Koichiro Niwa

Formation of the venous thrombus after venous occlusion in the experimental mouse model of metabolic syndrome

INTRODUCTION The metabolic syndrome is considered to be a risk factor for the venous thromboembolism (VTE) as well as arterial thrombosis. Although obesity, hyperglycemia and dyslipidemia are considered to be important triggering factors, it is difficult to evaluate the relationship between VTE and the metabolic syndrome in a clinical study. Furthermore the mechanism of venous thrombosis initiation still remains elusive. MATERIALS AND METHODS 20 min clamp of superior mesenteric vein was applied to 7 w, 16 w-old KK-A(y) mouse and 16 w-old B6J mouse (n = 6 in each group), after de-clamp, the view of the mesenteric vein and intestinal submucosal venule were observed by the intravital microscopy. RESULTS Massive thrombi formed in the mesenteric vein in 16 w-old KK-A(y) mice, moderate thrombi formation was observed in 7 w-old KK-A(y) mice, while very few thrombi were observed in B6 J mice. The first event in submucosal venule after de-clamp was the adhesion of leukocytes to the endothelium. Subsequently, leukocytes assembled and platelets covered the leukocyte cluster. These leukocyte-platelet aggregates move from the venule to the vein and finally formed a venous thrombus. CONCLUSION Metabolic syndrome is a risk factor for venous thrombosis. Intravital microscopic examination revealed leukocyte and platelet recruitment to the venule in the early stages of venous thrombosis formation.

Investigation of free cancer cells in peripheral blood using CEA mRNA expression in perioperative colorectal cancer patients

The aim of this study was to evaluate the impact of laparoscopic surgery (Lap) on circulating free tumor cells in colorectal cancer patients. In this study, we selected carcinoembryonic antigen (CEA) mRNA expression in peripheral blood as the marker of the circulating tumor cells and compared this marker between Lap and open colectomy (OC), to investigate differences due to surgical approach. A total of 50 patients underwent curative surgery for solitary colorectal cancer at our department, between June, 2008 and February, 2011. The patients were divided into OC and Lap groups (25 patients each). Total RNA was extracted subsequent to peripheral blood collection prior to surgery, immediately following surgery and 1, 3 and 7 days after surgery. CEA mRNA was detected with reverse transcription polymerase chain reaction (RT-PCR) and the association between peripheral blood CEA mRNA-positive rate, surgical findings and clinicopathological characteristics was investigated. The peripheral blood CEA mRNA-positive rate was significantly increased immediately after surgery, compared to the preoperative rate (P=0.001), but decreased over time. No significant differences were observed at any blood-sampling time point after postoperative day 1. The positive rate was significantly increased in the OC group immediately after surgery, compared to the preoperative rate (P=0.004). However, there were no significant differences between the rates prior to and immediately after surgery in the Lap group. The patients were then divided into those who were peripheral blood CEA mRNA-positive and -negative after surgery (postoperative positive and negative groups, respectively) and the clinicopathological characteristics were compared. Significant differences were identified between the groups in lower rectal cancer patients and patients with a large intraoperative blood loss (P=0.001 and P=0.01, respectively). In conclusion, in colorectal cancer patients, there were no significant differences in the perioperative peripheral blood CEA mRNA-positive rate or its short-term changes between patients undergoing OC and Lap surgery. It was suggested that Lap is equivalent to OC with regard to free cancer cells.

Ascending Colon Cancer Associated with Dermatomyositis Which Was Cured after Colon Resection

A 76-year-old woman with muscle ache, weakness of the extremities, and skin rash was diagnosed with dermatomyositis (DM). Upon the diagnosis of DM, a systemic survey of malignancy revealed an advanced carcinoma of the ascending colon. The patient underwent right hemicolectomy approximately 2 months after the onset of DM. The symptoms and signs of DM disappeared after the surgery without additional therapy. DM is an idiopathic systemic inflammatory disease characterized by muscle ache, muscle weakness, and skin rash. In some cases, DM develops as paraneoplastic syndrome, and it is assumed that 30% of DM patients have cancer. Symptoms and signs of DM can be attenuated by treatment of the malignancy, and they reappear if the malignancy recurs. It is essential to perform a systemic survey of malignancy in DM patients, and treatment of the malignancy has to precede treatment of DM.

Combined laparoscopic abdominoperineal resection and robotic-assisted prostatectomy for synchronous double cancer of the rectum and the prostate.

Here we report a combined laparoscopic abdominoperineal resection and robotic‐assisted prostatectomy. A 74‐year‐old man was diagnosed with T4b low rectal and prostate cancer. The operation was performed after neoadjuvant chemotherapy for the rectal cancer. The procedure used eight ports in total, five for laparoscopic abdominoperineal resection and six for robotic‐assisted prostatectomy. First, laparoscopic total mesorectal excision including division of the inferior mesenteric artery was performed, and then, robotic dissection of the prostate was performed. The en bloc specimen was removed through the perineal wound. Then, robotic urethrovesical anastomosis was performed. An extraperitoneal end colostomy was created to finish the operation. The operating time was 545 min, and blood loss was 170 mL. The postoperative course was uneventful, and the patient discharged on postoperative day 17. The combined laparoscopic abdominoperineal resection and robotic‐assisted prostatectomy were performed safely without any additional technical difficulty, as both procedures shared port settings and patient positions.

Unusual False-Positive Mesenteric Lymph Nodes Detected by PET/CT in a Metastatic Survey of Lung Cancer.

Positron emission tomography/computed tomography (PET/CT) is a credible diagnostic modality for detecting primary and metastatic malignancy. PET/CT sometimes shows false positives and negatives, which make clinical diagnosis difficult. A 42-year-old man who had undergone right upper lobectomy for lung cancer 1 year previously had PET/CT for a metastatic survey of the lung. The lung cancer was stage IB (pT2N0M0) bronchioloalveolar carcinoma. PET/CT showed massive 18F-fluorodeoxyglucose (FDG) uptake in the mesenteric lymph nodes. Because the mesentery is an unusual site of metastasis, the patient was under watchful observation. Another PET/CT after 6 months still showed FDG uptake in the same location, with a slightly increased standard uptake value. A systemic survey was performed, but it did not reveal any malignancies or inflammatory diseases. Eventually, the patient underwent probing laparoscopic surgery. For complete resection of the lymph nodes, laparoscopic ileocecal resection was performed. Histologically, the resected lymph nodes showed reactive lymphadenitis. Glucose transporter 1 immunostainings of the lung cancer and the lymph node were positive and partially positive, respectively. Although PET/CT is a powerful diagnostic modality, clinical interpretation of unusual results is difficult.

Two Cases of Rectal Neuroendocrine Tumor Resection Combined with Dissection of the Circular Muscle Layer Using the Endoscopic Submucosal Dissection Technique.

Generally, lesions of rectal neuroendocrine tumors (NETs) 10 mm or smaller are less malignant and are indicated for endoscopic therapy. However, the vertical margin may remain positive after conventional endoscopic mucosal resection (EMR) because NETs develop in a way similar to submucosal tumors (SMTs). The usefulness of EMR with a ligation device, which is modified EMR, and endoscopic submucosal dissection (ESD) was reported, but no standard treatment has been established. We encountered 2 patients in whom rectal NETs were completely resected by combined dissection and resection of the circular muscle layer using the ESD technique. Case 1 was an 8-mm NET of the lower rectum. Case 2 was NET of the lower rectum treated with additional resection for a positive vertical margin after EMR. In both cases, the circular muscle layer was dissected applying the conventional ESD technique, followed by en bloc resection while conserving the longitudinal muscle layer. No problems occurred in the postoperative course in either case. Rectal NETs are observed in the lower rectum in many cases, and it is less likely that intestinal perforation by endoscopic therapy causes peritonitis. The method employed in these cases, namely combined dissection and resection of the circular muscle layer using the ESD technique, can be performed relatively safely, and it is possible to ensure negativity of the vertical margin. In addition, it may also be useful for additional treatment of cases with a positive vertical margin after EMR.

An effective 5-fluorouracil, levofolinate, and oxaliplatin therapy for recurrent breast cancer: a case report

IntroductionTherapy comprising 5-fluorouracil, levofolinate, and oxaliplatin is currently the most common chemotherapy for colorectal cancer. We experienced a successful case of advanced colon cancer and recurrent breast cancer with 5-fluorouracil, levofolinate, and oxaliplatin therapy.Case presentationA 43-year-old Japanese woman who had already undergone surgery three times for bilateral breast cancer was admitted to our hospital for the treatment of advanced transverse colon cancer. Preoperative computed tomography demonstrated a swollen lymph node at her right upper clavicle, and fine-needle aspiration biopsy of the lymph node showed that it was a metastasis from the breast cancer. A laparoscopic-assisted colectomy was performed and the pathology demonstrated that the final stage was IIIC (T4aN2aM0, Union for International Cancer Control, 7th edition). The pathological findings and immunohistochemistry showed that the transverse colon tumor was not a metastatic lesion from the breast cancer, but was a de novo colon cancer. Chemotherapy was necessary for both the recurrent breast cancer and the Stage IIIC colon cancer. Therapy of 5-fluorouracil, levofolinate, and oxaliplatin was administered; the therapy included 5-fluorouracil, which is considered to be effective for both colon and breast cancer. After two courses of 5-fluorouracil, levofolinate, and oxaliplatin, the lymph node began to shrink and almost completely disappeared after eight courses of 5-fluorouracil, levofolinate, and oxaliplatin.ConclusionWe surmise that 5-fluorouracil, levofolinate, and oxaliplatin have the potential to provide a good response for tumors that are sensitive to fluorinated pyrimidine and platinum-containing anticancer drugs such as breast cancer.

Case of idiopathic and complete appendiceal intussusception: Idiopathic appendiceal intussusception

Appendiceal intussusception is a rare disease in which the appendix invaginates into the cecum. It is often caused by organic diseases. The present case involved an appendiceal intussusception without an organic disease, and laparoscopic resection of part of the cecum was performed. Appendiceal intussusception has various causes, including malignant diseases. Therefore, diagnosis and selection of operative method are complex and could potentially lead to an excessively invasive option. By performing SILS with a multiuse single‐site port, we were able to provide an appropriate, non‐invasive treatment that had a good esthetic outcome.

Abstract 5254: Postoperative adjuvant chemotherapy improves survival in stage II colon cancer? A propensity score matching analysis

Objective : Stage II colon cancer with high-risk features have been traditionally considered more likely to benefit from postoperative adjuvant chemotherapy (POAC). National Comprehensive Cancer Network (NCCN) guidelines do not recommend routine administration of adjuvant chemotherapy for Stage II patients, except for those with high risk features, such as poorly-differentiated tumors, T4 disease, perforated tumors and those with inadequate lymph node sampling. However, the use of POAC after surgery for patients with Stage II colon cancer remains controversial. The current study was conducted to investigate the effectiveness of POAC using propensity score (PS) matching analysis, which can reduce or minimize the confounding that is seen frequently in observational studies of the effect of treatment on outcomes, based on prognostic factors. Materials : Two hundred and nineteen patients with Stage II colon cancer who underwent surgery with curative intent between 1995 and 2005 were enrolled. The decision regarding the use of POAC was made for each case based on individual patient/physician discussions. All patients were required to provide informed consent. During the present study period, patients received 5-FU drugs orally, starting 4~8 weeks after surgery. The median observation period was 73.4 months (range: 2.2 - 184.2 months). Methods : PS matching analysis was used to adjust for differences in clinicopathological severity between the patients with and without POAC. Recurrence-free and cancer-specific survival were calculated using the Kaplan-Meier method and univariate analyses were performed using the log-rank test. The Cox proportional-hazard model was used to determine Hazard ratios and 95% confidence intervals. Results : One hundred and nineteen patients (54.3%) underwent POAC. In univariate analysis, there were significant differences in age, invasion depth, lymphatic invasion and venous invasion between the patients with and without POAC. After PS matching analysis, in univariate analysis, there were no significant differences with respect to the clinicopathological factors between the patients with and without POAC. Before PS matching analysis significant survival benefits from POAC were not recognized for recurrence-free survival (Hazard ratio= 0.76, 95% CI 0.40-1.45, P=0.41) or cancer-specific survival (Hazard ratio= 0.52, 95% CI 0.22-1.19, P=0.12). After PS matching analysis significant survival benefits from POAC were not recognized for recurrence-free survival (Hazard ratio= 0.55, 95% CI 0.23-1.23, P=0.15) or cancer-specific survival (Hazard ratio= 0.46, 95% CI 0.16-1.18, P=0.11). Conclusions : The one-to-one pair PS matching successfully balanced the clinicopathological factors between the patients with and without POAC. The PS matching analysis demonstrated no significant difference in survival in the patients with Stage II colon cancer. Citation Format: Ryoichi Tsukamoto, Kiichi Sugimoto, Shingo Kawano, Koichiro Niwa, Shun Ishiyama, Hirohiko Kamiyama, Hiromitsu Komiyama, Makoto Takahashi, Yutaka Kojima, Michitoshi Goto, Yuichi Tomiki, Kazuhiro Sakamoto. Postoperative adjuvant chemotherapy improves survival in stage II colon cancer? A propensity score matching analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5254. doi:10.1158/1538-7445.AM2017-5254

Abstract 2256: Semaphorin 3C has a possibility of a new prognostic marker in colorectal cancer

Background: Generally, Semaphorins are secretary or transmembrane-bound molecules that act as axon guidance cues in the nervous system. Recent research showed increased expression of semaphorin 3C correlates with cancers that possess higher invasive and metastatic characteristics. For example, in breast cancer, inhibition of semaphorin 3C reduces adhesion and invasion. The aim of this study was to evaluate a possibility that semaphorin 3C might be a new prognostic marker in colorectal cancer. Material and methods: We used two cohorts. Cohort 1 was the 192 patients with colorectal cancer resected surgically between 2009 and 2010. We used GSE 14333 dataset as Cohort 2 which included 226 patients with the colorectal cancer. In each cohorts, we divided the patients in to the two groups i.e., high or low semaphorin 3C expression group using receiver operating characteristic (ROC) curve based on the information of the recurrence of colorectal cancer. Disease-free-survival (DFS) rates were calculated using Kaplan-Meier methods. Differences between curves were evaluated with the log-rank test. Results: In the cohort 1, the DFS in the patients with higher expression was worse than that in the patients with lower expression (P = 0.0467). Semaphorin 3C has two probes (203788_s_at and 203789_s_at) in GSE14333. In the cohort 2, using each two probe of semaphorin 3C, the DFS in the patients with higher expression was worse than that of those patients with lower expression (P = 0.0015 and P = 0.0003). Conclusions: This study suggested that Semaphorin 3C might be a new prognostic marker in colorectal cancer. Citation Format: Shingo Kawano, Kota Amemiya, Yuki Tsuchiya, Toshiaki Hagiwara, Hirokazu Matsuzawa, Yurika Makino, Shunsuke Motegi, Ryoichi Tsukamoto, Ryosuke Ichikawa, Kazumasa Kure, Kumpei Honjo, Hisashi Ro, Shingo Ito, Yu Okazawa, Rina Takahashi, Kosuke Mizukoshi, Masaya Kawai, Shinya Munakata, Koichiro Niwa, Shun Ishiyama, Kiichi Sugimoto, Hirohiko Kamiyama, Hiromitsu Komiyama, Makoto Takahashi, Yutaka Kojima, Michitoshi Goto, Atsushi Okuzawa, Yuichi Tomiki, Kazuhiro Sakamoto, Motohiro Kojima, Atsushi Ochiai. Semaphorin 3C has a possibility of a new prognostic marker in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2256. doi:10.1158/1538-7445.AM2017-2256