Preoperative prediction of malignancy and surgical treatment strategy in appendiceal tumors: multicenter review of 51 consecutive cases.

PURPOSE: A diagnostic and treatment strategy for appendiceal tumors (ATs) has not been established. We aimed to evaluate our treatment strategy in ATs, including laparoscopic surgery (LS), and to identify preoperative malignancy predictors. METHODS: A total of 51 patients between 2011 and 2021 were retrospectively reviewed. Data, including tumor markers and imaging findings, were compared between carcinoma and non-carcinoma patients. Validity of planned operation was evaluated based on pathological diagnosis. RESULTS: Twenty-five patients were diagnosed with carcinoma, 13 with low-grade mucinous neoplasm, and 13 with other diseases. Symptoms were more commonly present in carcinoma patients than in non-carcinoma patients (68.0% vs. 23.1%, p = 0.001). Elevated CEA and CA19-9 were more frequently observed in carcinoma patients than in non-carcinoma patients (p < 0.01 and p = 0.04, respectively). Five carcinoma patients had malignancy on biopsy, compared with zero non-carcinoma patients. Significant differences were noted in the percentages of carcinoma and non-carcinoma patients with solid enhanced mass (41.7% vs. 0%, p < 0.001) and tumor wall irregularity (16.7% vs. 0%, p = 0.03) on imaging. Although the sensitivity was not high, the specificity and positive predictive value of these findings were 100%. Forty-two patients (82.4%) underwent LS as minimally invasive exploratory and/or radical operation, of whom 2 were converted to open surgery for invasion of adjacent organ. No patients had intraoperative complications or postoperative mortality. CONCLUSION: Clinical symptoms, elevated tumor markers, and worrisome features of solid enhanced mass and tumor wall irregularity on imaging can be malignancy predictors. For management of ATs, LS is feasible and useful for diagnosis and treatment.

Long-term effects of laparoscopic lateral pelvic lymph node dissection on urinary retention in rectal cancer.

BACKGROUND: The addition of lateral pelvic lymph node dissection (LPLND) in rectal cancer surgery has been reported to increase the incidence of post-operative urinary retention. Here, we assessed the predictive factors and long-term outcomes of urinary retention following laparoscopic LPLND (L-LPLND) with total mesorectal excision (TME) for advanced lower rectal cancer. METHODS: This retrospective single-institutional study reviewed post-operative urinary retention in 71 patients with lower rectal cancer who underwent L-LPLND with TME. Patients with preoperative urinary dysfunction or who underwent unilateral LPLND were excluded. Detailed information regarding patient clinicopathologic characteristics, post-void residual urine volume, and the presence or absence of urinary retention over time was collected from clinical and histopathologic reports and telephone surveys. Urinary retention was defined as residual urine > 100 mL and the need for further treatment. RESULTS: Post-operative urinary retention was observed in 25/71 patients (35.2%). Multivariate analysis revealed that blood loss ≥ 400 mL [odds ratio (OR) 4.52; 95% confidence interval (CI) 1.24-16.43; p = 0.018] and inferior vesical artery (IVA) resection (OR 8.28; 95% CI 2.46-27.81; p < 0.001) were independently correlated with the incidence of urinary retention. Furthermore, bilateral IVA resection caused urinary retention in more patients than unilateral IVA resection (88.9% vs 47.1%, respectively; p = 0.049). Although urinary retention associated with unilateral IVA resection improved relatively quickly, urinary retention associated with bilateral IVA resection tended to persist over 1 year. CONCLUSION: We identified the predictive factors of urinary retention following L-LPLND with TME, including increased blood loss (≥ 400 mL) and IVA resection. Urinary retention associated with unilateral IVA resection improved relatively quickly. L-LPLND with unilateral IVA resection is a feasible and safe procedure to improve oncological curability. However, if oncological curability is guaranteed, bilateral IVA resection should be avoided to prevent irreversible urinary retention.

Quantitative evaluation of the intratumoral distribution of platinum in oxaliplatin-treated rectal cancer: In situ visualization of platinum via synchrotron radiation X-ray fluorescence spectrometry.

Oxaliplatin (l-OHP), a platinum-based drug, is a key chemotherapeutic agent for colorectal cancer (CRC), but drug resistance and toxic effects have been major limitations of its use. Synchrotron radiation X-ray fluorescence spectrometry (SR-XRF) is a rapid, nondestructive technique for monitoring the distribution of metals and trace elements in cells or tissue samples. We applied SR-XRF to visualize the distribution of platinum and other elements in 30 rectal cancer specimens resected from patients who received l-OHP-based preoperative chemotherapy and quantified platinum concentration in the tumor epithelium and stroma, respectively, using calibration curves. The platinum concentration in rectal cancer tissue ranged 2.85-11.44 ppm, and the detection limit of platinum was 1.848 ppm. In the tumor epithelium, the platinum concentration was significantly higher in areas of degeneration caused by chemotherapy than in nondegenerated area (p < 0.001). Conversely, in the tumor stroma, the platinum concentration was significantly higher in patients with limited therapeutic responses than in those with strong therapeutic responses (p < 0.001). Furthermore, multivariate analysis illustrated that higher platinum concentration in the tumor stroma was an independent predictive factor of limited histologic response (odds ratio; 19.99, 95% confidence interval; 2.04-196.37, p = 0.013). This is the first study to visualize and quantify the distribution of platinum in human cancer tissues using SR-XRF. These results suggest that SR-XRF analysis may contribute to predicting the therapeutic effect of l-OHP-based chemotherapy by quantifying the distribution of platinum.

Deregulated Mucosal Immune Surveillance through Gut-Associated Regulatory T Cells and PD-1+ T Cells in Human Colorectal Cancer.

Disturbed balance between immune surveillance and tolerance may lead to poor clinical outcomes in some malignancies. In paired analyses of adenocarcinoma and normal mucosa from 142 patients, we found a significant increase of the CD4/CD8 ratio and accumulation of regulatory T cells (Tregs) within the adenocarcinoma. The increased frequency of Tregs correlated with the local infiltration and extension of the tumor. There was concurrent maturation arrest, upregulation of programmed death-1 expression, and functional impairment in CD8+ T cells (CTLs) isolated from the adenocarcinoma. Adenocarcinoma-associated Tregs directly inhibit the function of normal human CTLs in vitro. With histopathological analysis, Foxp3+ Tregs were preferentially located in stroma. Concurrent transcriptome analysis of epithelial cells, stromal cells, and T cell subsets obtained from carcinomatous and normal intestinal samples from patients revealed a distinct gene expression signature in colorectal adenocarcinoma-associated Tregs, with overexpression of CCR1, CCR8, and TNFRSF9, whereas their ligands CCL4 and TNFSF9 were found upregulated in cancerous epithelium. Overexpression of WNT2 and CADM1, associated with carcinogenesis and metastasis, in cancer-associated stromal cells suggests that both cancer cells and stromal cells play important roles in the development and progression of colorectal cancer through the formation of a tumor microenvironment. The identification of CTL anergy by Tregs and the unique gene expression signature of human Tregs and stromal cells in colorectal cancer patients may facilitate the development of new therapeutics against malignancies.

Vascular anatomy of the transverse mesocolon and bidirectional laparoscopic D3 lymph node dissection for patients with advanced transverse colon cancer.

Laparoscopic D3 lymph node dissection for transverse colon cancer is technically demanding because of complicated anatomy. Here, we reviewed the vascular structure of the transverse mesocolon, explored the extent of the base of the transverse mesocolon, and evaluated the feasibility and oncological safety of D3 lymph node dissection. We retrospectively reviewed the clinical records of 42 patients with advanced transverse colon cancer who underwent curative surgery and D3 dissection at Kyushu University Hospital between January 2008 and December 2015. We examined the venous and arterial anatomy of the transverse mesocolon of each resection and compared surgical outcomes between patients who underwent laparoscopic D3 (Lap D3) and open D3 (Open D3) dissection. Patients included two with Stage I, 18 with Stage II, 20 with Stage III, and two with Stage IVA. Thirty-six (85.7%) and six (14.3%) patients underwent Lap D3 or Open D3, respectively. The tumor sizes of the Open D3 and Lap D3 groups were 7.8 and 3.7 cm, respectively (P < 0.001). The Lap D3 group had significantly less blood loss (26 mL vs 272 mL, P = 0.002). The other outcomes of the two groups were not significantly different, including 3-year overall survival (87.7% vs 83.3%, P = 0.385). We observed four patterns of the middle colic artery (MCA) arising from the superior mesenteric artery (SMA), and the frequency of occurrence of a single MCA was 64.3%. The right-middle colic vein (MCV) was present in 92.9% of resections and served as a tributary of the gastrocolic trunk, and 90.5% of the left MCVs drained into the superior mesenteric vein (SMV). The root of the transverse mesocolon was broadly attached to the head of the pancreas and to the surfaces of the SMV and SMA. Laparoscopic D3 lymph node dissection may be tolerated by patients with advanced transverse colon cancer.

Risk factors for postoperative pneumonia in elderly patients with colorectal cancer: a sub-analysis of a large, multicenter, case-control study in Japan.

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.

Efficacy and safety analysis of chemotherapy for advanced colitis-associated colorectal cancer in Japan.

Chemotherapy for advanced colitis-associated colorectal cancer (CAC) has been insufficiently evaluated. The goal of this study was to clarify the efficacy and safety of chemotherapy for CAC in Japan. CAC patients who were treated with chemotherapy between 2005 and 2015 were retrospectively examined. Twenty-nine patients (median age, 48 years; 23 men) were assessed. Eighteen patients had ulcerative colitis, and 11 had Crohn's disease. Three ulcerative colitis and four Crohn's disease patients were in the active disease phase. Primary tumors were located in the rectum/anus (n=16), the left colon (n=9), or the right colon (n=4). Palliative or adjuvant chemotherapy was performed in 13 and 16 patients, respectively. First-line palliative chemotherapy regimens were as follows: fluorouracil, leucovorin, and oxaliplatin (FOLFOX; n=6), FOLFOX+bevacizumab (n=3), and others (n=4). Adjuvant chemotherapy regimens were S-1 (n=7), oxaliplatin-based (n=4) and others (n=5). In palliative chemotherapy, the objective response rate was 15%, and the median progression-free survival and overall survival were 182 and 315 days, respectively. In adjuvant chemotherapy, the 5-year relapse-free survival rate was 78%. Grade 3/4 adverse events (AEs) were observed in 16 patients (55%). Active and remission inflammatory bowel disease patients suffered grade 3/4 nonhematological AEs at an incidence of 71 and 23%, respectively (P<0.01). Dose reduction was required in 11 patients (38%), eight of whom required it for hematological AEs. Adjuvant chemotherapy for CAC exhibited sufficient efficacy, whereas modest efficacy was shown for palliative chemotherapy for CAC. AEs, particularly nonhematological AEs, were closely associated with disease activity of colitis.

Laparoscopic lateral pelvic lymph node dissection is achievable and offers advantages as a minimally invasive surgery over the open approach.

BACKGROUND: Laparoscopic lateral pelvic lymph node dissection (LPLD) is a minimally invasive alternative to open surgical therapy for advanced low rectal cancer patients. This study assessed potential risk factors for lateral pelvic lymph node metastasis (LPLM) and evaluated the feasibility and oncological safety of laparoscopic LPLD compared with the conventional open approach. METHODS: We retrospectively reviewed the clinical records of 90 patients with advanced low rectal cancer who underwent LPLD following total mesorectal excision at Kyushu University Hospital between January 2001 and July 2014. We compared the clinicopathological features between the patients with and without LPLM and the surgical outcomes between patients who underwent laparoscopic LPLD (LL) and open LPLD (OL). RESULTS: Fourteen (15.6 %) patients had LPLM. Univariate analysis revealed that undifferentiated cancer, positive lymphatic invasion, >50 % circumferential cancer extent, mesorectal lymph node metastases (MLM), and distant metastasis were associated with LPLM. In the multivariate analysis, MLM was the only independent risk factor for LPLM. Forty-six (51.1 %) patients underwent LL, and 44 (48.9 %) patients underwent OL. The mean surgical duration was longer in the LL group than in the OL group (641.0 vs. 312.0 min, P < 0.001). The LL group also had less hemorrhage (252.0 vs. 815.0 mL, P < 0.001) and a shorter hospital stay (22.9 vs. 29.1 days, P = 0.04) than the OL group. The mean number of harvested lateral pelvic lymph nodes was larger in the LL group than in the OL group (19.5 vs. 15.8, P < 0.05). The morbidity rate and overall survival (3-year OS: 94.7 vs. 82.9 %, P = 0.25) did not differ between the two groups. CONCLUSIONS: Patients with advanced low rectal cancer presenting MLM are good candidates for LPLD. Laparoscopic LPLD enables retrieval of more lymph nodes and may be acceptable for the treatment of advanced low rectal cancer.

A longitudinal study of gender differences in quality of life among Japanese patients with lower rectal cancer treated with sphincter-saving surgery: a 1-year follow-up.

BACKGROUND: Up to 80% of patients with rectal cancer undergo sphincter-saving surgery, and almost 90% of them experience subsequent physical changes. The number of studies on gender differences in response to this surgery has increased, and the connection between gender and symptoms and patient outcomes has generated increasing interest. Nevertheless, little is known about the gender differences in quality of life and cancer-related symptoms. We examined gender differences and quality of life changes over a 1-year period among patients with lower rectal cancer who were treated with sphincter-saving surgery. METHODS: Patients (men = 42; women = 33) completed a self-administered questionnaire on their quality of life and related factors before surgery and 1, 6, and 12 months afterwards. The questionnaire was developed by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30/CR-38). RESULTS: Scores on physical, role, and social functioning and global health status/quality of life decreased 1 month after surgery, improved after 6 months, and returned to baseline within 12 months, with the exception of social functioning in men. Factors related to quality of life changed after surgery and differed between men and women. Women's global health status/quality of life was affected by fatigue, weight loss, defecation problems, and future perspective, while that of men was affected by fatigue, weight loss, future perspective, and role functioning, which was affected by pain, defecation problems, and financial difficulties. CONCLUSIONS: Gender differences should be considered when predicting the quality of life of cancer patients undergoing surgery. Identifying gender differences will help health care providers anticipate the unique needs of patients undergoing surgery for rectal cancer.

Risk of cancer in the rectal remnant after ileorectal anastomosis in patients with familial adenomatous polyposis: single center experience.

BACKGROUND AND AIM: We aimed to evaluate the long-term risk of cancer in the rectal remnant in patients with familial adenomatous polyposis after ileorectal anastomosis. METHODS: Cumulative incidence and clinicopathological characteristics of cancer in the rectal remnant were retrospectively investigated in 27 patients with familial adenomatous polyposis who had undergone ileorectal anastomosis. RESULTS: During the follow-up period ranging from 3.0 to 35.0 years (median, 21.1 years), cancer in the rectal remnant developed in 10 patients. Cumulative risk of cancer in the rectal remnant 30 years after surgery was 57%. Five patients had metastases and three patients died of cancer in the rectal remnant after proctectomy. There was a trend towards a higher incidence of cancer in the rectal remnant in patients with small-intestinal adenoma and congenital hypertrophy of the retinal pigment epithelium. Multivariate analysis revealed that the ocular lesion was an independent risk factor associated with cancer in the rectal remnant. CONCLUSION: Subtotal colectomy with ileorectal anastomosis does not seem to be an appropriate prophylactic surgery in patients with familial adenomatous polyposis.

[FEMALE SURGEONS SHOULD BE AWARE OF THE IMPORTANCE OF A CLEAR VISION FOR THEIR CAREER AND LIFE PLANS TO ACHIEVE THEIR CAREER DEVELOPMENT.: A SURVEY OF 20 FEMALE SURGEONS AT THE DEPARTMENT OF SURGERY AND ONCOLOGY, KYUSHU UNIVERSITY].

A shortage of surgeons has been a serious problem in recent years. There is an urgent need to utilize female surgeons who tend to resign because of bearing and raising of children. To examine possible measures to deal with the issue, we performed questionnaire survey about work-life balance and career planning on 20 female surgeons in the Department of Surgery and Oncology, Kyushu University. The response rate was 80.0%. In the 16 respondents, seven were unmarried and nine were married. A large fraction of the respondents recognized the importance of work-life-balance. Female surgeons have many difficulties to continue working with good work-life balance; therefore, understanding and cooperation of both their spouses and coworkers is considered to be necessary. Married female surgeons considered that improvement of the working environment and sufficient family support were more important for good work-life balance compared to those who were unmarried. Female surgeons should recognize the importance of improvement of their environment, including the workplace and the family to continue working with good work-life balance in youth and should have the prospects about their career plan of their own.

Tumor deposit is a poor prognostic indicator for patients who have stage II and III colorectal cancer with fewer than 4 lymph node metastases but not for those with 4 or more.

BACKGROUND: Extranodal tumor deposits are involved in TNM classification. However, it is uncertain whether a tumor deposit is a regular lymph node metastasis, and its prognostic significance in patients with stage II or III colorectal cancer remains to be established. OBJECTIVE: This study aimed to determine the prognostic significance of tumor deposits for stage II and III colorectal cancer. DESIGN: This study is a retrospective review of clinicopathological data. SETTING: This study was conducted at a tertiary care hospital/referral center in Japan. PATIENTS: We reviewed the clinical course of 171 stage II and 173 stage III consecutive patients between January 1999 and December 2006. MAIN OUTCOME MEASURES: We examined the clinicopathological features of colorectal cancers with tumor deposits and calculated overall survival and recurrence-free survival of the patients according to the status of tumor deposits. The primary outcome was the impact of tumor deposits on patient survival. RESULTS: Thirty-five (10.2%) patients with colorectal cancers had tumor deposits in the pericolic and/or mesocolic region. Survival rates among the patients with tumor deposits were significantly lower than those without (5-year overall survival: 58.4% vs 81.0%, p < 0.0001; 5-year recurrence-free survival: 47.1% vs 73.4%, p < 0.0001). Tumor deposit was an independent prognostic factor for patients with colorectal cancer in multivariate analysis (overall survival: HR, 2.30; 95% CI, 1.26-4.04; p = 0.04; recurrence-free survival: HR, 2.42; 95% CI, 1.04-4.90; p = 0.04). Tumor deposit was an independent prognostic factor in N0 and N1 colorectal cancer, whereas N2 cancer had poor survival outcome regardless of tumor deposit. LIMITATIONS: Our study was a single-institution retrospective study, and the numbers of patients were relatively small to draw firm conclusions. CONCLUSION: Tumor deposit may be an independent adverse prognostic factor for stage II and III N1 colorectal cancer.

Sugars, sucrose and colorectal cancer risk: the Fukuoka colorectal cancer study.

OBJECTIVE: A diet high in sugars may promote colorectal carcinogenesis, but it remains uncertain whether high intake of sugars or sucrose confers increased risk of colorectal cancer. The authors investigated the associations of sugars and sucrose intake with colorectal cancer risk in a community-based case-control study in Japan. METHODS: The study subjects comprised 816 incident cases of colorectal cancer and 815 community controls. Consumption frequencies and portion sizes of 148 food and beverage items were ascertained by a computer-assisted interview. The authors used the consumption of 29 food items to estimate sugars and sucrose intake. The odds ratios of colorectal cancer risk according to intake categories were obtained using a logistic regression model with adjustment for potential confounding variables. RESULTS: Overall, intakes of sugars and sucrose were not related to colorectal cancer risk either in men or women. The association between sugars intake and colorectal cancer risk differed by smoking status and alcohol use in men, but not in women. In men, sugars intake tended to be associated with colorectal cancer risk inversely among never-smokers and positively among male ever-smokers (interaction p=0.01). Sugars intake was associated with an increased risk among men with no alcohol consumption, but was unrelated to the risk among male alcohol drinkers (interaction p=0.02). Body mass index did not modify the association with sugars intake in either men or women. CONCLUSION: Sugars intake was associated with increased risk of colorectal cancer among smokers and non-alcohol drinkers in men selectively.

[A case of gastrointestinal stromal tumor of the jejunum successfully treated by preoperative induction chemotherapy with imatinib mesylate administered through jejunostomy and subsequent surgical resection].

A 70 -year-old female patient with a palpable mass in the left upper abdomen suffered from abdominal pain and fever. Abdominal computed tomography showed a jejunal tumor 11 cm in diameter with ascites, suggesting rupture of the tumor. Histological diagnosis via endoscopic ultrasound-guided fine needle aspiration indicated c-kit-positive gastrointestinal stromal tumor. Diagnostic laparoscopy demonstrated a large jejunal tumor possibly invading the stomach and pancreas. The patient then underwent tube jejunostomy. Thereafter, preoperative induction chemotherapy with imatinib mesylate(400mg/ body/day)via jejunostomy was administered for 6 months, resulting in 20%reduction of the tumor diameter and disappearance of any indication of stomach and pancreas invasion. The patient then underwent radical partial resection of the jejunum without combined resection of either the stomach or pancreas. Postoperative adjuvant chemotherapy with imatinib mesylate (400mg/body/day)was also indicated. No sign of recurrence has been detected to date after 1 year of follow-up.

Estrogen receptor-ß gene polymorphism and colorectal cancer risk: effect modified by body mass index and isoflavone intake.

Estrogen receptor (ER)-ß signaling has generally been implicated in protection against colorectal cancer. The ER-ß gene cytosine-adenine (ESR2 CA) repeat polymorphism was reported to be associated with colorectal cancer, although showing contradicting results probably caused by ethnicity or age distribution of the subjects. We investigated the association between this polymorphism and the colorectal cancer risk in a community-based case-control study in Japan (685 cases/778 controls), including only subjects younger than 75. The effect modifications of the body mass index (BMI) and isoflavone intake were also examined. ESR2 CA repeat polymorphism was determined by polymerase chain reaction using fluorescein-labeled primers. CA repeat alleles were classified into short (S) allele (<22 repeats) and long (L) allele (≥ 22 repeats). Subjects were divided into three genotype groups (SS/SL/LL). The risk of colon cancer, but not of rectal cancer, was increased with an increasing number of L alleles among postmenopausal women; age-adjusted odds ratio (OR) for SL and LL genotypes compared with the SS genotype were 1.78 and 2.91, respectively (trend p = 0.002). Increased risks of colon cancer associated with the L allele were more evident among postmenopausal women with low BMI (<25 kg m(-2)) or with high isoflavone intake. Such associations were not observed among men or premenopausal women. Having longer ESR2 CA repeat increases colon cancer risk among postmenopausal women younger than 75, possibly with modification of BMI and isoflavone intake. Aging and estrogenic condition may be important in the colon cancer pathogenesis associated with ESR2 CA repeat polymorphism.

Microsomal epoxide hydrolase polymorphisms, cigarette smoking, and risk of colorectal cancer: the Fukuoka Colorectal Cancer Study.

Microsomal epoxide hydrolase (EPHX1) plays an important role in the activation and detoxification of polycyclic aromatic hydrocarbons, carcinogens found in cigarette smoke. Polymorphisms in exon 3 (Y113H) and exon 4 (H139R) of the EPHX1 have been associated with enzyme activity. We investigated the risk of colorectal cancer in relation to the EPHX1 Y113H and H139R polymorphisms and assessed effect modifications of cigarette smoking and the other covariates. The interaction between the EPHX1 polymorphisms and selected genetic polymorphisms was also examined. We used data from Fukuoka Colorectal Cancer Study, a community-based case-control study, including 685 cases and 778 controls. In-person interviews were conducted to assess lifestyle factors. The EPHX1 Y113H and H139R polymorphisms were determined by the TaqMan assay and the polymerase chain reaction-restriction fragment length polymorphism, respectively. Neither of the two polymorphisms nor the imputed EPHX1 phenotype was associated with colorectal cancer risk. Cigarette smoking and alcohol intake showed no effect modification on the association with the EPHX1 polymorphisms or the imputed EPHX1 phenotype. Increased risks of colorectal cancer associated with the 113Y allele and imputed EPHX1 phenotype were observed among individuals with high body mass index (BMI; ≥25.0 kg/m(2)), but not among those with low BMI (<25.0 kg/m(2)). The risk decreased with an increasing number of the 139R allele in the null genotypes of GSTM1/GSTT1. It is unlikely that the EPHX1 polymorphisms play an important role in colorectal carcinogenesis. The observed interactions of the EPHX1 polymorphisms with BMI and the GSTM1/GSTT1 genotypes warrant further investigation.

[Surgical treatment of gastroentero-pancreatic neuroendocrine tumor].

The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is resection. Because it is difficult to determine the histological grade of NET before operation, the treatment strategy is usually made based on an imaging study including the tumor's size. Some selected gastrointestinal NETs are indicated for endoscopic resection, while others are resected surgically with lymph node dissection. The types of resections for pancreatic NETs vary from enucleation to pancreatectomy with or without regional lymph node dissection, based on the type of excessive hormone, tumor size, distance from the main pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic metastases are also resected, if indicated, and even in patients having unresectable metastatic lesions, multidisciplinary therapy including reduction surgery of over 90% of tumor volume might lead to a favorable prognosis. Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while there is no evidence to support adjuvant therapy for curatively resected well-differentiated NET.

Dietary intakes of retinol, carotenes, vitamin C, and vitamin E and colorectal cancer risk: the Fukuoka colorectal cancer study.

It has long been a matter of interest whether antioxidant vitamins are protective against colorectal cancer as well as human cancers in general, but epidemiological evidence is inconclusive. We investigated associations of dietary intakes of retinol and antioxidant vitamins with colorectal cancer risk in 816 incident cases of histologically confirmed colorectal cancer and 815 controls randomly selected for the Fukuoka colorectal cancer study in Japan. Dietary intakes were assessed by a PC-assisted interview regarding 148 food items. Statistical adjustment was made for body mass index, physical activity, calcium, and n-3 fatty acid intake and other factors. Retinol intake was significantly, inversely associated with colorectal cancer risk; the odds ratio for the highest vs. lowest was 0.55 (95% CI: 0.35, 0.88; P (trend) = 0.01) in women, but a modest increase in the risk was observed among men with the highest intake of retinol. Liver was the major source of retinol intake and showed similar associations with colorectal cancer risk in men and women. Intake of carotenes, vitamin C, and vitamin E were not related to colorectal cancer risk in either men or women. The study did not support a hypothesis that dietary intake of antioxidant vitamins is protective in the development of colorectal cancer.

Human STEAP3 maintains tumor growth under hypoferric condition.

Iron is essential in cellular proliferation and survival based on its crucial roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients with low serum iron, although their actual mechanisms are not well known. To elucidate molecular mechanisms of efficient tumor progression under the hypoferric condition, we studied the roles of six-transmembrane epithelial antigen of the prostate family member 3 (STEAP3), which was reported to facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human STEAP3-overexpressing cells were established. The impact of STEAP3 expression was analyzed about the amount of iron storage, the survival under hypoferric conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even in hypoferric mice, while parental Raji cells grew less rapidly. In addition, iron deficiency enhanced STEAP3 mRNA expression in tumor cells. Furthermore, human colorectal cancer tissues exhibited more STEAP3 mRNA expression and iron storage compared with normal colon mucosa. These findings indicate that STEAP3 maintains iron storage in human malignant cells and tumor proliferation under the hypoferric condition.

Genetic polymorphisms of XRCC1, alcohol consumption, and the risk of colorectal cancer in Japan.

BACKGROUND: X-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk. METHODS: This case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects. RESULTS: The XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01-2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26-0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02-2.87) and 1.57 (95% CI 1.05-2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418). CONCLUSIONS: The findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.