Postoperative therapy with infliximab for Crohn's disease: a 2-year prospective randomized multicenter study in Japan.

PURPOSE: The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence. METHODS: We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery. RESULTS: Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]). CONCLUSION: The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

Gene-expression profiles correlate with the efficacy of anti-EGFR therapy and chemotherapy for colorectal cancer.

BACKGROUND: Comprehensive gene-expression analysis is very useful for classifying specific cancers into subgroups on the basis of their biological characteristics; it is used both prognostically and predictively. The purpose of this study was to classify unresectable advanced or recurrent colorectal cancer (CRC) by gene-expression profiling of formalin-fixed paraffin-embedded tissues and to correlate CRC subgroups with clinicopathological and molecular features and clinical outcomes. METHODS: One hundred patients with advanced or recurrent CRC were enrolled. RNA extracted from FFPE tissues was subjected to gene-expression microarray analysis. RESULTS: The patients were stratified into four subgroups (subtypes A1, A2, B1, and B2) by unsupervised hierarchical clustering. By use of principle-components analysis (PCA), the patients were divided into subtypes A and B on the basis of component 1 and into subtypes 1 and 2 on the basis of component 2. Subtype A was significantly enriched among patients without the KRAS mutation and with an earlier clinical stage at diagnosis. With regard to anti-EGFR therapy, progression-free survival (PFS) was better for patients in subtype A without the KRAS mutation than for those with the KRAS mutation (P = 0.047). PFS for patients without the KRAS mutation in subtype B was comparable with that for patients with the KRAS mutation (P = 0.55). Similar results were observed in a validation set. CONCLUSION: We found that gene-expression profiles enabled stratification of CRC patients into four subgroups. The efficacy of anti-EGFR therapy was correlated with component 1 from PCA. This comprehensive study may explain the heterogeneity of unresectable advanced or recurrent CRC and could be useful for identifying novel biomarkers for CRC treatment.

Risk factors for surgical site infection in Japanese patients with ulcerative colitis: a multicenter prospective study.

PURPOSE: A prospective, multicenter, observational study was performed to investigate the risk factors of surgical site infection (SSI) in patients with ulcerative colitis (UC). METHODS: From 2009 to 2010, perioperative clinicopathological data were collected from patients who had undergone surgery for UC within the research period, for up to 6 consecutive months in 13 hospitals in Japan. The primary outcome was the development of SSI. RESULTS: A total of 195 patients with UC who underwent colorectal surgery were enrolled. SSI was diagnosed in 38 (19.5 %) patients, in the form of incisional infection in 23 (11.8 %), organ/space infection in 16 (8.2 %), and both in 1 (0.5 %). There were no significant risk factors associated with an increased risk of development of incisional SSI. An American Society of Anesthesiologists physical status of ≥ 3 was indicated as the only significant risk factor for organ/space SSI (P = 0.02) compared with other factors, such as a neutrophil count of >100 × 10(2)/mm(3), albumin level of <3.5 g/dl, perioperative packed red blood cell transfusion, fair or poor colonic cleanliness, and therapeutic use of antibiotics. CONCLUSION: Poor general physical status was the significant independent risk factor for organ/space SSI in patients with UC in Japan.

Suppressed expression of NDRG2 correlates with poor prognosis in pancreatic cancer.

Pancreatic cancer is a highly lethal disease with a poor prognosis; the molecular mechanisms of the development of this disease have not yet been fully elucidated. N-myc downstream regulated gene 2 (NDRG2), one of the candidate tumor suppressor genes, is frequently downregulated in pancreatic cancer, but there has been little information regarding its expression in surgically resected pancreatic cancer specimens. We investigated an association between NDRG2 expression and prognosis in 69 primary resected pancreatic cancer specimens by immunohistochemistry and observed a significant association between poor prognosis and NDRG2-negative staining (P=0.038). Treatment with trichostatin A, a histone deacetylase inhibitor, predominantly up-regulated NDRG2 expression in the NDRG2 low-expressing cell lines (PANC-1, PCI-35, PK-45P, and AsPC-1). In contrast, no increased NDRG2 expression was observed after treatment with 5-aza-2' deoxycytidine, a DNA demethylating agent, and no hypermethylation was detected in either pancreatic cancer cell lines or surgically resected specimens by methylation specific PCR. Our present results suggest that (1) NDRG2 is functioning as one of the candidate tumor-suppressor genes in pancreatic carcinogenesis, (2) epigenetic mechanisms such as histone modifications play an essential role in NDRG2 silencing, and (3) the expression of NDRG2 is an independent prognostic factor in pancreatic cancer.

Results of modified uncut Roux-en-Y reconstruction after distal gastrectomy for gastric cancer.

BACKGROUND/AIMS: The frequent occurrence of bile gastritis and esophagitis associated with dehiscence of 'uncut' jejunal portion was of concern for "uncut" Roux-en-Y reconstruction after distal gastrectomy. Our aim was to study if our technique of a modified, uncut Roux-en-Y procedure would decrease this dehiscence. METHODOLOGY: Ten patients with gastric cancer underwent distal gastrectomy with a modified, uncut Roux-en-Y reconstruction. Transmural silk stitches were added around the staples at the "uncut" portion in attempt to prevent dehiscence of the staple line. Dehiscence of the jejunum at the enterically closed site was investigated endoscopically or fluoroscopically. RESULTS: Mean operative time and intraoperative blood loss were 246 minutes and 381 mL, respectively. Morbidity occurred in three patients. No dehiscence was observed in any of the patients examined. CONCLUSIONS: These results suggest the possibility that our technique of a modified, uncut Roux-en-Y reconstruction after distal gastrectomy decreases dehiscence of enterically closed portion.

Young-onset peri-anorectal leiomyomatosis: report of a case.

A 23-year-old female was referred with constipation that lasted for 2 years. Preoperative examinations revealed multiple submucosal tumors beside the anorectum, along with subcutaneous tumors in the left buttock. The pathological diagnosis was leiomyoma. Low anterior resection of the rectum with regional lymph node dissection, along with the resection of the subcutaneous tumors in the left buttock through the transdermal approach, was performed, since multiple tumor formation indicated a high malignant potential. The tumors were diagnosed as multiple leiomyomas with no malignancy. Disease categories such as intravenous leiomyomatosis, leiomyomatosis peritonealis disseminata, Alport syndrome, and Currarino syndrome have been reported to be associated with leiomyomatosis; however, the current case of "peri-anorectal leiomyomatosis" was not classified into any of these. The patient was monitored with careful checkups, and the postoperative course was satisfactory for over 5 years without any sign of recurrence or metastasis. Although the clinicopathological features of this case are quite rare and no therapeutic guidelines for such a disease have yet been established, radical resection should be considered, and the elucidation of the histogenesis of this disease will help establish future therapeutic guidelines.

Runt-related transcription factor 2 in human colon carcinoma: a potent prognostic factor associated with estrogen receptor.

Runt-related transcription factor 2 (RUNX2) belongs to the RUNX family of heterodimeric transcription factors, and is mainly associated with osteogenesis. Previous in vitro studies demonstrated that RUNX2 increased the cell proliferation of mouse and rat colon carcinoma cells but the status of RUNX2 has remained unknown in human colon carcinoma. Therefore, we examined clinical significance and biological functions of RUNX2 in colon carcinoma. RUNX2 immunoreactivity was examined in 157 colon carcinoma tissues using immunohistochemistry. RUNX2 immunoreactivity was evaluated as percentage of positive carcinoma cells [i.e., labeling index (LI)]. We used SW480 and DLD-1 human colon carcinoma cells, expressing estrogen receptor-ß (ER) in subsequent in vitro studies. RUNX2 immunoreactivity was detected in colon carcinoma cells, and the median value of RUNX2 LI was 67%. RUNX2 LI was significantly associated with Dukes' stage, liver metastasis and ERß status. In addition, RUNX2 LI was significantly associated with adverse clinical outcome of the colon carcinoma patients, and turned out an independent prognostic factor following multivariate analysis. Results of in vitro studies demonstrated that both SW480 and DLD-1 cells transfected with small interfering RNA against RUNX2 significantly decreased their cell proliferation, migration and invasive properties. In addition, RUNX2 mRNA level was significantly decreased by ER antagonist in these two cells. These findings all suggest that RUNX2 is a potent prognostic factor in human colon carcinoma patients through the promotion of cell proliferation and invasion properties, and is at least partly upregulated by estrogen signals through ERß of carcinoma cells.

The long-term clinical course of pouchitis after total proctocolectomy and IPAA for ulcerative colitis.

BACKGROUND: Pouchitis is the most common long-term complication after restorative total proctocolectomy and IPAA for ulcerative colitis. OBJECTIVE: We examined the incidence, clinical aspects, and long-term outcome of patients with idiopathic pouchitis. DESIGN: This study was a retrospective review of medical records. PATIENTS: Included in the study were 284 patients with ulcerative colitis who underwent a total proctocolectomy and IPAA. MAIN OUTCOME MEASURES: We evaluated the cumulative risk and long-term outcome of pouchitis including the duration of disease, pattern of relapse, and responsiveness to antibiotic therapy. RESULTS: Sixty-four patients developed idiopathic pouchitis. The cumulative risk was 10.7% at 1 year, 17.2% at 2 years, 24.0% at 5 years, and 38.2% at 10 years. At their first pouchitis episode, 45 patients had acute pouchitis, 19 patients had chronic pouchitis, and all patients received antibiotic therapy with oral ciprofloxacin and/or metronidazole. The efficacy of the therapy was 96.6% initially. Forty-five patients had antibiotic-responsive pouchitis, 17 patients had antibiotic-dependent pouchitis, and 2 patients had antibiotic-refractory pouchitis at their first episode. Whereas 20 of 45 patients (44.4%) with initially acute pouchitis experienced 2 or more relapses, 16 of 19 patients (84.2%) with initially chronic pouchitis had 2 or more relapses. After taking into account the relapses, the number of patients with antibiotic-responsive pouchitis decreased from 45 to 40, the number with antibiotic-dependent pouchitis increased from 17 to 20, and the number with antibiotic-refractory pouchitis increased from 2 to 4. Among the 4 patients with antibiotic-refractory pouchitis, 3 patients had Clostridium difficile-associated pouchitis. LIMITATIONS: This study was retrospective. CONCLUSION: The patients with chronic pouchitis at the first episode tend to have a higher incidence of relapse. In some patients, the responsiveness to antibiotic therapy changes during follow-up. When patients with pouchitis do not respond to standard antibiotic therapy, then the occurrence of C difficile infection should be considered.

Large-scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega-Study (JMMS).

BACKGROUND AND AIM: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD. METHODS: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated. RESULTS: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication. CONCLUSIONS: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.

A shift from colon- to ileum-predominant bacteria in ileal-pouch feces following total proctocolectomy.

BACKGROUND: We previously investigated fecal flora of the pouch after total proctocolectomy using terminal restriction fragment polymorphism analysis. Although the results of the cluster analysis demonstrated clearly that bacterial populations, including an unidentified bacteria generating a 213-bp PCR fragment, moved toward a colon-like community in the pouch, it did not track changes in the individual species of fecal bacteria. AIMS: The aim of the present study was to estimate genome copy number of ten bacterial species, clusters, groups, or subgroups (including the bacteria generating 213-bp fragment in the previous study) in feces samples from pouches at various times following ileostomy closure. METHODS: A total of 117 stool samples were collected from patients with ulcerative colitis after surgery as well as healthy volunteers. We used real-time polymerase chain reaction of the 16S rRNA gene to estimate genome copy numbers for the nine bacterial populations and the bacteria generating 213-bp fragment after identification by DNA sequencing. RESULTS: We demonstrated a time-dependent increase in the number of anaerobic and colon-predominant bacteria (such as Clostridium coccoides, C. leptum, Bacteroides fragilis and Atopobium) present in proctocolectomy patients after stoma closure. In contrast, numbers of ileum-predominant bacterial species (such as Lactobacillus and Enterococcus faecalis) declined. CONCLUSIONS: Our data confirm previous findings that fecal flora in the pouch after total proctocolectomy changes significantly, and further demonstrate that the number and diversity of ileal bacteria decreases while a more colon-like community develops. The present data are essential for the future analysis of pathological conditions in the ileal pouch.

Current status of pylorus-preserving gastrectomy for the treatment of gastric cancer: a questionnaire survey and review of literatures.

PURPOSE: This study was designed to investigate the current status of pylorus-preserving gastrectomy (PPG) for the treatment of gastric cancer by sending a questionnaire to institutions in Japan. METHODS: The questionnaire was prepared and sent to 930 institutions approved by the Japanese Society of Gastroenterological Surgery. Questions were the indications for PPG, preservation of the vagus nerves and the infra-pyloric artery, whether suprapyloric lymph nodes are dissected, distance between the pylorus and the gastrogastrostomy, and the advantages and disadvantages of PPG. RESULTS: Responses were obtained from 345 institutions (37.1%). In 148 institutions, PPG was included in the choices of operations for gastric cancer and indicated for patients with tumors no deeper than the submucosal layer for differentiated-type carcinoma, or for tumors limited to the mucosa even in poorly differentiated types in 105 institutions. The vagus was preserved in 73.5%, the infrapyloric artery was preserved in 49.4%, and the dissection of suprapyloric lymph nodes were partly performed in 56.2%. The distance between gastrogastrostomy and the pyloric ring was 3-3.9 cm in 43.4% and 2-2.9 cm in 39%. Layer-to-layer anastomosis was the most representative technique for gastrogastrostomy. The advantages of PPG with decreased incidence of dumping syndrome and remnant gastritis were quoted in 130 and 82 institutions, respectively. Delayed gastric emptying was considered as the most frequent disadvantage of PPG, as quoted by 111 institutions. CONCLUSIONS: These results indicate that standard technique in PPG includes the preservation of the vagus and infrapyloric artery, in part dissection of suprapyloric lymph nodes, and layer-to-layer anastomosis for reconstruction. The optimal length of the antral cuff is still controversial.

Time trend and risk factors for reoperation in Crohn's disease in Japan.

BACKGROUND/AIMS: We aimed to evaluate time changes in reoperation rate after initial surgery in Crohn's disease (CD) over the last five decades in Japan and to assess the risk factors for reoperation, given that a decrease in the reoperation rate for CD remains controversial. METHODOLOGY: CD patients (n-476) who underwent initial intestinal surgery were examined. Case records were collected from 13 institutions and scrutinized retrospectively. The primary outcome measure was the reoperation rate needing intestinal surgery. To evaluate the time changes, we compared medical treatment and reoperation rate in patients from two different periods of time; before and after 2002 when infliximab became available in Japan (1963-2002 and 2003-2008 groups). Univariate and multivariate analyses were performed to examine the influence of independent variables on the cumulative reoperation rate. RESULTS: A total of 201 patients underwent reoperation. Overall 5-year and 10-year cumulative reoperation rates were 31.4% and 61.2%, respectively. In multivariate analysis, an onset of the disease between 1963-2002 (p=0.0199) and postoperative administration of infliximab (p=0.0003) and immunosuppressants (p<0.0001) were significant risk factors for reoperation. The cumulative 5-year reoperation rate decreased significantly in the 2003-2008 group compared to the 1963-2002 group (6.3% vs. 32.9%, p<0.05). CONCLUSIONS: The reoperation rate for CD has decreased significantly in recent years in Japan. However, to further confirm this time trend, we need to evaluate CD patients with a longer follow-up period.

Differentiating rectal carcinoma by an immunohistological analysis of carcinomas of pelvic organs based on the NCBI Literature Survey and the Human Protein Atlas database.

The treatments and prognoses of pelvic organ carcinomas differ, depending on whether the primary tumor originated in the rectum, urinary bladder, prostate, ovary, or uterus; therefore, it is essential to diagnose pathologically the primary origin and stages of these tumors. To establish the panels of immunohistochemical markers for differential diagnosis, we reviewed 91 of the NCBI articles on these topics and found that the results correlated closely with those of the public protein database, the Human Protein Atlas. The results revealed the panels of immunohistochemical markers for the differential diagnosis of rectal adenocarcinoma, in which [+] designates positivity in rectal adenocarcinoma and [-] designates negativity in rectal adenocarcinoma: from bladder adenocarcinoma, CDX2[+], VIL1[+], KRT7[-], THBD[-] and UPK3A[-]; from prostate adenocarcinoma, CDX2[+], VIL1[+], CEACAM5[+], KLK3(PSA)[-], ACPP(PAP)[-] and SLC45A3(prostein)[-]; and from ovarian mucinous adenocarcinoma, CEACAM5[+], VIL1[+], CDX2[+], KRT7[-] and MUC5AC[-]. The panels of markers distinguishing ovarian serous adenocarcinoma, cervical carcinoma, and endometrial adenocarcinoma were also represented. Such a comprehensive review on the differential diagnosis of carcinomas of pelvic organs has not been reported before. Thus, much information has been accumulated in public databases to provide an invaluable resource for clinicians and researchers.

[Surgery for pancreatic neuroendocrine tumors].

Approximately half of pancreatic neuroendocrine tumors (PNETs) are nonfunctioning, and insulinoma and gastrinoma are frequent forms of functioning tumors. The treatment of patients with PNETs should be based on the consideration that more than half are malignant except for insulinomas. Multiple endocrine neoplasia type 1 (MEN1) is often complicated with gastrinoma. Endoscopic ultrasound and somatostain receptor scintigraphy are useful in diagnosing PNETs, and the selective arterial secretagogue injection test is performed if necessary. WHO2010 is available as a histopathologic grading system of malignancy. Although surgical resection should first be considered as a treatment for PNETs, liver metastasis is a major factor hindering resection. In Japan, the choices of drugs to treat liver metastases are too few. In patients with MEN1 in whom PNETS are frequently multiple, we should perform procedures that preserve pancreatic function, although some patients may require total pancreatectomy for the complete resection of tumors. The indications for total pancreatectomy should be determined individually based on the tumor status and patient age.

Alternative pre-mRNA splicing in digestive tract malignancy.

Alternative precursor messenger RNA (pre-mRNA) splicing plays an important role in the generation of functional diversity of the genome. The process of pre-mRNA splicing is regulated by cis- and trans-elements, and their deregulations result in aberrantly spliced individual variants and aberrant expression profiles. Accumulating evidence has revealed that aberrant splicing contributes to a number of diseases including human neoplasms. It is well known that germ line mutations in the cis-element of tumor suppressor genes such as mismatch repair (MMR) genes, the adenomatous polyposis coli (APC) gene and the E-cadherin (CDH1) gene are involved in Lynch syndrome, familial adenomatous polyposis and hereditary diffuse gastric cancer, respectively. In addition, somatic mutations in cis-elements also play a role in tumorigenesis. These genetic alterations including nonsense, missense or silent mutations in cis-elements led to aberrant transcripts by exon skipping, retention of the intron or introduction of a new splice site. The majority of erroneous transcripts with a premature termination codon are eliminated through nonsense-mediated mRNA decay. However, it is difficult to accurately predict the resulting transcripts with current in silico strategies. Correct interpretation of genetic alterations and the investigation of aberrant transcripts are crucial for genetic diagnosis of hereditary diseases and elucidation of the molecular characteristics of neoplasms from a clinical point of view. In this review we summarize the current knowledge of the regulatory mechanism underlying alternative pre-mRNA splicing and aberrant splicing, with particular focus on digestive tract malignancies.

Infiltration of CD14-positive macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis.

BACKGROUND/AIMS: To clarify the distribution of CD14+ macrophages in colorectal cancer using flow cytometry and immunohistochemistry, and to elucidate the roles of CD14+ macrophages in colorectal cancer. METHODOLOGY: We studied the paired cancerous and corresponding normal tissues from 52 patients with colorectal cancer for the distribution of CD14+, CD1a+, CD83+ and CD68+ cells, and correlated the findings with the clinicopathological characteristics and with the expression of CD86 and CD80 in the CD14+ macrophages, which are co-stimulatory factors for T cell activation. RESULTS: 1) CD14+ macrophages were distributed predominantly at the invasive front of colorectal cancer tissues, rather than in the normal tissues, 2) a high percentage of the CD14+ macrophages expressed CD86 and CD80, and 3) in the colorectal cancer cases with lymph node metastasis, the 5-year overall survival rate of the high CD14 group, in which the number of CD14+ macrophages was higher than the median, was better than that of the low CD14 group. CONCLUSION: The infiltration of CD140 macrophages at the invasive front indicates a favorable prognosis in colorectal cancer patients with lymph node metastasis. In addition, the activation of CD14+ macrophages and T cells may facilitate the development of new immunotherapeutic strategies for colorectal cancer patients.

Effect of viscosity of enteral nutrient on gut motility and hormone secretion in dogs.

BACKGROUND/AIMS: Our aim was to study the effect of the viscosity of enteral nutrient solutions on upper gut motility and gut hormone secretion. METHODOLOGY: We used 5 beagle dogs equipped with strain gauge force transducers to measure upper gastrointestinal motility. Upper gut motility and gut hormone secretion were compared across 6 experimental conditions; control (oral solid meal), liquid-120, liquid-5 (liquid enteral nutrients administered for 120 and 5 min, respectively), low, middle, and high viscosity conditions. RESULTS: The magnitude of receptive relaxation was decreased in the liquid-120 compared to control, but this decrease was reversed with the increase of viscosity. The duration of the postprandial contractions in the proximal jejunum was decreased in the liquid-5 compared to the control, but this decrease was reversed in the middle and high viscosity conditions (p < 0.05). Rapid increase in plasma concentrations of gastric inhibitory polypeptide observed in the liquid-5 compared to the control was reversed in the low, middle, and high viscosity conditions. CONCLUSIONS: Although patterns of upper gut motility and gut hormone secretion after liquid enteral nutrients were considerably altered compared to those after solid meal ingestion, increasing the viscosity of liquid enteral nutrients reversed those altered patterns.

Inhibitor of apoptosis protein family as diagnostic markers and therapeutic targets of colorectal cancer.

The apoptosis and antiapoptotic signaling pathways are important for regulating carcinogenesis and cancer progression, and for determining prognosis. Molecules involved in apoptosis represent potential cancer diagnostic markers and therapeutic targets. The inhibitor of apoptosis protein (IAP) family includes several important molecules involved in apoptosis that might represent such targets. Increasing evidence has demonstrated that the IAP family of proteins is integral for antiapoptotic and nuclear factor-κB signal transduction, and enhanced expression of IAPs contributes to colon carcinogenesis and its poor prognosis, as well as to drug resistance of tumors. X-linked IAP, cIAP1, cIAP2, and survivin are prognostic markers of colorectal cancer, and survivin and cIAP2 are also utilized to predict the effect of anticancer treatment in colorectal cancer patients. Novel therapies such as YM155 and LY2181308 targeting survivin, AEG35156 and phenoxodiol targeting X-linked IAP, AT-406 as a Smac mimetic, and survivin peptides are currently being evaluated in clinical trials. This report reviews the involvement of the IAP family in colorectal adenocarcinoma in order to summarize the role of the IAP family members as diagnostic and therapeutic targets, and to provide an overview of the future course of research in this area.

Antimesenteric cutback end-to-end isoperistaltic anastomosis (Sasaki-Watanabe anastomosis) for Crohn's disease: Novel surgical technique and early results of surgical anastomotic recurrence.

BACKGROUND: Antimesenteric cutback end-to-end isoperistaltic anastomosis (Sasaki-Watanabe anastomosis; Sasaki-W anastomosis), which was developed in our department, is a novel hand-sewn anastomotic technique for Crohn's disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. AIM: The aim of the present study is to present the surgical technique of Sasaki-W anastomosis and to assess the safety and the early results of the surgical anastomotic recurrence of Sasaki-W anastomosis. PATIENTS AND METHODS: The present study was a single-center retrospective cohort study. As an early-period group, 13 patients with Crohn's disease, who were mainly selected from cases considered to be at high risk of recurrence, underwent 15 Sasaki-W anastomoses from August 2009 to January 2012. As a late-period group, 36 patients with Crohn's disease, who were selected regardless of risk factors, underwent 37 Sasaki-W anastomoses from September 2016 to March 2020. The medical data including patient characteristics, surgical records, postoperative details, and surgical recurrences were assessed. RESULTS: There were no intraoperative complications. With a median follow-up of 107 mo, surgical recurrence occurred in one patient at 106 mo after surgery in the early-period group. The cumulative surgical recurrence-free rate in the early-period group was 100% at 5 y and 86% at 10 y after surgery. No patients required reoperation in the late-period group. CONCLUSION: Sasaki-W anastomosis is safe and feasible. Although long-term study is needed, this anastomotic technique can be a reasonable operative option for Crohn's disease.

[A case of stage IV gastric cancer with multiple liver metastases surviving for more than 4 years by treatment with chemotherapies without surgery].

A 75-year-old male who with type 3 gastric cardia cancer with multiple liver metastases was initially treated with S-1 in July of 2005. After 4 courses of the treatment, the liver metastases became undetectable on abdominal CT scan, with reduction in size of the primary tumor of the stomach. After 7 months of S-1 treatment, however, the progression of the primary lesion was endoscopically detected, and irinotecan was administered, demonstrating primary tumor regression. When re-growth of the primary tumor was observed, 3 courses of paclitaxel treatment showed little effect and was replaced by docetaxel treatment for 5 months, which had a grade 3 adverse effect. The next 10 courses of 5-FU combined with methotrexate were applied for one year until the primary tumor showed enlargement. Then 12 courses of CDDP with S-1 were administered until now, and the size of the primary carcinoma is under control. The patient is being followed on an outpatient basis without any surgical treatment, while the liver metastases have not relapsed on abdominal imaging.