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TPS882 Background: The RAISE study demonstrated the superiority of FOLFIRI + ramucirumab (Ram) to FOLFIRI in second-line metastatic colorectal cancer patients progressed after oxaliplatin, fluoropyrimidine with bevacizumab. But no prospective data is existed that the efficacy and toxicity of FOLFIRI + Ram pretreated oxaliplatin, fluoropyrimidine without an anti-angiogenesis therapy. Methods: RAINCLOUD study is a multicenter single-arm phase II trial. Key eligibility criteria is as follows: histologically or cytologically confirmed colorectal cancer, confirmed recurrent colorectal cancer, refractory to fluoropyrimidine, refractory or intolerant of oxaliplatin without pretreated anti-angiogenesis therapy, has measureable or non-measurable lesion, PS = 0 or 1, has adequate coagulation function, 20 years or older. Primary endpoint of this study is progression-free survival. Secondary endpoints are overall survival, time to treatment failure, response rate, disease control rate and safety. Patients receive FOLFIRI (irinotecan: 180 mg/m2, l-levofolinate: 200 mg/m2, bolus fluorouracil: 400mg/m2, and continuous fluorouracil: 2400 mg/m2) plus Ram (8 mg/kg) every two weeks until progression or the development of unacceptable toxicity. We hypothesized that threshold of PFS in FOLFIRI + Ram is 3.9 months and expected PFS is 6.9 months and designed to have an 80% power to detect clinically meaningful improvement in PFS at the one-sided significance level of 0.05, minimal patient registration number is 44 in order that power 1-β outperforms 0.8. Taking a few ineligibility patients and dropout patients into consideration, number of target patients is set to be 48. Study recruitment started on September 2017. The association of exploratory biomarker study will be planned. Clinical trial information: UMIN000028677.

844 Background: Obstructive colorectal cancer is an oncological emergency that requires emergency treatment. In Japan, laparoscopic resection after decompression with metallic-stent placement is becoming mainstream as a bridge to surgery (BTS). However, there are reports of worse prognoses due to stent placement, and the European Gastroenterology Society of Endoscopy guidelines do not recommend BTS. In our department, since 2011 the first choice of the treatment has been laparoscopic resection after decompression with a trans-anal or trans-nasal drainage tube. STo investigate the safety and short- and long-term results of laparoscopic resection after decompression with a drainage tube. Methods: Eighty-one cases of obstructive colorectal cancer that underwent surgery at our hospital from 2011 to 2016 were investigated with regards to the short- and long-term outcomes of treatment strategies for obstructive colorectal cancer. Results: The median age was 72 years old (39-94). The ratio of male to female was 46:29. The success rate of decompression was 86.7% (66 cases). Stages II, III and IV were involved in 25, 28 and 28 cases, respectively. The causes of the emergency operations were an inability to insert both the ileus tube and the stent (9.3%, 7 cases), and perforation (2.7%, 2 cases) when the trans-anal ileus tube was inserted. In the cases in which decompression was possible, the laparoscopic operation rate was 89.4% (56 cases) and the primary resection rate was 90.9% (59 cases). The median surgical time was 194 minutes (27-325), the median blood loss was 10 g (0-660 g),The median postoperative hospital stay was 14 days (5-147 days). The rate of anastomotic leak was 4.5%. There were no deaths within 30 and 90 days after surgery. The relapse free survival rate in Stage II and III were 72% and 67.9%, respectively. The median months of overall survival in Stage II, III and IV were 60.4, 56.3 and 18.7, respectively. Conclusions: A treatment strategy with laparoscopic resection followed by decompression with a drainage tube was performed feasibly and safely. At this time, the effects of a stent on oncological prognosis is unclear, and this strategy could be an effective treatment for obstructive colorectal cancer.

Large-scale deformation processes and mechanisms of the model aggregates comprising close-packed spherical particles are examined by the use of a discrete element method (DEM). It is demonstrated that the movement of grain groups, i.e., the cooperative grain-boundary sliding (CGBS), is essential in the large-scale elongation of polycrystalline materials. The strain energy of grain aggregates during CGBS is also estimated as a function of true strain, yielding a good agreement with the theoretical prediction of CGBS process. The discrete element analysis used in this study is an efficient technique in examining the large-scale deformation mechanism such as the superplastic deformation of polycrystalline materials.

The quality of life in patients who have undergone surgery for esophageal cancer is frequently disturbed by postoperative gastroesophageal reflux disease or pharyngolaryngeal reflux disease. Recently, there have been many reports on gastroesophageal reflux disease after esophagectomy, and only a few on pharyngolaryngeal reflux disease. There is not yet any convenient endoscopic classification of reflux pharyngolaryngitis. We designed a new classification for reflux pharyngolaryngitis based on endoscopic findings. Our new classification consists of the five grades from 0 to IV based on (i) the extent and severity of erythema and/or edema in the pharynx and the larynx, and (ii) the extent and severity of granulation or scarring stenosis in the vocal cords. Ninety-three patients after cervical esophagogastrostomy after esophagectomy (the CEG group) and 28 patients after intrathoracic esophagogastrostomy (the TEG group) were reviewed in this study. We investigated the relation between the severity of reflux pharyngolaryngitis and clinical symptoms in these patients, and the correlation between this new classification of reflux pharyngolaryngitis and the Los Angeles classification of reflux esophagitis. Reflux esophagitis was more severe in the TEG group than in the CEG group, while there was no difference in the grading of reflux pharyngolaryngitis between the two groups. The pharyngolaryngeal symptoms and F-scale scores were not correlated with the severity of reflux pharyngolaryngitis in each group. The grading of reflux pharyngolaryngitis and that of reflux esophagitis was correlated in each group (P

A fabrication process for making three-dimensionally close-packed structures of SiO 2 -microparticles was proposed by utilizing external mechanical vibration. An experimental device was designed to make three-dimensional arrays through vibrating colloidal particles in suspension. The optimum condition for the vibration was examined to yield the most sufficient close-packed structures in their large dimensions. The experimental technique proposed in this study is efficient tool for eliminating defects undesirably induced and included in the particulate aggregates with close-packed structures. The microscopic processes of the formation of three-dimensionally ordered aggregates were also examined using the discrete element method (DEM). The experimental observations for the nucleation and the growth of close-packed structures associated with appropriate mechanical vibrations were well realized in the DEM simulation, suggesting the useful information on the efficient engineering fabrication of close-packed structures of particulate aggregate.

Background: Colorectal cancer (CRC) patients have an increased risk of developing other malignancies. Understanding the characteristics of the second primary cancer is important to establish an effective surveillance program. Methods: This study investigated 301 CRC patients to assess the risk factors for postoperative primary cancers arising from organs distinct from the colorectal area (extracolorectal cancers). The observed/expected ratio (O/E ratio) was calculated using the Osaka Cancer Registry, to determine the rate of increase in extracolorectal cancers. Results: The frequency of postoperative extracolorectal cancers was 12.6%. A logistic regression analysis showed only age to be an independent risk factor for postoperative extracolorectal cancer development. The O/E ratio of overall postoperative extracolorectal cancer was significantly higher than one (O/E ratio 2.6, p < 0.01). In each organ, the frequency of lung and gastric cancers were significantly higher than one, with O/E ratios of 3.2 and 2.7 (p < 0.01 and p < 0.05, respectively). Conclusion: The frequency of postoperative extracolorectal cancers in CRC patients was significantly higher than that in the normal population, especially for lung and gastric cancers. Clinicians should carefully follow patients for a possible recurrence of CRC and educate CRC patients with regard to the high risk of a second primary cancer.

Purpose: Connexin 26 (Cx26) is one of the gap junction–forming family members classically considered to be tumor suppressors. However, recent studies show association of elevated expression of Cx26 with poor prognosis in several human malignancies. Furthermore, Cx26 has been observed to be indispensable to spontaneous metastasis of melanoma cells. Here, we assessed Cx26 expression in primary colorectal cancer (CRC) and the metastatic lesions to elucidate its role in metastasis. Experimental Design: Cx26 expression was assessed in 25 adenomas, 167 CRCs, and normal mucosa, together with the metastatic lesions. Results: Normal mucosa and adenomatous tissue expressed Cx26 mainly in the plasma membrane, whereas cancer cells mostly contained Cx26 in the cytoplasm. The incidence of aberrant Cx26 expression varied widely in CRC (mean, 49.5 ± 35.5%), and the expression levels were confirmed by Western blot and quantitative reverse transcription–PCR. Clinicopathologic survey revealed association of high expression with less differentiated histology and venous invasion (P = 0.0053 and P = 0.0084, respectively). Notably, high Cx26 expression was associated with shorter disease-free survival and shorter lung metastasis–free survival in 154 curatively resected CRC sets (P = 0.041 and P = 0.028, respectively). Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively). Conclusions: These findings suggest that aberrant expression of Cx26 plays an essential role in lung metastasis. Thus, Cx26 is a promising therapeutic target, particularly for CRC patients who develop lung metastasis.

Background: Several investigators have previously reported the prognostic factors affecting survival after a surgical resection of pulmonary metastasis from colorectal cancer (CRC). However, there have so far been no reports describing prognostic factors related to the tumor doubling time (TDT) of pulmonary metastasis. Methods: 65 patients with solitary pulmonary metastasis from CRC were retrospectively reviewed and the prognostic factors after pulmonary resection including TDT were analyzed. Results: The 5-year intrapulmonary recurrence-free survival rates after pulmonary resection was 59.9%. The TDT of pulmonary metastasis (Conclusions: The TDT of solitary pulmonary metastasis is a significant prognostic factor after surgery for solitary pulmonary metastasis from CRC.

Background: Patients undergoing a curative rectal cancer resection have a risk of developing locoregional recurrence. A curative resection for local recurrence is the option of improvement in prognosis. However, a curative resection is sometimes too invasive and should be considered in selected patients. Methods: A total of 43 patients with locally recurrent rectal cancer who had been treated by operation between 1989 and 2007 were retrospectively reviewed and the factors, including doubling time of carcinoembryonic antigen (CEA-dt), were analyzed. Results: The 5-year overall survival rate after the operation for local recurrence was 50.8%. Gender, presence of distant metastasis, tumor size, CEA-dt and curability were found to be significant prognostic factors. A multivariate analysis demonstrated the presence of distant metastasis, CEA-dt and tumor size to be significant prognostic factors for overall survival. The 5-year overall survival rates of patients with a CEA-dt ≧150 days and a tumor size Conclusions: The tumor size and CEA-dt were useful prognostic factors that were recognizable before surgery. Patients with locally recurrent rectal cancer with a CEA-dt ≧150 days and a recurrent tumor size

A 61-year-old man underwent a curative operation for advanced esophageal cancer (CT-pT3N2M0, pStage Ⅲ), which had been downstaged with docetaxel, CDDP, 5-FU (DCF) neoadjuvant chemotherapy. Five months after the operation, we diagnosed the patient with recurrence of esophageal cancer with para-aortic lymph node (PALN) metastasis. Systemic chemotherapy was initiated using a regimen of weekly paclitaxel (PTX) administration. After 2 courses, abdominal computed tomography examination indicated regression of the PALN swelling. Eighteen months have passed since the curative operation, and the patient has been doing well with no signs of recurrence. In summary, we successfully treated a case of lymph node metastases from esophageal cancer with weekly PTX chemotherapy.

Here, we report the case of a 43-year-old man who was diagnosed with sigmoid colon cancer with synchronous multiple liver metastases following resection of a primary lesion. Subsequent mFOLFOX+BV therapy elicited a marked response in the liver metastases, which led to the patient undergoing hepatic (S7) radiofrequency ablation (RFA), hepatic resection (lateral segmentectomy and partial [S5] resection), and cholecystectomy. Six months later, transluminal RFA was repeated because liver (S7) metastasis recurred, and 8 courses of XELOX plus BV therapy were administered. As obstructive jaundice due to recurrence of the liver metastases developed after a 6 months hiatus in chemotherapy, we endoscopically inserted a biliary stent. Despite reducing IRIS plus BV therapy, obstructive jaundice developed again, and 3 intrahepatic biliary stents were inserted with percutaneous transhepatic biliary drainage. To date, the patient has been alive for 4 years since the initial resection of the primary lesion after undergoing consecutive systemic chemotherapy with different regimens. Some studies have shown that in cases of obstructive jaundice caused by advanced gastrointestinal cancer, longer survival could be expected by reducing the severity of jaundice, suggesting that resuming chemotherapy as well as improving the severity of jaundice could contribute to better outcomes. The patient in the present case was successfully treated twice with biliary drainage for occlusive jaundice and chemotherapy, suggesting that a combination of multidisciplinary therapy and adequate local therapy such as biliary drainage could be important for the treatment of metastatic liver cancer.

It is considered difficult to perform laparoscopic surgery for colorectal cancer with T4b that is directly invades to adjacent organs. This retrospective study evaluated pT4b colorectal cancer in terms of the efficacy of laparoscopic surgery.Forty-six cases with pT4b colorectal cancer that occurred between 2006 and 2014 were investigated. Laparoscopic surgery (LAC) was performed in 20 cases, of which 5 were conversions, and open surgery (OC) was performed in 26 cases. Pathologically-proven invaded organs resected by LAC were the abdominal wall (n=6), greater omentum (n=5), small intestine or colon (n=3), bladder, appendix, or ovary (n=1). Organs resected by OC were the abdominal wall (n=8), bladder (n=5), colon, greater omentum, or small intestine (n=3), stomach, ovary, spermatic duct (concurrent with bladder), prostate, or sacrum (n=1). Operation time (median) was 275 min for LAC and 260 min for OC. Blood loss (median) was 100 mL for LAC and 410 mL for OC. The duration of hospital stay (median) was 15 days after LAC and 18 days after OC. There were 2 cases with morbidities greater than Grade 3 after LAC and 1 case after OC. There was 1 hospital death in the OC group.Laparoscopic surgery for T4b colorectal cancer can be feasible in select cases.

A 100-year-old man was admitted to our hospital because of bloody stool. Colonoscopy revealed a type-2 tumor in the rectum, which was diagnosed as moderately differentiated adenocarcinoma. There was no distant metastasis on CT. After meticulous preoperative evaluation of surgical risks considering his age, laparoscopic high anterior resection was performed. During surgery, the edge of the descending colon showed ischemia; therefore, we performed conversion to open surgery and transverse colon resection. However, the edge of the transverse colon showed ischemia; therefore, ascending colon resection and ascending colon-rectum anastomosis were performed. On day 5 after surgery, the patient developed aspiration pneumonia, for which respirator management was conducted. As his condition improved, he was discharged on postoperative day 32. The pathology results were tub2, pT3, ly0, v2, PM0, DM0, RM0, pN1, Stage Ⅲa. One year 6 months after the surgery, when the patient was 102 years old, CT revealed liver metastasis. RFA was performed for the liver lesion. In people aged 100 years or older, few reports are available on colectomy, and there is no report of treatment for metastasis.

A 66-year-old woman was admitted to our hospital because of epigastralgia, and she was diagnosed with a type 2 tumor at the antrum of the stomach. Pathological examination suggested a moderately differentiated adenocarcinoma with negative staining for HER2 on immunohistochemistry. Abdominal CT showed gastric wall thickening and enlarged lymph nodes. Although the clinical finding was Stage ⅢB(T4aN2M0), a liver metastasis (S2) was found during the operation. We performed distal gastrectomy with D2 lymph node dissection and partial hepatic resection in December 2010. A post-operative pathological diagnosis of gastric cancer, pT4aN2M1, pStage Ⅳ, was made. Although adjuvant chemotherapy of S-1 was administered, CT revealed a liver metastasis in S3 5 months after the operation, and the patient underwent transcatheter arterial chemoembolization (TACE) followed by a regimen of S-1 plus CPT-11. After 3 courses of this regimen, grade 2 anorexia was observed, and the treatment schedule was changed to a regimen of capecitabine plus cisplatin (XP). After 7 courses of this regimen, CT revealed multiple liver metastases in S2, S3, and S8, and the treatment schedule was changed to several other chemotherapy regimens. However, liver metastases continued to grow, and the patient died 51 months after surgery. Although the prognosis of gastric cancer with synchronous liver metastases is very poor, it is possible to prolong survival with multimodal therapy.

To examine the regeneration of mesothelium under a bioresorbable membrane. A 1 cm2 piece of peritoneum was resected from both sides of the abdominal wall of retired female mice. A piece of hyaluronate and carboxymethyl-cellulose (Seprafilm®) was placed over the wound on one side and the other side was left uncovered. We evaluated the degree of adhesion and regeneration of mesothelial cells macroscopically and histologically using immunohistochemistry at different times. Macroscopically, the degree of postoperative adhesion in the treated site was significantly less than that in the untreated site. The membrane was left in place for 7 postoperative days (PODs). By POD 5, the regenerated peritoneum mesothelial cells covered part of the area and by POD 7, they had regenerated over almost all of that area in the abdominal wall. The anti-adhesion membrane worked as a physical barrier to prevent postoperative adhesion until the mesothelial cells had regenerated completely. To our knowledge, this is the first study conducted to assess the regeneration of peritoneum mesothelial cells under a bioresorbable membrane using immunohistochemistry.

This prospective cohort study was designed to compare the short-term and intermediate health-related quality of life of Japanese patients after laparoscopic colectomy (LC) or open colectomy (OC) for colonic cancer.Seventeen hospitals participated, and 240 colonic cancer patients with T3 or T4 invasion that were estimated as curatively resected were enrolled. Three patients were excluded as ineligible, one patient died suddenly before operation, and one patient was not registered based on the doctor's decision. Therefore, analysis was done on 235 patients who underwent either LC (n = 165) or OC (n = 70) in accordance with their stated preference. The major outcome scale end-point was health-related quality of life as assessed by the 36-item Short Form Health Survey (Japanese version 2.0). Accessory end-points were feeling of satisfaction 1 month after operation and recovery time needed to perform normal activities after operation. Observations were performed on enrollment, postoperative day 3, postoperative day 7, discharge day or postoperative month 1, and postoperative month 6.Defecation condition, wound pain score, and abdominal pain score were better in the LC group than in the OC group on postoperative day 7 and in postoperative month 1. Recovery time to normal daily activity took 30 days in the LC group, whereas the OC group needed 44 days.Patients' subjective responses indicated that LC was more beneficial than OC for patients with stage II or III colonic cancer. LC's superiority was seen particularly in the following indicators: (i) health-related quality of life during early postoperative days; (ii) recovery to normal daily activities; and (iii) defecation after surgery.

Purpose: We reported in a retrospective study that the presence of micrometastasis in lymph nodes, when assessed by carcinoembryonic antigen (CEA)-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer. The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. Experimental Design: From November 2001 to December 2005, a total of 419 colorectal cancer cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II colorectal cancer cases were enrolled. After RNA quality check, 304 colorectal cancer cases were analyzed for CEA mRNA in lymph nodes by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Postoperative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-fluorouracil derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for 1 year, whereas chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (high MMV, n = 95) was an independent poor prognostic factor for 5-year disease-free survival (DFS; P = 0.001) and 5-year overall survival (OS; P = 0.016). Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II colorectal cancer. Clin Cancer Res; 22(13); 3201–8. ©2016 AACR.

Purpose: One of the main reasons for cancer treatment resistance is the existence of cancer stem-like cells (CSCs). Here, we elucidated the relationship between low proteasome activity cells (LPACs) and CSCs. Experimental Design: The human colorectal cancer cell lines HCT116, SW480, DLD1, and KM12SM were engineered to stably express a green fluorescent molecule fused to the degron of ornithine decarboxylase, resulting in an accumulation of the fluorescence in LPACs. LPACs were isolated by flow cytometry. Treatment resistance (radio- and chemotherapy) and the capacity of LPACs to act as CSCs were analyzed. Microarray analysis was performed to reveal genes related to treatment resistance. The prognostic impact of potent genes was examined in 190 patients with colorectal cancer. Results: LPACs had a significantly increased capacity for radioresistance and chemoresistance (5-fluorouracil and oxaliplatin), significantly lower reactive oxygen species activity, and significantly increased sphere formation capacity compared with non-LPACs. The number of cells in the G0–G1 phase was significantly higher among LPACs. Subcutaneous injection of as few as 20 LPACs led to tumor formation in immunologically incompetent mice. Microarray analysis revealed that the expression of EP300-interacting inhibitor of differentiation 3 (EID3) was significantly increased in LPACs. In vitro assay revealed that EID3 positively controlled cell proliferation and treatment resistance. The high expression of EID3 was an adverse prognostic indicator in patients with colorectal cancer (P = 0.0400). Conclusions: LPACs have characteristic treatment resistance and act as CSCs in colorectal cancer. In addition, EID3 is one of the potential regulators of treatment resistance in colorectal cancer and may be a potential therapeutic target. Clin Cancer Res; 22(21); 5277–86. ©2016 AACR.

Metastatic gastric cancer is uncommon, and metastasis of colorectal cancer to the stomach is extremely rare. We report a case of metastatic gastric cancer that originated from transverse colon cancer. A 52-year-old woman underwent a left hemicolectomy and D3 lymph node dissection based on a diagnosis of transverse colon cancer. The pathology results were as follows: mucinous adenocarcinoma, type 2, 6 × 11 cm, ss, ly1 v1, pm (-), dm (-), n1 (+), P0, H0, M0, Stage IIIa. The patient received XELOX as postoperative adjuvant therapy for 6 months. One year and 3 months after the left hemicolectomy, gastroscopy revealed a submucosal tumor in the lower body of the stomach and an incipient cancer in the cardia of the stomach, and a colonoscopy revealed an incipient cancer in the transverse colon. An endoscopic ultrasonography fine needle aspiration biopsy of the submucosal tumor in the lower body of the stomach was performed. Histology showed that this tumor was a mucinous adenocarcinoma similar to the primary transverse colon cancer, which led to a diagnosis of metastatic gastric cancer originating from transverse colon cancer. Distant metastasis was not detected. Endoscopic submucosal dissection of the incipient gastric cancer was performed, as were distal gastrectomy and partial colectomy. Peritoneal dissemination and para-aortic lymph node recurrence were detected 7 months after the second surgery.

We retrospectively evaluated the clinical outcomes of 192 consecutive patients with local recurrence after complete resection of non-small cell lung cancer NSCLC). The initial local recurrent site was the resection stump in 5 patients the chest wall in 3 patients, mediastinum in 1 patient, and diaphragm in 1 patient), and the hilar and/or mediastinal lymph node (HMLN) in 17 patients. The sites of distant metastasis were the lungs in 10 patients, pleura in 4 patients, brain in 7 patients, liver in 5 patients, bone in 4 patients, and other sites in 4 patients. Treatments after initial recurrence included surgery in 2 patients, radiotherapy in 5 patients, chemotherapy in 9 patients, and chemo-radiotherapy in 5 patients. Only 1 patient received supportive care. The response to radiotherapy was a complete response (R) in 1 patient, partial response (PR) in 5 patients, stable disease (SD )in 3 patients, and progressive disease (PD )in 1 patient. The best response of all lines of chemotherapy was CR in 3 patients, PR in 4 patients, SD in 3 patients, and PD in 4 patients. The median post-recurrence survival (PRS) time with local recurrence was better than that with distant metastasis (23 vs 14 months); however, the best PRS was obtained in patients with recurrence in the lungs (29 months). A CR for more than 2 years was obtained in 1 patient after surgery, in 1 patient after radiotherapy, and in 2 patients after chemotherapy. Although local recurrence of resected NSCLC can be potentially controlled by using local treatments - such as surgery and radiotherapy - or systemic chemotherapy, curative aggressive treatment should be considered when required.

A 66-year-old man underwent a curative operation for advanced gastric cancer (T4aN0M0, Stage IIB). A gastric cancer recurrence with paraaortic lymph node (PALN) metastasis was diagnosed fifteen months after the operation. Systemic chemotherapy was initiated, using a regimen of S-1/CDDP. After 7 courses, abdominal computed tomography (CT) examination indicated the regression of PALN swelling. However, peritoneal dissemination was detected in the neighborhood of the right kidney. S-1/docetaxel (S-1/DOC) was selected as the second-line chemotherapy. After 3 courses, the peritoneal dissemination could not be detected. Five years since the curative operation, the patient has been doing well, with no signs of recurrence. In summary, we successfully treated a case of peritoneal dissemination from gastric cancer with S-1/DOC chemo- therapy.

A 47-year-old man with no history of anal fistula was admitted to our hospital with a complaint of perianal pain. Computed tomography (CT) imaging revealed perianal abscess. Incision and drainage were performed under spinal anesthesia. Ten months after drainage, magnetic resonance imaging revealed anal fistula on the left side of the anus. Subsequently, core-out and seton procedures were performed for ischiorectalis type III anal fistula. Pathological examination of the resected specimen of anal fistula revealed a moderately differentiated adenocarcinoma, leading to the diagnosis of carcinoma associated with anal fistula. No distant metastases or enlarged lymph nodes were observed on positron emission tomography (PET)/CT. We performed abdominoperineal resection with wide resection of ischiorectalis fat tissue. The pathology results were tub2, A, ly0, v0, n0, PM0, DM0, RM0, H0, P0, M0, Stage II. Negative pressure wound therapy was performed for perineum deficiency, after which rapid wound healing was observed. Left inguinal lymph node recurrence was detected 8 months after surgery, for which radiotherapy was administered. Distant metastasis was detected 11 months after surgery. The patient died 21 months after surgery.

A 68-year-old man presenting with anorexia was admitted to our hospital; he was diagnosed with pyloric stenosis arising from a type 3 tumor in the antrum of the stomach. Pathological examination revealed a poorly differentiated adenocarcinoma; immunohistochemical staining tested positive for alpha fetoprotein(AFP), and negative for human epidermal growth factor receptor 2(HER2). Abdominal computed tomography (CT) showed a portal vein thrombus and enlarged lymph nodes. Since the clinical finding was Stage IV(T4aN3M1), curative surgery was ruled out. Following stent placement for food intake, TS-1 plus cisplatin (CDDP) neoadjuvant chemotherapy was initiated. TS-1(80 mg/m² / day) was administered orally for 2 weeks followed by a drug-free 1-week period, and CDDP (60 mg/m²) was administered intravenously on day-1 as 1 course. After 5 courses of this regimen, lymph nodes were reduced in size and the portal vein thrombus disappeared. However, grade 4 thrombocytopenia was observed, and the treatment schedule was modified to include several other chemotherapies. Two years after the initiation of chemotherapy, liver metastasis was detected via elevated AFP. The patient died 27 months after initial treatment. Although the prognosis for gastric cancer with portal vein thrombus is very poor, it is possible to prolong survival with multimodality therapy.

Circulating microRNAs (miRNAs) have been reported as a biomarker for human malignancies, including colorectal cancer (CRC). The purpose of this study was to identify a novel biomarker for CRC through examination of serum miRNAs from the patients with CRC. Microarray analysis of miRNA expression was performed using paired pre- and post-operative serum from 10 CRC patients. miR-103 and miR-720 decreased significantly in the post-operative serum when compared to pre-operative serum. With an extended scale validation by qRT-PCR (quantitative real-time polymerase chain reaction) in 30 CRC patients, we confirmed that serum miR-103 and miR-720 decreased significantly after surgery (P=0.0004, and P=0.0274, respectively). Next, we examined serum miR-103 and miR-720 levels in 32 non-cancer patients and 84 CRC patients, and we found that expression of these two miRNAs was significantly higher in CRC patients than non-cancer patients. Furthermore, clinical and pathological survey indicated that high expression of miR-103 was significantly associated with histological differentiation grade, and lymphatic invasion and high expression of miR-720 was significantly associated with male gender and lymph node metastasis. Our data suggest that circulating miR-103 and miR-720 show potential as novel serum biomarkers for CRC.

The outcome after resection of advanced pancreatic cancers is extremely poor because of the high incidence of the postoperative development of liver metastasis and local recurrence. We performed a combination of chemoradiation and liver perfusion chemotherapy and extended pancreatectomy. Nineteen patients with T3 pancreatic head cancers were enrolled. A total of 24 Gy in 12 fractions of 10-MV x-rays with a concurrent intravenous infusion of 5-fluorouracil (5-FU; 3 g/12 days) was administered to the pancreatic head area. An extended pancreaticoduodenectomy was performed, and catheters were placed into the gastroduodenal artery and the superior mesenteric vein. During the first 28 postoperative days, 5-FU was continuously infused via the hepatic artery and portal vein (3.5 g/28 days × 2). Finally, 36 Gy in 18 fractions with 5-FU (3 g/6 days) was applied to the pancreatic bed. After preoperative chemoradiation, four patients did not undergo surgical resection because of distant metastases. Fifteen patients underwent pancreaticoduodenectomy, liver perfusion chemotherapy, and postoperative chemoradiation. No patient developed grade 3 toxicity as a result of preoperative chemoradiation, but one patient (7%) developed grade 3 leukopenia during the postoperative treatments. The morbidity rate was 20% (3 of 15 patients), and the mortality rate was 0%. The overall 3-year survival rate was 53%. The 3-year disease-free survival rate was 66% in patients who pathologically responded well (>50%), versus 0% in patients with poor responses (P = .04). A combination of preoperative and postoperative chemoradiation plus postoperative liver perfusion chemotherapy with an extended pancreatectomy is feasible, and the long-term outcomes are also promising.

A considerable percentage of gallbladder cancers are accompanied by superficial cancer spread adjacent to the main tumor, therefore cholecystectomy for early gallbladder cancer must be performed carefully to avoid leaving cancer cells at the surgical margins.Thirty-two patients with gallbladder cancer invading no more than perimuscular connective tissue underwent surgical resection at our medical center. After the operation, resected specimens were investigated macroscopically and microscopically to clarify the clinicopathological features and the risk factors of superficial cancer spread.Sixty-six percent of all cases (21 cases) had superficial cancer spread. Comparison between the cases having superficial cancer spread and the cases without it revealed that the macroscopic morphology of the primary tumor and the depth of cancer invasion in the gallbladder wall were significantly different between the two groups. Furthermore, multivariate analysis indicated that 'superficial raised type' in macroscopic morphology was an independent predictive factor for having superficial cancer spread. Superficial cancer spread from the main tumor located in the neck of the gallbladder grows predominantly in the direction of the fundus. More advanced gallbladder cases were accompanied by more extensive superficial spread.Superficial cancer spread is frequently observed adjacent to the gallbladder cancer, especially in the superficial raised type. A negative margin should be confirmed by intraoperative frozen section histology while performing cholecystectomy.

腹腔内出血をきたした胃原発の巨大なGISTの手術例を報告する.症例は61歳,男性. 10年以上前より腹部に腫瘤を自覚し,近日当院受診予定であった.平成16年11月,急な腹痛にて当院救急外来を受診し, CTにて多量の腹水貯留と原発不明の腫瘤を認めたことから消化管穿孔や腫瘍破裂を疑い緊急手術を施行した.腹腔内には約20cm大の嚢腫様病変が,頭側端を胃に癒着させ横行結腸間膜に載るようにして存在しており,腫瘍からは静脈性出血が続いていた.胃壁を一部合併切除して腫瘍を摘出した.摘出標本の免疫染色ではc-kit, CD34がともに陽性でGISTと診断した. GIST破裂による腹腔内出血は比較的稀な病態であり術前診断に難渋することが多い.文献的には(1) 原発不明の腹部腫瘤, (2) 急な腹痛, (3) 腹水貯留の三徴候を有する症例に対しては本疾患を視野に入れて開腹手術を検討すべきであると考えられた.

Background The objectives of the present study are to determine the long-term changes in glucose tolerance function after pancreaticoduodenectomy and to compare the effects of pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG). Patients and methods The present study consisted of 51 patients who received a pancreaticoduodenectomy for tumors of the pancreatic head area and survived more than 7 postoperative years without tumor recurrence. According to the type of pancreatic anastomosis, they were classified into 2 groups of 25 PJ patients and 26 PG patients. Changes in the patterns of a 75-g oral glucose tolerance test (OGGT) (normal, impaired glucose tolerance [IGT], and diabetic [DM] patterns) and the need for beginning diabetic treatment (oral hypoglycemic agents or insulin) were compared between groups. Results Within 3 months after surgery, 14 (56%) patients in the PJ group had normal OGTT patterns, 8 (32%), IGT patterns, and 3 (25%), DM patterns. In the PG group, the patterns of OGTT were similar with 16 (62%) normal patterns, 6 (23%) IGT patterns, and 4 (15%) DM patterns. During the first 7 postoperative years, the 2 groups showed similar results: (1) none of the patients with normal patterns developed functional decline in glucose tolerance; (2) a high percentage of patients with initial IGT or DM patterns developed worsening glucose intolerance (7 [64%] of 11 PJ patients vs 7 [70%] of 10 PG patients); (3) the onset of functional decline in glucose tolerance occurred predominantly within the first 3 postoperative years; and (4) no specific causative event prior to the subsequent functional decline was detected. Conclusion The decline of glucose tolerance after pancreaticoduodenectomy seems to be associated with a low reserve of endocrine function rather than anastomotic procedures or their related complications. Regardless of the types of pancreatic anastomosis, a close follow-up of glucose tolerance function is recommended during the first 3 postoperative years, especially among IGT or DM patients.

気管支嚢胞は胎生期に発生する奇形で, 通常は縦隔内にみられ腹部領域に発生することは少なく, その悪性化の報告はこれまで2例にすぎない. 我々は術前に悪性と診断し切除しえた後腹膜気管支嚢胞腺癌の1例を経験したので報告する. 症例は57歳の男性. 主訴は背部痛. 腹部CT検査にて左横隔膜脚に接し膵体部を前方へ圧排する8cmの多房性腫瘤を認めた. 経皮的穿刺細胞診にて腺癌細胞を認め, 後腹膜に発生した嚢胞性悪性腫瘍と診断し手術を施行した. 広範囲に膵と接していたため, 膵体尾部および脾臓と共に腫瘍を摘出した. 病理所見では嚢胞壁は線毛を有し平滑筋で裏打ちされた円柱上皮で覆われており, またその一部において乳頭状に増殖する腺癌を認めたため, 後腹膜気管支嚢胞腺癌と診断した.

隣接臓器に浸潤した大腸癌は, 積極的な他臓器合併切除によって良好な予後が期待できる. しかし, 尿路再建法としての回腸導管は, QOLを著しく低下させる. 我々は膀胱全摘後の尿路再建に回腸代用膀胱 (ilealneobladder) を用い, 良好な結果を得ているので報告する. 症例は進行大腸癌3症例で, 47歳～61歳の男性. 術前膀胱鏡では癌は粘膜内に露出し, 三角部から2cm以内に浸潤していた. 再建は, 回腸をW字型に配置し腸間膜対側で縦切開を入れ袋状に形成し, 順蠕動性の輸入脚を追加してパウチを作成し尿管および尿道と吻合した. 1例で間欠的自己導尿が必要となったが, これは代用膀胱の後方支持が得られず, 十分に圧がかからなかったためと推測された. 本来の尿道から自己排尿可能で尿禁制も得られる回腸代用膀胱は, 膀胱浸潤大腸癌に対する有用な尿路再建法として期待される. しかし, 患者に対して十分な説明の上, 適応を限って実施する必要もあると考えられた.

The caudal spread of esophageal squamous cell carcinoma (ESCC) frequently involves the stomach. An extended surgical treatment may provide a tumor-free margin; however, its clinical benefit has not been elucidated.Sixty-three of 582 patients with ESCC (11%) had massive gastric involvement and underwent esophagectomy with combined resection of the stomach and other organs. The mode of gastric involvement was classified as direct invasion from primary tumor (PT invasion) or invasion from metastatic lymph nodes (LN invasion).In addition to the removal of either the proximal (83%) or the whole (17%) stomach, 46 patients (73%) underwent the combined resection of adjacent organs, including the diaphragm, pancreas, liver, lung, and pericardium. This surgical treatment resulted in a high rate (83%) of curative resection and a low rate (8%) of operative mortality. Postoperative survival rates were 53%, 33%, and 25% at 1, 2, and 5 years, respectively. The first tumor recurrence was frequently in the abdominal paraaortic lymph nodes (41%) and the liver (28%), followed by the mediastinal lymph nodes, local recurrence, the lung, and other organs. The mode of gastric involvement strongly affected clinical outcome, with a 5-year survival rate of 36% for those with PT invasion but of only 7% with LN invasion (P.0086). No significant difference was seen in the number and location of metastatic lymph nodes between the 2 groups; however, the size of the largest metastatic lymph node was significantly smaller with PT invasion than with LN invasion (12 mm vs 37 mm in diameter; P.0001).Surgical treatment of ESCC involving the stomach was considered safe and successful. A favorable prognosis can be expected for gastric invasion from the primary tumor but not from metastatic lymph nodes.

Background/Objective: Oral tegafur/uracil and leucovorin (UFT/LV) therapy is effective and safe for elderly patients with advanced or metastatic colorectal cancer (CRC). However, there are few studies on the combination of bevacizumab with UFT/LV. This clinical study evaluated the efficacy and safety of UFT/LV plus bevacizumab as a first-line therapy for elderly patients with advanced or metastatic CRC. Methods: Forty patients with advanced or metastatic CRC aged ≥75 years were enrolled in this multicenter, open-label, single-arm phase II study. All patients received oral UFT (300-600 mg) and LV (50 mg) twice daily on days 1-21 and intravenous bevacizumab (5 mg/kg) on days 1 and 15 of a 4-week cycle (University Hospital Medical Information Network No. UMIN000003447). Results: The median follow-up period was 14.7 months. The response rate was 20.0% [95% confidence interval (CI): 9.1-35.6], median progression-free survival was 8.9 months (95% CI: 5.3-11), and median overall survival was 21.7 months (95% CI: 13.7-23.4). The only grade 3 hematological toxicity was neutropenia (3.0%), and the incidence rates of grade 3 nonhematological toxicity were low at ≤10%. Conclusion: UFT/LV plus bevacizumab is a promising first-line regimen for elderly patients with advanced or metastatic CRC. The combination is well tolerated and efficacious.

Background Postoperative survival of patients with esophageal cancers after curative surgery is strongly affected by the presence of lymph node metastasis. The number and location of lymph node metastases have been evaluated and graded, but the clinical significance of their size has not been well investigated. Methods Of 322 esophageal cancer patients who underwent curative operations with radical lymph node dissection, 170 (53%) had lymph node metastasis. A total of 784 metastatic lymph nodes were obtained, and the area of the cancer nests was measured microscopically in the cross section. The data from each patient included the area of the largest cancer nest in the positive nodes (Nmax), classified as Na ( 100 mm2). Results The 170 patients were classified according to the Nmax value: Na, 31 (18.2%); Nb, 35 (20.5%); Nc, 49 (28.8%); and Nd, 55 (32.4%). The 5-year survival rate was 77.7% in patients without lymph node metastasis and 35.4% in those with lymph node metastasis. When classified by Nmax, the 5-year survival rate was 77.8% for Na, 63.9% for Nb, 18.8% for Nc, and 12.8% for Nd. There was no significant difference in the survival rate between Na patients and those without lymph node metastasis. Nmax showed significant correlation with the primary tumor size, depth of tumor invasion, and number and location of metastatic lymph nodes, but not with histologic type or primary tumor location. In multivariate analysis, the Nmax value, the number of lymph node metastases and depth of tumor invasion were independent prognostic factors, while the location of the lymph node metastases was not statistically significant. Conclusions The area of the largest cancer nest in the lymph nodes was one of the most significant prognostic factors for esophageal cancers. This estimation is objective and reproducible and may be of great importance when deciding the therapeutic modality for patients with esophageal cancers. J. Surg. Oncol. 2003;82:19–27. © 2002 Wiley-Liss, Inc.

Background. Cytokeratin immunostaining is the most common method used to identify micrometastatic cancer cells from the lymph nodes. However, contamination with hyalinized cytokeratin particles, frequently observed in the lymph nodes of esophageal cancer patients, can lead to misinterpretation of cytokeratin immunostaining. Materials and methods. Cytokeratin immunostaining (AE1/AE3) of surgically removed lymph nodes was performed for 41 cases of node-negative, but locally advanced (T3, T4), esophageal cancer patients. Cytokeratin immunoreactivity (CK) was classified as micrometastasis (MM) or cytokeratin deposit (CD) by the presence or absence of tumor nuclei in serial sections given hematoxylin–eosin staining. Results. CK (+) was observed in 18 patients (44%), including 11 with MM (+) (27%) and 10 with CD (+) (24%). There was no correlation between MM and CD, and neither was associated with clinicopathological factors, except for a high incidence of preoperative chemotherapy in CD (+) patients. The presence of CK did not affect postoperative survival of esophageal cancer patients at this limited stage, showing a 5-year survival rate of 57% for CK (+) and 64% for CK (−) ( P = 0.6064). Interestingly, patients with MM (+) showed poorer prognosis than MM (−) (5-year survival: 28% vs 79%, P = 0.0188), while CD (+) patients tended to display better prognosis than CD (−) ones (5-year survival: 78% vs 56%, P = 0.1860). Conclusions. Evaluation by cytokeratin immunostaining of lymph nodes requires careful discrimination of CD from MM, in order to allow MM to be used as a prognostic factor for esophageal cancer patients.

Objective: S100A6 and S100A4, two of S100 protein family, have been suggested to be associated with cancer tumorigenesis and metastasis. The aim of this study was to evaluate the expression levels of S100A6 and S100A4 in matched samples of primary human colorectal adenocarcinomas (T), adjacent normal colorectal mucosa (N) and liver metastases (M). This gave us the advantage of directly comparing levels of S100A6 and S100A4 expression within the same genetic background. Methods: In matched samples of N, T and M from 10 colorectal adenocarcinoma patients, expressions of S100A6 and S100A4 were studied by Western blot and immunohistochemical analyses using specific antibodies against each protein. Results: The expression levels of S100A6 were significantly higher in T than in N (p < 0.05), while those of S100A4 showed no difference between T and N. There were no significant differences in the expression levels of S100A6 or S100A4 between M and T. Similar results were obtained by immunohistochemical analysis. Moreover, S100A6 was stained more intensely in invading fronts than in central portions of both T and M. Conclusions: The observed differential expression of S100A6 and S100A4 suggests that S100A6, rather than S100A4, is associated with human colorectal adenocarcinoma tumorigenesis and invasion/metastasis.

症例は47歳の女性. 2年8か月前に左大腿部皮下軟部腫瘍にて広範切除術施行. 8か月前に同右肺転移にてS8部分切除施行. 今回貧血の精査中に腸重積を発症し手術. 回腸腫瘤を先進部とした横行結腸への重積で, 右半結腸切除を施行した. Bauhin弁より15cm口側に56×45×36mmの有茎性腫瘤を認めた. 病理所見では腫瘍性類骨形成が著明で骨肉腫と診断された. 左大腿部および右肺S8転移巣の病理像では類骨形成が認められなかったため, 当初MFHと診断されていたが, 三病巣の詳細な病理学的検討の結果, 大腿皮下原発の骨外性骨肉腫が肺と小腸に転移したものと結論された. 術後2か月から多臓器に腫瘍が再燃し4か月目に原病死した. 骨外性骨肉腫は成人に発生する予後不良な軟部悪性腫瘍である. 肺転移が多いが小腸転移の報告は極めてまれである. 検索した限りでは本例が6例目であり, 文献的考察を含めて報告した.

597 Background: We reported in a retrospective study that the presence of micrometastasis in lymph nodes (LNs), when assessed by CEA-specific RT-PCR, is a significant prognostic factor in stage II colorectal cancer (CRC). The aim of this study was to clarify the clinical value of micrometastasis in a prospective multicenter trial. Methods: From November 2001 to December 2005, a total of 419 CRC cases were preoperatively registered at a central data center. Of them, 315 node-negative stage II CRC were enrolled. After RNA quality check, 304 CRC cases were analyzed for CEA mRNA in LNs by both conventional RT-PCR (a band method) and quantitative RT-PCR. Long-term prognosis of the patients was determined by each method. Results: A positive band for CEA mRNA was detected in 73 (24.0%) of 304 patients. Post-operative adjuvant chemotherapy was applied in 31 CEA band-positive cases with an oral 5-FU derivative HCFU (1-hexylcarbamoyl-5-fluorouracil) for one year, while chemotherapy was not administered to CEA band-negative group. Multivariate Cox regression analyses revealed that a high micrometastasis volume (High-MMV, n = 95) was an independent poor prognostic factor for 5-year DFS ( P= 0.001) and 5-year OS ( P= 0.016). Conclusions: This prospective clinical trial demonstrates that micrometastasis volume is a useful marker in identifying patients who are at high or low risk for recurrence of stage II CRC.

Background Postoperative adjuvant chemotherapy for patients with stage III Colorectal cancer (CRC) is now internationally accepted as standard care for improving patient outcomes. The Adjuvant Chemotherapy Trial of S-1 for Colorectal Cancer (ACTS-CC) confirmed the non-inferiority of S-1 to tegafur/urcail/leucovorin in terms of overall survival and disease-free survival in patients with stage III CRC after curative surgery. However, the 6-month completion rate of S-1 treatment was 76.5 % in the ACTS-CC. Therefore, treatment completion remains an unresolved problem. Methods/Design A randomized phase II trial was designed to evaluate the efficacy and safety of oral daily administration and alternate-day administration of S-1 as adjuvant chemotherapy in curatively resected stage III CRC. Enrolled patients were assigned to either S-1 daily administration (Arm A) or alternate-day S-1 administration (Arm B). Assigned treatment will start within 8 weeks after surgery. In both arms, S-1 dosing (oral) will be based on body surface area (80 mg/day for body surface area 1.5 m2). In Arm A, S-1 will be administered orally for 28 days, followed by a 14-day rest. Administration will be conducted for 24 weeks from the date of therapy start. In Arm B, S-1 will be administered orally on alternate days for 28 weeks from the date of the start of therapy. After treatment, all patients will be observed without additional therapy unless recurrent lesions or other cancer lesions occur. The primary endpoint is treatment completion rate. Secondary endpoints include 3-year disease-free survival, compliance, and adverse events. Discussion Previously, S-1 alternate-day intake maintained the efficacy of chemotherapy while reducing adverse effects for patients with R0-resected stage II/III gastric cancer. Improvement of chemotherapy completion rate for patients with colorectal cancer will lead to an improved patient prognosis. Therefore, a randomized phase II trial has been designed to examine the efficacy of alternate-day versus current standard daily S-1 administration as adjuvant chemotherapy for R0-resected stage III colorectal cancer. Trial registration This study was registered on 18 February 2014 with University Hospital Medical Information Network Clinical Trials Registry: UMIN000013185 Electronic supplementary material The online version of this article (doi:10.1186/s12885-015-1476-6) contains supplementary material, which is available to authorized users.

This phase II trial was performed to evaluate the efficacy and tolerability of tegafur/uracil (UFT) and oral leucovorin (LV) in elderly patients with advanced or metastatic colorectal cancer who had not received prior chemotherapy.Patients agedor = 70 years were eligible. UFT and LV were taken orally on days 1-28 of the cycle at doses of 300 mg/m2/day and 75 mg/m2/day, respectively. Treatment was administered on an outpatient basis every 35 days and consisted of at least two cycles until disease progression.A total of 30 patients were enrolled in this study. The median age of the patients was 81.5 years (range: 74-88 years). The observed overall response rate was 17.9%. The estimated median overall survival time was 23.5 months. Two patients (7%) experienced toxicities with a worst grade of 3, and one patient (4%) experienced toxicities with a worst grade of 4. There were no treatment-related deaths. No patients experienced grade 3 or 4 hematological adverse events.Although the response rate to UFT/LV was moderate, a favorable survival time was observed. Lower hematological adverse event rate of UFT/LV may introduce second line therapy safely to elderly colorectal cancer patients and contribute longer survival.

Recent studies have suggested that microRNA-29 (miR-29) family members may play important roles in human cancer by regulating cell proliferation, differentiation, apoptosis, migration, and invasion. The present study aimed to investigate the clinical significance and biological function of miR-29b in colorectal cancer (CRC). Real-time polymerase chain reaction was used to quantify miR-29b expression. The association between miR-29b and survival was evaluated in 245 patients with CRC. We transfected an miR-29b mimetic into CRC cells to explore the functional role of miR-29b in vitro, based on a proliferation assay, flow cytometry, and Western blotting. In clinical samples of CRC, miR-29b expression was significantly reduced in tumor tissues compared with normal mucosa (p

はじめに: 大腸手術における自動縫合器を用いたfunctional end-to end法では, 縫合器の腸管内への挿入が必要なため, 腸管閉鎖時に腹腔内汚染を伴い, 術後創感染の原因となることが予想される. そこで, 0.5%グルクロン酸クロルヘキシジンによる自動縫合器の消毒を施行し, 施行以前の非消毒例との比較検討を行った. 対象・方法: 大腸癌手術症例のうち, 前期非消毒24例 (C群) と, 0.5%グルクロン酸クロルヘキシジンにて30秒間自動縫合器消毒を行った後期消毒22例 (S群). 結果: S群の19例に細菌学的検討を行い, 消毒前後の接触培養にて細菌検出率が79%から16%と有意に減少した(p

Multiple cancer associated with esophageal cancer is not uncommon; however, synchronous esophageal and renal cell carcinoma is very rare. Only three cases have been reported to date, and one of these patients was treated in our institution. We have since successfully treated another patient. Here, we report the two cases treated in our institution. In the first case, esophagectomy, nephrectomy, and reconstruction using a gastric tube were carried out in one stage. Post-operative renal function was temporarily impaired by the complications of anastomotic leakage and pyothorax but no hemodialysis was needed. In the second case, as the patient had undergone distal gastrectomy because of gastric cancer, we chose a two-stage operation, i.e. esophagectomy and nephrectomy as the first stage, followed by reconstruction using a colon substitute after 4 weeks, resulting in only slight renal dysfunction. Patients 1 and 2 are alive and well 7 years and 2 years after the operations respectively.

To investigate mechanisms for regulation of intracellular cAMP involved in cancer cell invasion, phosphodiesterase (PDE) activity in a colon cancer cell line, DLD-1, was studied. Activities of PDE 2, 4, and 5 were detected in DLD-1 cells by pharmacological approach. Specific and cell permeable inhibitors for those PDEs were used to determine which PDE is responsible for cAMP turnover involved in cancer cell motility. Treatment of DLD-1 cells with rolipram and Ro-20-1724, inhibitors for PDE 4, elevated intracellular cAMP contents three to five times of control. EHNA, an inhibitor for PDE 2, and zaprinast, an inhibitor for PDE 5, did not affect cAMP levels. To assess cellular motility, we utilized chemotaxis assay. EHNA and zaprinast did not suppress serum-induced chemotaxis. In contrast, rolipram and Ro-20-1724, suppressed chemotaxis in a dose dependent fashion. These suggest that PDE 4 plays a critical role in regulating intracellular cAMP levels of colon cancer cells and is involved in cancer invasion. PDE 4 can be a novel target of anti-invasion drug.

The effect of a naturally occurring flavonoid apigenin on the development of bombesin-enhanced peritoneal metastasis from intestinal adenocarcinomas induced by azoxymethane was investigated in male Wistar rats. From the start of the experiment, rats were given weekly s.c. injections of azoxymethane (7.4 mg/kg body weight) for 10 weeks and s.c. injection of bombesin (40 μg/kg body weight) every other day, and from week 16, s.c. injections of apigenin (0.75 or 1.5 mg/kg body weight) every other day until the end of the experiment in week 45. Bombesin significantly increased the incidence of intestinal tumors and cancer metastasis to the peritoneum in week 45. It also significantly increased the labeling index of intestinal cancers. Although administration of apigenin at either dose with bombesin had little or no effect on the enhancement of intestinal carcinogenesis by bombesin, the location, histologic type, depth of involvement, infiltrating growth patterns and labeling index, it was found to decrease significantly the incidence of cancer metastasis. Apigenin significantly decreased the incidence of lymphatic vessel invasion of adenocarcinomas, which was enhanced by bombesin. In vitro experiments revealed that apigenin inhibited bombesin-enhanced phosphorylation of mitogen-activated protein kinase (MAPK), but not matrix metalloprotease (MMP)-9 expression. Our findings indicate that apigenin inhibits cancer metastasis through inhibition of phosphorylation of MAPK.

子宮体部から大腸への転移は, 自験例を含め本邦報告2例とまれであり, 今回, 子宮体癌の上行結腸転移に, 悪性リンパ腫を合併した1切除例を経験したので報告する. 症例は, 58歳の女性. 子宮体癌 (高分化腺癌) にて準広範子宮全摘術施行. 2年8か月後に腟断端再発をきたし, CDDP 120mg, CPA1,000mgの投与を3クール, 骨盤内に総量60Gyの放射線照射を行った. 1か月後右上腹部痛出現, 上行結腸に径4cm大の腫瘤を認め, 結腸右半切除 (D3郭清) 施行. 迅速組織診にて, 骨盤腔内に子宮体癌の再燃を確認, 一方, 結腸切除標本における病巣の主座は粘膜下層にあり, 組織像も酷似しており子宮体癌の大腸転移と診断した. また, リンパ節の迅速組織診にて悪性リンパ腫の所見を得た. 現在, 再燃傾向なく生存中. 放射線や化学療法が奏効しやすい子宮癌の術後には, 造血器腫瘍も念頭に置いたフォローが望まれる.

Background: Endoscopic resection for treatment of early gastric cancer (EGC) is widely performed. Recently, however, surgeons began performing a limited operation for EGC when endoscopic resection was not indicated. This report discusses the surgical technique and the results of the limited operation, which is generally referred to as “segmental resection” (SR). Methods: Since 1990, a total of 50 patients with intramucosal invasive EGC of the middle stomach underwent SR. The procedure included a limited gastrectomy, limited lymph node dissection, and preservation of the vagal nerve. We examined the surgical risk, postoperative complications, and patient survival rates and compared the results for the SR-treated patients (group A) with results for patients with EGC who underwent subtotal gastrectomy and systemic lymph node dissection (group B). Results: Blood loss was less in group A (239±180 ml) than in group B (342±176 ml) (P