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Biomedical subjects

F Konishi

Publications and source records attributed to F Konishi.

At least 19 recordsLinked to original sources
PubMed2006

A multicenter study on laparoscopic surgery for colorectal cancer in Japan.

BACKGROUND: Laparoscopic colectomy for malignant disease technically is feasible but not widely accepted because there are no large-series studies or data on long-term outcomes. A retrospective, multicenter study investigating a large series of patients was conducted in Japan to evaluate preliminary long-term results of laparoscopic surgery for colorectal cancer. METHODS: The study group comprised 2,036 patients who underwent laparoscopic colorectal resection April 1993 to August 2002 in 12 participating surgical units (Japanese Laparoscopic Surgery Study Group). RESULTS: Of the 1,495 patients with colon cancer, 781 (59%) had International Union Against Cancer (UICC) stage I, 248 (19%) had stage II, and 284 (22%) had stage III disease. Cancer recurred for 61 (4.1%) of 1,367 curatively treated patients (median follow-up period, 32 months; range, 6-125 months). The 5-year survival rate was 96.7% for stage I, 94.8% for stage II, and 79.6% for stage III disease. Of the 541 patients with rectal cancer, 220 (56%) had stage I, 62 had (16%) stage II, and 108 (28%) had stage III disease. Cancer recurred for 30 (5.6%) of 476 curatively treated patients (median follow-up period, 25 months; range 6-102 months). The 5-year survival rate was 95.2% for stage I, 85.2% for stage II, and 80.8% for stage III disease. CONCLUSIONS: The findings indicate that laparoscopic surgery for colorectal cancer yields an oncological outcome as good as that reported for conventional open surgery in the Japanese Registry for all disease stages.

Colonic Neoplasms↗
PubMed2006

Frequent involvement of ras-signalling pathways in both polypoid-type and flat-type early-stage colorectal cancers.

The development of colorectal neoplasms proceeds mainly via the adenoma-carcinoma sequence. BRAF and RASSF1A are members of Ras-signaling pathways, but the roles of their aberrations in colorectal carcinogenesis remain unclear. The authors studied mutations of the BRAF and K-ras genes, RASSF1A promoter methylation, and p53 overexpression in 43 polypoid-type and 30 flat-type early-stage colorectal cancers. No tumor simultaneously showed any combination of K-ras mutations, BRAF mutations, and RASSF1A promoter methylation. Three of the 73 tumors (4.1%) had BRAF mutations. All BRAF mutation-positive tumors were flat-type cancers, not associated with coexisting adenoma or p53 overexpression. RASSF1A promoter methylation was detected in 12 out of 73 tumors (16.4%), and the proportion of positive cases was similar in polypoid-type and flat-type cancers. BRAF mutations, K-ras mutations, and RASSF1A promoter methylation independently participate in early-stage colorectal carcinogenesis. BRAF mutations are involved only in flat-type cancers, whereas RASSF1A promoter methylation is involved in both polypoid-type and flat-type cancers. Thus, BRAF mutations most likely participate in de novo colorectal carcinogenesis, K-ras mutations in the adenoma-carcinoma sequence of colorectal carcinogenesis, and RASSF1A promoter methylation in both cascades.

Adenocarcinoma↗
PubMed2004

Natural history of a patient with malignant nonfunctioning islet cell tumor associated with unresectable multiple liver metastases.

Islet cell tumors of the pancreas are uncommon. Approximately 15% of islet cell tumors are nonfunctioning and have a higher malignancy rate than their functioning counterparts. Though, because of the rarity of malignant nonfunctioning islet cell tumors, the natural history of a patient with this tumor has not been clearly defined. We describe a young patient with unresectable malignant nonfunctioning islet cell tumor associated with multiple liver metastases. He was treated with palliative therapies to improve his quality of life, but did not undergo surgical removal of tumors or systemic chemotherapy. He survived for 46 months since laparotomy for histological diagnosis. Our findings may represent the natural history of patients with unresectable malignant nonfunctioning islet cell tumor, and suggest that palliative therapy may contribute not only to the improvement of a patients' quality of life but also the prolongation of survival.

Adult↗
PubMed2003

Flat and depressed lesions of the colon and rectum: Pathogenesis and clinical management.

INTRODUCTION: It is not clear whether flat lesions play a role in the pathogenesis of colorectal carcinoma. Flat lesions are being increasingly recognised with new colonoscopic techniques. MATERIALS AND METHODS: A total of 10,939 consecutive colonoscopies were performed over a 9-year period. After bowel preparation with polyethylene glycol electrolyte lavage solution, high-resolution video colonoscopy and indigocarmine spraying were performed to detect flat lesions. All lesions suggesting neoplastic change were removed by polypectomy or surgery. Cancers invading beyond the submucosal layer were excluded from this analysis. The gross appearance of flat-type lesions was classified as flat elevated type or flat depressed type based on the presence or absence of central depression. RESULTS: A total of 5408 neoplastic lesions were index lesions, including 5035 adenomas and 373 carcinomas (124 with submucosal invasion). The prevalence of flat depressed and flat elevated lesions were 2.8% and 18.1%, respectively. Submucosal invasion rates were 17.1% in the flat depressed, 0.8% in the flat elevated, 1.6% in the sessile, 4.0% in pedunculated lesions and 9.3% in creeping lesions. The submucosal invasion rate in the flat depressed lesions was significantly higher than in any others, except for creeping lesions (P = 0.06). The percentage of flat elevated and flat depressed carcinomas among all carcinomas invading the submucosa was 6.5% and 21.0%, respectively. CONCLUSION: Flat lesions were common during routine colonoscopy. One-quarter of colorectal cancers may be derived from flat lesions. Training in dye spray technique may result in a higher detection rate of flat colonic lesions.

Adenoma↗
PubMed2003

Runme Shaw Memorial Lecture 2002. Modern management of colorectal polyps: Are they all premalignant?

There are various types of polyps in the colon and rectum. Most colorectal polyps in the colon and rectum are either adenomas or hyperplastic polyps. In general, adenomas are considered to be premalignant. Adenoma-carcinoma sequence is an established theory of carcinogenesis in the large bowel in Western countries. However, small adenomas are ubiquitous phenomena, and it is questionable whether they are actually precancerous. Most small adenomas did not become larger in our colonoscopic follow-up study of small adenomas measuring 5 mm or less. It was considered safe to leave such small adenomas behind, particularly in a situation in which follow-up examination is periodically performed, such as in patients who have undergone colorectal cancer surgery before. In Japan, small flat carcinomas have been reported as an important precursor of advanced colorectal carcinoma. They are also found in Western population. The malignancy rate of small flat and depressed lesions was significantly higher than that of polypoid lesions. Although small flat carcinomas are less frequently seen than polypoid-type carcinomas in the early stages, they are considered to be an important precursor of advanced colorectal cancer.

Adenoma↗
PubMed2001

Absence of endothelial cells, central necrosis, and fibrosis are associated with aggressive inflammatory breast cancer.

We recently established a new human inflammatory breast cancer (IBC) xenograft (WIBC-9) originating from a patient with IBC. The graft was transplantable in BALB/c nude and severe combined immunodeficient (SCID) mice. WIBC-9 was frequently accompanied by lung metastasis and exhibited erythema of the overlying skin, reflecting its human counterpart. Histological study of the original tumor and WIBC-9 revealed invasive ductal carcinoma with a hypervascular structure of solid nests and marked lymphatic permeation in the overlying dermis. In the central part of the solid nests, absence of endothelial cells, central necrosis, and fibrosis were observed. In vitro, WIBC-9 formed tube-like structures and loops, reflecting its in vivo feature and its human counterpart. WIBC-9 exhibited aneuploidy, ErbB-2 gene amplification, and an absence of estrogen receptor and progesterone receptor, which is consistent with IBC. Comparative studies of WIBC-9, three established non-IBC xenografts, and a human breast cancer cell line (SK-BR3) by reverse transcription-PCR, ELISA, and immunohistochemistry indicated that certain human genes (interleukin 8, vascular epidermal growth factor, basic fibroblast growth factor, angiopoietin 13, Flt-1, Tie-2, and Tie-1) and certain murine genes (integrin alpha(v)beta3, flt-1, tie-2, vascular epidermal growth factor, and CD31) were overexpressed in exposure to tumor cells. The molecular basis and these unique histological features may be associated with aggressive IBC on angiogenic and nonangiogenic pathways.

Angiogenesis Inducing Agents↗
PubMed2001

Detection of pinpoint tenderness on the appendix under ultrasonography is useful to confirm acute appendicitis.

HYPOTHESIS: Ultrasonography can be efficiently performed using new criteria for the diagnosis of acute appendicitis. DESIGN: Prospective trial. PATIENTS: Eighty-nine patients admitted to the hospital with suspected appendicitis between March 1998 and November 2000. INTERVENTION: At hospital admission, a staff surgeon evaluated each patient and determined whether the patient had appendicitis requiring immediate surgery or another disease. Patients then underwent ultrasonography. A sonographic transducer was placed on the area of maximal tenderness. When the pathological manifestation was depicted, the examiner slipped a fingertip between the transducer and the patient's skin and then pressed the area of depicted pathological manifestation to find pinpoint tenderness. When maximal pinpoint tenderness was noted on the appendix or on pathological manifestations contiguous to the appendix, we diagnosed the condition as appendicitis. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive and negative predictive values, and overall accuracy. RESULTS: The diagnosis of appendicitis by this criteria had a sensitivity of 86.7%, a specificity of 89.7%, a positive predictive value of 94.5%, a negative predictive value of 76.5%, and overall accuracy of 87.6%. All 50 patients with pinpoint tenderness noted on the appendix had appendicitis. The surgeon's initial clinical impression had a sensitivity of 83.3%, a specificity of 44.8%, a positive predictive value of 75.8%, a negative predictive value of 56.5%, and overall accuracy of 70.8%. CONCLUSIONS: The efficacy of ultrasonography using the simple criteria was superior to that of the surgeon's initial clinical impression (P<.001). Our ultrasonographic criteria for the diagnosis of appendicitis are simple to use and efficient.

Acute Disease↗
PubMed2001

Frequent activation of the beta-catenin-Tcf signaling pathway in nonfamilial colorectal carcinomas with microsatellite instability.

It has been reported that wild-type APC protein forms a complex with beta-Catenin and GSK3beta, inducing degradation of beta-Catenin in normal cells. Both beta-Catenin and APC gene mutations have recently been shown to activate the same signaling pathway. Frequent mutations of beta-Catenin in hereditary nonpolyposis colorectal carcinomas have also been reported. It was, however, controversial whether the mutation of the beta-Catenin gene was frequent in nonfamilial colorectal carcinomas with high-frequency microsatellite instability (MSI-H). We analyzed the mutations of the APC and beta-Catenin genes in 56 nonfamilial colorectal carcinomas stratified according to the presence or absence of microsatellite instability (MSI). APC mutations were identified in 11 of 22 (50%) cases of MSI-H and 14 of 34 (41%) cases of microsatellite-stable (MSS)/low-frequency microsatellite instability (MSI-L). In contrast, the frequency of beta-Catenin mutations was significantly higher in MSI-H (6/22; 27%) than in MSS/MSI-L (1/34; 3%) (P = 0.01). beta-Catenin mutations were not detected in carcinomas with APC mutation. APC mutation occurred irrespective of MSI status. beta-Catenin mutation, however, occurred frequently in MSI-H carcinomas. Our data suggest that activation of the beta-Catenin-Tcf signaling pathway, through either beta-Catenin or APC mutation, frequently contributes to MSI-H nonfamilial colorectal carcinomas (17/22; 77%).

Cadherins↗
PubMed2001

Pelvic floor disturbance after childbirth: vaginal delivery damages the upper levels of sphincter innervation.

PURPOSE: Vaginal delivery disturbs pelvic floor innervation, which has previously been studied as a single mechanism. The effects of childbirth on innervation at different levels of the anal sphincter system were studied after childbirth. METHODS: Both anal manometry and motor latencies were measured in 67 females. Twenty-nine females (30.8 +/- 4.4 years) were examined four days after vaginal delivery. Eleven of these 29 females were re-examined five months after vaginal delivery. Nineteen females (33.6 +/- 4.6 years) who were examined five to nine days after undergoing an elective cesarean section and 19 asymptomatic, nonpregnant females (26.8 +/- 6.9 years) served as controls. Motor latencies were bilaterally measured within the anal sphincter system at 5, 3.8, 2.6, and 1.5 cm from the perineal skin by using a concentric needle electrode after sacral magnetic stimulation. Means of the bilateral latencies were analyzed. RESULTS: In postpartum females who gave birth vaginally, motor latencies at 5 and 3.8 cm, although not those at 2.6 and 1.5 cm, from the perineal skin were significantly prolonged, and anal pressure monitored by maximum resting and squeeze pressures was significantly decreased compared with that in control females. The decreased anal pressure normalized spontaneously. The prolonged motor latencies at the upper two levels of the anal sphincter system persisted in these females for five months after vaginal delivery. CONCLUSIONS: The disturbance of innervation of the upper anal sphincter system after vaginal delivery may last for a long time, whereas the decreased anal pressure normalizes in a short time. The protracted disturbance of innervation of the upper anal sphincter system may be associated with later development of fecal incontinence.

Adult↗
PubMed2001

Extensive methylation of hMLH1 promoter region predominates in proximal colon cancer with microsatellite instability.

BACKGROUND & AIMS: Methylation of the hMLH1 promoter region has been suggested to cause microsatellite instability (MSI) in sporadic colorectal carcinoma (CRC). We studied the methylation profile in a wide region of the hMLH1 promoter and compared with the hMLH1 protein expression and MSI status in 88 cases of sporadic CRC. METHODS: Na-bisulfite treatment and polymerase chain reaction single-strand conformation polymorphism analysis was performed using 5 sets of polymerase chain reaction primers spanning the promoter region of the hMLH1 to examine methylation status. Results were compared with immunostaining using anti-hMLH1 monoclonal antibody and MSI status of the tumor samples. RESULTS: Methylation status was classified as full or partial methylation. Full methylation indicates the methylation of all CpG sites in the examined regions. Methylation of the hMLH1 promoter was observed in 88.9% (16 of 18) of CRCs showing high frequency MSI (MSI-H), among which 89% (14 of 16) had full methylation with reduced hMLH1 protein expression. All cases showing full methylation were proximal colon tumors with MSI-H. In cases with partial methylation, only the upstream region of the hMLH1 promoter was methylated. Partial methylation was also shown in 33.3% (6 of 18) of the normal mucosa of MSI-H cases. Frequencies of methylation were significantly correlated with female gender (P = 0.0009) and aging (P = 0.007). CONCLUSIONS: Full methylation of the hMLH1 promoter region and subsequent gene inactivation may play a crucial role in the carcinogenesis of MSI-H CRCs in the proximal colon. Methylation upstream of the hMLH1 promoter appears to be an early event in the carcinogenesis of MSI-H tumors.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Allelotype frequency of the thiopurine methyltransferase (TPMT) gene in Japanese.

Polymorphisms at three loci in the thiopurine methyltransferase (TPMT) gene are known to be responsible for azathioprine and 6-mercaptopurine (6MP) toxicity. Among them, only TPMT*3C variant allele with A719G mutation was found in 15/522 (2.9%; 17/1044 alleles; 1.6%) Japanese individuals including two homozygotes. The allele frequency was different from that in Caucasians, and investigation of TPMT polymorphisms with consideration of ethnic differences before administration of azathioprine or 6MP may provide clinically useful information.

Alleles↗
PubMed2001

Microsatellite instability in inflamed and neoplastic epithelium in ulcerative colitis.

BACKGROUND: Several genetic alterations have been documented in dysplasia and cancer developing in ulcerative colitis (UC). However, the microsatellite instability (MSI) status has rarely been described, especially in the inflamed epithelium of UC. AIMS: To study MSI status during neoplastic and inflammatory changes in UC. METHODS: Seventy five surgically resected samples of colorectal mucosa, taken from 16 colectomy specimens of patients with UC were examined: five patients had a long duration with dysplasia or cancer (UC-LD with neoplasm), seven patients had a long duration without neoplastic changes (UC-LD without neoplasm), and four patients had a short duration without neoplastic changes (UC-SD). In addition to MSI status examined by six microsatellite markers, p53 expression was compared among the three groups. RESULTS: With regard to non-neoplastic inflamed epithelium, MSI in two or more loci (MSI> or =2) was seen more frequently in the UC-LD without neoplasm group than in the UC-SD group (six of 14 v one of 12; p = 0.060), and significantly more often than in the UC-LD with neoplasm group (six of 14 v two of 23; p = 0.016). In the UC-LD without neoplasm group, MSI> or =2 was detected significantly more frequently in patients with severe inflammation than in those with mild inflammation (six of nine v none of five; p = 0.028). With regard to neoplastic epithelium in the UC-LD with neoplasm group, MSI in two or more loci was found in three of 17, and p53 overexpression was seen in 11 of 17 of the neoplastic lesions. CONCLUSIONS: A high incidence of MSI in long standing UC with severe inflammation probably reflects genomic instability caused by repeated inflammatory stress. Thus, the influence of inflammation should be considered when estimating MSI in UC. It is possible that changes in p53 expression are important in the development of cancer in UC.

Adult↗
PubMed2001

Cross-reactive mechanism for the false elevation of free triiodothyronine in the patients treated with diclofenac.

We report three cases of patients exhibiting a false elevation of serum free triiodothyronine (FT3) as a result of a cross-reaction with diclofenac. The first case is a 66-yr-old woman with a long history of rheumatoid arthritis (RA). The patient was receiving diclofenac for the treatment of her RA. The patient was subsequently diagnosed as having thyroid papillary adenocarcinoma and received a subtotal thyroidectomy. After the operation, the patient exhibited postoperative hypothyroidism except for a gradual elevation of FT3. The other two patients also exhibited an elevated serum FT3 level after the administration of diclofenac. Serum FT3 levels in these patients decreased to normal or below normal after diclofenac administration was discontinued. In the first case, the elimination of immunoglobulin from the sera using polyethylene glycol precipitation did not reduce the FT3 level. In our hospital, Vitros ECi (enhanced chemiluminescence enzyme immunoassay) system and Vitros FT3 kit were used for FT3 assay. The patient's FT3 levels were normal or below normal when they were measured using other FT3 kits. FT3 was also detected when diclofenac was dissolved in a phosphate buffered saline. Therefore, we concluded that a cross-reaction between FT3 and diclofenac was the mechanism causing the false elevation of FT3 in these patients.

Aged↗
PubMed2000

Exaggerated vascular and renal pathology in endothelin-B receptor-deficient rats with deoxycorticosterone acetate-salt hypertension.

BACKGROUND: Endothelin (ET)-1 plays an important role in the pathogenesis of deoxycorticosterone acetate (DOCA)-salt-induced hypertension. We evaluated the pathological role of ET(B) receptors in DOCA-salt-induced hypertension, cardiovascular hypertrophy, and renal damage by using the spotting-lethal (sl) rat, which carries a naturally occurring deletion in the ET(B) receptor gene. METHODS AND RESULTS: Homozygous (sl/sl) rats exhibit abnormal development of neural crest-derived epidermal melanocytes and the enteric nervous system, and they do not live beyond 1 month because of intestinal aganglionosis and intestinal obstruction. The dopamine ss-hydroxylase (DssH) promoter was used to direct ET(B) transgene expression in sl/sl rats to support normal enteric nervous system development. DssH-ET(B) sl/sl rats live into adulthood and are healthy, expressing ET(B) receptors in adrenal glands and other adrenergic neurons. When homozygous (sl/sl) and wild-type (+/+) rats, all of which were transgenic, were treated with DOCA-salt, homozygous rats exhibited earlier and higher increases in systolic blood pressure than did wild-type rats. Chronic treatment with ABT-627, an ET(A) receptor antagonist, completely suppressed DOCA-salt-induced hypertension in both groups. Renal dysfunction and histological damage were more severe in homozygous than in wild-type rats. Marked vascular hypertrophy was observed in homozygous rats than in wild-type rats. Renal and vascular injuries were significantly improved by ABT-627. In DOCA-salt-treated homozygous rats, there were notable increases in renal, urinary, and aortic ET-1, all of which were normalized by ABT-627. CONCLUSIONS: ET(B)-mediated actions are protective in the pathogenesis of DOCA-salt-induced hypertension. Enhanced ET-1 production and ET(A)-mediated actions are responsible for the increased susceptibility to DOCA-salt hypertension and tissue injuries in ET(B) receptor-deficient rats.

Acetylglucosaminidase↗