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DUSP6 (alias PYST1), one of the dual-specificity tyrosine phosphatases, is localized on 12q21, one of the regions of frequent allelic loss in pancreatic cancer. This gene is composed of three exons, and two forms of alternatively spliced transcripts are ubiquitously expressed. Although no mutations were observed in 26 pancreatic cancer cell lines, reduced expressions of the full-length transcripts were observed in some cell lines, which may suggest some role for DUSP6 in pancreatic carcinogenesis. [ABSTRACT FROM AUTHOR]

We report a successful case of gastric cancer with esophageal hiatal hernia treated by laparoscopic surgery. The patient was a 75-year-old woman who was referred to our hospital with a diagnosis of early gastric cancer with esophageal hiatal hernia. Laparoscopic distal gastrectomy with lymph node dissection and esophageal hiatal hernia repair using primary suture method without mesh were performed simultaneously. She had a good postoperative course without the recurrence of both cancer and hernia.

Occurrences of thyroid cancer and breast cancer metachronously or synchronously are common for women. Explanations for these associations include detection bias, shared hormonal risk factors, and genetic susceptibility, but the etiology behind specific associations is not elucidated well. The importance of the relationship between breast and thyroid cancer will continue to become evident and physicians should be aware of this association in caring for thyroid and breast cancer survivors. We report a case of synchronous papillary thyroid cancer and breast ductal cancer.

A 69-year-old woman presented with persistent nauseous, underwent upper gastrointestinal endoscopy, and was diagnosed with type 2 advanced gastric cancer at the antrum. Abdominal contrast CT image data revealed that there was a large, swollen, pancreatic superior lymph node invading the common hepatic artery. We determined that the tumor was unresectable and systemic chemotherapy was performed using S-1 plus oxaliplatin(SOX)therapy. After 5 courses of chemotherapy, the abdominal contrast CT image data indicated reduction of both the primary lesion and lymph node metastasis. A laparotomy was performed. As the No. 8a lymph node was forming hard scar tissue, we could not dissected clearly it from the common hepatic artery wall. We strongly suspected that cancer tissue remained at the artery wall. A distal gastrectomy and Roux-en-Y reconstruction were performed. Histologically, the resected specimen was determined to be Grade 3, with a pathological complete response(pCR). The patient was administered S-1 for 6 months after the operation and has enjoyed 2.5 years of recurrence-free survival. SOX therapy for unresectable gastric cancer and surgical intervention as conversion surgery were effective. This case demonstrated the possibility of life prolongation using these therapies.

Purpose: Postoperative pneumonia affects the length of stay and mortality after surgery in elderly patients with colorectal cancer (CRC). We aimed to determine the risk factors of postoperative pneumonia in elderly patients with CRC, and to evaluate the impact of laparoscopic surgery on elderly patients with CRC., Methods: We retrospectively investigated 1473 patients ≥ 80 years of age who underwent surgery for stage 0-III CRC between 2003 and 2007. Using a multivariate analysis, we determined the risk factors for pneumonia occurrence from each baseline characteristic., Results: Among all included patients, 26 (1.8%) experienced postoperative pneumonia, and restrictive respiratory impairment, obstructive respiratory impairment, history of cerebrovascular events, and open surgery were determined as risk factors (odds ratio [95% confidence interval], 2.78 [1.22-6.20], 2.71 [1.22-6.30], 3.60 [1.37-8.55], and 3.57 [1.22-15.2], respectively). Furthermore, postoperative pneumonia was more frequently accompanied by increasing cumulative numbers of these risk factors (area under the receiver operating characteristic curve = 0.763)., Conclusions: Laparoscopic surgery may be safely performed in elderly CRC patients, even those with respiratory impairment and a history of cerebrovascular events.

Background: Adjuvant chemotherapy with oral fluoropyrimidine alone after D3/D2 lymph node dissection improves disease-free survival and overall survival in patients with stage III colon cancer. Adjuvant S-1 has been shown to be non-inferior to uracil and tegafur plus leucovorin in terms of disease-free survival. This study aims to confirm the non-inferiority of S-1 compared with capecitabine as adjuvant treatment in patients with stage III colorectal cancer., Methods: This study was an open-label, non-inferiority, randomised, phase 3, multicentre trial done in 56 Japanese centres to assess the non-inferiority of S-1 to capecitabine as adjuvant chemotherapy. Eligible patients were aged 20-80 years with stage III colorectal adenocarcinoma, as defined by the presence of an inferior margin of the primary tumour above the peritoneal reflection; R0 resection; and colectomy with D3 or D2 lymph node dissection. Patients were randomly assigned (1:1) to receive eight courses of capecitabine (1250 mg/m 2 orally twice daily, days 1-14, every 21 days) or four courses of S-1 (40 mg/m 2 orally twice daily, days 1-28, every 42 days). Randomisation was done via phone call, fax, or web-based systems to the Japan Clinical Oncology Group Data Center and used a minimisation method with a random component adjusted by institution, tumour location (colon vs rectosigmoid and upper rectum), number of positive lymph node metastases (≤3 vs ≥4), and surgical technique (conventional vs non-touch isolation). The primary endpoint was disease-free survival with a non-inferiority margin for the hazard ratio (HR) set at 1·24, analysed by intention to treat. This trial was registered with UMIN Clinical Trial Registry, number UMIN000003272., Findings: Between March 1, 2010, and Aug 23, 2013, 1564 patients were randomly assigned to capecitabine (n=782) or S-1 (n=782), all of whom were included in the efficacy analysis; 777 patients in the capecitabine group and 768 in the S-1 group were included in the safety analysis. At the prespecified second interim analysis after final accrual, 258 (48%) of 535 required events were reported, and the Data and Safety Monitoring Committee recommended early publication because S-1 could not show non-inferiority compared with capecitabine for disease-free survival. With a median follow-up of 23·7 months (IQR 14·1-35·2), 3-year disease-free survival was 82·0% (95% CI 78·5-85·0) for the capecitabine group and 77·9% (74·1-81·1) for the S-1 group (HR 1·23, 99·05% CI 0·89-1·70; one-sided p non-inferiority =0·46). The most frequent grade 3 or higher adverse events in the capecitabine group were hand-foot skin reactions (123 [16%] of 777 patients), and in the S-1 group were diarrhoea (64 [8%] of 768 patients) and neutropenia (61 [8%]). There was one (<1%) treatment-related death in each group., Interpretation: Adjuvant capecitabine remains one of the standard treatments for stage III colorectal cancer in Japan; S-1 is not recommended., Funding: National Cancer Center and Ministry of Health, Labour and Welfare of Japan., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Postoperative adhesions are the major cause of postoperative complications including intestinal obstruction, infertility, and chronic pelvic pain. In order to reduce postoperative adhesions, Terumo Corporation (Tokyo, Japan) has developed an adhesion barrier system (TCD-11091) which is easy to use at the treatment site in various surgical procedures including laparoscopic surgeries. We conducted a prospective randomized single-blind study in patients who underwent laparotomy with ileostomy., Methods and Results: One hundred twenty-six patients were randomly assigned to TCD-11091 group (n = 62) or non-treatment group (n = 62). Patient backgrounds were similar between the groups. At the time of ileostomy closure (the second-look surgery), the observation was performed on 55 in the TCD-11091 group and 43 in the control group. The incidence of adhesions observed at the second-look surgery was significantly lower in the TCD-11091 group (52.7 versus 90.7%; p < 0.001). For the secondary endpoints, the incidence of wide extent adhesions (grade 2 or higher) was significantly reduced (38.2 versus 79.1%; p < 0.001). Regarding the severity of adhesions, the incidence of grade 2 or higher adhesions was also significantly lower in the TCD-11091 group (47.3 versus 88.4%; p < 0.001). No differences in the incidence of adverse events were found between the TCD-11091 group and the non-treatment group (85.2 versus 75.4%; p = 0.225)., Conclusions: Use of TCD-11091 was safe and associated with significantly lower incidence of adhesion and severity of adhesions compared with non-treatment procedure.

Sphincter-preserving procedures (SPPs) for surgical treatment of low-lying rectal tumors have advanced considerably. However, their oncological safety for locally advanced low rectal cancer compared with abdominoperineal resection (APR) is contentious. We retrospectively analyzed cohort data of 1500 consecutive patients who underwent elective resection for stage II-III rectal cancer between 2010 and 2011. Patients with tumors 2-5 cm from the anal verge and clinical stage T3-4 were eligible. Primary outcome was 3-year local recurrence rate, and confounding effects were minimized by propensity score matching. The study involved 794 patients (456 SPPs and 338 APR). Before matching, candidates for APR were more likely to have lower and advanced lesions, whereas SPPs were carried out more often following preoperative treatment, by laparoscopic approach, and at institutions with higher case volume. After matching, 398 patients (199 each for SPPs and APR) were included in the analysis sample. Postoperative morbidity was similar between the SPPs and APR groups (38% vs 39%; RR 0.98, 95% CI 0.77-1.27). Margin involvement was present in eight patients in the SPPs group (one and seven at the distal and radial margins, respectively) and in 12 patients in the APR group. No difference in 3-year local recurrence rate was noted between the two groups (11% vs 14%; HR 0.77, 95% CI 0.42-1.41). In this observational study, comparability was ensured by adjusting for possible confounding factors. Our results suggest that SPPs and APR for locally advanced low rectal cancer have demonstrably equivalent oncological local control.

Background: Although several markers, including the lymph node ratio (LNR), have been proposed as a clinically prognostic tool for colorectal cancer (CRC), it remains unclear which markers have the most relevance in determining recurrence following adjuvant chemotherapy for stage III CRC., Methods: Independent risk factors for recurrence-free survival (RFS) were retrospectively determined using the Cox proportional hazard model in 360 stage III CRC patients and validated using an independent cohort comprising 172 stage III CRC patients., Results: The LNR was independently associated with RFS (HR, 1.96; 95% CI, 1.11 to 3.28; P = 0.020). A higher LNR value was significantly associated with recurrence, microsatellite stable, and shorter time to recurrence. A combination of the LNR with pre-chemotherapy CEA and CA19-9, other independent risk factors, provided accurate risk stratification of RFS and conferred additional information on recurrence within each stage III CRC subgroup, which was then validated in an independent cohort. A beneficial effect in patients at risk of recurrence, and a reduced effect in patients at low risk, was exhibited by the addition of oxaliplatin to 5-fluorouracil-based adjuvant chemotherapy., Conclusion: A higher LNR is one of the most aggressive phenotypes with recurrence risk following adjuvant chemotherapy for stage III CRC.

Background: Laparoscopic surgery is becoming the preferred technique for most colorectal interventions. This study aimed to clarify the time trend of surgical treatment for familial adenomatous polyposis (FAP) and its relevance to clinical outcomes in Japan over a 13-year period., Methods: This was a multicenter retrospective cohort study comprising 23 specialist institutions for colorectal disease and a cohort of 282 FAP patients who underwent total colectomy or proctocolectomy during 2000-2012. Patient clinical backgrounds and surgical outcomes were compared between the first and second halves of the study period., Results: The proportion of surgical types adopted over the entire study period was 46, 21, 30, and 3 % for ileoanal anastomosis (IAA), ileoanal canal anastomosis, ileorectal anastomosis, and permanent ileostomy, respectively. FAP patients undergoing laparoscopic surgery have increased since 2008 and reached 74 % in the past 3 years. In particular, the number of patients undergoing laparoscopic proctocolectomy with IAA increased approximately four-fold from the first to the second half of the study period. A laparoscopic approach was increasingly used in patients with coexisting colorectal malignancies. Despite this trend, surgical results of the laparoscopic approach between the two study periods showed similar morbidity, pouch operation and stoma closure completion rates. No postoperative mortality was observed in this series, and laparoscopic surgery was comparable to open surgery in terms of stoma closure rate, incidence of intra-abdominal/abdominal desmoid tumors, and postoperative survival rate in both study periods., Conclusion: Laparoscopic approach is increasingly being adopted for prophylactic FAP surgery in Japan and may provide clinically acceptable practical outcomes.

Background: This observational study was conducted to compare the rate of symptomatic anastomotic leakage (AL), as defined by precise criteria, between laparoscopic and open surgery in patients with mid-to-low rectal cancer using a relatively novel statistical technique., Methods: A total of 1014 consecutive low anterior resection (LAR) patients were registered, of whom 936 were included in this prospective, multicenter, and cohort study (UMIN-CTR, Number 000004017). Patients with rectal cancer within 10 cm from the anal verge underwent either open or laparoscopic LAR at one of the 40 institutions in Japan from June 2010 to February 2013. The primary endpoint of this study was to compare the rate of symptomatic AL between the two groups before and after propensity score matching (PSM). The secondary endpoint was to analyze the risk factors for symptomatic AL in open and laparoscopic surgery., Results: After PSM, the incidence of symptomatic AL in open and laparoscopic surgery was 12.4 and 15.3 %, respectively (p = 0.48). AL requiring relaparotomy occurred after 3.8 % of open surgeries and 6.2 % of laparoscopic surgeries (p = 0.37). Multivariate analysis identified male gender as an independent risk factor for symptomatic AL following laparoscopic surgery (p = 0.001; odds ratio 5.2; 95 % CI 2.0-13.8), and male gender (p = 0.004; odds ratio 2.6; 95 % CI 1.3-5.6), tumor size (p = 0.002; odds ratio 1.2; 95 % CI 0.7-0.9), and number of stapler firing (p = 0.04; odds ratio 4.1; 95 % CI 1.0-15.0) following open surgery., Conclusion: The rate of symptomatic AL was comparable following laparoscopic and open LAR in this large, multicenter, cohort study after PSM. Male gender was associated with an increased risk of symptomatic AL after laparoscopic LAR.

Intestinal homeostasis is maintained by complex interactions between intestinal microorganisms and the gut immune system. Dysregulation of gut immunity may lead to inflammatory disorders and tumorigenesis. We previously have shown the tumor suppressive effects of aryl hydrocarbon receptor (AhR) in intestinal carcinogenesis. In the present study, we investigated AhR distribution in the mouse and human intestine by histochemical analysis. In the normal intestine, AhR was mainly localized in the stroma containing immune cells in the lamina propria and lymphoid follicles. On the other hand, in the tumor tissue from human colon cancer and that developed in Apc(Min/+)mice, AhR expression was elevated. AhR immunostaining was found in both stromal and tumor cells. Although AhR was localized in the cytoplasm of tumor cells in most cases, nuclear AhR was also observed in some. AhR knockdown using siRNA resulted in significant promotion of cell growth in colon cancer cell lines. Furthermore, AhR activation by AhR ligands supplemented in culture medium suppressed cell growth. Our study results suggest that tumor suppressive roles of AhR are estimated in two distinct ways: in normal tissue, AhR is associated with tumor prevention by regulating gut immunity, whereas in tumor cells, it is involved in growth suppression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A 67-year-old man was operated for sigmoid colon cancer. Histopathological examination revealed pT3 (SS), N0, M0, Stage Ⅱ cancer. In March 2005, abdominal computed tomography (CT) showed recurrences in the abdominal wall and associated localized dissemination. The patient underwent chemotherapy using TS-1 and CPT-11; however, the disease progressed. Therefore, surgery was performed to resect the recurrences. A re-recurrence developed during the adjuvant chemotherapy. The patient was operated 9 times for recurrences, which were macroscopically resectable, in addition to chemotherapy and radiation. It has been 3 years and 7 months since the last operation, and he is alive with no recurrence. Metachronous peritoneal seeding and distant metastasis developed, but we have observed that surgical resection of each recurrence can prolong patient survival. We conclude that surgical resection can become a treatment of choice for resectable metachronous peritoneal seeding from colon cancer.

Aim: To investigate the prognostic role of KRAS and BRAF mutations after adjustment for microsatellite instability (MSI) status in Japanese colorectal cancer (CRC) population., Methods: We assessed KRAS and BRAF mutations and MSI status in 813 Japanese patients with curatively resected, stage I-III CRC and examined associations of these mutations with disease-free survival (DFS) and overall survival (OS) using uni- and multivariate Cox proportional hazards models., Results: KRAS and BRAF mutations were detected in 312 (38%) of 812 and 40 (5%) of 811 tumors, respectively. KRAS mutations occurred more frequently in females than in males (P=0.02), while the presence of BRAF mutations was significantly associated with the female gender (P=0.006), proximal tumor location (P<0.001), mucinous or poorly differentiated histology (P<0.001), and MSI-high tumors (P<0.001). After adjusting for relevant variables, including MSI status, KRAS mutations were associated with poorer DFS (HR=1.35; 95%CI: 1.03-1.75) and OS (HR=1.46; 95%CI: 1.09-1.97). BRAF mutations were poor prognostic factors for DFS (HR=2.20; 95%CI: 1.19-4.06) and OS (HR=2.30; 95%CI: 1.15-4.71). Neither the BRAF by MSI interaction test nor the KRAS by MSI interaction test yielded statistically significant results for DFS and OS., Conclusion: KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected CRC.

Background: Although mucinous adenocarcinoma (MAC) is has been recognized as a separate entity in colorectal cancer (CRC), adenocarcinoma with a mucinous component (ACM) remains poorly understood., Methods: The association of MAC and ACM with disease-free survival (DFS) and overall survival (OS) was examined using the Cox proportional hazard model in 425 consecutive stage III CRCs., Results: Compared with conventional adenocarcinoma (CAC), patients with MAC exhibited independently worse DFS (hazard ratio [HR], 2.64; 95% CI, 1.21-5.80; P = 0.014) and OS (HR, 3.56; 95% CI, 1.53-8.30; P = 0.003). Unexpectedly, ACM was significantly associated with worse OS than CAC (P = 0.002), despite having a similar DFS to CAC. Further, ACM patients after recurrence exhibited significantly worse OS than CAC patients (P < 0.001), similar to MAC., Conclusions: Although ACM is similar to CAC with regard to estimated risk of recurrence, the outcome is extremely poor once recurrence occurs and is identical to MAC; one of the most aggressive phenotypes of stage III CRC. Thus, both MAC and ACM are adverse prognostic factors for OS., (© 2014 Wiley Periodicals, Inc.)

Background: The clinical relevance of combined microsatellite instability (MSI) and BRAF status for adjuvant treatment in stage III colorectal cancer (CRC) remains elusive., Methods: In 405 patients with curatively resected stage III CRC, the prognostic value of combined MSI and BRAF status was assessed in four groups, as follows: high-levels of microsatellite instability (MSI-H) and BRAF-wild type, MSI-H and BRAF-mutation, microsatellite stable (MSS) and BRAF-wild type, and MSS and BRAF-mutation., Results: Combined MSI and BRAF status provided significant prognostic stratification of disease-free survival (DFS), and was independently associated with worse DFS. The MSI-H and BRAF-wild type group had similar outcomes to stage II CRC patients, despite no benefit from 5-FU monotherapy. Further, patients in the MSS and BRAF-wild type group with stage IIIA CRC had favorable outcomes to 5-FU monotherapy, similar to those with stage II CRC. In contrast, 5-FU monotherapy was insufficient among patients in the MSS and BRAF-wild type group with stage IIIB or IIIC CRC or patients in the MSS and BRAF-mutation group with stage III CRC., Conclusions: The combination of MSI and BRAF status serves as both a prognostic and predictive marker and may provide much-needed guidance during the planning of therapeutic strategies., (© 2014 Wiley Periodicals, Inc.)

When a relatively small anastomotic recurrence of colorectal cancer is detected in the low rectum, trans-anal resection (TAR) might be an option both for curative intent and for preservation of anal function. We report 3 such cases. Case No. 1: A 58-year-old woman presented with an anastomotic recurrence of sigmoid colon cancer. Low anterior resection(LAR)was performed. Two small recurrent nodules were detected at the suture line 1 year after LAR, which were successfully treated with TAR. The depth of the nodules indicated T2 cancer. The patient remained cancer free 5 years after TAR. Case No. 2: A 56-year-old man developed a severe anastomotic stenosis and an anastomotic recurrence 6 months after LAR for low rectal cancer. TAR was performed circumferentially to resect both the stricture and the recurrence. The depth of the nodule indicated T2 cancer. The patient was cancer free for 7 years after TAR. Case No. 3: A 54-year-old man developed 2 small recurrent nodules at the suture line after LAR for low rectal cancer. TAR was performed. The depth of the nodule indicated T1 cancer. One of the nodules was not resected, which necessitated intersphincteric resection (ISR) 10 months later. In conclusion, in cases of a relatively small recurrence of low rectal anastomosis after colorectal cancer surgery, TAR is an effective treatment option.

We experienced three hepatectomies in patients with a history of bile duct-gastrointestinal (GI) tract anastomosis at the porta hepatis. Patient 1 had a history of pancreaticoduodenectomy for bile duct cancer. Because the third liver metastasis of cecal cancer postoperatively invaded the right kidney, after 5 courses of FOLFOX we performed partial resection of the liver (S6) and the right kidney using microwave pre-coagulation and a cavitron ultrasonic surgical aspirator (CUSA) without the Pringle method. Patient 2 had a history of splenectomy for congenital spherocytosis, cholecystectomy, choledocholithotomy, and bile duct duodenal anastomosis for hepatolithiasis. Partial (S5) liver resection was performed to treat hepatocellular carcinoma. Patient 3 had a history of bile duct resection and choledochojejunostomy for congenital cystic dilatation of the common bile duct. She had repeated episodes of cholangitis in the year following surgery. Extended liver segmental (S4) resection was performed to treat intrahepatic bile duct carcinoma. Bile duct jejunum anastomosis was performed, and the portal vein and the hepatic artery in the porta hepatis were exfoliated. Hepatectomy was performed using the Pringle method and a CUSA. Surgical procedures using various devices are necessary for hepatectomy in patients with a history of bile duct-GI tract anastomosis at the porta hepatis.

A 6 8-year-old man was admitted to our hospital with lower abdominal pain. Lower gastrointestinal endoscopy showed type 2 advanced cancer in the ascending colon. Histopathological examination after endoscopical biopsy revealed both moderately differentiated adenocarcinoma and well-differentiated squamous carcinoma. Subsequently, right hemicolectomy was performed. The tumor was 55 × 40 mm in size and was diagnosed as an adenosquamous carcinoma A, type 2, pSS, pN0, sH0, sP0, sM0, fStageII. Adenosquamous carcinoma is extremely rare, represents about 0.1% of all colorectal cancer, and usually has a poor prognosis. Thirty-one months after surgery, the patient is still in good health and displays no signs of recurrence.

A 66-year-old man presented to the urology clinic with hematuria. Cystoscopy with biopsy was performed for suspected bladder cancer, and a pathological diagnosis of adenocarcinoma was made. Colonoscopy revealed sigmoid colon cancer, and he was referred to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) showed sigmoid colon cancer with urinary bladder invasion. Sigmoidectomy with lymph node dissection and partial cystectomy were performed under laparotomy. The pathological diagnosis was moderately differentiated adenocarcinoma: T4b (bladder), N1, M0, and the bladder margin was negative. Four months after surgery, CT revealed a small mass in the bladder. Cystoscopy showed a papillary pedunculated tumor at the bladder trigone, and a transurethral resection was performed. Pathological examination revealed a moderately differentiated adenocarcinoma, similar to the prior sigmoid colon cancer, which was diagnosed as an intravesical recurrence of the tumor. More than 8 years after the transurethral resection, the patient has shown no signs of recurrence.

At present, molecular markers of colorectal cancer (CRC), including KRAS, NRAS and BRAF mutations, and the microsatellite status are evaluated for the development of personalized treatments. However, clinicopathological and molecular characteristics and the prognostic role of NRAS mutations remain unclear. In the present study, a total of 1,304 consecutive stage 0-IV CRC tumor samples were analyzed for KRAS (exon 2, 3 and 4), NRAS (exon 2 and 3) and BRAF (exon 15) mutations. Multivariate analysis was performed to assess the prognostic impact of NRAS mutations. KRAS, NRAS and BRAF mutations were identified in 553 (42.4%), 35 (2.7%), and 59 (4.5%) of 1,304 CRC cases, respectively. Tumors with NRAS mutations were more frequently located in the distal colorectum compared with those with KRAS or BRAF mutations. Multivariate analysis indicated that KRAS and BRAF mutations were found to be associated with poor prognosis [hazard ratio (HR)=1.44, 95% confidence interval (CI), 1.18-1.76 and HR=2.09; 95% CI, 1.33-3.28, respectively], whereas NRAS mutations were associated with a trend toward favorable prognosis (HR=0.53; 95% CI, 0.27-1.03). Characteristics and prognosis of CRC with NRAS mutations are different from those with KRAS or BRAF mutations.

Background: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis., Methods: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum., Results: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection., Conclusions: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

The MSH6 gene is one of the mismatch repair genes involved in Lynch syndrome and its mutations account for 10-20% of Lynch syndrome. Although previous studies suggested that the difference of the geographical region affects the clinical phenotype of Lynch syndrome, there has been no report on the detailed features of Japanese Lynch syndrome patients carrying an MSH6 mutation. The aim of the present study was to investigate the clinical and molecular features of MSH6 mutation carriers in Japan. Surgically resected 1720 colorectal carcinoma specimens were screened by microsatellite instability (MSI) testing and the MSI-high cases were subjected to a germline mutation analysis of the mismatch repair genes MLH1, MSH2 and MSH6. We investigated the clinical and molecular features of the MSH6 variants, such as the family cancer history, pathological findings, immunohistochemistry, methylation status of the MLH1 promoter and BRAF mutation in the colorectal tumor. Furthermore, the impact of the missense variants on MSH6 protein was predicted by using in silico tools. We identified nine novel pathogenic mutations and eight unclassified missense variants. Among the eight missense variants, three were suspected pathogenic by in silico analysis. We also found that most colorectal cancers in the MSH6 mutation carrier were diagnosed after the age of 50 and were localized distally. Furthermore, the mean age at diagnosis of endometrial cancer in Japanese MSH6 mutation carriers (49.2 years) was earlier than previous reports from Western countries (56.5 years). These results may improve the surveillance program for Japanese MSH6 mutation carriers.

A 69-year-old woman with chronic hepatitis B and esophageal varices was admitted to our hospital because of a hepatocellular carcinoma( HCC) measuring 3 cm in segment S3. Computed tomography( CT) scan revealed splenomegaly, and the platelet count was 6.0×104/μL. Partial hepatectomy and splenectomy were performed sequentially under laparoscopic guidance in a right half-lateral decubitus position, using 7 working ports. The operation time was 237 min, and the amount of bleeding was 26 mL. Her postoperative course was uneventful, and she was discharged on the 10th day after the operation.

We examined the clinical course of patients with multiple liver metastases (≥10) from colorectal cancer after hepatectomy. Of 455 patients, 336 patients had 1-4 metastases, 71 had 5-9 metastases, and 48 had ≥10 metastases (31 patients had undergone chemotherapy along with hepatectomy and 17 had not undergone chemotherapy). Chemotherapy was effective in improving the 5-year survival rate of patients with 5 or more metastases. The 5-year survival rate in patients who underwent hepatectomy along with chemotherapy (52.7%[1-4 metastases], 49.9%[5-9 metastases], and 42.3% [≥10; n=5]) was better than that in patients who did not undergo chemotherapy( 56.1%[not significant: ns], 13.1% [p=0.0003], and 0%[p<0.0001], respectively). Five patients with ≥10 liver metastases survived for 5 years after hepatectomy, of which, 1 received FOLFOX (Leucovorin plus 5-FU plus oxaliplatin) adjuvant chemotherapy, 2 received preoperative FOLFOX, and 2 received LV5FU2 (5-FU plus Leucovorin) hepatic arterial infusion chemotherapy. Our results suggest that long-term improvement in prognosis could be possible with aggressive repeat hepatectomy along with effective chemotherapy.

An upper gastrointestina(l GI) series revealed a diverticulum in the anterior wall of the middle thoracic esophagus of a 72-year-old man. Endoscopy revealed a type 0-IIc lesion in the esophageal diverticulum. The margin of the lesion was unclear. Biopsy proved that it was squamous cell carcinoma. Endoscopic ultrasonography showed that the deepest layer of the tumor was the lamina propria mucosae (cT1a-LPM) and that the underlying muscularis propria was thinning. No distant metastasis or regional lymph node metastasis was detected. Diverticulectomy or endoscopic submucosal dissection (ESD) was out of indication due to the unclear margin and thin muscularis propria. We conducted mediastinoscopy-assisted esophagectomy. The pathological diagnosis of the resected specimen was moderately differentiated squamous cell carcinoma with invasion to the lamina propria mucosae (pT1a-LPM). Pathological examination proved the thinning of the underlying muscularis propria in the diverticulum. The patient is alive without recurrence at 6 months after surgery.

Endoscopic local resection is currently feasible for the treatment of early colorectal cancer (CRC) with submucosal invasion. Approximately 10% of patients with CRC with submucosal invasion have lymph node( LN) metastasis. The JSCCR guidelines have established surgical indications following endoscopic treatment based on analysis of patients with submucosal invasive CRC( T1 CRC) who had undergone further surgical resection. We reviewed the outcomes of 314 patients who had undergone surgical resection for T1 CRC from 2001 to 2009. The incidence of LN metastasis overall and in cases treated by further bowel resection was 10.5% and 10%, respectively. Curative surgical resection was performed in all cases. Recurrence occurred in 17 cases( 5.4%), including 14 cases exhibiting distant metastases; the other cases of recurrence exhibited LN metastasis,local recurrence, and peritoneal dissemination. There was no statistically significant difference in postoperative survival between patients treated by D2 dissection and D3 surgery.

In gastric tube reconstruction, anastomotic leakage and stricture occasionally occur. Additionally, new or recurrent cancer may occur in the esophageal remnant or at the anastomotic site. Such complications, after cervical anastomoses, led to our adoption of a procedure to approach the anastomosis by manubrium and proximal left clavicle resection. This procedure was applied to seven patients between April 2000 and March 2011. The mean age of the patients was 69.9 years (range, 65-76 years); all were men. The mean operative time was 506 min (range, 374-845 min), with an average blood loss of 297 ml (range, 180-606 ml). Esophagogastric anastomoses were performed in two cases, and free jejunal graft transplantations were performed in the remaining five cases; oral intake became possible for all patients. Limited range of motion or other movement disorders of the neck and upper limbs, due to the upper sternum and clavicle resection, were not observed. This invasive surgical procedure can be acceptable for patients who are facing life-threatening consequences or significant decreases in quality of life and are resistant to conservative treatment.

Background/aims: We performed staging laparoscopy (SL) for advanced gastric cancer with suspicion of positive peritoneal cytology (CY) or peritoneal metastasis (P). This study was designed to show SL's utility in advanced gastric cancer., Methodology: This was a retrospective study of 124 patients with primary gastric cancer who underwent SL between October 2001 and March 2009., Results: There were no perioperative complications without a case of bleeding. The patient breakdown was P0CY0, 67; P0CY1, 19; P1CY0, 6; and P1CY1, 32. Chemotherapy was administered as the initial treatment in 33 patients and the period from SL to chemotherapy was 19.5 days. In 7 patients undergoing laparotomy as the initial treatment but later requiring exploratory laparotomy or palliative surgery followed by chemotherapy, the period from laparotomy to chemotherapy was 36.8 days. The difference was significant (p<0.0001). P1 was confirmed in 10 (14.5%) of 69 patients undergoing laparotomy as the initial treatment. CY was re-examined in 53 of these 69 patients and CY1 was confirmed in 6 (13.3%) of 45 patients who were CY0 according to SL., Conclusion: With SL, early initiation of chemotherapy was possible for P1 patients. Although improved accuracy is required, SL, which can be carried out safely with minimal invasiveness, was suggested to be useful.

We report a rare case of a 78-year-old woman with metachronous axillary lymph node metastasis originating from descending colon cancer. Her past medical history included right mastectomy for breast cancer at age 53 and distal gastrectomy for gastric cancer at age 70. She underwent a left hemicolectomy for descending colon adenocarcinoma in April 2011. Four months after that operation, 3 enlarging nodules in the left lung and a swollen left axillary lymph node were detected by computed tomography. No tumor was detected in the left breast by ultrasonography and mammography. The lung tumors were resected thoracoscopically, and the left axillary lymph node was excised. These specimens were histologically diagnosed as moderately differentiated adenocarcinoma, which had metastasized from colon cancer, not from the previous breast or gastric cancer. She received adjuvant chemotherapy with uracil and tegafur (UFT) plus Leucovorin for 6 months and is still alive after 12 months without recurrence.

In many practical cases, we cannot perform further surgical treatment for patients with T1 lower rectal cancer after local excision due to the patient's desire to avoid abdominoperineal resection. We reviewed the outcome of 15 patients in which local excision was performed for T1 lower rectal cancer from 2001 to 2009. The cases were classified into 3 groups [SM1 (n=3), SM2 (n=11), and SM3 (n=1)] by dividing the submucosal layer equally. In the initial operation, the round margins of all resected specimens were negative for cancer cells. We performed only 1 additional bowel resection after initial local excision for the SM3 case. The specimen removed by ultra-low anterior resection revealed lymph node metastasis in the mesorectum. Among the SM2 cases, recurrence occurred in only 1 patient, and ultra-low anterior resection was performed after the diagnosis of recurrence. Even though patients who had cancer with SM2 invasion did not undergo further bowel resection due to having other cancers or comorbidities or because of personal preference, there have been no other recurrences.

A 51-year-old male presented with lower abdominal mass and thigh and lumbar pain. CT scan showed a large retroperitoneal tumor compressing the lumbar vertebrae and IVC. Arterial infusion of mitomycin C, epirubicin and DSM was performed for unresectable tumor. The tumor was shrunken and the infusion repeated in 6 and 10 weeks later until right femoral palsy occurred. Radical resection with lumbar fascicles and psoas muscle and IORT (25 Gy) was performed. Local recurrence appeared before the sacrum in the next year. Arterial infusion and resection was done. Local recurrence invading the right common iliac artery was found five years later. The tumor and the artery were resected, followed by extra-anatomical ilio-iliac bypass. Local recurrences occurred in the 6th, 7th and 9th year. Radiation therapy was effective. But for the last recurrence, no radiation was applicable because of over dosage. As the most important thing in the treatment of MFH is to resect the tumor with curative margin at the initial operation, and the retroperitoneum and pelvic cavity are not good places to obtain good margins, multimodal treatment including irradiation should have been considered even preoperatively. Also consultation with orthopedic oncologists, radiologists, vascular surgeons and team practice are essential to get curative margins.

We report a rare case of a 68-year-old man with long-term survival after a surgical treatment of solitary metachronous small intestinal metastasis from lung cancer. He underwent a right upper lobectomy for primary lung adenocarcinoma. Thirty -four months after the operation, a tumor of small bowel was detected by computed tomography. The tumor was resected and diagnosed as a metastasis from lung cancer. Eighteen months after resection of metastasis, a tumor located at mesentery of the jejunum was pointed out. The tumor was resected and also diagnosed as a metastasis from lung cancer. The postoperative course was uneventful, and the patient is still alive without recurrence for 3 years after the last operation. We reviewed of 222 Japanese cases that underwent a resection of small intestinal metastasis from lung cancer. Although the prognosis was extremely poor for those who underwent a resection of the primary lung cancer and who had no remnant metastatic lesion at the time of metastasectomy, they seem to have a longer survival time.

A 61-year-old woman, who had undergone total gastrectomy and distal splenopancreatectomy with Roux-en Y reconstruction for a gastric cancer 16 years earlier, was found primary small intestinal cancer located in intestinal loop of Roux- en Y in gastrointestinal endoscopy for abdominal pain. Computed tomography showed liver metastases which were 8 cm in diameter at lateral segment and 1 cm in diameter at segment 8 of the liver. In the operation, the small intestinal cancer was located in the ρ-anastomosis in the loop of Roux-en Y with the other jejunum fistula. We performed lateral segment hepatectomy, partial hepatectomy of segment 8, partial resection of small intestine including loop of ρ-Roux-en Y, partial resection of transverse colon, and restoration Roux-en Y again. We succeeded in preserving double tract anastomosis at duodenum. Histological examination revealed a moderately differentiated adenocarcinoma of the small intestine and segment 8 of the liver, and angiomyolipoma of lateral segment of the liver. It is extremely rare for small intestinal cancer to arise in a loop of Roux-en Y reconstruction caused by total gastrectomy.

A 56-year-old woman was referred to our hospital because of melena. After examinations she was diagnosed with rectal cancer. Anterior resection was performed and the final diagnosis was Stage IIIa. She was treated with adjuvant chemotherapy consisting of UFT/Uzel for one year, followed by UFT alone for one year. Two years after the surgery, abdominal CT suggested solitary paraaortic lymph node metastasis. As the patient denied a surgical treatment, mFOLFOX6 chemotherapy was induced. However, the patient developed a grade 3 allergic side effect, FOLFIRI was administered. Six months after the chemotherapy was started, the paraaortic lymph node metastasis had disappeared. After 50 courses, the case was considered to have achieved a clinical CR which has been maintained now. FOLFIRI was effective for recurrent rectal cancer with paraaortic LN metastasis.

A 72-year-old man underwent sigmoidectomy for sigmoid colon cancer in January 1999. Histopathological examination revealed a moderately differentiated adenocarcinoma, tub 2, SS, ly2, v2, N1, H0, P0, M0, Stage IIIa, cur A. In March 2001, he complained of an anal bleeding and underwent colonoscopy. It showed a submucosal tumor 15 mm in diameter at the anal canal and the biopsy indicated a moderately differentiated adenocarcinoma. This tumor was suspected of metastasis from sigmoid colon cancer and transanal resection was performed in May 2001. Histopathological examination revealed a moderately differentiated adenocarcinoma, which was the same histological type as primary sigmoid colon cancer, tub 2, A, ly2, v2, RM0. The diagnosis of anal metastasis was made on the basis of three points. First, tumor was covered with anal epithelium. Secondly, there were severe lymphatic and venous involvements. Thirdly, there were no findings of other primary anal cancer. By removing anal canal metastases twice, inguinal lymph node metastases three times and lung metastases in each time, he survived for 11 years after a primary surgery. We reported here because it was a very interesting and rare case that the patient was cancer-free after surgeries as many as seven times.

The patient was a 76-year-old woman. One year ago, she was diagnosed as ascending colon cancer with the multiple metastases. Chest and abdominal CT showed more than 50 metastases in the liver, lung metastasis and the lesser curvature lymph metastases. She was received chemotherapy (mFOLFOX6, 5-FU/LV regimen). After 10 months, CT showed disappearance of lung metastasis and a reduction of liver metastases. We diagnosed as resectable. She had undergone right hemicolectomy, dissection of the lesser curvature lymph nodes, partial hepatectomy (17 places) and microwave coagulonecrotic therapy for liver metastases (20 places). After the operation, the number of platelets decreased from 14 × 10(4) to 30 × 10(4)/mm3. Anticoagulant therapy was effective and the platelet count increased. Postoperative bleeding, infection and liver dysfunction were not confirmed. We assumed the cause of thrombocytopenia was local intravascular coagulation due to ablation of the liver.

A case of hepatocellular carcinoma, successfully treated with multimodal loco-regional treatments, is reported. An 80-year-old male presented with multiple pulmonary and peritoneal metastases 4 months after right heimihepatectomy for ruptured HCC. Bronchial artery infusion of mitomycin C induced pulmonary tumor regression and stabilization. Peritoneal tumor was treated by arterial infusion of SMANCS, followed by percutaneous injection of absolute ethanol, which ended in surgical removal in 28-postoperative month due to abscess formation. He had been well until right adrenal and left pulmonary metastases appeared. Resection of both metastases was carried out in 39-post hepatectomy month. Recurrent left pulmonary metastasis was treated with two sessions of bronchial artery infusion with no effect this time. Video-assisted partial resection of the left lung was performed in 54 post-hepatectomy month. But his AFP level kept rising. Eventually pulmonary metastasis recurred and tumor thrombus reached the left atrium 58 months after hepatectomy. He wanted no more treatment. He died of cerebral infarction caused by tumor thrombus. He enjoyed a good QOL for five years through multimodal loco-regional treatments.