Correction to: Purse-string approximation vs. primary closure with a drain for stoma reversal surgery: results of a randomized clinical trial.

In the original publication, surname of first author is misspelt as "Amamo". It should be "Amano" as given in this Correction.

Purse-string approximation vs. primary closure with a drain for stoma reversal surgery: results of a randomized clinical trial.

PURPOSE: Stoma reversal carries a risk of surgical site infection (SSI). Purse-string approximation (PSA) has been reported as an attractive alternative to conventional primary wound closure for stoma reversal, but its efficacy is still under debate. METHODS: Patients undergoing elective stoma reversal were randomized to undergo PSA or primary closure with a drain (PCD). All patients received preoperative bowel cleansing and antimicrobial prophylaxis. The primary endpoint was the incidence of wound healing at the stoma site 30 days after surgery. The secondary endpoint was the 30-day SSI rate after surgery. RESULTS: A total of 159 patients (PCD group, n = 79; PSA group, n = 80) were eligible for this study. The incidence of wound healing at the stoma site was 92.4% in the PCD group and 62.5% in the PSA group [difference (95% confidence interval - 29.9% (- 42.9 to - 16.9%)]. The 30-day SSI rate at the stoma site, as the secondary endpoint, was 8.9% in the PCD group and 5.0% in the PSA group (P = 0.35). CONCLUSIONS: These results suggest that PCD may remain the standard procedure for stoma reversal surgery.

Prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancer in a Japanese hospital-based population.

BACKGROUND: The prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancers in the Japanese population have scarcely been investigated. METHODS: Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary epithelial ovarian cancers in patients who underwent oophorectomy at our institution between April 2005 and September 2014. Genetic and/or epigenetic alterations of the mismatch repair genes were investigated in patients with loss of any mismatch repair proteins in the tumor. RESULTS: There were 305 patients with a median age of 54 years (range, 18-83 years). Loss of expression in the ovarian tumor of one or more mismatch repair proteins was observed in 3 of the 305 patients (0.98%): 2 patients MLH1/PMS2 loss and 1 patient showed MSH2/MSH6 loss. Genetic testing of these three patients failed to reveal any pathogenic germline mutations of MLH1 or MSH2. One patient with MLH1/PMS2 loss showed hypermethylation of the promoter region of MLH1. Somatic mutations were found in each of the alleles of MLH1 (c.545dupG and deletion of exons 2-19) in the other patient with MLH1/PMS2 loss. In the patient with MSH2/MSH6 loss, two somatic mutations were detected in MSH2 (c.229_230delAG and c.1861C>T), although we could not determine whether these mutations were biallelic or not. CONCLUSIONS: The prevalence of defective mismatch repair epithelial ovarian cancer in the Japanese hospital-based population was extremely low. Molecular mechanism involved in such defective mismatch repair ovarian cancers seems to be epigenetic events through MLH1 promotor hypermethylation or somatically mutated mismatch repair genes without germline mismatch repair mutation.

[A Case of Cecal Cancer Associated with Preoperatively Diagnosed Lynch Syndrome Caused by EPCAM Deletion].

A 43-year-old woman underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy for endometrioid adenocarcinoma of the uterine body(Stage ⅢC)at 40 years of age. Screening of the adenocarcinoma samples for Lynch syndrome by immunohistochemistry for mismatch repair proteins indicated a loss of MSH2/MSH6 proteinexpression . A genetic test revealed a deletion of about 20 kb, including exons 8 and 9 of the EPCAM gene. Colonoscopy revealed a type 1 tumor in the cecum. The risk of developing metachronous colorectal cancer and postoperative survival according to the extent of colectomy(total colectomy versus segmental colectomy)and her marked obesity were considered collectively. The patient subsequently selected total colectomy with ileorectal anastomosis. Pathological findings revealed mucinous carcinoma(Stage Ⅱ). Patients with Lynch syndrome caused by deletion of EPCAM are not usually at a high risk of uterine body cancer, but the risk of developing uterine body cancer should be noted when the range of EPCAM deletion extends near to MSH2, as inthis case.

Update on our investigation of malignant tumors associated with Peutz-Jeghers syndrome in Japan.

PURPOSE: To investigate the recent incidence of malignant tumors associated with Peutz-Jeghers syndrome (PJS) in Japan to clarify if there are any differences in malignant tumor risk and the spectrum of malignancies by reviewing the literature on this subject. METHODS: We reviewed PJS cases reported in 1115 papers in Japan between January, 1989 and December, 2014. RESULTS: Malignant tumors were identified in 186 of the total 583 PJS cases from 523 evaluable studies. The estimated cumulative risk of a malignant tumor was 83.0 % at 70 years of age. Compared with a previous study, on a collective 91 cases reported up until 1988 in Japan, the reported proportion of gastrointestinal malignancies decreased, from 82.4 to 48.3 %, whereas that of gynecological malignancies increased, from 8.8 to 34.3 % (P < 0.01). Moreover, breast cancers were occasionally reported (4.8 %), even though none were reported in the previous study. Adenocarcinoma of the uterine cervix was the most common malignant tumor (46.8 %) among women with PJS. CONCLUSIONS: The increased number of reports of cervical adenocarcinoma in women with PJS is the prominent trend in Japan, and a subject of concern among gynecologists. The risk of breast cancer seems to be increasing, but confirmation of this trend will require further investigation.

Comparison of the risk of surgical site infection and feasibility of surgery between sennoside versus polyethylene glycol as a mechanical bowel preparation of elective colon cancer surgery: a randomized controlled trial.

PURPOSE: To validate the usefulness of sennoside as a substitute for polyethylene glycol (PEG) as a mechanical bowel preparation (MBP) for elective colon cancer surgery. METHODS: We performed a prospective randomized non-inferiority trial comparing the use of sennoside and PEG in MBP for elective colon cancer surgery, in terms of the risk of surgical site infection (SSI) and the feasibility of surgery. RESULTS: The overall incidence of SSIs was 2.9 % in the sennoside group (n = 68) and 6.3 % in the PEG group (n = 63) with a difference of 3.4 % (95 % confidence interval 6.9-10.6 %). The intraoperative spillage of the stool materials in the sennoside and PEG groups was 4.4 and 3.1 %, respectively, and was not significantly different (p = 0.71), even the upstream stool consistency, was more frequently observed to be non-stool in the PEG group (65.1 vs. 30.9 %, p < 0.01). CONCLUSION: MBP with sennoside could be a substitution for PEG in elective colon cancer surgery.

Lower prevalence of Lynch syndrome in colorectal cancer patients in a Japanese hospital-based population.

PURPOSE: The aim of this study was to investigate the prevalence of Lynch syndrome among Japanese patients with surgically resected colorectal cancer at a single institution. METHODS: Of 616 colorectal cancer patients who underwent surgical operation in our institution from January 2005 to August 2010, immunohistochemistry analyses for mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) and microsatellite instability (MSI) testing for surgically resected, formalin-fixed paraffin-embedded colorectal cancer specimens from 138 colorectal cancer patients under 60 years of age were undertaken. Hypermethylation of the MLH1 promoter and BRAF mutation were analyzed where necessary. RESULTS: Seven patients were identified as candidates for genetic testing by mismatch repair protein loss (n = 7) or MSI-H (n = 6). Methylation of MLH1 was detected in one case. Three patients were diagnosed with Lynch syndrome, comprising 2.2 % of the total colorectal cancer patients younger than 60 years of age. CONCLUSION: The prevalence of Lynch syndrome among hospital-based diagnosed cancer patients may therefore be lower than expected in Japan compared with Western populations.

[Lynch Syndrome Caused by Germline Alteration of MLH1 in a Young Patient Who Developed Colon and Endometrial Cancer - A Case Report].

A 39-year-old woman underwent right colectomy for type-3 transverse colon cancer, which was histologically identified as well-differentiated stage II A adenocarcinoma with a mucinous component and tumor-infiltrating lymphocytes. The patient was suspected of having Lynch syndrome(LS)since she fulfilled 2 of the revised Bethesda criteria, even though there was no family history of LS. Twelve months after colectomy, abdominal CT revealed thickening of the uterine endometrium. Histopathological examination of biopsy specimens revealed well-differentiated endometrioid carcinoma. Extended hysterectomy with bilateral oophorectomy was performed. Histological examination of the resected specimen revealed well-differentiated endometrioid carcinoma of stage I . Immunohistochemistry analysis of mismatch repair proteins demonstrated loss of MLH1/ PMS2 expression in the colon cancer, but normal expression in the uterine cancer. Genetic testing identified duplication of exons 10-15 of the MLH1 gene, leading to a definitive diagnosis of LS. The patient has not shown any evidence of recurrence or new LS-associated tumors in the 12 years since the last surgery. There is an ongoing debate regarding the pathogenesis of endometrioid cancer, and this case emphasizes the importance of surveillance for gynecological malignancies after colon cancer surgery in female LS patients.

[A Case of Metachronous Multiple Thyroid Papillary Carcinoma with FAP].

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, the result of a germ line mutation in the adenomatous polyposis coli (APC) gene. FAP can be associated with various extracolonic lesions, including thyroid cancer, which frequently occurs in women. We report the case of a 36-year-old woman diagnosed as having FAP with multiple metachronous thyroid papillary carcinomas. She underwent left thyroidectomy at the age of 19 years without a diagnosis of FAP. Multiple polyps in her stomach were detected by medical examination and more than 100 polyps in the colon were found by colonoscopy. She was referred to our hospital after a diagnosis of non-profuse FAP. Multiple tumors with a maximum diameter of 10mm were detected in the right lobe of the thyroid gland during the preoperative examination. Papillary carcinoma was suspected based on fine-needle aspiration cytology. We performed a right thyroidectomy after prophylactic colectomy. Pathological findings revealed a cribriform-morula variant of papillary thyroid carcinoma. The patient remains well after 2 year 6 months with no recurrence.

[A Case of a Desmoid Tumor the Developed Around Ileostomy in a Patient with FAP].

A 21-year-old woman who underwent laparoscopic total colectomy for familial adenomatous polyposis (FAP) 1 year 3 months previously presented with a mass larger than 10 cm around the ileostomy. Multiple tumors in the mesentery around the ileostomy and anterior to the sacrum, accompanied by bilateral hydronephrosis, were detected by computed tomography. The patient was diagnosed with intraabdominal desmoid tumors, stage Ⅳ according to the Church's classification. The desmoid tumor (15×9 cm) around the ileostomy was completely resected surgically, whereas another desmoid tumor (5×4 cm) was incompletely resected. We found a desmoid tumor of more than 10 cm in size and many fibromatous plaques in the mesentery. We then performed 4 courses of systemic chemotherapy with dacarbazine and doxorubicin in for the residual desmoid tumors after surgery. There was no growth of the residual desmoid tumors for 12 months after chemotherapy. Genetic tests detected a pathogenic germline mutation of the APC gene in the high-risk region of the desmoid tumor. We also confirmed somatic mutations in the resected specimens.

[A Case of FAP Who Underwent Mucosectomy for Intramucosal Cancer That Repeatedly Developed in the Residual Rectal Mucosa after Stapled Ileal-Pouch Anal Anastomosis].

When we perform stapled ileal pouch anal anastomosis (IPAA) for familial adenomatous polyposis (FAP), some rectal mucosa persists. There is no consensus on surgical treatment when cancer develops at the residual mucosa. We report the case of a 43-year-old woman who repeatedly underwent endoscopic resection for intramucosal cancer that developed in the residual rectal mucosa 6 years after stapled IPAA, which she received at age 33. She was referred to our department for surgical treatment. We performed mucosectomy for the residual rectum mucosa, including a 0-Ⅱa lesion at the anterior wall. Two months later, stenosis was observed at the anastomotic site. We repeatedly conducted balloon expansion of the stenotic lesion. Six months later, the resected lesion was covered with white epithelium, and columnar epithelium was confirmed by step biopsy of the epithelium from the dentate line to the ileoanal pouch anastomotic site. This finding indicated that the regenerating epithelium was derived from the epithelium from the anal side. The patient remains well after 2 year 4 months with no complaints.

[A Case of Carcinoma of the Uterine Body, Right Ovary, and Duodenum in a Patient with Familial Adenomatous Polyposis].

We report a case of 4 carcinomas of the uterine body, right ovary, and duodenum in a patient with familial adenomatous polyposis (FAP). Her mother's family line carries FAP. She underwent proctocolectomy with ileoanal anastomosis for FAP when she was 20 years old. She was diagnosed with carcinoma of the uterine body and right ovary, and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy at 48 years of age. The pathological examination revealed endometrioid adenocarcinoma of the uterine body (Stage ⅠB) and endometrioid adenocarcinoma of the right ovary (Stage ⅠA). Her diagnosis was Stage Ⅳ according to the Spigelman classification of duodenal polyposis, and she underwent pancreas-preserving total duodenectomy at 50 years of age. The pathological examination was conclusive for 2 carcinomas in the adenoma, which were 20 mm and 25 mm in diameter, respectively. She has been well without any evidence of cancer recurrence 20 months after the pancreas-preserving total duodenectomy.

[Is PCI effective in predicting prognosis in the era of oxaliplatin-based chemotherapy in stage IV colorectal cancer with peritoneal dissemination ?].

PURPOSE: Peritoneal dissemination is expected to be present in P1, P2, and P3 according to the 8th edition of colon cancer handling convention. The peritoneal carcinomatosis index (PCI) plays a central role in classification of peritoneal metastases. PATIENTS AND METHODS: Peritoneal dissemination was examined during surgery in patients with colon cancer and peritoneal metastasis undergoing treatment with oxaliplatin-based chemotherapy. RESULTS: Correlation between PCI and P1, P2, and P3 was found. Moreover, using a PCI cut-off value of 6 for peritoneal dissemination, there was a significant difference in survival. CONCLUSION: Positive correlation was found between PCI and P classification of colon cancer. Regardless of the presence metastases to other organs, there is a possibility that PCI is effective in predicting prognosis of patients with peritoneal dissemination- positive colon cancer.

[The efficacy and safety of FOLFIRI or combined FOLFIRI and bevacizumab treatment as second-line chemotherapy for metastatic colorectal cancer patients aged 75 years and older].

The safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer patients ≥ 75 years was retrospectively evaluated. We analyzed 106 patients, who received FOLFIRI or a combination of FOLFIRI and bevacizumab following oxaliplatin-based first-line chemotherapy. The clinical characteristics and outcome in elderly patients ≥75 years(elderly[EP]group; n=18)were compared with those in patients aged<75 years(control group; n=88). The number of patients treated by a combination of FOLFIRI and bevacizumab in the EP group was lower than that in the control group (27.8% vs 55.7%; p=0.03). The comparison revealed no significant differences in response rate, progression-free survival, overall survival, and the frequency of overall adverse events after the start of second-line chemotherapy, although the frequency of anemia(Bgrade 3, p=0.07)and alopecia(grade 1/2, p=0.054)tended to be higher in the EP group than in the control group. Although this study retrospectively analyzed a limited number of patients, our results indicate that the safety and efficacy of FOLFIRI as second-line chemotherapy for metastatic colorectal cancer are almost equal in patients ≥ 75 years and those aged<75 years.

Comparative analysis of anti-osteoporosis medications in preventing vertebral body fractures after balloon kyphoplasty.

This retrospective study compared the efficacy of anabolic agents (romosozumab and teriparatide) with that of alendronate in preventing subsequent vertebral body fractures (SVBFs) after balloon kyphoplasty (BKP). All anabolic agents significantly reduced SVBFs. Romosozumab was most effective in increasing bone mineral density (BMD) and completely suppressed distant vertebral body fractures. INTRODUCTION: To determine optimal anti-osteoporosis medications, we compared romosozumab and teriparatide to alendronate as a control from perioperative BKP to the 1st postoperative year for treatment and secondary fracture prevention in osteoporosis. METHODS: A total of 603 patients who underwent initial BKP for osteoporotic vertebral fractures were evaluated and categorized into five groups based on drug administration: romosozumab (group R, 155 patients), twice-weekly teriparatide (group TW, 48), weekly teriparatide (group W, 151), daily teriparatide (group D, 138), and alendronate (control) (group C, 111). The 1-year incidence of SVBFs, BMD change rate, and probability of requiring BKP were compared among the groups. RESULTS: SVBF incidence was 3.9%, 6.5%, 8.3%, 6.0%, and 14.4% in groups R, D, TW, W, and C, respectively, with all other groups exhibiting significantly lower rates than group C. The groups that administered the anabolic agents had a notably lower incidence of distant fractures than group C. Compared with group C, group R showed significantly higher BMD change rates in lumbar vertebral bodies at 4, 8, and 12 months and group D at 12 months. Anabolic agent groups exhibited significantly higher improvement rates than group C after conservative treatment alone. CONCLUSION: The anabolic agents were found to be more effective at reducing the incidence of SVBF (especially distant vertebral fractures) than alendronate. These agents decreased the rate of repeat BKP even after the occurrence of a fracture. Overall, the use of an anabolic agent for the treatment of osteoporosis after BKP is better than the use of alendronate, even when treatment is initiated in the perioperative stage.

Gallbladder hemorrhage associated with segmental arterial mediolysis: a case report.

BACKGROUND: Gallbladder hemorrhage is a rare but fatal condition. The reported causes of gallbladder hemorrhage include iatrogenesis, atherosclerotic changes in the cystic arteries, acute cholecystitis or cholelithiasis, malignancy, trauma, hemophilia, pseudoaneurysm, and the use of oral anticoagulant medications. Recently, segmental arterial mediolysis (SAM) has been reported as a possible etiology of life-threatening abdominal, retroperitoneal, and intracranial hemorrhages. However, no previous reports have described the association between gallbladder hemorrhage and SAM. CASE PRESENTATION: A 59-year-old man was transferred to our hospital complaining of upper abdominal pain and vomiting. Contrast-enhanced computed tomography revealed high-density images of the gallbladder and common bile duct. However, there were no obvious findings of gallstones, cholecystitis, tumors, or aneurysms. He was diagnosed with gallbladder hemorrhage and bile duct obstruction. We performed a laparoscopic cholecystectomy after endoscopic biliary drainage. The gross appearance of the surgically resected specimen showed 12 small (3-12 mm), slightly elevated lesions on the gallbladder mucosa. Histologically, these slightly elevated lesions consisted of dilated muscular arteries of the gallbladder wall with fibrinoid degeneration of the media and focal loss of the internal and external elastic laminae. The histopathological diagnosis was confirmed as SAM. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a gallbladder hemorrhage associated with SAM. Our case report shows that SAM can cause gallbladder hemorrhage, suggesting that SAM should be considered in the differential diagnosis of gallbladder hemorrhage.

[Analysis of KRAS status in cancer tissue with submucosal or deeper invasion in patients with familial adenomatous polyposis].

The KRAS status in cancer tissue with submucosal or deeper invasion was investigated in patients with familial adenomatous polyposis (FAP). Fifteen cancerous lesions in 10 FAP patients were subjected to analysis for KRAS status. The clinical features of FAP were the dense type in 2 patients and the sparse type in 8 patients. Of the 15 cancerous lesions, 6 (40%) were identified as having wild-type KRAS and the remaining 9 (60%), as having mutated KRAS. Of the 9 mutated lesions, the G13D mutation was recognized in 4 patients and was the most frequent pattern. With regard to the KRAS status in patients with multiple cancerous lesions, 1 patient had 3 cancerous lesions of which 2 were of the mutated type and 1 was of the wild type and another patient had 4 cancerous lesions of which 3 were of the mutated type and 1 was of the wild type. These results suggest that the frequency of wild-type KRAS in cancer associated with FAP was approximately 40%, although it was lower than that in sporadic cancer. Moreover, we need to analyze the KRAS status in all cancerous lesions in clinical practice when chemotherapy with anti-epidermal growth factor receptor (EGFR) antibody is required for the treatment of FAP patients with unresectable advanced multiple cancers.

Chemistry of fullerene epoxides: synthesis, structure, and nucleophilic substitution-addition reactivity.

Fullerene epoxides, C60O(n), having epoxide groups directly attached to the fullerene cage, constitute an interesting class of fullerene derivatives. In particular, the chemical transformations of fullerene epoxides are expected to play an important role in the development of functionalized fullerenes. This is because such transformations can readily afford a variety of mono- or polyfunctionalized fullerene derivatives while conserving the epoxy ring arrangement on the fullerene surface, as seen in representative regioisomeric fullerene polyepoxides. The first part of this review addresses the synthesis and structural characterization of fullerene epoxides. The formation of fullerene epoxides through different oxidation reactions is then explored. Adequate characterization of the isolated fullerene epoxides was achieved by concerted use of NMR and LC-MS techniques. The second part of this review addresses the substitution of fullerene epoxides in the presence of a Lewis acid catalyst. Most major substitution products have been isolated as pure compounds and their structures established through spectroscopic methods. The correlation between the structure of the substitution product and the oxygenation pattern of the starting materials allows elucidation of the mechanistic features of this transformation. This approach promises to lead to rigorous regioselective production of various fullerene derivatives for a wide range of applications.

[Colon cancer with portal vein tumor thrombosis-a case report and review of the literature].

Colon cancer with portal vein tumor thrombosis has a poor prognosis. However, little is known about the clinicopathological characteristics of these patients. In this study, we attempted to clarify the clinicopathological characteristics of such patients reported in the Japanese literature, including our own case. This case concerns a 48-year-old female patient diagnosed as having transverse colon cancer with severe portal vein tumor thrombosis. Despite curative resection, the patient was found to have multiple liver metastases six months later, and chemotherapy did not prove to be adequately effective; she died 18 months after surgery. A search of the relevant literature revealed 9 reports of similar patients. The patients consisted of 4 males and 6 synchronous cases, with a median age of 70 years. Portal vein tumor thrombosis was observed in 6 patients. While the portal vein was the most frequent site of thrombosis, other patients showed tumor thrombosis of the superior and inferior mesenteric veins. Despite curative resection, 3 patients eventually developed liver metastases after the operation. The median disease-free survival of the patients who had undergone curative resection was 300 days, and the overall median survival of the patients was 420 days. Thus, for the portal vein tumor thrombosis, we need to adopt adjuvant chemotherapy in consideration of a high risk for the liver metastases.

[A long-term survivor of colorectal cancer associated with multiple liver metastases and peritoneal carcinomatosis treated through a multidisciplinary approach].

Even in the era of new anticancer drugs, an optimal treatment strategy for colorectal cancer associated with liver metastasis and peritoneal carcinomatosis has yet to be established. Here we report the case of a long-term survivor with very advanced colon cancer who underwent repeated resective surgery and chemotherapy. This 69-year-old man underwent a Hartmann's procedure and the resection of peritoneal metastases of cancer of the rectosigmoid, which had infiltrated the retroperitoneum giving rise to multiple liver metastases and peritoneal carcinomatosis. The resection margin was positive for cancer. After 14 courses of a modified FOLFOX6 (mFOLFOX6) regimen, a partial response with no development of new lesions was obtained. Multiple partial hepatectomies were subsequently performed. After the completion of an additional 6 courses of mFOLFOX6, a positron-emission tomography (PET)/computed tomography (CT) examination demonstrated a hot spot in segment 4. This hot deposit disappeared after a further 8 courses of mFOLFOX6. The patient then underwent a left lateral segmentectomy for a newly developed lesion in segment 3, which was detected 2 years and 7 months after the first operation. The patient has remained free from recurrence for 2 years since his last operation.