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Preclinical studies suggest that statins contribute to the prevention of pancreatic cancer; however, the results of epidemiologic studies are inconsistent. Furthermore, sufficient data are unavailable for the general population of Asia. Here, we conducted an observational study using a comprehensive patient-linked, longitudinal health insurance database comprising the records of 2,230,848 individuals residing in Shizuoka Prefecture, Japan, from April 2012 to September 2018. We included individuals older than 40 years with data for medical examinations and statin exposure (≥365 statin prescription days). To balance baseline characteristics between the statin exposure and statin nonexposure groups, we used inverse probability of treatment propensity score weighting method. We estimated hazard ratios for associations with pancreatic cancer using the Cox proportional hazards regression model. Among 2,230,848 individuals, we included 100,537 in the statin exposure group (24%) and 326,033 in the statin nonexposure group (76%). Among the statin exposure group (352,485 person-years) and the statin nonexposure group (1,098,463 person-years), 394 (1.12 per 1,000 person-years) and 1176 (1.07 per 1,000 person-years) developed pancreatic cancer, respectively (P = 0.464). After adjustments using inverse probability of treatment weighting, the statin exposure group was associated with a decreased incidence of pancreatic cancer (hazard ratio, 0.84; 95% confidence intervals, 0.72–0.99; P = 0.036). In conclusion, the current Japanese regional population-based cohort study shows that statin exposure was associated with a lower incidence of pancreatic cancer. Prevention Relevance: This study may support the possible role of statins in preventing pancreatic cancer in the general population in Japan.

Background Hepatocellular carcinoma (HCC) can grow in a mosaic pattern, often combined with various non-hepatocellular cells. However, HCC combined with a neuroendocrine carcinoma (NEC) component is rarely reported, and its clinical features, origin, diagnosis, and behavior have not been established. In the literature, mixed HCC–NEC tumors are categorized as either collision type or combined type, depending on their microscopic features. Here, we report a patient with a combined-type HCC–NEC tumor. Case presentation An asymptomatic 84-year-old woman was found to have a solid mass in the right lobe of the liver. Laboratory and radiologic examinations showed typical findings of HCC, including arterial-phase enhancement, and portal- and delay-phase washout. She was treated by partial laparoscopic hepatectomy of segment 5. Pathological examination showed that the tumor was predominantly HCC, partly admixed with an NEC component. A transitional zone between the HCC and NEC tissues was also observed. The tumor was finally diagnosed as a combined-type primary mixed NEC–HCC tumor. After the preoperative diagnosis, the patient underwent somatostatin receptor scintigraphy to detect the primary NEC lesion, but no accumulation was found in any other part of her body. She has been free of recurrence for 9 months since the surgery. Conclusion Mixed HCC–NEC tumors are extremely rare, and correct diagnosis requires multidisciplinary collaboration. The accumulation of further cases is needed to help understand the exact pathology, diagnosis, and treatment of this disease.

Introduction: Total mesorectal excision is the standard treatment for clinical T2 (cT2) rectal cancer; however, this procedure can result in postoperative dysfunction, decreased quality of life, and stoma creation in some patients. We investigated neoadjuvant chemoradiotherapy (nCRT) plus local excision (LE) as an alternative treatment strategy for patients with cT2N0 rectal cancer. Method: Fifty-six patients with cT2N0M0 rectal cancer who exhibited the following characteristics (an anal verge of ≤8 cm, tumor size of 2) or S-1 (tegafur/gimeracil/oteracil; 80 mg/m2). Results: Fifty-five patients (98%) completed nCRT as planned. Histologically, the excision margin was negative in all patients, and four patients with ypT3 disease underwent total mesorectal excision. Recurrence was observed in 15 patients (27%), local recurrence in 7 (13%), and distant recurrence in 10 (18%). The salvage surgery was possible for the local recurrence group. The 5-year disease-free and overall survival rates were 68.4% and 84.9%, respectively. Multivariate analysis showed that only the tumor regression grade (TRG) was an independent risk factor for recurrence (p = 0.025). Although 7 (26%) out of 27 patients with a TRG of 3 or 4 developed local recurrence and 6 (22%) had distant metastasis, 25 patients with a TRG of 1 or 2 did not exhibit local recurrence, and only 1 (4%) experienced distant metastasis. Conclusion: nCRT plus LE may be an alternative treatment for patients with cT2N0 rectal cancer who achieved a TRG of 1 or 2. However, additional treatment was required in patients who achieved a TRG of 3 or 4.

Aim This study aimed to evaluate the association between surgeons certified via the Endoscopic Surgical Skill Qualification System (ESSQS) of the Japan Society for Endoscopic Surgery (JSES) and surgical outcomes of laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR). Methods Japanese National Clinical Database data on the patients undergoing LDG and LLAR between 2014‐2016 were analyzed retrospectively. The proportion of cases performed by ESSQS‐certified surgeons was calculated for each procedure, and clinicopathological factors with or without participation of ESSQS‐certified surgeons as an operator were assessed. Then, effects of operations performed by ESSQS‐certified surgeons on short‐term patient outcomes were analyzed using generalized estimating equations logistic regression analysis. Results There were 110 610 and 65 717 patients who underwent LDG and LLAR, respectively. The operations performed by ESSQS‐certified surgeons in each procedure totaled 28 467 (35.3%) and 12 866 (31.2%), respectively. A multivariable logistic regression model showed that odds ratios of mortality for LDG and LLAR performed by ESSQS‐certified surgeons were 0.774 (95% CI, 0.566‐1.060, P = 0.108) and 0.977 (0.591‐1.301, P = 0.514), respectively. Odds ratios for secondary endpoints of anastomotic leakage in LDG and LLAR performed by ESSQS‐certified surgeons were 0.835 (95% CI, 0.723‐0.964, P = 0.014) and 0.929 (0.860‐1.003, P = 0.059), respectively, whereas that of ileus/bowel obstruction for LLAR performed by ESSQS‐certified surgeons was 1.265 (1.132‐1.415, P, This study aimed to evaluate the association between surgeons certified via the Endoscopic Surgical Skill Qualification System (ESSQS) of the Japan Society for Endoscopic Surgery (JSES) and surgical outcomes of laparoscopic distal gastrectomy (LDG) and laparoscopic low anterior resection (LLAR). The ESSQS contributes to favorable outcomes regarding anastomotic leakage following LDG and LLAR.

Introduction Although partial cystectomy has been performed by laparoscopy in patients with benign disease, there have only been a few reports regarding the laparoscopic partial resection of urinary bladder–adherent colorectal cancer. This study was conducted to evaluate the short-term surgical outcomes of laparoscopic partial resection of urinary bladder–adherent colorectal cancer. Case presentation Between April 2014 and February 2017, 6 patients with colorectal cancers that were adherent to the urinary bladder underwent laparoscopic colorectal cancer resection combined with partial cystectomy. Their surgical outcomes were reviewed retrospectively. The primary colorectal cancer was located in the sigmoid colon in 5 patients and the upper rectum in 1 patient. None of the patients required conversion to open surgery. The median duration of surgery was 411 minutes, and the median amount of intraoperative blood loss was 284 mL. In the patients with sigmoid colon cancer, the bladder was primarily closed under direct visualization via the small lower abdominal incision used to remove the tumor. In the patient with upper rectal cancer, the bladder was primarily closed laparoscopically. None of the patients demonstrated urinary leakage on retrograde cystography or anastomotic leakage, and there were no cases of perioperative mortality or morbidity. None of the patients developed recurrence of cancer at the median follow-up of 21 months. Conclusion Laparoscopic partial resection of urinary bladder–adherent colorectal cancer produces good short-term outcomes without increasing morbidity. Performing bladder closure under direct visualization via a small lower abdominal incision might be useful in selected patients.

Introduction: There are several reports on the use of the over-the-scope clip (OTSC) for gastrointestinal bleeding/fistula and endoscopic iatrogenic perforation. However, there are almost no reports on OTSC use for anastomotic leakage (AL) after colorectal cancer surgery. The purpose of this study was to evaluate the outcome of AL closure using the OTSC.Material and methods: Five patients who had undergone AL after laparoscopic surgery for colorectal cancer from April 2017 to April 2019 were evaluated.Results: The average distance from the anal verge of the anastomosis site was 12 (5-18) cm. The average diameter of the dehiscent part was 10.9 (9.3-14.4) mm. The average number of OTSC days after the occurrence of AL was 11 (5-22). On the contrast examination immediately after OTSC, all cases were completely closed, but in the later contrast examination, only one case remained completely closed. The average incompletely closed diameter was 3.6 (2.9-5.1) mm, and the diameter of the dehiscent part was reduced in all cases. Only one patient ultimately underwent colostomy; the rest were cured with OTSC alone.Conclusion: AL site closure using the OTSC after colorectal cancer surgery is a useful minimally invasive treatment when combined with appropriate drain management.

Carcinosarcoma of the gallbladder (CSGB) is very rare, accounting for less than 1% of gallbladder malignancies. Therefore, the biological behavior is not well known. We report the case of a patient with CSGB who showed long-term survival after treatment with surgery and postoperative adjuvant chemotherapy.A 79-year-old man was referred to our department with suspected gallbladder cancer after undergoing positron emission tomography-computed tomography (PET-CT) scan for preoperative examination of lung cancer, which showed strong accumulation in the gallbladder. Abdominal contrast-enhanced computed tomography (CT) demonstrated a heterogeneous enhanced, 25-mm mass in the anterior wall of the gallbladder fundus. Cholecystectomy and hepatoduodenal mesenteric lymph node sampling revealed a polypoid tumor. Histopathological findings showed a mixture of adenocarcinoma and sarcoma with spindle-shaped cells. Immunohistochemical s taining of the s arcoma s howed negative results for the epithelial markers and positive results for the mesenchymal markers, leading to a diagnosis of true CSGB. We administered S-1 as postoperative adjuvant chemotherapy and was reported to be alive 45 months after surgery without recurrence.CSGB has a poor prognosis, but if radical resection can be performed, there is a possibility of long-term survival. Further case studies and treatment options are needed to help understand this disease.

There is a paucity of evidence pertaining to long-term survival outcomes of laparoscopic versus open surgery for locally advanced rectal cancer.This study aimed to evaluate the long-term survival outcomes of laparoscopic surgery for locally advanced rectal cancer and to investigate the recurrence pattern.This was a prospective analysis of a registered cohort.This study was conducted at 69 institutions across Japan.A total of 1500 patients with clinical stage II-III rectal cancer located below the peritoneal reflection between January 2010 and December 2011 were included. After propensity score matching, all eligible patients, including the matched patients registered in 2014, were prospectively followed up.Five-year relapse-free survival was the primary outcome.The median follow-up period was 5.6 years. Among the 964 matched patients, the 5-year relapse-free survival was 65.1% in the open group versus 63.5% in the laparoscopic group (HR 1.04; p = 0.71). Distant recurrences at rare sites, which were more frequently observed in the laparoscopic group, were significantly less salvaged (adjusted OR 0.74; p = 0.045). Postrecurrence 5-year overall survival was significantly better for patients who underwent salvage surgery than for those who did not; 55.3% vs 29.5% for patients with initial local recurrence ( p = 0.03) and 64.4% vs 30.7% for patients with distant recurrence alone ( p0.001).Potential heterogeneity and influence of unknown confounding.Five-year follow-up data demonstrated that laparoscopic surgery for locally advanced rectal cancer was safely performed in terms of long-term prognosis. In addition, salvage surgery for recurrent lesions was associated with prolonged postrecurrence survival, both in patients with local and distant recurrence. However, recurrence at rare sites may require further investigation. See Video Abstract at http://links.lww.com/DCR/B793 .ANTECEDENTES:Existe una escasez de pruebas relacionadas con los resultados de supervivencia a largo plazo de la cirugía laparoscópica versus abierta para el cáncer de recto localmente avanzado.OBJETIVO:Este estudio tuvo como objetivo evaluar los resultados de supervivencia a largo plazo de la cirugía laparoscópica para el cáncer de recto localmente avanzado e investigar el patrón de recurrencia.DISEÑO:Fue un análisis prospectivo de una cohorte registrada.ENTORNO CLÍNICO:El estudio se llevó a cabo en 69 instituciones en todo Japón.PACIENTES:Se incluyó un total de 1500 pacientes con cáncer de recto en estadio clínico II-III ubicados por debajo de la reflección peritoneal, entre enero del 2010 y diciembre del 2011. Después del pareamiento por puntaje de propensión, se realizó un seguimiento prospectivo de todos los pacientes elegibles, incluidos los pacientes emparejados registrados en 2014.PRINCIPALES MEDIDAS DE VALORACIÓN:La supervivencia sin recaídas a cinco años fue el resultado primario.RESULTADOS:El período de seguimiento medio fue de 5,6 años. Entre los 964 pacientes emparejados, la supervivencia libre de recaída a 5 años fue del 65,1% en el grupo abierto frente al 63,5% en el grupo laparoscópico (cociente de riesgo 1,04; p = 0,71). Las recurrencias a distancia en sitios raros, que se observaron con mayor frecuencia en el grupo laparoscópico, tuvieron menor sobrevida (razón de posibilidades ajustada 0,74; p = 0,045). La supervivencia general a los 5 años después de la recidiva fue significativamente menor en los pacientes sometidos a una cirugía de rescate; 55,3% frente al 29,5% para los pacientes con recidiva local inicial ( p = 0,03) y 64,4% frente al 30,7% para los pacientes con recidiva a distancia sola ( p0,001).LIMITACIONES:Potencial heterogeneidad e influencia de factores de confusión desconocidos.CONCLUSIONES:El seguimiento a cinco años demostró que la cirugía laparoscópica para el cáncer de recto localmente avanzado es segura en términos de pronóstico a largo plazo. Además, la cirugía de rescate de las lesiones recurrentes se asoció con una mayor supervivencia posrecurrencia, tanto en pacientes con recurrencia local como a distancia. Sin embargo, la recurrencia en sitios raros puede requerir una mayor investigación. Consulte Video Resumen en http://links.lww.com/DCR/B793 . (Traducción- Dr. Ingrid Melo ).

[Background] Smoking is an established risk factor for breast cancer incidence. As for breast cancer prognosis, the effect of patient’s smoking on her mortality is also substantial. However, there are very few reports of investigating patient’s smoking and smoking cessation effects on breast cancer recurrence, especially those with controlling for treatment effects. [Methods] We conducted a prospective cohort study (Cohort 05 of the Rainbow of KIBOU study) for the patients enrolled in the N-SAS BC 05 trial (AERAS, UMIN:000000818). The N-SAS BC 05 trial is the randomized multi-center open-label phase III trial to assess the effect of the extended use of anastrozole for an additional 5 years where postmenopausal patients with stage I-III, hormone-receptor-positive breast cancer, disease-free after 5 years of either anastrozole alone or tamoxifen 2-3 years followed by anastrozole 3-2 years were randomized to continual group with anastrozole for an additional 5 years or stop group without an additional anastrozole. Our primary end point was disease-free survival. Since the data came from well controlled randomized trial of treatment comparison, precise recurrence and treatment data were available. [Results] We enrolled 1,510 women from the participants of the NSAS BC 05 trial. After a median follow up of 5.1 years, there were 144 events including breast cancer recurrences, secondary cancers, and deaths. The 5-year disease-free survival rates from the entry of the study (10 year from diagnosis) were 89.4% (95% confidence interval [CI], 87.4 to 91.5) in nonsmokers, 87.7% (95% CI: 82.0 to 93.4) in quitters (both before and after diagnosis), and 76.1% (95% CI, 62.7 to 89.4) in smokers (P=0.02 by a two sided log-rank test). Hazard ratios are 2.13 (95% CI, 1.14 to 3.97) for smokers and 1.35 (95% CI, 0.83 to 2.20) for quitters compared to nonsmokers after controlling treatment and age effects. If the quitters were divided into two groups by the time of cessation, hazard ratios are 1.31 (95% CI, 0.74 to 2.34) for those who quitted before diagnosis and 1.47 (95% CI, 0.64 to 3.34) for those who quitted after diagnosis. The results were not substantially changed if the events were restricted to recurrence. [Conclusion] Ten year disease-free survival for smokers was significantly worse than that of nonsmokers after almost perfectly controlling treatment effects. Compared to that, 10 year disease-free survival for quitters was not different from that of nonsmokers. The risk was decreased if they quit smoking even after diagnosis. Our study shows the importance of smoking cessation for breast cancer patients. Citation Format: Yuri Mizota, Takuji Iwase, Yasuo Ohashi, Hirofumi Mukai, Seiichiro Yamamoto. The effects of smoking and smoking cessation on postmenopausal breast cancer recurrence -Results from the Cohort 05 of the Rainbow of KIBOU (ROK) study: A prospective breast cancer survivor cohort in Japan [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-36.

Background: In patients with colorectal cancer, the rate of recurrence increases as the histologic stage progresses. However, the prediction of recurrence in individual patients is difficult. Many studies have reported on the relation between outcomes and tissue-infiltrating lymphocytes (TILs). The aim of our study was to clarify the relation between TILs and oncologic outcomes in patients with colon cancer using propensity score matching analysis. Methods: The study group comprised 513 patients with colon cancer who received curative resection. By using propensity score matching for sex, age, tumor location, T stage, N stage, histologic type, and adjuvant therapy as conventional prognostic factors, 61 patients with recurrence and 61 patients with no recurrence were selected. Hematoxylin-eosin staining and immunohistochemical staining using CD3, CD8, CD4, and FoxP3 were performed for lymphocytes in the primary tissue. The results were evaluated separately in the whole tumor, the central part, and the invasive margin. Results: The median follow-up period was 53 months. Among the 513 patients, 70 had recurrence and 443 had no recurrence. In the comparison of outcomes between the 61 patients with recurrence and the 61 patients with no recurrence, univariate analysis showed that the disease-free survival rate was significantly higher among the patients with positive TILs in the whole tumor and in the invasive margin (p = 0.016 and p = 0.012, respectively) and with CD8+ cells in the central part (p = 0.039) than among those with negative results. A multivariate analysis showed that TILs in the invasive margin (hazard ratio 1.81; 95% confidence interval, 1.03–3.05; p = 0.037) and CD8+ cell density in the central part (hazard ratio 1.76; 95% confidence interval, 1.07–2.93; p = 0.023) were prognostic factors that were independent from conventional prognostic factors. Conclusions: In patients with curatively resected colon cancer, TILs in the invasive margin and CD8+ cell density in the central part may be prognostic factors suggesting host antitumor immune response.

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision surgery is a standard treatment for locally advanced rectal cancer (LARC). Tumor-infiltrating lymphocytes (TILs) have been reported to be associated with tumor response; however, this remains to be established. We previously reported that histological changes on biopsy specimens obtained 7 days after starting nCRT are strong predictors of response to nCRT. Methods: The subjects were 208 patients with LARC who received nCRT. TILs on hematoxylin-eosin staining together with immunohistochemical staining of lymphocyte surface markers including CD3, CD4, CD8, and FoxP3 were performed both on the biopsy specimens before and 7 days after starting nCRT. Results: The proportions of patients with high densities of CD3+, CD4+, CD8+, and FoxP3+ cells 7 days after starting CRT were significantly lower than the respective values before starting nCRT (p < 0.0001, p < 0.0001, p = 0.0023, and p = 0.0046). In biopsy specimens obtained before treatment, high-density CD4+ cells and FOXP3+ cells were significantly associated with tumor shrinkage rate. High-density FOXP3+ cells were significantly associated with marked tumor regression. In biopsy specimens obtained 7 days after starting treatment, high-density CD4+ cells were significantly associated with marked tumor regression, tumor regression grade 1, and tumor shrinkage rate. High-density FoxP3+ cells were significantly associated with marked tumor regression and tumor shrinkage rate. Conclusions: In patients who received nCRT for LARC, the evaluations of immunohistochemical staining for CD4+ and FOXP3+ TILs were more intimately related to histological response to CRT and tumor shrinkage rates in biopsy specimens obtained 7 days after starting treatment than in biopsy specimens obtained before CRT.

Background Conventional lymphangiography cannot detect leakage sites of hepatic lymphatic vessels. Percutaneous transhepatic lymphangiography can be used to visualize leakage sites, and once the leakage site has been confirmed, effective sclerotherapy can be performed. Case presentation A rare case of intractable hepatic lymphorrhea due to injury of the hepatoduodenal ligament following pancreaticoduodenectomy is reported. Drainage of massive ascites from the drainage tube continued after surgery. Percutaneous transhepatic lymphangiography visualized the intrahepatic lymphatic vessels and the leakage site at the hepatic hilum. An 8-Fr drainage catheter was inserted adjacent to the leakage point under fluoroscopic computed tomography guidance. Repeated sclerotherapy using intraperitoneal administration of OK-432 (picibanil) through the catheter was performed, which exposed the leakage site, and control of the ascites was finally achieved. Conclusions To the best of our knowledge, this is the first successful case of detection of a leakage site using intrahepatic lymphangiography, followed by sclerotherapy using OK-432.

Background/aim Intracorporeal anastomosis (IA) in laparoscopic colectomy for colon cancer is technically difficult, and there is a lack of consensus on the risk of bacterial contamination and cancer cell dissemination. In this study, short- and long-term outcomes of IA were examined. Patients and methods Short and long-term outcomes of those who underwent IA (n=44) or extracorporeal anastomosis (EA) (n=61) were compared. Results IA was better than EA for blood loss, incision length, and first stool. Maximum temperature and C-reactive protein on postoperative day 1 were higher for the IA group. The rate of positive cultures from intraoperative lavage was higher for IA. The rate of positive cultures improved to an equivalent level by replacing mechanical pretreatment with chemical pretreatment. IA and EA were equivalent for the results of ascites cytology from lavage. Conclusion With the use of appropriate preoperative treatment, IA takes advantage of the minimally invasive nature of laparoscopic surgery.

Studies to date have shown that individual invitation (call) and re-invitation (recall) are effective in improving cancer screening rate. Also, by dividing subjects into segments and sending unique messages to each segment, the cancer screening rate is further improved. However, this approach is not realistic in the local governments due to limited resources, so we used social marketing and nudge techniques to develop cancer screening recommendation materials that do not need to send separately. This study therefore aimed to verify the effect of these materials in the real world. We compared the cancer screening rates in municipalities within Japan that used the invitation materials we developed (colorectal, breast, lung, cervical and stomach cancer), with those from the previous year. In addition, the usefulness of the materials in the real world was examined multilaterally using RE-AIM framework (Reach, Effectiveness, Adaption, Implementation, Maintenance). From 2015 to 2018, 4.3 million residents (Reach) from 787 municipalities (Adaption) were sent invitation materials for cancer screening. Of 167 municipalities that were compared, 141 (83%) showed an increase in screening rate when our materials were used. Overall, the screening rate improved by 2.6% or 1.44 fold (p 0.001) (Effectiveness). However, the screening rate varied greatly depending on how screening is provided. Of the four years studied, 75 municipalities used the same materials for two or more years (Implementation). The material developed in this study improved the cancer screening rate in the real world, and it may be possible to further improve the screening rate if the number of opportunities for screening and its capacity is increased at the timing of sending materials. The materials can be found on the website (http://rokproject.jp/kenshin/) and free electronic files are available to municipalities wishing to use them.

Managements for refractory proficient mismatch repair (pMMR) or microsatellite stable (MSS) metastatic colorectal cancer (mCRC) were still challenging and controversial. Our study sought to investigate the efficacy and safety of anti-programmed cell death protein 1 (anti-PD-1) antibodies plus regorafenib in refractory pMMR/MSS mCRC.We retrospectively analyzed the efficacy and safety of 103 pMMR/MSS mCRC patients treated with at least one dose of anti-PD-1 antibodies plus regorafenib (80 mg once daily for 21 days on/7 days off 28 days as a cycle) between July 2019 and June 2021 at the Hunan Cancer Hospital. All patients had previously received at least second-line treatment. The patients were evaluated by computed tomography every 2 or 3 treatment cycles until progression or being lost to follow-up. The primary end point was overall survival (OS).The median follow-up period was 5.30 (range, 0.50-22.50) months. The median OS (mOS) and medical progression-free survival (mPFS) were 8.40 and 2.50 months for the entire cohort, respectively. The mOS and mPFS were 16.07 and 3.10 months in patients who received1 cycle of anti-PD-1 antibodies and regorafenib (n=55), which were significantly longer than 4.37 and 1.11 months in those received only 1 cycle (n=48) (both P0.001, respectively). The Cox multivariate regression analysis demonstrated that the number of cycles of regorafenib plus PD-1 and previously undergone surgery were independent risk factors for OS, whereas Sintilimab was confirmed to have a significant better PFS compared to other anti-PD-1 antibodies. Of the 55 patients who were evaluated, 7 were diagnosed with a partial response (PR) and another 16 were diagnosed with stable disease (SD), but no patient showed a complete response (CR). Thus, the objective response rate (ORR) was 12.7% and the disease control rate was 41.8%. Treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 13 (12.6%) patients.The combination of regorafenib plus anti-PD-1 antibodies has a manageable safety profile and may improve prognosis for pMMR/MSS mCRC patients, especially those who received1 cycle. Compared to the other anti-PD-1 antibodies, sintilimab may be more efficacious; however, further prospective studies need to be conducted to confirm our findings.

Background Pulmonary metastases from pancreatic ductal adenocarcinoma (PDAC) are relatively rare. Systemic chemotherapy is the first choice of treatment in patients with distant metastases, and the role of metastasectomy is controversial. The aim of the present study was to evaluate the outcome of patients with pulmonary metastases after resection of PDAC and the indications for metastasectomy. Methods We retrospectively analysed patients with pulmonary metastases as the first recurrence after resection of primary PDAC between January 2006 and December 2018. Clinical data were obtained from the patients’ medical records. Relapse-free survival (RFS) and overall survival (OS) were analysed using the Kaplan–Meier method, and statistical significance was evaluated by the log-rank test. Results Of the 417 patients with resected PDACs, 24 (7.9%) had pulmonary metastases. Six patients (25.0%) underwent pulmonary resection and 18 (75.0%) received systemic chemotherapy and best supportive care. There were no major complications requiring therapeutic intervention after pulmonary resection. The median RFS was 24.0 months (95% CI 10.8–37.2), and the 1-, 3-, and 5-year RFS rates were 66.7%, 33.3%, and 4.2%, respectively. The median OS was 50.0 months (95% CI 15.9–84.1), and the 1-, 3-, and 5-year OS rates were 95.8%, 70.3%, and 46.4%, respectively. All patients with resected pulmonary metastases were alive at the end of the study, whereas the median OS of the patients who did not undergo resection was 37.0 months (95% CI 34.4–39.6). Therefore, patients with resected pulmonary metastases had a significantly better prognosis (p = 0.008). Conclusions Pulmonary resection may improve the prognosis in selected patients with pulmonary metastases from PDAC. However, the present study is based on a small number of patients and may include a selection bias; therefore, a multi-institutional prospective study is needed to clarify the indications for pulmonary resection.

Lateral pelvic node (LPN) dissection (LPND) is considered a promising technique for treating low rectal cancer; however, there is insufficient evidence of its prognostic value. Using centrally reviewed preoperative pelvic magnetic resonance (MR) images, this study aimed to find the patient population who has benefited from LPND. MR images of patients from 69 institutes with stage II–III low rectal cancer were reviewed by experienced radiologists. Recurrence-free survival (RFS), overall survival (OS), and short-term outcomes were measured. In total, 731 preoperative MR images were reviewed (excluding patients with short-axis LPN ≥ 10 mm). Of these, 322 underwent total mesorectum excision (TME) without LPND (non-LPND group), and 409 underwent TME with LPND (LPND group). Preoperative treatment was performed for 40% and 25% of patients in the non-LPND and LPND groups, respectively. The incidence of postoperative complications was higher in the LPND group (44.5%) than in the non-LPND group (33.2%; P = 0.002). Among patients with LPNs < 5 mm, OS and RFS curves were not significantly different between the groups. Among patients with LPNs ≥ 5 mm, the LPND group had significantly higher 5-year OS and RFS than the non-LPND group (OS: 81.9% versus 67.3%; RFS: 69.4% versus 51.6%). On multivariate analysis of LPN ≥ 5 mm cases, LPND was independently associated with RFS. Despite the high incidence of postoperative complications, this study showed the prognostic impact of LPND on low rectal cancer patients with LPNs (≥ 5 mm, < 10 mm short axis) measured by experienced radiologists. Trial registration UMIN-ID: UMIN000013919

The treatment outcomes of unresectable pancreatic cancer(URPC)have improved due to the advent of gemcitabine with nab-paclitaxel(GnP)and FOLFIRINOX as first-line therapy. There have been increasing reports of URPC responding to chemotherapy or chemoradiation and that conversion surgery(CS)can help to achieve long-term survival. This study aims to assess the treatment outcomes of URPC in our department and consider CS adaptation. Thirty-six patients with URPC who were treated with GnP or FOLFIRINOX between 2015 and 2018 were included in this retrospective analysis. Thirty-five patients had GnP, while 1 patient had FOLFIRINOX. The median age of the patients was 68.0 years and included 17 males and 19 females. Twenty-eight of the tumors were located in the pancreas head and 8 in the body-tail. Twenty-one cases were locally advanced(UR-LA), and 15 cases had distant metastases(UR-M). CS was performed in 9 cases(25.0%). The 2-year survival rate for patients that underwent CS was 53.3%, and 34.1% for patients that did not undergo CS. The prognosis of patients who underwent CS tended to be better, but there was no significant difference(p=0.141). In the patients that underwent CS, there were cases of early recurrence in which the period of preoperative chemotherapy was short, and the tumor markers were not normalized. Therefore, it is thought that prolonging preoperative treatment could help to select more suitable patients for CS.

Background: Hepatocellular carcinoma (HCC) can grow in a mosaic pattern, often combined with various non-hepatocellular cells. However, HCC combined with a neuroendocrine carcinoma (NEC) component is very rarely reported, and its clinical features, origin, diagnosis and behavior have not been established. In the literature, mixed HCC–NEC tumors are categorized as either collision type or combined type, depending on their microscopic features. Here we report a patient with a combined-type HCC–NEC tumor.Case presentation: An asymptomatic 84-year-old woman was found to have a solid mass in the right lobe of her liver. Laboratory and radiologic examinations showed findings typical of HCC, including arterial-phase enhancement, and portal- and delay-phase washout. She was preoperatively diagnosed with HCC, and treated with partial laparoscopic hepatectomy of her S5 segment. The tumor was 5.0 × 6.0 cm in diameter, and was predominantly HCC, partly admixed with a NEC component. A transitional zone between the HCC and NEC tissues was also observed. The tumor was finally diagnosed as a combined-type primary mixed NEC–HCC tumor. After the diagnosis, the patient underwent somatostatin receptor scintigraphy to look for the primary NEC lesion, but no accumulations were found in any other part of her body. She has been free of recurrence for 6 months since the surgery.Conclusion: Mixed HCC–NEC tumors are very rare. Correct diagnosis requires multidisciplinary collaboration. Accumulating cases is needed to help understand their exact pathology, diagnosis and treatment.

A 64-year-old man visited our hospital because of weight loss and after being detected with a tumor in the pancreatic body and tail on abdominal ultrasonography at a nearby hospital. Abdominal contrast-enhanced CT revealed a 45 mm tumor with celiac artery invasion in the pancreatic body and tail. This case was diagnosed as unresectable pancreatic cancer. After 2 regimens of systemic chemotherapy(5 courses of gemcitabine plus nab-paclitaxel and 2 courses of S-1), CT revealed a partial response(ie, reduction in the tumor size). Therefore, distal pancreatectomy was performed with en bloc celiac axis resection, portal vein resection, and left adrenalectomy, as well as lymph node dissection. The pathological diagnosis was adenosquamous carcinoma, and R0 resection was achieved. The histological response was Grade 1b. However, the patient developed lung metastasis 16 months after surgery and liver metastasis 18 months after surgery; he died 33 months after starting treatment.

Intussusception occurs when one part of the intestines slides into the adjacent intestine resulting in bowel obstruction. It is a rare condition in adults, accounting for only 5% of all intussusceptions. It has multiple causes, with inflammatory fibroid polyps (IFPs) very infrequently being the cause. We present a rare case of intussusception in an adult due to an IFP.A 72-year-old woman visited our hospital complaining of abdominal pain. Abdominal contrast-enhanced computed tomography (CT) demonstrated an ileo-ileal intussusception due to a round mass. An emergency surgery involving a partial ileal resection with laparoscopic assistance was performed. Pathological findings of the tumor showed proliferation of spindle-shaped cells, edematous stroma, dilation of lymphatic vessels, and infiltration of inflammatory cells, which were mainly eosinophils. Immunohistochemistry was positive for vimentin and SMA and negative for CD117, CD34, S-100, and desmin. Based on these findings, the tumor was diagnosed as an IFP.Bowel obstruction in adults due to intussusception is rare, and those due to IFPs are even more rare. Preoperative diagnosis of IFP is difficult, but surgeons must keep in mind that it can be a cause of adult intussusception.

Background In Japan, incidence of gastric cancer is expected to follow the current downward trend as the younger generation has lower incidence of Helicobacter pylori infection. In this study we aimed to estimate how long gastric cancer screening is deemed necessary in the future from epidemiologic perspectives. Methods Following the Japanese guidelines for gastric cancer screening 2014, recommendation of providing population-based gastric cancer screening is judged by balancing benefits and harms. Benefits and harms are estimated by number needed to screen (NNS)

Background:Laparoscopic surgery for rectal cancer is widely performed all over the world and several randomized controlled trials have been reported. However, the usefulness of laparoscopic surgery compared with open surgery has not been demonstrated sufficiently, especially for the low rectal area.

Fluoropyrimidine has been commonly used not only in unresectable cases of metastatic colorectal cancer, but also in adjuvant therapy. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down more than 80% of standard doses of 5-fluorouracil (5-FU) and capecitabine, an oral prodrug of 5-FU. The lack of enzymatic activity increases the half-life of the drug, resulting in excess drug accumulation and toxicity which may lead to life-threatening side effects. There have been several published case reports about DPD deficiency in patients with colorectal cancer in Western countries. However, case reports of DPD deficiency in Japanese patients with colorectal cancer are rare because measuring DPD activity is not covered by public medical insurance in Japan, and it is not examined in our daily clinical practice currently. Therefore, we think that it is important to accumulate such case reports for further understanding. This report describes the case of a Japanese patient with colon cancer who experienced severe side effects while taking capecitabine, due to DPD deficiency. A 68-year-old man with ascending colon cancer underwent curative laparoscopic right hemicolectomy. Because final pathologic staging was Stage IIIa, standard adjuvant chemotherapy with capecitabine (3600 mg/body/day, days 1–14, every 3 weeks) was started on postoperative day 50. After 2 weeks, he started to experience Grade 3 diarrhea and was admitted to the hospital on postoperative day 66. On day 70, the patient had Grade 4 febrile neutropenia. Antibiotics and granulocyte-colony-stimulating factor were administered until his blood tests recovered to the normal degree. After 1 week of diarrhea, antidiarrheal agents were administered, and the patient gradually recovered. During the occurrence of diarrhea, specimen cultures were negative for infection. He was discharged on day 21 of the hospital stay. DPD deficiency was suspected, and 2 weeks later the DPD activity of the peripheral blood mononucleocytes was examined. The result was 10.3 U/mg protein which was remarkedly low (reference range 22.6–183.6 U/mg protein), and DPD deficiency was diagnosed. We always must consider the possibility of DPD deficiency in patients who experience severe side effects while taking capecitabine.

Surgery is the standard of care for T1bN0M0 esophageal squamous cell carcinoma (ESCC), whereas chemoradiotherapy (CRT) is a treatment option. This trial aimed to investigate the noninferiority of CRT relative to surgery for T1bN0M0 ESCC.Clinical T1bN0M0 ESCC patients were eligible for enrollment in this prospective nonrandomized controlled study of surgery versus CRT. The primary endpoint was overall survival, which was determined using inverse probability weighting with propensity scoring. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissection. CRT consisted of 2 courses of 5-fluorouracil (700 mg/mFrom December 20, 2006 to February 5, 2013, a total of 368 patients were enrolled in the nonrandomized portion of the study. The patient characteristics in surgery arm and CRT arm, respectively, were as follows: median age, 62 and 65 years; proportion of males, 82.8% and 88.1%; and proportion of performance status 0, 99.5% and 98.1%. Comparisons were made using the nonrandomized groups. The 5-year overall survival rate was 86.5% in the surgery arm and 85.5% in the CRT arm (adjusted hazard ratio, 1.05; 95% confidence interval, 0.67-1.64 [1.78]). The complete response rate in the CRT arm was 87.3% (95% confidence interval, 81.1-92.1). The 5-year progression-free survival rate was 81.7% in the surgery arm and 71.6% in the CRT arm. Treatment-related deaths occurred in 2 patients in the surgery arm and none in the CRT arm.CRT is noninferior to surgery and should be considered for the treatment of T1bN0M0 ESCC.

Endoscopic submucosal dissection (ESD) has become popular as an alternative to laparoscopy-assisted colectomy (LAC) for early colorectal cancer. To validate postoperative quality of life (QOL) based on subjective symptoms of patients from questionnaire survey. We prospectively enrolled patients planned to undergo ESD for adenoma or Tis/T1a cancer at our institution between December 2011 and January 2013. Controls were prospectively enrolled LAC patients diagnosed with T1b cancer. Patients answered questionnaire survey on QOL on postoperative day (POD) 1 and POD14. Questions were scored using visual analog scale (0 points = worst condition, 100 points = best condition) and were classified into six categories: health status, mental status (MeS), motor status (MoS), bodily painless, passage and anorectal function (PAF), and stress for the treatment. Total score was also calculated. We compared the median scores among categories using the Wilcoxon rank-sum test. A total of 82 ESDs and 41 LACs were included. Median score for the factors in questionnaire (POD1/POD14) in ESDs versus LACs for colonic lesion (rectal lesion) was as follows: MeS, 74/83 versus 54/73 (72/85 vs. 42/62); MoS, 98/96 versus 51/75 (95/90 vs. 66/67); PAF, 90/96 versus 80/80 (90/95 vs. 70/53); total score, 83/91 versus 58/75 (81/87 vs. 51/66). These items showed statistical significant differences between ESDs and LACs. Postoperative QOL and symptoms are significantly better on POD1 and POD14 following ESD compared with LAC.

Mesorectal excision with lateral lymph node dissection is the standard treatment for locally advanced low rectal cancer in Japan. However, the safety and feasibility of laparoscopic lateral lymph node dissection remain to be determined.The purpose of this study was to evaluate the safety and feasibility of laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.This was a retrospective cohort study using an exact matching method.We conducted a multicenter study of 69 specialized centers in Japan.Patients with consecutive midrectal or low rectal adenocarcinoma cancer stage II to III who underwent mesorectal excision with curative intent between 2010 and 2011 were recruited.Short-term and oncological outcomes were compared between the laparoscopic and open-surgery groups.Of the 1500 eligible patients, 676 patients who underwent lateral lymph node dissection were analyzed, including 137 patients who were treated laparoscopically and 539 patients who were treated with open surgery. After matching, the patients were stratified into laparoscopic (n = 118) and open-surgery (n = 118) groups. Operative times in the overall cohort were significantly longer (461 vs 372 min) in the laparoscopic versus the open-surgery group. In the laparoscopic group, the blood loss volume was significantly smaller (193 vs 722 mL), with fewer instances of blood transfusion (7.3% vs 25.5%) compared with the open-surgery group. The postoperative complication rates were 35.8% and 43.6% for the laparoscopic and open-surgery groups (p = 0.10). The 3-year relapse-free survival rates were 80.3% and 72.6% for the laparoscopic and open-surgery groups (p = 0.07).The study was limited by its retrospective design and potential selection bias.Laparoscopic lateral lymph node dissection is safe and feasible for cancer stage II to III low rectal cancer and is associated with similar oncological outcomes as open lateral lymph node dissection. See Video Abstract at http://links.lww.com/DCR/A334.

The fluvial to marine transition zone (FMTZ) is the area of coastal rivers in which sedimentation is controlled by the interaction of fluvial and marine processes. This study examines the FMTZ of the Mekong River delta, along a total channel length of ~660 km. Methods consist of collection and analysis of channel bed sediment samples, measurements of channel morphological parameters, and recognition of mangrove, molluscan, and diatom species. The process regime, salinity, morphological, and sedimentary trends recognized were used to define two main tracts for this FMTZ: an upstream, fluvial-dominated tract and a downstream, tide-dominated tract. In more detail, they allow the identification of four subzones, from upstream to downstream: 1) fluvial-dominated, tide-affected; 2) fluvial-dominated, tide-influenced; 3) tide-dominated, fluvial-influenced; and 4) tide-dominated, fluvial-affected. Tide-induced water-level changes affect the entire study area and extend into Cambodia. Measured salinity intrusion extends ~15 km upstream of the river mouth during wet season, and ~50 km during dry season. Brackish water species of mangroves, mollusks, and diatoms, however, occur landward of these limits, suggesting that highly diluted brackish water may reach ~160 km upstream of the river mouth during the dry season. In the fluvial-dominated tract, channels are sinuous and show a seaward-deepening trend, whereas width is relatively constant. In the tide-dominated tract, channels are straight, and show seaward-widening and seaward-shallowing trends. Natural levees are present in the fluvial-dominated, tide-affected subzone, but are replaced by mangroves elsewhere along the FMTZ. In the fluvial-dominated tract, mud content is low, sand grain size fines seaward, and gravelly sand and sand are the dominant facies. In the tide-dominated tract, mud content is high, sand grain size is constant, recycled sand is common, and tidal rhythmites are the dominant facies. Mud pebbles are common in sediments throughout a large part of the FMTZ. These trends characterizing the FMTZ of the Mekong River delta seem to be present in other systems and likely represent a general FMTZ pattern. Nonetheless, minor differences may be observed between different types of systems, or because of differences in local conditions. The comprehensive description of trends and their mutual relationships along the FMTZ presented herein provides critical information that can form the basis of a general conceptual model and can help to better understand these complex zones.

The aim of this study was to determine the risk factors for anastomotic leakage after laparoscopic rectal surgery.We conducted a prospective trial involving 395 patients with stage 0/I rectal carcinoma who underwent laparoscopic low anterior resection using a double stapling technique. Data concerning variables related to patient background, tumors and surgical factors were evaluated. The outcomes with respect to anastomotic leakage were recorded, and univariate and multivariate analyses were performed to identify relevant risk factors.The overall anastomotic leakage rate was 8.4%. A univariate analysis showed male gender (P = 0.006) and preoperative blood sugar level (P = 0.0034) to be significantly associated with anastomotic leakage. The variables of gender, preoperative blood sugar level, American Society of Anesthesiologists (ASA) classification (P = 0.15), transanal decompression tube (P = 0.06) and number of stapler cartridges used for rectal transection (P = 0.18) were selected for the multivariate analysis because of their P values being0.2. The multivariate analysis identified male gender (odds ratio 4.12, P = 0.006) and the absence of a transanal decompression tube (odds ratio 3.11, P = 0.0484) as independent risk factors predicting anastomotic leakage.Male gender and the absence of a transanal decompression tube appeared to be independent risk factors for anastomotic leakage. Insertion of a transanal decompression tube may help prevent anastomotic leakage after low anterior resection, particularly in male patients.

Purpose Screening programs using fecal occult blood testing help reduce mortality from colorectal cancer (CRC). Colonoscopy and colonoscopy combined with fecal occult blood testing are considered alternatives with higher sensitivity than fecal tests; however, to our knowledge, randomized controlled trials (RCTs) providing such evidence have not been reported. Therefore, this study aimed to compare screening using the fecal immunochemical test (FIT) combined with colonoscopy and FIT alone to evaluate the efficacy of colonoscopy screening in reducing CRC mortality. Methods This multicenter, prospective, randomized, controlled study included average-risk individuals for CRC living in the study areas and aged 40–74 years. The exclusion criteria were history of CRC, hereditary non-polyposis CRC, familial adenomatous polyposis, inflammatory bowel diseases, history of cancer other than CRC within the past 5 years, and not expected to survive from comorbid illness. The intervention group underwent one-time colonoscopy and annual FIT, while the control group underwent annual FIT. The primary endpoint was mortality from CRC, while the secondary endpoints were cumulative incidence of invasive CRC, advanced CRC (invasion into the muscle layer or deeper), invasive cancer and screening sensitivities and specificities of invasive CRC, whole CRC, advanced neoplasia, and prevalence of adverse events. The intervention and control groups comprised 4876 and 4875 participants, respectively. Conclusion This explanatory RCT evaluated the efficacy of colonoscopy screening by valid statistical inference based on randomization. Data on adverse events from this kind of screening are necessary when considering implementation of future screening programs. Trial registration UMIN Clinical Trials Registry, number UMIN000001980.

Introduction In recent years, laparoscopic surgery (LS) has been performed for small bowel obstruction (SBO). However, the indications and short-term and long-term outcomes of LS for SBO have not yet been established. Aim To evaluate the usefulness of LS for SBO compared to open surgery (OS), as well as to identify risk factors for poor outcomes after LS. Material and methods A total of 105 patients who underwent surgery for SBO were divided into OS (n = 64) and LS (n = 41) groups, and propensity score-matched analysis was used to compare the short-term and long-term outcomes of the groups. Risk factors for conversion to OS, postoperative complications, and intraoperative bowel injury in LS were also identified. Results The incidences of surgical site infection and postoperative ileus were significantly lower in the LS group. The incidence of recurrent bowel did not differ significantly between the two groups. Prior bowel obstruction was a risk factor for conversion of LS to OS (odds ratio (OR) = 24.79, p = 0.0025). Bowel diameter was a risk factor for postoperative complications (OR = 1.50, 95% CI: 1.01-2.22) and for bowel injury (OR = 1.33, 95% CI: 1.05-1.67). Conclusions LS for SBO had better postoperative short-term outcomes than OS. The outcomes of LS for SBO were significantly affected by prior bowel obstruction and bowel diameter.

Intracorporeal anastomosis (IA) in laparoscopic colectomy for colon cancer is technically difficult, and there is a lack of consensus on the risk of bacterial contamination and cancer cell dissemination. In this study, short- and long-term outcomes of IA were examined.Short and long-term outcomes of those who underwent IA (n=44) or extracorporeal anastomosis (EA) (n=61) were compared.IA was better than EA for blood loss, incision length, and first stool. Maximum temperature and C-reactive protein on postoperative day 1 were higher for the IA group. The rate of positive cultures from intraoperative lavage was higher for IA. The rate of positive cultures improved to an equivalent level by replacing mechanical pretreatment with chemical pretreatment. IA and EA were equivalent for the results of ascites cytology from lavage.With the use of appropriate preoperative treatment, IA takes advantage of the minimally invasive nature of laparoscopic surgery.

Fluoropyrimidine has been commonly used not only in unresectable cases of metastatic colorectal cancer, but also in adjuvant therapy. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down more than 80% of standard doses of 5-fluorouracil (5-FU) and capecitabine, an oral prodrug of 5-FU. The lack of enzymatic activity increases the half-life of the drug, resulting in excess drug accumulation and toxicity which may lead to life-threatening side effects. There have been several published case reports about DPD deficiency in patients with colorectal cancer in Western countries. However, case reports of DPD deficiency in Japanese patients with colorectal cancer are rare because measuring DPD activity is not covered by public medical insurance in Japan, and it is not examined in our daily clinical practice currently. Therefore, we think that it is important to accumulate such case reports for further understanding. This report describes the case of a Japanese patient with colon cancer who experienced severe side effects while taking capecitabine, due to DPD deficiency. A 68-year-old man with ascending colon cancer underwent curative laparoscopic right hemicolectomy. Because final pathologic staging was Stage IIIa, standard adjuvant chemotherapy with capecitabine (3600 mg/body/day, days 1–14, every 3 weeks) was started on postoperative day 50. After 2 weeks, he started to experience Grade 3 diarrhea and was admitted to the hospital on postoperative day 66. On day 70, the patient had Grade 4 febrile neutropenia. Antibiotics and granulocyte-colony-stimulating factor were administered until his blood tests recovered to the normal degree. After 1 week of diarrhea, antidiarrheal agents were administered, and the patient gradually recovered. During the occurrence of diarrhea, specimen cultures were negative for infection. He was discharged on day 21 of the hospital stay. DPD deficiency was suspected, and 2 weeks later the DPD activity of the peripheral blood mononucleocytes was examined. The result was 10.3 U/mg protein which was remarkedly low (reference range 22.6–183.6 U/mg protein), and DPD deficiency was diagnosed. We always must consider the possibility of DPD deficiency in patients who experience severe side effects while taking capecitabine.

To assess intra-tumoral heterogeneity (ITH) via fractal analysis of preoperative contrast-enhanced computed tomography (CT) images to predict pathological grades in non-functioning pancreatic neuroendocrine tumors (NF-PNETs) and verify its impact on patient survival.This retrospective study enrolled 40 patients with NF-PNET resected in our institution during a period from July 2005 to December 2018, except functioning tumors, unidentified tumors in CT, patients without preoperative contrast-enhanced CT. CT images were analyzed using plugin software for calculating fractal dimension (FD), and the maximum value was denoted as "FDmax," and compared with pathological grades and patient survival between G1 and G2/3 group separating according to two different Ki-67 index thresholds (3% and 5%). All CT images were acquired in three-phases and arterial phase images were examined.Ki-67 index and FDmax showed a direct correlation with significance (p 0.01). The mean FDmax of the G2/3 tumor group was significantly higher than that of the G1 tumor group (p 0.01 in both 3% and 5% thresholds). In the ROC analysis, FDmax showed 0.773 of AUC, and cut-off value of 1.036 reported 62.5 % sensitivity, 90.0 % specificity, 86.2 % PPV, and 70.6 % NPV to distinguish G2/3 patients. The high-FD (≥1.036) group showed a significantly shorter disease-free survival (DFS) than the low-FD group (p = 0.0128). In multivariate analysis of prognostic factors, high FD was the only significant factor for DFS (HR, 5.793; 95 % CI: 1.213-27.664; p = 0.028).The tumor's FDmax using CE-CT analysis might be a potential biomarker for preoperative prediction of G2/3 tumors, and predicting recurrence.

[Background] Past studies revealed that a moderate to high level of physical activity after diagnosis of breast cancer reduces both the risk of breast cancer-related death and death from all causes. Furthermore, some randomized studies suggested that exercise programs improve the percentage of patients who complete the chemotherapy and quality of life, and decrease fatigue, and adverse events. The issues to be determined include defining an established uniform exercise program and the efficacy of a long-term exercise program after breast cancer surgery. [Object] To elucidate the efficacy of a long-term exercise program and to verify the safety and feasibility of a uniform exercise program using an ‘existing social resource’ after primary therapy of breast cancer. [Design] A multi-center, randomized trial. [Method] Subjects: The subjects included patients who had completed treatment for primary breast cancer, including surgery and/or adjuvant chemotherapy. Patients with metastatic breast cancer were excluded. Randomization & intervention: The patients were randomly assigned to three groups. The first group followed an exercise program at Curves® that involved 30 minutes of exercise, including aerobics, weight training, and stretching 3 times a week for 4 months. The second group was given life-style guidance at least once that patients participate in a lecture program about recommended exercise at this point and the importance of weight control after diagnosis of breast cancer using a brochure. The third group served as controls that the patients receive a brochure used same one in the second group. The variables included age and weight. Outcome: The primary endpoint is level of physical activity at 1 year after randomization, and the secondary endpoints are the percentage of those completing the exercise program, patient reported outcomes (QOL, cancer or treatment associated symptoms, fatigue, depression, and anxiety), body mass index, bone density, and level of lymphedema. Period of research: The study will last 2 years beginning March 2016. Sample size: We plan to enroll 400 patients to detect 20% difference with 90% power. Additional study: Some biochemical markers in the blood will be evaluated to determine the mechanism of the effect of exercise on the human body. Citation Format: Kawada K, Taira N, Hatono M, Takahashi Y, Miyoshi Y, Nogami T, Iwamoto T, Motoki T, Sien T, Matsuoka J, Doihara H, Ikeda M, Ogasawara Y, Takabatake D, Yoshitomi S, Kiyoto S, Yamamoto S, Mizota Y, Oka K. Influence of exercise or educational programs on long-term physical activity by patients after surgery for primary breast cancer: A randomized trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT3-07-02.

Introduction The optimal surgical management strategy for isolated para-aortic lymph node (PALN) metastases from colorectal cancer (CRC) remains unclear. However, the complication rates for open approaches remain high. In this study, the outcomes of laparoscopic para-aortic lymphadenectomy in patients with clinically suspected PALN metastasis were evaluated. Methods Between April 2013 and April 2018, we performed laparoscopic primary resection and para-aortic lymphadenectomy in 11 patients with advanced colorectal cancer and clinically suspected PALN metastasis. This study was a single-center, retrospective, case series analysis, and the surgical outcomes were reviewed. Results There were no cases of perioperative mortality, and conversion to open surgery was necessary in only one patient (9%) because of invasion into a rib. One patient (9%) required a blood transfusion. Postoperative complications occurred in three patients, and the morbidity rate was 27% (3/11). Pathologically, PALN metastasis was confirmed in five patients (45%), all of whom received postoperative chemotherapy. The median survival time for all patients was 25 months, and one patient died of recurrence at 25 months after the initial surgery. Two other patients were alive with recurrence after 47 and 36 months, and two patients were alive without recurrence after 17 and 2 months. Conclusion Laparoscopic para-aortic lymphadenectomy for advanced colorectal cancer with clinically suspected PALN is technically feasible and may be beneficial in selected patients. It is necessary to investigate the feasibility of this procedure in a future case series, and information regarding true oncologic outcome will require long-term follow-up.