% at the two-year mark, and 48% at the five-year follow-up). The primary outcome was change in PA participation. At the five-year follow-up, PA (median: 120 minutes/day) was significantly higher than at baseline (86 minutes/day) and the two-year follow-up (90 minutes/day). The results of the multivariate analysis indicated that PA among older adults-the primary target population of the CWI-increased significantly at the five-year follow-up, compared to those aged 20-64 (mean difference of change between groups: 14.7 minutes/day, P= 0.029). Among older adults, PA was significantly lower in those with poorer perceived economic status than in their more well-off counterparts at the two-year follow-up (P= 0.003); however, there was no significant difference at the five-year follow-up (P= 1.000). There was a positive interaction between group and period (mean difference of change between groups: 40.9 minutes/day, P= 0.001). In conclusion, the five-year CWI targeting older adults, incorporating national guidelines, improved population-level PA.

Efficacy of modified bevacizumab-XELOX therapy in Japanese patients with stage IV recurrent or non-resectable colorectal cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) has been conducted for patients with non-resectable colorectal cancer; however, few reports of a systematic approach to NAC exist. At our hospital, bevacizumab with capecitabine and oxaliplatin (B-mab XELOX) has been used as chemotherapy for Stage IV colorectal cancer since 2014. We aimed to evaluate the efficacy and safety of NAC with a molecular-targeting agent for Stage IV colorectal cancer. METHODS: A retrospective, single-institute analysis was performed including 27 patients with advanced recurrent cancer following primary tumor resection and 43 patients with non-resectable tumors and remote metastasis. At the time of resection, 17 were receiving chemotherapy. All 70 patients received at least 3 cycles of B-mab XELOX (total: 920 cycles). We determined the 1-year progression-free survival (1Y-PFS), 1-year overall survival (1Y-OS), 3Y-PFS, 3Y-OS, and number of treatment cycles. The objective response rate, clinical benefit rate, and adverse events were assessed. The number of chemotherapy cycles, survival time, and R0 surgery rate were determined for patients who underwent RO conversion surgery. RESULTS: The 1Y-PFS was 28.5% [median survival time (MST): 7.4 months], 1Y-OS was 76.6% (MST not reached), 3Y-PFS was 5.5% (MST: 7.4 months), and 3Y-OS was 26.4% (MST: 25.2 months). The mean and median number of cycles of B-mab XELOX was 13.1 and 10.5, respectively. The objective response rate was 28.6%, and the clinical benefit rate was 58.6%. Grade 1 or Grade 2 adverse events occurred in 60 patients (85.7%); however, they all resolved without intervention. A single Grade 4 event (perforation of the primary tumor) occurred in 1 patient (1.4%). RO conversion surgery was performed in 7 patients (10.0%; primary + liver in 2 patients, primary + lung in 1 patient, liver in 3 patients, and primary in 1 patient). These patients received 3 to 10 cycles preoperatively (mean: 7.3; median: 6.5). R0 surgery was achieved in 5 of the 7 patients (71.4%). Postoperative survival ranged from 1 to 26 months (MST: 8 months). CONCLUSIONS: This modified regimen was safe and effective in Japanese patients, and a high quality of life/quality-adjusted life-year was achieved. To further evaluate PFS and OS, more patients are being investigated.

Pelvic local recurrence as first relapse predicts prognosis for clinical stage II/III lower rectal cancer: A clinicopathological investigation.

The present study investigated the association between the mode of tumor recurrence and prognosis in 123 patients with clinical stage II/III rectal cancer. In the past 10 years, patients received systemic chemotherapy following radical (R0, with no macroscopic residual tumor lesions) resection using total or tumor-specific mesorectal excision. Patients with rectosigmoid cancer and T4 + chemoradiation therapy were excluded from the present study. The 5-year relapse-free survival rate (5Y-RFS), 5-year overall survival rate (5Y-OS), and associations between early post-operative complications, recurrence mode and prognosis, as well as the 5Y-OS of patients with relapsed cancer, were calculated. The overall 5Y-RFS and 5Y-OS were 71.4 and 83.5%, respectively, and the overall recurrence rate was 22.8% (28/123 patients). Among relapses, remote metastases were observed in 17/123 patients (13.8%): The lung in 8 patients (6.5%), the liver in 5 patients (4.1%) and elsewhere in 4 patients (3.3%). A total of 11 patients (8.9%) had pelvic local recurrence as the first relapse, which was located anterior to the sacrum in 7 patients (5.7%), at the anastomosis site in 2 patients (1.6%), and in the inner pelvis in 2 patients (1.6%). Among relapsed patients, the 5Y-OS was 69.3% in those with distant metastases and 27.3% in those with local relapse (P=0.02; no significant differences in patient demographics). The results indicated that advanced rectal cancer and control of pelvic local recurrence are manageable by R0 resection and postoperative chemotherapy. However, for patients whose initial relapse was pelvic local recurrence, the relapsed tumor initiated a new metastatic cascade to organs, such as the lung and liver, and affected prognosis.

Perforated gastrointestinal stromal tumor in the small intestine: A rare case of Torricelli-Bernoulli sign.

The Torricelli-Bernoulli sign is a computed tomography (CT) finding that occurs when ulceration/necrosis of a submucosal gastrointestinal tumor releases a stream of air bubbles into the intestinal lumen. A 75-year-old man developed acute abdominal pain at night and presented to a local doctor. Acute abdomen was diagnosed and he was referred to the Emergency Department at Tokai University Oiso Hospital. On CT scans, disseminated intestinal tumor-like lesions were seen in the right lower abdomen. The Torricelli-Bernoulli sign and free intraabdominal gas were observed, so perforation of an intestinal tumor was diagnosed and emergency surgery was performed. At operation, there was scanty opaque ascites in the right lower abdomen and an ileal tumor associated with nodules that suggested peritoneal dissemination. Partial resection of the ileum was performed and peritoneal lavage was conducted. The patient was discharged on postoperative day 11. Histopathological examination revealed a high risk gastrointestinal stromal tumor. The abdominal nodules were metastases, indicating that the tumor was Stage IV. The patient is currently on treatment with an oral tyrosine kinase inhibitor (imatinib).

Single-center analysis of appendiceal neoplasms.

The purpose of the present study was to evaluate the recent trend of diagnosing appendiceal diseases through the analysis of appendectomy materials, stressing the importance of their pathological examination. A clinicopathological assessment of patients undergoing an appendectomy was conducted, based on the pathological examination of resected appendiceal lesions. Using a pathological database of surgical specimens from patients who underwent an appendectomy between March 2002 and September 2014, a retrospective, single-center analysis was performed. Among the 803 patients identified, 752 with appendiceal disease were selected for clinicopathological analysis. The diagnosis was inflammation (i.e. appendicitis) in 97.7% (n=735) and appendiceal neoplasm in 2.3% (n=17) of the patients. The most frequent type of appendiceal neoplasm was an intramucosal neoplasm (23.5%, n=4). In conclusion, the incidence of appendiceal neoplasms has increased in recent years, potentially due to increased and earlier detection by newer imaging modalities.

Community-wide physical activity intervention based on the Japanese physical activity guidelines for adults: A non-randomized controlled trial.

Very few community intervention studies that promote physical activity (PA) using guidelines and its dissemination and implementation have been conducted. Consequently, we evaluated the effectiveness of a community-wide intervention (CWI) of PA with adults based on the Japanese guidelines for promoting PA. This was a non-randomized controlled trial, with four administrative districts in Fujisawa city assigned to the intervention group and nine to the control group. The CWI, conducted from 2013 to 2015, comprised information dissemination, education, and community support. The primary outcome was change in PA participation. Secondary outcomes were CWI awareness and PA guideline knowledge. Outcomes were assessed using questionnaires distributed to two independent, random samples of 3000 community-based adults (aged ≥20years). Two separate samples-1230 adults at baseline and 1393 at the two-year follow-up-responded to the survey. The median time spent in PA did not differ between intervention and control groups after adjusting for potential confounders (adjusted difference between groups=-0.02min/day [95% confidence interval (CI): -0.11, 0.10]). However, intervention group participants were more aware of the CWI (33.8%) than were control group participants (25.2%) at the two-year follow-up (odds ratio=1.44 [95% CI: 1.06, 1.95]). A significant difference was also observed in participants' PA guideline knowledge (adjusted difference between groups=0.82% [95% CI: 0.33, 1.31]). Although significant differences in awareness and knowledge were observed between groups, this CWI did not change PA levels over two years. Future studies should investigate the long-term effects of CWIs beyond two years. TRIAL REGISTRATION NUMBER: UMIN-CTR UMIN000018389.

Expandable Metallic Stent for Endobronchial Metastasis from Colorectal Cancer: Reports of 2 Cases.

In recent years, there have been many reports about the efficacy of stenting for central bronchial stenosis. When central bronchial stenosis is due to metastasis of a malignant tumor to the trachea and/or bronchi (endobronchial metastasis: EM), it is classified as "narrow EM" and "broad EM." [1] We managed two patients in whom bilateral stent placement was required for narrow and broad EM arising from colorectal cancer. Case 1: In September 2011, a 66-year-old man underwent low anterior resection for advanced colorectal cancer associated with unresectable liver metastasis. The liver metastasis became resectable after chemotherapy, with two resection procedures and radiofrequency ablation (RFA) being performed. Thereafter, lung metastasis occurred and a tumor in the left lung was resected. In May 2015, he developed respiratory distress. CT identified multiple lesions protruding into the lumen of the trachea and the left and right main bronchi. There was no evidence of mediastinal relapse or local relapse at the resection margin, and tumors were only detected in the tracheobronchial walls. Accordingly, narrow EM was diagnosed. An expandable metallic stent (EMS) was placed on the right side where stenosis was more severe, and radiation therapy was conducted for the non-stented tumors. The patient died 8 months later. Case 2: A 69-year-old woman had undergone laparoscopic right hemicolectomy and adjuvant chemotherapy for Stage lllb cancer of the ascending colon. Due to subsequent elevation of tumor markers, PET-CT was conducted and abnormal uptake was seen in the apex of the right lung and right upper abdomen. Both lesions were resected, and omental and lung metastases were diagnosed. She received treatment with UFT / calcium folinate, but relapse occurred at the resection margin in the right lung. At 7 years and 5 months after initial surgery, she complained of respiratory distress at an outpatient visit. CT demonstrated displacement of the trachea and right main bronchus due to enlargement of upper mediastinal lymph nodes. There was also severe stenosis of the right main bronchus due to tumor infiltration. Because there was both infiltration from local recurrence after resection and upper mediastinal lymph node enlargement, broad EM was diagnosed. An EMS was placed at the site of severe stenosis in the right main bronchus. Similar to Case 1, radiation therapy was also conducted, but respiratory distress occurred after 3 months due to tumor re-growth at the stent margin. Accordingly, stent-in-stent placement was performed and her respiratory symptoms improved. However, superior vena cava syndrome occurred 1 month later and the patient died. We consider that placing an EMS is effective in patients with tracheal stenosis due to EM that is judged to be an oncological emergency.

Comparison of hand-assisted laparoscopic surgery (HALS) and conventional laparotomy in patients with colorectal cancer: Final results from a single center.

In recent years, the use of laparoscopic surgery has been expanded to include radical curative resection. In a previous study, 212 patients with primary colorectal cancer (stages I-III) underwent radical curative resection by hand-assisted laparoscopic surgery (HALS) (n=98) or conventional laparotomy (CL) (n=114) and were compared with respect to 3-year relapse-free survival (3Y-RFS) and 3-year overall survival (3Y-OS). The study included 210/212 patients who were followed up to 5 years, including 96 patients who underwent HALS and 114 treated with CL. The two groups were matched for stage, clinical background, and postoperative management. Patient characteristics were compared and the 5Y-RFS and 5Y-OS were determined. The 5-year follow-up rate was 97.6%. In stage I-III patients, 5Y-RFS and 5Y-OS showed no significant differences between HALS and CL. The patients with stage I disease accounted for 41.7% (40/96) of the patients undergoing HALS, while stage I patients only accounted for 23.7% (27/114) of the patients undergoing CL, and the difference was significant (P=0.005). Stage II patients undergoing CL were older than those treated with HALS (P=0.017). However, there were no differences in the characteristics of stage III patients undergoing HALS or CL. In conclusion, HALS achieved a similar survival to CL in patients with stage I to III colorectal cancer. Compared with CL, HALS was performed more safely and achieved superior cosmetic results.