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Background In rectal cancer surgery, insertion of transanal tube has been shown to have efficacy to prevent anastomotic leakage. This randomized controlled study aims to clarify the incidence of anastomotic leakage with or without transanal tube in patients with rectal cancer. Methods Patients who underwent elective low anterior resection were randomly allocated to either have transanal tube insertion or not for five days after surgery. We examined the incidence of anastomotic leakage, postoperative 30-day morbidity and mortality. Results 157 patients were randomized to the transanal tube group or the no-transanal tube group. Symptomatic anastomotic leakage occurred in six patients (7.6%) of the former group and eight patients (10.3%) in the latter group, without significant difference (p = 0.559). There was also no significant difference in morbidity between groups (p = 0.633) and no mortality was detected. Conclusions Transanal tube insertion had no significant benefit towards prevention of anastomotic leakage in rectal cancer surgery.

Preoperative ctDNA status in relation to recurrence in cases of CRC remains unclear. We examined preoperative ctDNA detection by targeting KRAS gene mutations as a predictive marker for recurrence after CRC surgery. We measured the preoperative KRAS mutated ctDNA status and analyzed the correlation with clinicopathologic features of 180 patients that underwent surgery for CRC. We studied the association between preoperative KRAS mutated ctDNA and postoperative recurrence in patients (n = 150) that underwent radical surgery. KRAS mutated ctDNA was detected in 59 patients (32.8%). Median mutant allele frequency of KRAS in ctDNA was 0.20%. KRAS status in ctDNA and lymph node metastasis and distant metastasis were not significantly different. Among patients that underwent radical resection, recurrence occurred in 21 (14.0%, median follow-up 24 months). In Kaplan–Meier analysis, preoperative detection of KRAS mutated ctDNA was associated with inferior recurrence-free interval (RFI) (p = 0.002) and recurrence-free survival (RFS) (p = 0.025). In a multivariate Cox proportional hazards model, preoperative detection of KRAS mutated ctDNA was an independent factor related to both RFI (HR = 3.08; p = 0.012) and RFS (HR = 2.18; p = 0.044). Preoperative measurement of KRAS mutated ctDNA could be useful to decide postoperative treatment.

Background: Anastomotic leakage (AL) is arguably the most troublesome complication of anterior resection (AR). In recent years, however, indocyanine green (ICG) fluorescence imaging has been recent...

Background: Synchronous colorectal peritoneal carcinomatosis (SCPC) is not a rare entity, and the prognosis is extremely poor compared to other metastatic sites such as the liver and lung. Therefore, optimal treatment based on tumor characteristics is needed. Recently, the tumor sidedness of colorectal cancer has been reported as one of the prognostic factors and also as a key factor for the treatment strategy. The purpose of this study was to assess the clinical impact of tumor sidedness in patients with SCPC. Methods: A total of 189 cases of SCPC were identified in a retrospective database at Wakayama Medical University Hospital (WMUH) between 1998 and 2014, and were analyzed with a special focus on tumor location. Results: In multivariate analysis, a right-sided location (p = 0.02) and the presence of liver metastases (p < 0.001) were found to be the worst prognostic factors. The median survival time (MST) with right-sided and with left-sided SCPC was 10 and 16 months, respectively. The right-sided SCPC group included more aged patients (p = 0.045) and fewer patients who received postoperative chemotherapy (p = 0.034). When we focused on patients with macroscopically complete resection (n = 39), the MST and disease-free survival in the right-sided SCPC group was significantly shorter than in the left-sided SCPC group (p = 0.030 and p = 0.043, respectively). The MST of the right-sided and the left-sided SCPC patients among the completely resected patients was 24 and 73 months, respectively. Conclusion: Tumor sidedness may be a potent prognostic indicator for patients with SCPC. The survival time with right-sided SCPC is dramatically reduced compared to that with left-sided SCPC, especially among completely resected cases. We should change the treatment strategy according to the location of SCPC.

Risks for postoperative small bowel obstruction have been demonstrated in several reports, most of which indicated male sex was a risk factor, but with the reason remaining unknown. We tested the hypothesis that it could be because males have more visceral fat than females. This prospective observational study aims to examine risks of early postoperative small bowel obstruction (EPSBO) after colorectal cancer surgery and the association between visceral to subcutaneous fat area ratio (V/S ratio) and EPSBO.Four hundred and seventy-four patients who underwent colectomy for colorectal cancer in our hospital were enrolled in this study. The influence of several factors including V/S ratio on the development of EPSBO was analyzed.Thirty-one of the 474 patients (6.5%) developed EPSBO. EPSBO occurred more frequently in males (p = 0.03) and cases who developed postoperative anastomotic leakage (p 0.001) or wound infection (p = 0.02). Higher V/S ratio was strongly related to male sex (p 0.001). Multivariate analysis revealed higher V/S ratio (OR 2.25; p = 0.049) and anastomotic leakage (OR 5.86; p 0.001) were independent risk factors for EPSBO.Higher V/S ratio was significantly related to EPSBO, suggesting that one of the reasons EPSBO was more likely to occur in males because they have more visceral fat than females. Preoperative identification of this risk factor could help us watch out for this potential complication.

Background This study is intended to assess whether the use of pelvic drain reduces incidence of pelvic sepsis in the era of laparoscopic low anterior resection (LAR). Patients and methods In total, 200 of consecutive patients who underwent laparoscopic LAR for rectal cancer with diverting stoma were analyzed. Results Pelvic sepsis occurred in 14 of 110 patients (12.7%) in the drain group and in 9 of 90 patients (10.0%) in the no drain group (P=0.548). Furthermore, there were no differences in the incidence of anastomotic leakage, time to diagnosis of pelvic sepsis, and type of treatments for pelvic sepsis. Conclusions Prophylactic pelvic drain use after laparoscopic LAR in patients with diverting stoma does not reduce incidence of pelvic sepsis. Routine use of pelvic drain is not recommended. This study was registered at UMIN (Registration Number: UMIN000026076).

Creation of defunctioning loop ileostomy is a standard procedure in laparoscopic lower rectal surgery. Stoma-related obstruction sometimes occurs, but its cause has not been fully analyzed. This study aims to assess stoma obstructive complications and clarify the risk factors of stoma-related obstructions. Two hundred and thirty consecutive patients who underwent laparoscopic rectal cancer surgery with defunctioning loop ileostomy between April 2007 and December 2017 were recruited, numbering 230. We statistically examined the frequency and risk factor of stoma outlet obstruction. Postoperative stoma-related complications developed in 41 patients (17.8%) overall, and there was no 30-day mortality. Stoma outlet obstructions occurred in 16 patients (7.0%) during postoperative course. Thick subcutaneous fat at the stoma-marking site (vertical distance ≥ 20 mm) and body mass index (≥ 22.2) were significantly associated with the risk of stoma outlet obstruction in univariate analysis. Thick subcutaneous fat was a significant predictive factor of stoma outlet obstruction according to multivariate analysis (odds ratio 3.80). This report investigates significant predictors of stoma outlet obstruction in laparoscopic rectal cancer surgery for the first time. In laparoscopic procedure, stoma outlet obstruction should be particularly considered in obese patients who have especially thick subcutaneous fat of the abdominal wall.

Anastomotic leakage (AL) is one of the most troublesome complications in colorectal surgery. Recently, near-infrared fluorescence (NIRF) imaging has been used intraoperatively to detect sentinel lymph nodes and visualize the blood supply at the region of interest (ROI). The aim of this study was to evaluate the role of visualization and quantification of bowel perfusion around the anastomosis using NIRF system in predicting AL. A prospective study was conducted on patients who had laparoscopic surgery for colorectal cancer at our institution. Perfusion of the anastomosis was evaluated with NIRF imaging after intravenous injection of indocyanine green (ICG). The time course of fluorescence intensity was recorded by an imaging analyzer We measured the time from ICG injection to the beginning of fluorescence (T0), maximum intensity (Imax), time to reach Imax (Tmax), time to reach Imax 50% ( $$T_{{{ \text{max} }_{1/2} }}$$ ) and slope (S) after the anastomosis. Tumor locations were as follows; cecum: 2, ascending colon: 2, transverse colon: 7, descending colon: 1, sigmoid colon: 2, rectosigmoid colon: 3 and rectum: 6 (one case with synchronous cancer). All operations were performed laparoscopically. Four patients were diagnosed with or suspected to have AL (2 patients with grade B anastomotic leakage after low anterior resection, 1 patient with minor leakage in transverse colon resection and 1 patient needing re-anastomosis intraoperatively in transverse colon resection). T0 was significantly longer in the AL group than in patients without AL (64.3 ± 27.6 and 18.2 ± 6.6 s, p = 2.2 × 10−3). Perfusion of the anastomosis could be successfully visualized and quantified using NIRF imaging with ICG. T0 might be a useful parameter for prediction of AL.

A 39-year-old female patient underwent anterior resection with locoregional lymph node dissection for rectosigmoid cancer at another hospital. The procedure involved transection of the superior rectal artery just below the origin of the left colic artery. Postoperative diagnosis was stage III B. The patient received adjuvant chemotherapy with oxaliplatin plus capecitabine for 6 months. Sixteen months after the operation, PET-CT scans revealed regional lymph node metastases around the root of the inferior mesenteric artery. The patient was referred to our hospital with a recurrence of rectosigmoid cancer. We performed laparoscopic lymph node dissection with real-time indocyanine green fluorescent images superimposed on color images to prevent intraoperative vascular insufficiency. We were able to successfully observe the sufficient blood flow in the descending colon. Postoperative pathological findings showed lymph node recurrence after initial surgery. She was discharged 7 days after the operation. In the 8 months since the second operation, the patient has not had any indication of further recurrence.

Background: Preoperative chemoradiation therapy (pCRT) is a standard procedure for patients with advanced lower rectal cancer. It has been reported that pCRT cannot prolong the survival of patients with advanced lower rectal cancer. The aim of this study is to address the controllable and uncontrollable pathological factors of pCRT in predicting local and distant recurrences. Methods: One hundred two patients with stages 2 and 3 cancer were consecutively enrolled to the study. The first 51 patients (October 2008-August 2010) underwent curative resection without pCRT. The latter 51 patients (September 2010-May 2015) underwent curative resection after pCRT. Pathological factors of patients were evaluated to assess the association between local and distant recurrences. Results: Multivariate analyses for local and distant recurrences of patients without pCRT revealed that the independent risk factors were tumor deposit and perineural invasion respectively. pCRT was able to diminish circumferential resection margin, tumor deposit, venous invasion, and lymphatic permeation but not neural invasion and lymph node involvement. Kaplan-Meier curve of local and distant recurrence-free survival of patients with pCRT illustrated that tumor deposit is controllable, whereas perineural invasion is uncontrollable by pCRT. Conclusion: pCRT-uncontrollable perineural invasion may be a factor for distant recurrence of advanced rectal cancer patients, leading to poor survival.

Because anorectal melanoma, a rare cancer with a poor outcome, does not respond well to local radiation therapy or systemic chemotherapy, surgery is the primary treatment. Herein, we present a case of anorectal melanoma with lateral and inguinal lymph node metastases. A 61-year-old woman presented with rectal bleeding. Colonoscopy revealed a black tumor with ulceration in the anorectum. A CT scan revealed an anorectal tumor with left lateral lymph node swelling and right inguinal lymph node swelling. We performed a laparoscopic abdominoperineal resection with lateral lymph node dissection and right inguinal lymph node dissection. One year after the initial operation, pulmonary metastases were observed, and pulmonary resection was performed. After the pulmonary resection, brain metastases developed, and surgical resection was performed. Despite the recurrence of disease, the patient has survived for 52 months since the initial surgery and continues to receive systemic chemotherapy.

To determine whether the beneficial effects of alcohol on lipid concentrations are mediated by insulin levels, we performed a cross-sectional analysis in 2103 nondiabetic men and women aged 40 to 79 years from a general Japanese population in Hisayama. The multivariate-adjusted sum of fasting and 2-hour postloading insulin levels and the insulin resistance index significantly decreased with elevating alcohol intake levels in men (P < 0.01 for the trend) but not in women. No dose-response relations between alcohol intake and glucose levels were observed. In both sexes, high-density lipoprotein cholesterol (HDLC) significantly increased with elevated alcohol intake (P < 0.01), whereas total cholesterol and low-density lipoprotein cholesterol (LDLC) were inversely correlated with alcohol intake (P < 0.01). In contrast, triglycerides (TGs) levels in men showed a J-shaped relation to alcohol dose, with moderate drinkers (10-29 g/d) having the lowest levels. Estimates using regression models indicated that for men, 10% of the alcohol-induced increase in HDLC and 2% of the alcohol-induced decrease in LDLC were insulin mediated. It was also estimated for male subjects that 36% of the reduction in TGs due to low to moderate alcohol intake was mediated by low levels of insulin and that this insulin-mediated pathway reduced the positive alcohol-TG relation by 13% in cases of moderate to heavy drinking. Our data suggest that regular alcohol consumption dose-dependently increased insulin sensitivity among male nondiabetics, but the insulin-mediated beneficial effects of alcohol on lipid concentrations were relatively small.

Insulin resistance may be a factor in the etiology of hypertension, and habitual alcohol intake may modify this relationship. We prospectively examined this hypothesis in 1,133 nonhypertensive, nondiabetic Japanese subjects, aged 40–79 years. Alcohol drinkers were more frequent among men than women at baseline (57.7 vs. 8.2%). The age-adjusted incidence of hypertension significantly increased with the elevating baseline insulin levels in women (P = .003 for trend), but not in men. The age- and sex-adjusted insulin levels and insulin resistance index decreased with elevating alcohol intake, while fasting glucose levels remained unchanged, suggesting that alcohol improves insulin sensitivity. Among nondrinkers, the age-adjusted incidence of hypertension significantly increased with elevating insulin tertiles in both sexes (P = .048 and .002 for trend in men and women, respectively), but not among drinkers. Our findings suggest a close association between insulin resistance and the incidence of hypertension in Japanese. However, alcohol modified and reduced this relationship.

Background The question remains as to whether light to moderate alcohol intake is associated with an increased risk of hypertension. Methods In 1978, a total of 1101 residents (433 men and 668 women) in a subrural community, Hisayama, in Japan, aged 40 years or more, with normal blood pressure, who were free from cardiovascular disease, were enrolled in a 10-year follow-up study. Inquiries regarding regular drinking were made in an interview based on a self-administered questionnaire. Results During the follow-up, 101 men and 166 women developed hypertension (blood pressure ≥140/90 mm Hg or use of antihypertensive drugs). The age-adjusted incidence of hypertension among current male drinkers increased significantly even with a light intake of alcohol (

The International Study Group of Rectal Cancer (ISREC) has proposed a new definition of anastomotic leakage (AL) which was simply classified into three grades; however, these criteria have not been assessed well. The aims of this study are to assess the new definition and to show the clinical features of AL after an anterior resection for rectal cancer. Fifty consecutive patients developed AL after an anterior resection for rectal cancer was retrospectively assessed. AL was defined by the ISREC criteria. Twenty-seven (54 %) patients with AL were diagnosed by drain contents. The postoperative day of diagnosis for AL was later in grade A versus grades B and C (p = 0.038 vs p = 0.006, respectively). Permanent stoma (PS) was significantly more frequent in patients with grade C but not grade B compared to the patients with no AL (p

PURPOSE This study evaluated the impact of the pelvic pillow on a single surgeon's learning how to perform laparoscopic low anterior resection (LAR) for rectal cancer. METHODS We compared the outcomes for 23 patients with rectal cancer including the first 11 patients who underwent laparoscopic LAR without the pelvic pillow, and the latter 12 patients with the pelvic pillow by a single surgeon. RESULTS The stage of the pelvic pillow (+) was more advanced than that of the pelvic pillow (-). The length of the operation and postoperative start of oral intake for the pelvic pillow (+) were shorter and earlier than those of the pelvic pillow (-). The pelvic surgical field in the pelvic pillow (+) was better and allowed better evaluation than the pelvic pillow (-). CONCLUSIONS Maintaining an excellent view of the pelvic surgical field with the pelvic pillow might have an impact on learning laparoscopic LAR.

Background and Purpose —We estimated the incidence of first-ever cerebral infarction in regard to its subtypes and analyzed their risk factors separately in a community-based prospective cohort study in Japan. Methods —Stroke-free subjects (n=1621) aged ≥40 years were followed up for 32 years from 1961. During this period, 298 cerebral infarctions occurred and were divided into 167 lacunar, 62 atherothrombotic, 56 cardioembolic, and 13 undetermined subtypes of infarction on the basis of clinical information including brain imaging and autopsy findings. Results —The age-adjusted incidence of lacunar infarction (3.8 per 1000 person-years for men and 2.0 for women) was higher than that of atherothrombotic infarction (1.2, 0.7) and cardioembolic infarction (1.3, 0.5) in both sexes. Time-dependent Cox’s proportional hazard analysis revealed systolic blood pressure as well as age to be independent risk factors for all subtypes of cerebral infarction except for cardioembolic infarction in men. Additionally, ST depression on ECG, glucose intolerance, and smoking in men and left ventricular hypertrophy on ECG and body mass index in women remained significant risk factors for lacunar infarction. ST depression was also significantly related to events of atherothrombotic infarction in women. The risk of atrial fibrillation for cardioembolic infarction was outstandingly high in both sexes, and left ventricular hypertrophy and lower total cholesterol were additional risk factors for cardioembolic infarction in women. Conclusions —In this Japanese population, lacunar infarction was the most common subtype of cerebral infarction and had a greater variety of risk factors, including not only hypertension but also ECG abnormalities, diabetes, obesity, and smoking, than did atherothrombotic infarction or cardioembolic infarction.

Background and Purpose —Subarachnoid hemorrhage is a life-threatening disease that occurs mostly because of the rupture of intracranial saccular aneurysms. However, little is known about the prevalence of ruptured and unruptured aneurysms in the general population. The aim of the present study was to examine the prevalence of intracranial aneurysms on the basis of a consecutive autopsy series over a 30-year observation period in a general Japanese population in Hisayama. Methods —We evaluated 1230 consecutive autopsy cases with craniotomy among the total deaths of Hisayama residents during 1962 through 1991 (overall autopsy rate, 80.1%). Results —A total of 73 intracranial saccular aneurysms were found in 57 cases (4.6%). The prevalence of aneurysms for women was 2.4 times higher than that for men (7.1% versus 2.9%). Among men, the prevalence of aneurysms remained unchanged across the range of age groups. In contrast, there were 2 peaks in the prevalence of aneurysms for women falling in the 40- to 49-year (14.3%) and 60- to 69-year age groups (14.5%). The most common site of the aneurysms was the middle cerebral artery (31.5%), followed by the anterior communicating artery (30.1%), anterior cerebral artery (15.1%), vertebrobasilar artery (12.3%), and internal carotid artery (11.0%). Among these 73 aneurysms, 29 (39.7%) were ruptured. Ruptured aneurysms were common in subjects Conclusions —Our data suggest that intracranial aneurysms are more frequent in women in the general Japanese population. Aneurysms are more prevalent in the middle cerebral artery, but the risk of rupture is highest in the vertebrobasilar system.

Effect of hyperinsulinemia on renal function in a general Japanese population: The Hisayama study.BackgroundInsulin resistance and hyperinsulinemia induce glomerular hypertension and hyperfiltration, which may result in glomerulosclerosis. However, the relationship between hyperinsulinemia and renal function is uncertain.MethodsTo elucidate whether hyperinsulinemia plays a significant part in the initiation and development of renal dysfunction, we examined in 1988 the relationship between serum insulin and renal function on data from a cross-sectional community survey conducted among residents from Hisayama Town, Japan, who were aged 40 to 79years old. A total of 1065 men (72.0% of the total population in the same age range) and 1381 women (79.0%) without renal failure (creatinine clearance of more than 30ml/min) underwent a comprehensive examination, including a 75g oral glucose tolerance test.ResultsThe correlation analysis showed that serum insulin, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index were all negatively correlated with the reciprocal of serum creatinine level (P < 0.01), and alcohol intake was positively correlated (P < 0.05) in both sexes. High-density lipoprotein cholesterol and smoking habits were positively correlated (P < 0.05) in men. When the subjects were divided into quartiles based on the sum of fasting and two-hour postloading insulin levels, the averages of the reciprocal of serum creatinine were significantly lower in the fourth quartile (0.90 ± 0.10 for men and 1.10 ± 0.14 for women) compared with the lowest quartile (0.95 ± 0.12 and 1.13 ± 0.13, respectively) in both sexes (P < 0.05). In multiple regression analysis, the correlation between the sum of insulin levels and the reciprocal of serum creatinine remained significant even after controlling for age, sex, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, alcohol intake, and smoking habits. We could not find appropriate correlations of creatinine clearance calculated by the Cockcroft-Gault formula with the covariates including serum insulin.ConclusionsThe findings of this study suggest that hyperinsulinemia is a significant relevant factor of renal function in the general population.

This study demonstrated the usefulness of the post/preoperative serum carcinoembryonic antigen (CEA) ratio as a predictor of survival after surgery for stage III rectal cancer patients. One hundred and four patients with stage III rectal cancer who underwent surgery between 1991 and 2000 were enrolled. The ratio of the postoperative serum CEA value divided by the preoperative serum CEA value was defined as post/preoperative serum CEA ratio, and the patients were separated into two groups: post/preoperative serum CEA ratio ≤1 (n = 86) and >1 (n = 18). The multivariate analyses demonstrated that the intraoperative blood loss, lack of a sphincter-saving procedure and a post/preoperative serum CEA ratio >1 were independent factors predicting a poor prognosis for the overall and disease-free survival. The overall and disease-free survival rates among patients with a high preoperative serum CEA level (>5 ng/ml) or patients with a high postoperative serum CEA (>5 ng/ml) were longer in patients with a post/preoperative serum CEA ratio ≤1, in comparison to those with a post/preoperative serum CEA ratio >1. Liver metastasis was observed more frequently in patients with a post/preoperative serum CEA ratio >1. The post/preoperative serum CEA ratio may be a predictor of the prognosis after surgery for stage III rectal cancer patients.

It is generally accepted that the difficulty in obtaining a sufficient number of functional dendritic cells (DCs) is a serious problem in DC-based immunotherapy. Therefore, we used the induced pluripotent stem (iPS) cell-derived DCs (iPSDCs). If the therapeutic efficacy of iPSDCs is equivalent to that of bone marrow-derived DCs (BMDCs), then the aforementioned problems may be solved. In our study, we induced iPSDCs from iPS cells and examined the capacity for maturation of iPSDCs compared to that of BMDCs in addition to the capacity for migration of iPSDCs to regional lymph nodes. We adenovirally transduced the hgp100 gene, natural tumor antigens, into DCs and immunized mice once with the genetically modified DCs. The cytotoxic activity of CD8 (+) cytotoxic T lymphocytes (CTLs) was assayed using a (51) Cr-release assay. The therapeutic efficacy of the vaccination was examined in a subcutaneous tumor model. Our results showed that iPSDCs have an equal capacity to BMDCs in terms of maturation and migration. Furthermore, hgp100-specific CTLs were generated in mice immunized with genetically modified iPSDCs. These CTLs exhibited as high a level of cytotoxicity against B16 cells as BMDCs. Moreover, vaccination with the genetically modified iPSDCs achieved as high a level of therapeutic efficacy as vaccination with BMDCs. Our study clarified experimentally that genetically modified iPSDCs have an equal capacity to BMDCs in terms of tumor-associated antigen-specific therapeutic antitumor immunity. This vaccination strategy may therefore be useful for future clinical application as a cancer vaccine.

To elucidate the risk factors for initiating glucose intolerance, the relevant factors were explored in a cross-sectional survey conducted in a sample population aged 40–79 years old selected from a Japanese community, Hisayama, Japan in 1988. A 75-g oral glucose tolerance test was used to classify 1,073 men (72.5% of the entire population in the same age range) and 1,407 women (80.5%) into normal, impaired glucose tolerance and diabetes mellitus groups. In all age and sex groups with normal glucose tolerance, the sum of fasting and 2-h post-load insulin values varied widely and demonstrated significant positive correlations with triglycerides, body mass index, waist-hip ratio, systolic and diastolic blood pressure, while it negatively correlated to HDL cholesterol (p

The authors studied mortality from major causes of death and risk factors in the elderly in a long-term prospective survey conducted in a Japanese suburban community, Hisayama. In the baseline survey in 1961, we scrutinized 1658 residents of the town aged 40 years or older accounting for 92% of the total population in this age range. Of those, 591 residents (245 men and 346 women) aged 60 years or older, who were free from major cardiovascular disease, were selected for the present study. They were followed-up for 26 years from 1961 to 1987. The average age was 67 years for men and 70 years for women, being significantly higher for women than for men. During the follow-up period, 529 subjects (89.5%) died, and 448 were autopsied (autopsy rate 84.7%). The all-cause mortality (per 1,000 person-years) after adjustment for age was 89.9 for men and 56.7 for women, the former being significantly higher than the latter (p0.01). The age-adjusted mortality from cerebrovascular disease was estimated to be 21.4 for men and 9.9 for women, i.e. 8.9 and 8.8 from heart disease, and 19.9 and 10.6 from neoplasm, and 18.1 and 12.2 from-pneumonia, respectively. There was significant sex difference in mortality from cerebrovascular disease, neoplasm and pneumonia (p0.01) but not from heart disease (p0.1). Multiple Cox's proportional hazards regression analysis showed systolic blood pressure and male sex to be significant risk factors for death by cerebrovascular disease. Systolic blood pressure was also a predictor for death by heart disease.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of this study was to show the clinical features of up-front surgery of the primary tumor in asymptomatic patients with incurable colorectal PC.Forty-six patients that were diagnosed between 1998 and 2007 with asymptomatic colorectal PC who could not be successfully cured by surgery were assessed retrospectively.A univariate analysis revealed the presence of liver metastases, without the use of oxaliplatin (OX)/irinotecan (IRI) and without a primary tumor resection to be poor prognostic factors for survival (p = 0.044, p = 0.030, p0.001, respectively). According to a multivariate analysis, no use of OX/IRI and no primary tumor resection, were found to be independent poor prognostic factors for survival (HR 2.57; p = 0.047, HR 6.62; p = 0.003, respectively). The median survival time of patients treated with and without OX/IRI was 18 and 7 months, respectively. The median survival time of patients with and without primary tumor resection was 10 and 2 months, respectively. The number of patients needing surgical intervention for intestinal obstruction after surgery significantly increased in patients treated with OX/IRI (p = 0.001).Improvement of survival may be related to widespread use of modern systemic chemotherapy and primary tumor resection. However, an increased number of patients that needed surgery for an intestinal obstruction were observed, even after up-front surgery, when patients were treated with modern systemic chemotherapy.

Hyperinsulinemia has been closely associated with hypertension in several epidemiological studies, but little is known about this condition in the elderly. The authors studied the relationship between serum insulin and blood pressure levels, and the prevalence of hypertension according to insulin levels in the elderly in a Japanese rural community, Hisayama. In 1988, 75 g oral glucose tolerance test was performed on 426 male and 567 female Hisayama residents aged 60 to 79 years. Fasting and 2 hr serum insulin values were measured by radioimmunoassay. In the subjects, excluding those receiving antihypertensive drugs, the sum of fasting and 2 hr postload insulin (sigma IRI) significantly correlated with systolic (r = 0.15 and 0.25 for males and females, respectively) and diastolic blood pressure (r = 0.20, 0.16). In multiple regression analyses, the correlation with systolic blood pressure remained significant in females after controlling for age, body mass index, alcohol intake, smoking habits, serum total cholesterol, HDL-cholesterol, triglycerides, and fasting plasma glucose. In contrast, sigma IRI did not remain as an independent variable relevant to blood pressure among males. The age-adjusted prevalence rates of hypertension (> or = 160/95 mmHg or receiving drug treatment) significantly increased with increasing quartiles of sigma IRI in females. The prevalence of hypertension which was not treated with drugs also increased significantly with increasing sigma IRI in females. However, no significant association was observed in males. In conclusion, the present study suggests that hyperinsulinemia can be related to hypertension in the female elderly in the general population of Japan.

To elucidate the effect of glucose intolerance on cardiovascular disease in the current Japanese population, we performed a 75-g oral glucose tolerance test in 2,427 Hisayama residents aged 40–79 years in 1988, who were free from a previous history of stroke or myocardial infarction, and followed them prospectively for 5 years. The prevalence of diabetes (NIDDM) among men was 13% and that of impaired glucose tolerance (IGT) was 20%; the corresponding values for women were 9 and 19%, respectively. The age- and sex-adjusted incidence of cerebral infarction (6.5 per 1,000 person-years, P 0.01) and coronary heart disease (5.0 per 1,000 person-years, P 0.05) was significantly higher in subjects with NIDDM than in those with normal glucose tolerance (1.9 and 1.6 per 1,000 person-years, respectively). In addition, subjects with IGT and NIDDM had a higher risk of cardiovascular disease including stroke and coronary heart disease than did those with normal glucose tolerance after adjustment for age and sex, namely the relative risk for IGT was 1.9 (95% CI 1.2–3.2), and the relative risk for NIDDM was 3.0 (95% CI 1.8–5.2). These associations remained significant even after controlling for six other risk factors including hypertension in multivariate analysis. Our data suggest that NIDDM is a significant risk factor for both cerebral infarction and coronary heart disease and also that IGT itself is a risk factor for cardiovascular disease in the general Japanese population today.

No population-based cohort studies have been undertaken to evaluate the incidence and prognosis of gastric cancer. The purpose of this investigation was to clarify the incidence and fatal prognosis of gastric cancer and to determine the factors that contribute to the prognosis in a general Japanese population in Hisayama using a prospective study design.From 1988 to 1998 a total of 2605 subjects aged 40 years or older with no history of gastrectomy or gastric cancer were followed-up prospectively after a health examination. The diagnosis of gastric cancer was based on clinical records or autopsy findings.During the follow-up period, 76 subjects developed gastric cancer. The age-adjusted incidence of gastric cancer for men (4.9 per 1000 person-years) was 4-fold higher than that for women (1.2, P0.05). In men, the incidence of gastric cancer increased with advancing age, but this trend was not observed in women. The age- and sex-adjusted 5-year survival rate was significantly higher in cancers of the middle third of the stomach than in those of the upper third of the stomach. The survival rate was higher in cancers of well-differentiated adenocarcinoma than in those of the other histological types. There were no cases of cancer-related death among the early gastric cancers during the follow-up period.Our data suggest that men are at higher risk of gastric cancer than women in the general Japanese population. Clinical stage, histological type, and site of cancer in the stomach contribute to a fatal prognosis.

Moderately elevated plasma total homocyst(e)ine (tHcy) levels have been linked with cardiovascular disease. However, the findings of previous studies regarding the relationship between tHcy levels and subtypes of cerebral infarction (CI) have been conflicting. The aim of the present study was to examine this issue in a community-based case-control study performed in Hisayama Town in Japan. Fasting tHcy levels were compared among 75 CI cases, of which 43 were lacunar (LI), 24 atherothrombotic (ATI) and 8 cardioembolic infarctions (CEI), and 248 age- and sex-matched healthy controls. The mean tHcy concentrations were higher in CI than in controls (13.0 vs. 11.8 micromol/l; p = 0.018). LI and CEI also had significantly higher tHcy levels than did the corresponding controls (12.3 vs. 11.3 micromol/l for LI; p = 0.037 and 16.3 vs. 12.7 micromol/l for CEI; p = 0.036). The same tendency was also observed for ATI, but the difference was only marginally significant probably due to the small number of the cases (13.4 vs. 11.9 micromol/l; p = 0.087). After adjustment for age, sex, hypertension, serum creatinine, total protein, folate and vitamin B(12) levels, the risk of LI was not significant in the second tertile of the tHcy distribution, but significantly increased in the third compared with the first tertile (adjusted odds ratio, AOR, 3.4; 95% confidence limits, CL, 1.3-8.9; p = 0.015), while the risk of ATI was significant even in the second tertile (AOR, 5.0; 95% CL, 1.0-23.7; p = 0.042) and higher in the third tertile (AOR, 7.5; 95% CL, 1.5-38.3; p = 0.015). However, the odds ratios for CEI could not be estimated, as there was no case of CEI in the first tertile. These findings suggest that elevated tHcy is an independent risk factor for all subtypes of CI, but that its impact is higher in ATI and probably in CEI than in LI.

Several nested case-control studies have reported the potentially causal relationship between Helicobacter pylori infection and the development of gastric cancer. However, there has been no prospective study evaluating this issue. The purpose of this study is to examine the impact of H pylori infection on gastric cancer occurrence in a general Japanese population (Hisayama, Japan) stratified according to sex, using a prospective study design.A total of 2602 subjects aged 40 years or older (1070 men; mean age, 57 years; 1532 women; mean age, 59 years) without a history of gastrectomy or gastric cancer were classified according to the status of the serum IgG antibodies to H pylori and observed prospectively for 9 years from 1988.Infection of H pylori was more common in men (71.5%) than in women (62.5%; P.001). The age-adjusted incidence of gastric cancer for men (5.3 per 1000 person-years) was 4-fold higher than that for women (1.3; P.001). In men, the age-adjusted incidence of gastric cancer was significantly higher in the subjects with H pylori infection than in those without it (6.2 vs 2.5; relative risk, 2.59 [95% confidence interval, 1.03-6.50]), whereas no significant difference was observed in women (1.2 vs 1.1; relative risk, 0.99 [95% confidence interval, 0.36-2.68]). These results were similar even after controlling for other risk factors in multivariate analysis. It was estimated that 40.1% of gastric cancers for men in this cohort were attributable to H pylori infection.A significant relationship exists between infection with H pylori and subsequent occurrence of gastric cancer for men but not for women in this Japanese population.

An 86-year-old woman with a 13-year history of hypertension was admitted because of consciousness disturbance, hypotension, tachycardia, and cyanosis at her extremities. Enhanced computed tomography showed a thrombus in the truncus pulmonalis and right pulmonary artery, and also showed a left renal mass and a right renal cyst. Under a diagnosis of pulmonary embolism we started anticoagulant therapy, but the patient died five days after admission. At autopsy, a saddle-like thrombus was found in the truncus pulmonalis and bilateral trunks of pulmonary arteries. Microscopic examination showed smooth muscle cells in the thrombus. We could not find any other thrombus in the inferior vena cava, intrapelvic veins, nor in veins of lower extremities by milking. We also found tumors in both kidneys. Microscopically all tumors were diagnosed as angiomyolipoma. There were many fibrin thrombi in the sinuses of the tumors but there was no evidence of malignancy. We finally diagnosed pulmonary embolism due to renal angiomyolipoma because there was no other thrombus origin and microscopically the same smooth muscle cells were found both in the renal tumor and the pulmonary thrombus. There is only one case report concerning pulmonary embolism due to renal angiomyolipoma which happened during operative treatment. The treatment method of renal angiomyolipoma is determined by tumor size and symptoms, and usually intensive treatment is not performed in cases without symptoms. Our patient had no symptoms until the onset of severe complication of pulmonary embolism, suggesting that radical treatment is necessary for renal angiomyolipoma with a thrombus even when there are no symptoms.

To obtain a relatively true mortality from malignant neoplasms, we studied the frequency of cancers in the different sites and the changing patterns of the frequency and sites over time among residents of the community of Hisayama, where an autopsy-based population survey (autopsy rate, 80%) has been conducted since 1961. During the 30-year period from 1962 to 1991, we found 438 malignant neoplasms in 407 cases among 1,250 consecutive autopsies. Stomach cancer was most frequent in type of cancer, with 123 cases (9.8%), followed by lung cancer in 62 (5.0%), colorectal cancer in 42 (3.4%), liver cancer in 37 (3.0%), and pancreatic cancer in 30 (2.4%). We compared the mortality from cancers for both autopsy and nonautopsy cases (the proportional mortality) among three 10-year periods, which included early (1962 to 1971), middle (1972 to 1981), and late (1982 to 1991) periods. The proportional mortality from all cancers, as well as for lung, colorectal, and liver cancers, showed an increase in recent years, while stomach and pancreatic cancer showed a decrease. These figures were nearly similar to the mortality statistics for the Japanese population as a whole except for the observed decreasing trend in mortality from pancreatic cancer.

We followed 828 nondemented residents of Hisayama Town, Kyushu, Japan, aged 65 years or older (88.3% of the elderly population) for 7 years starting in 1985 in order to determine the type-specific incidence of dementia and its risk factors in the general Japanese population. Only two subjects were lost to the follow-up, during which period 103 subjects developed dementia. Morphologic examination of the brains of 89 subjects (86.4%) was made by autopsy or CT. We made the initial diagnosis of dementia based on the DSM-III-R criteria, with the diagnoses of vascular dementia (VD) being based on the NINDS-AIREN criteria and Alzheimer's disease (AD) on the NINCDS-ADRDA criteria. The incidence of VD and AD increased with age for both sexes. The age-adjusted total incidence (per 1,000 person-years) of dementia was 19.3 for men and 20.9 for women. The corresponding rates for VD were 12.2 for men and 9.0 for women, and for AD, 5.1 for men and 10.9 for women. Among the VD subjects whose brain morphology we examined, the most frequent type of stroke was multiple lacunar infarcts (42%), but half these subjects lacked a stroke episode in their histories. Multivariate analysis showed that age, prior stroke episodes, systolic blood pressure, and alcohol consumption were significant independent risk factors for the occurrence of VD. In contrast, age and a low score on Hasegawa's dementia scale were significant risk factors for AD, and physical activity was a significant preventive factor for AD.(ABSTRACT TRUNCATED AT 250 WORDS)

Background and Purpose The relationship between alcohol intake and stroke has been inconsistent in previous studies. We examined the separate and combined effects of drinking habits and hypertension on stroke incidence in a prospective survey of a general Japanese population. Methods A total of 1621 stroke-free Hisayama residents aged 40 years or older were classified by their alcohol intake into nondrinkers, light drinkers ( Results During the follow-up period, cerebral infarction developed in 244 subjects and cerebral hemorrhage in 60. For men, the incidence of cerebral hemorrhage increased significantly with rising alcohol consumption. In contrast, the incidence of cerebral infarction was slightly lower in light drinkers than in nondrinkers, while it increased significantly in heavy drinkers compared with light drinkers. Female drinkers had a lower incidence of cerebral infarction but a slightly higher incidence of cerebral hemorrhage than nondrinkers, as did male light drinkers. Among the hypertensive subjects, the age- and sex-adjusted relative risk of cerebral hemorrhage was significantly elevated in heavy drinkers versus abstainers (3.13; 95% confidence interval [CI], 1.08 to 9.10), but the increase was not significant for light drinkers. In contrast, the relative risk did not significantly increase for normotensive light and heavy drinkers. Compared with hypertensive light drinkers, the relative risk of cerebral infarction significantly increased in hypertensive heavy drinkers (1.96; 95% CI, 1.08 to 3.57) but remained unchanged in normotensive heavy drinkers. Significant associations between alcohol intake and stroke were substantially the same even after controlling for other risk factors in multivariate analysis. Conclusions Among hypertensive individuals, heavy alcohol consumption leads to a significant increase in the risk of cerebral hemorrhage, suggesting a synergistic effect of alcohol and hypertension, while light alcohol consumption significantly reduces the risk of cerebral infarction.

We determined the population-based prevalence of diabetes mellitus in members of the Japanese community, Hisayama aged 40–79 years old by a 75-g oral glucose tolerance test. The basic population used to calculate diabetic prevalence was 1,077 men (72.8% of the whole population in the same age range) and 1,413 women (80.8%) including ten diabetic patients on insulin therapy. In addition, we compared the prevalence of history of diabetes which was acquired by interview or questionnaire, between participants and non-participants in the 75-g oral glucose tolerance test, but they were not statistically different. The age-adjusted prevalence of diabetes to world population was 12.7% for men and 8.4% for women, and that of impaired glucose tolerance was 19.6% for men and 18.4% for women. These figures were much higher than those previously reported from several Japanese communities. The results obtained from the present study could reveal true prevalence of diabetes among the Japanese population. In addition, the reasons for the increasing prevalence of diabetes among the recent Japanese population are also discussed.

Cigarette smoking as a risk factor for cerebro- and cardiovascular diseases was studied in a long-term prospective population survey which has been carried out in a Japanese rural community, Hisayama. In this population, the incidence of thrombotic brain infarction (TBI) was much higher than that of coronary heart disease (CHD) over a 26-year follow-up period. Cigarette smoking was strongly related to the occurrence of CHD but not to TBI. Comparing the incidence of CHD and TBI between first or early cohort (1961-74) and second or recent cohort (1974-87) during the 13-year follow-up, the incidence remained unchanged for CHD, while it significantly decreased for TBI in recent population. The prevalence of cigarette smoking as well as hypertension decreased in recent years, while hypercholesterolemia, obesity, and glucose intolerance increased. Smoking is a major contributor to CHD for men in both cohorts, but it is not any more for women in the recent cohort.

The causes of death for the elderly were prospectively studied in Hisayama, Japan, a rural community. We compared 1,621 subjects, aged 40 years or over, recruited in 1961, and 2,053 subjects recruited in 1974. Each cohort was studied in a follow-up that lasted 10 years; they had autopsy rates of 82.1% and 86.1% during each 10-year period, respectively. The most common causes of death for those aged 70 years or over were cerebrovascular disease, malignant neoplasms, and pneumonia. Deaths due to cerebrovascular disease tended to decrease in the recent cohort, but the proportion of decline was more prominent in cases aged 40 to 69 years. There was a sex difference in the changing pattern of mortality from heart diseases including ischemic heart disease. Deaths by both heart diseases and ischemic heart disease increased in the more recent cohort of aged women, whereas they decreased in the aged men. Pneumonia was an important cause of death for the elderly in both cohorts. Deaths due to "senility" were rare, being only 1% of the deceased aged 70 or over. With prolonged lifespan, especially for women, the impact of atherosclerosis and its related disorders on the recent Japanese aged population appears to have increased.

OBJECTIVES To study the relationship between serum insulin and blood pressure, as well as the prevalence of hypertension according to the insulin level in a general Japanese population. DESIGN In 1988 a cross-sectional community survey was conducted among Hisayama residents aged 40-79 years. METHODS A total of 1073 males and 1407 females (72.5 and 80.5% of the total population, respectively) underwent comprehensive investigation, including a 75-g oral glucose-tolerance test. Fasting and 2-h serum insulin levels were measured by radioimmunoassay. RESULTS The sum of the fasting and 2-h postloading insulin levels was significantly correlated with the systolic blood pressure (SBP; r = 0.18 and 0.26 for males and females, respectively) and the diastolic blood pressure (DBP; r = 0.24 and 0.19, respectively) in the subjects not receiving antihypertensive drugs. In multiple regression analysis the correlation with blood pressure remained significant in both sexes even after controlling for age, body mass index, alcohol intake, smoking, a family history of hypertension, serum total cholesterol and fasting plasma glucose. The age- and sex-adjusted prevalence of hypertension (SBP > or = 160 mmHg or DBP > or = 95 mmHg, or both, or receiving drug treatment) increased significantly with an increase in the sum of fasting and 2-h postload insulin levels in both the non-obese subjects (body mass index or = 25 kg/m2). Multiple logistic regression showed that the sum of fasting and 2-h postload insulin levels was a significant factor with an independent relationship to hypertension, even after taking the other risk factors into account. CONCLUSION The present study suggests that hyperinsulinaemia is related to hypertension in a general Japanese population.

Twenty-six first episodes of subarachnoid hemorrhage occurred among 1,621 Hisayama residents aged greater than or equal to 40 years during the 22-year follow-up of a prospective study. Subarachnoid hemorrhage was confirmed by both clinical and autopsy findings. The average annual incidence (96.1/100,000 population) was 3-13 times higher than any previously reported and steeply increased with age in both sexes, being 2.3 times higher for women than for men after adjusting for age. Nine patients (35%) died less than or equal to 8 hours after the onset of subarachnoid hemorrhage. None was correctly diagnosed on the death certificates, and four of the nine (44%) were misdiagnosed as intracerebral hemorrhage. We found the survival rate of patients suffering subarachnoid hemorrhage to be much lower than previously reported because we detected a large number of sudden deaths due to subarachnoid hemorrhage through the high rate of autopsy in our cohort (81.4%).