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.

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.

[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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Biochemical and molecular characterization of senescence-related cysteine protease-cystatin complex from spinach leaf.

Cysteine proteases (CPs) with N-succinyl-Leu-Tyr-4-methylcoumaryl-7-amide (Suc-LY-MCA) cleavage activity were investigated in green and senescent leaves of spinach. The enzyme activity was separated into two major and several faint minor peaks by hydrophobic chromatography. These peaks were conventionally designated as CP1, CP2 and CP3, according to their order of elution. From the analyses of molecular mass, subunit structure, amino acid sequences and cDNA cloning, CP2 was a monomer complex (SoCP-CPI) (51 kDa) composed of a 41-kDa core protein, SoCP (Spinacia oleracea cysteine protease), and 14-kDa cystatin, a cysteine protease inhibitor (CPI), while CP3 was a trimer complex (SoCP-CPI)(3) (151 kDa) of the same subunits as SoCP-CPI and showed a wider range of specificity toward natural substrates than SoCP-CPI. Trimer (SoCP-CPI)(3) was irreversibly formed from monomers through association. The results of reverse transcription-polymerase chain reaction (RT-PCR) revealed that mRNAs of CPI and SoCP are hardly expressed in green leaves, but they are coordinately expressed in senescent leaves, suggesting that these proteases involve in senescence. Purified recombinant CPI had strong inhibitory activity against trimer SoCP, (SoCP)(3) , which had a cystatin deleted with K(i) value of 1.33 × 10(-9) M. After treatment of the enzyme with a succinate buffer (pH 5) at the most active pH of the enzyme, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and activity analyses showed that cystatin was released from both monomer SoCP-CPI and trimer (SoCP-CPI)(3) complexes with a concomitant activation. Thus, the removal of a cystatin is necessary to activate the enzyme activity.

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.

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.

Trans-anal reinforcing sutures after double stapling for lower rectal cancer: report of two cases.

To safely avoid the construction of a covering stoma in patients with advanced lower rectal cancer undergoing laparoscopy assisted colorectal surgery (LACS), we added circumferential manual reinforcing sutures via the transanal approach at the site of mechanical anastomosis. In June 2008, LACS was performed for a tumor of 6 cm in longer diameter in the Rb region of the lower rectum approximately 5 cm from the anal verge. After intraperitoneal coloproctal anastomosis was performed in the pelvis by the double stapling technique (DST), reinforcement was provided by manual trans-anal suturing (trans-anal reinforcing sutures: TARS). A covering stoma was constructed because this was a high-risk case. Complications such as mild wound infection and stoma trouble occurred, and the patient was discharged after conservative therapy. In June 2008, LACS was performed for a tumor of 5 cm in longer diameter in the Ra region of the lower rectum approximately 7 cm from the anal verge. After intraperitoneal colorectal anastomosis was performed in the pelvis by DST, TARS were added to avoid a covering stoma. Minor leakage occurred postoperatively, but this was controlled conservatively and the patient was discharged. In patients having surgical treatment of advanced lower rectal cancer, good results were obtained by adding circumferential reinforcing sutures via the trans-anal approach at the site of ultra-low anastomosis after DST.

Clinical comparison of QOL and adverse events during postoperative adjuvant chemotherapy in outpatients with node-positive colorectal cancer or gastric cancer.

The aim of this study was to evaluate the quality of life (QOL) from the performance status (PS) and face scale (FS), and to compare adverse events (AEs) during chemotherapy in 28 patients with node-positive colorectal cancer (NP-CRC) and 15 patients with node-positive gastric cancer (NP-GC). The anticancer regimen consisted of 5-FU/LV+CPT-11 for NP-CRC and 5-FU+low-dose CDDP for NP-GC. Results were evaluated after completion of three courses. QOL evaluation revealed no significant differences between the two groups with respect to PS and FS. Among hematological AEs, grade 1/2 mild leucopenia was significantly more common in NP-CRC than NP-GC patients (p<0.05), while grade 1/2 mild thrombocytopenia was significantly more common in NP-GC than NP-CRC patients (p<0.05). Among non-hematological AEs, grade 1/2 mild neuropathy (olfactory nerve) was significantly more common in NP-CRC than NP-GC patients (p<0.05). The monthly cost for one course was approximately euro586.8 for NP-CRC patients and approximately euro181.8 for NP-GC patients. These results suggest that first-line postoperative outpatient adjuvant chemotherapy for NP-CRC and NP-GC shows no significant differences with respect to QOL, but both AEs and the cost are higher for NP-CRC than for NP-GC.

Hybrid 2-port hand-assisted laparoscopic surgery for the 2-stage treatment of a complete bowel obstruction by distal sigmoid colon cancer: a case report.

In July 2008, a 40-year-old man presented to his local physician with diffuse abdominal pain and severe abdominal distension. Impending bowel rupture due to colonic obstruction was strongly suspected. Complete obstruction of the distal sigmoid colon by a tumor was diagnosed, and emergency surgery was performed. A sigmoid colon loop colostomy was created within the range of subsequent resection to relieve the obstruction. After his general condition had improved and the risks were assessed, curative resection including removal of the stoma was performed by hybrid 2-port hand-assisted laparoscopic surgery. The tumor showed invasion of the serosa without lymph node metastasis, and its pathological diagnosis was stage II. Postoperatively, mild wound infection occurred at the hand access site (stoma), but it resolved with conservative treatment, and the patient was discharged on postoperative day 13. This case is reported here because of the good results.