PURPOSE: Defunctioning ileostomy or colostomy is still routinely performed after low anterior resection in the belief that diverting the fecal stream will prevent anastomotic dehiscence. However, an ileostomy is not w...PURPOSE: Defunctioning ileostomy or colostomy is still routinely performed after low anterior resection in the belief that diverting the fecal stream will prevent anastomotic dehiscence. However, an ileostomy is not without morbidity for the patient. This study aims to determine if a diverting stoma is really necessary after a low anastomosis. METHODS: All low or ultralow anterior resections done in this department were performed by consultant-grade surgeons in a standardized manner. The patients were all monitored closely after surgery for clinical signs of an anastomotic leak. There were 1078 patients who underwent elective low or ultralow anterior resections in a ten-year period between 1994 and 2004. Twelve of them were irradiated before surgery; they were excluded from the study. During a seven-month period from February 2004 through August 2004, 324 patients who underwent such procedures were not defunctioned. These were compared with 742 patients who were previously defunctioned with a proximal stoma. The results were analyzed using the Pearson chi-squared test. RESULTS: Thirteen (4 percent) patients who were not defunctioned developed a clinical anastomotic leak, whereas the leak rate for those who were defunctioned was 3.8 percent. There was no statistical difference demonstrated. Ninety-five percent of patients who developed a leak required surgical intervention; the remaining 5 percent could be dealt with by radiologic drainage. The overall mortality rate for anastomotic leak in this department is 7.3 percent. CONCLUSION: A diverting stoma does not reduce postoperative anastomotic leak rate. Rather, it reduces the otherwise catastrophic effects of an anastomotic leak such as fecal peritonitis and septicemia. An ileostomy carries certain morbidity and also adds to the cost of the entire operation. Therefore, it should not be performed routinely. Instead, it should be performed selectively in patients with poorly prepared bowels, coupled with a distal limb washout, and in patients with significant comorbidities who can ill afford the complications of a leak.展开更多
Background:Pancreatic-fluid collections are frequent sequelae of acute and chronic pancreatitis,and endoscopic drainage of these collections has gained acceptance as an alternative to surgical drainage.Methods:Patient...Background:Pancreatic-fluid collections are frequent sequelae of acute and chronic pancreatitis,and endoscopic drainage of these collections has gained acceptance as an alternative to surgical drainage.Methods:Patient data,collection characteristics,drainage technique,and outcomes were obtained through chart review and prospective follow-up for 116 patients with attempted endoscopic drainage of symptomatic pancreatic-fluid collections.Results:A total of 116 patients presented with fluid collections classified as acute fluid collection(n = 5),necrosis(n = 8),acute pseudocyst(n = 30),chronic pseudocyst(n = 64),and pancreatic abscess(n = 9).The median diameter of the collection drained was 60 mm(15-275 mm).Median follow-up after drainage was 21 months.The drainage technique was transpapillary in 15 patients,transmural in 60,and both in 41.Successful resolution of symptoms and collection occurred in 87.9%of cases.No difference in success rates was observed between patients with acute pancreatitis and those with chronic pancreatitis.However,drainage of organized necrosis was associated with a significantly higher failure rate than other collections.No significant differences were observed regarding success when disease,drainage technique,or site of drainage was considered.Complications occurred in 13 patients(11%),and there were 6 deaths in the 30 days after drainage,including one that was procedure related.Conclusions:Endoscopic drainage of pancreatic-fluid collections is successful in the majority of patients and is accompanied by an acceptable complication rate.展开更多
Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum o...Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods: Specimens of normal human fundus were maintained in culture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations. Results: Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS (- 26% of NSE positive neurones; p = 0.016) and VIP (- 54% ; p = 0.09) neurones, and a concomitant increase in ChAT neurones (+ 16% ; p< 0.001) compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations (abolished by N-nitro-L-arginine methyl ester) was significantly decreased following incubation with serum from achalasia patients compared with controls (- 7.6 (2.6) v - 14.5 (5.0); p = 0.036). Conclusions: Serum from achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in achalasia.展开更多
Background and aim: A genetically impaired intestinal barrier Function has long been suspected to be a predisposing factor for Crohn’s disease (CD). Recently, mutations of the capsase recruitment domain family, membe...Background and aim: A genetically impaired intestinal barrier Function has long been suspected to be a predisposing factor for Crohn’s disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. Methods: We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC)were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. Results: Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% ofwild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. Conclusions: In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.展开更多
PURPOSE:Differences in conventional outcomes such as functional results and the rate of complications have caused a controversy about whether the ileal pouch anal anastomosis or the ileorectal anastomosis is the prefe...PURPOSE:Differences in conventional outcomes such as functional results and the rate of complications have caused a controversy about whether the ileal pouch anal anastomosis or the ileorectal anastomosis is the preferred surgical treatment for patients with familial adenomatous polyposis. We therefore sought to ascertain not only the surgical results but also the perceptions of patients about their outcomes. METHODS: Between 1981 and 1998, 152 patients at our institution had an ileal pouch-anal anastomosis and 32 patients had an ileorectal anastomosis for familial adenomatous polyposis. Of these 184 patients, 173 were sent a study-specific quality-of-life questionnaire and the Short Form 36 health survey to determine their health-related quality of life. RESULTS: Ninety-four ileal pouch patients and 21 ileorectal patients returned the surveys. No difference was found in early postoperative complications, 5-year probability for complications, or functional results after either procedure. On the Short Form 36 health survey, the ileorectal patients had a lower mental health summary score compared with that of the ileal pouch patients but a similar physical health summary score. The study-specific questionnaire found both groups to have a comparable quality of life. CONCLUSION: Because ileal pouch-anal anastomosis has the advantage of removing as much at-risk tissue as possible with similar functional results and better mental health, it may be considered the preferred operation for most patients with familial adenomatous polyposis.展开更多
PURPOSE: The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 80 years old compared with open colectomy. METHODS: Sixty-one patients undergoing laparos...PURPOSE: The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 80 years old compared with open colectomy. METHODS: Sixty-one patients undergoing laparoscopic colectomy for colorectal cancer were matched to 61 open colectomy patients for gender, age, year of surgery, site of cancer, and comorbidity on admission. Independence status on admission and at discharge from the hospital was also evaluated. RESULTS: Mean (standard deviation) age was 82.3 (3.5) years in the laparoscopy group and 83.1 (3.3) years in the open group. Conversion rate was 6.1 percent. Operative time was 49 minutes longer in the laparoscopy group (P = 0.001 ). The overall mortality rate was 2.4 percent. The morbidity rate was 21.5 percent in the laparoscopy group and 31.1 percent in the open group (P = 0.30). Patients in the laparoscopy group had a faster recovery of bowel function (P = 0.01) and a significant reduction of the mean length of hospital stay (9.8 vs. 12.9 days for the open group, P = 0.001). Laparoscopy allowed a better preservation of postoperative independence status compared with the that of the open group (P = 0.02). CONCLUSION: Laparoscopic colectomy for cancer in octogenarians is safe and beneficial including preservation of postoperative independence and a reduction of length of hospital stay.展开更多
A 25-year-old Japanese man was admitted to our hospital with a history of recurrent pancreatitis and a pseudocyst of the pancreas. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed an en...A 25-year-old Japanese man was admitted to our hospital with a history of recurrent pancreatitis and a pseudocyst of the pancreas. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed an encapsulated multilocular cystic mass 5 cm in diameter in the pancreatic tail. Endoscopic ultrasonography demonstrated a mural nodule, and endoscopic retrograde pancreatography showed a communication of the lesion with the main pancreatic duct. A neoplastic cystic tumor was suspected, and a resection of the body tail of the pancreas was performed. The lesion was a multilocular cyst having a common fibrous capsule and viscous content. Histologically, the cystic lesion was lined with a single layer of columnar cells with low-grade atypia. Ovarian-type stroma (OS) was confirmed, and it showed positive for antiestrogen receptor and antiprogesteron receptor staining. Based on these findings, the lesion was diagnosed as mucinous cystic neoplasm (MCN), an adenoma that shows extraordinarily high prevalence in women. Further study on the pathogenesis of MCN in male patients should be undertaken to elucidate the process of development.展开更多
PURPOSE: This study was designed to elicit patient’s preferences with regard to adjuvant postoperative chemoradiation therapy in rectal cancer. METHODS: Forty-seven previously treated colorectal cancer patients under...PURPOSE: This study was designed to elicit patient’s preferences with regard to adjuvant postoperative chemoradiation therapy in rectal cancer. METHODS: Forty-seven previously treated colorectal cancer patients underwent a structured interview and were presented with two scenarios involving surgery for rectal cancer: surgery alone, or surgery followed by postoperative chemoradiation therapy. Acute and long-term health states for each options were described. Their willingness to trade-off side-effects for treatment efficacy was evaluated by using the probability trade-off method. RESULTS: The age and gender distribution of the cohort were comparable with the general colon cancer population. Rectal cancer had been diagnosed in 20 individuals. The majority of patients valued their disease-free status in light of the anticipated long-term effects on their quality of life. The median point at which patients switched their preference was 5 percent, a value reflecting the critical local recurrence rate acceptable. The important items that influenced decisions were the effects on bowel function and fear of recurrence. CONCLUSIONS: This small study demonstrates a substantial variation in patient’s preferences with regard to postoperative chemoradiation for rectal cancer. Further studies in the preoperative setting are warranted.展开更多
PURPOSE: The proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon...PURPOSE: The proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon. We investigated the location of colorectal cancer with this phenotype in different age groups to determine whether different molecular mechanisms could account for the changes in distribution of colorectal cancers. METHODS: A representative sample of 230 colorectal cancers from three age groups (< 45 years, 60-70 years, >87 years)was selected from a subset of The Upper Midwest Oncology Medical Registries database. Microsatellite instability was determined by polymerase chain reaction using a panel of five microsatellite markers. The presence of new microsatellite alleles at two or more loci was scored as microsatellite instability. Tumors were otherwise considered microsatellite stable. MLH1 and MSH2 expression was determined by immunohistochemistry. Methylation of the MLH1 gene promotor was determined by methylation-specific polymerase chain reaction assay. RESULTS: The proportion of tumors of the microsatellite instability phenotype was 21 percent in the young group, 15 percent in the middle group, and 33 percent in the old group. More tumors of the microsatellite instability phenotype were proximal compared with microsatellite-stable tumors in all three age groups, but the differences were significant only for the old group. Tumors of the microsatellite instability phenotype in the older group were associated with MLH1 inactivation (24/29 or 83 percent), MLH1 promoter methylation (18/29 or 62 percent), and proximal location (25/29 or 86 percent), while tumors in the young group were associated with MSH2 inactivation (8/18 or 44 percent) and distal location (11/18 or 62 percent). CONCLUSION: The age-related proximal shift of colorectal cancers is associated with the microsatellite instability phenotype, MLH1 inactivation, and MLH1 promoter hypermethylation.展开更多
文摘PURPOSE: Defunctioning ileostomy or colostomy is still routinely performed after low anterior resection in the belief that diverting the fecal stream will prevent anastomotic dehiscence. However, an ileostomy is not without morbidity for the patient. This study aims to determine if a diverting stoma is really necessary after a low anastomosis. METHODS: All low or ultralow anterior resections done in this department were performed by consultant-grade surgeons in a standardized manner. The patients were all monitored closely after surgery for clinical signs of an anastomotic leak. There were 1078 patients who underwent elective low or ultralow anterior resections in a ten-year period between 1994 and 2004. Twelve of them were irradiated before surgery; they were excluded from the study. During a seven-month period from February 2004 through August 2004, 324 patients who underwent such procedures were not defunctioned. These were compared with 742 patients who were previously defunctioned with a proximal stoma. The results were analyzed using the Pearson chi-squared test. RESULTS: Thirteen (4 percent) patients who were not defunctioned developed a clinical anastomotic leak, whereas the leak rate for those who were defunctioned was 3.8 percent. There was no statistical difference demonstrated. Ninety-five percent of patients who developed a leak required surgical intervention; the remaining 5 percent could be dealt with by radiologic drainage. The overall mortality rate for anastomotic leak in this department is 7.3 percent. CONCLUSION: A diverting stoma does not reduce postoperative anastomotic leak rate. Rather, it reduces the otherwise catastrophic effects of an anastomotic leak such as fecal peritonitis and septicemia. An ileostomy carries certain morbidity and also adds to the cost of the entire operation. Therefore, it should not be performed routinely. Instead, it should be performed selectively in patients with poorly prepared bowels, coupled with a distal limb washout, and in patients with significant comorbidities who can ill afford the complications of a leak.
文摘Background:Pancreatic-fluid collections are frequent sequelae of acute and chronic pancreatitis,and endoscopic drainage of these collections has gained acceptance as an alternative to surgical drainage.Methods:Patient data,collection characteristics,drainage technique,and outcomes were obtained through chart review and prospective follow-up for 116 patients with attempted endoscopic drainage of symptomatic pancreatic-fluid collections.Results:A total of 116 patients presented with fluid collections classified as acute fluid collection(n = 5),necrosis(n = 8),acute pseudocyst(n = 30),chronic pseudocyst(n = 64),and pancreatic abscess(n = 9).The median diameter of the collection drained was 60 mm(15-275 mm).Median follow-up after drainage was 21 months.The drainage technique was transpapillary in 15 patients,transmural in 60,and both in 41.Successful resolution of symptoms and collection occurred in 87.9%of cases.No difference in success rates was observed between patients with acute pancreatitis and those with chronic pancreatitis.However,drainage of organized necrosis was associated with a significantly higher failure rate than other collections.No significant differences were observed regarding success when disease,drainage technique,or site of drainage was considered.Complications occurred in 13 patients(11%),and there were 6 deaths in the 30 days after drainage,including one that was procedure related.Conclusions:Endoscopic drainage of pancreatic-fluid collections is successful in the majority of patients and is accompanied by an acceptable complication rate.
文摘Background and aims: Achalasia is a disease of unknown aetiology. An immune mechanism has been suggested on the basis of previous morphological observations. The objective of this study was to test whether the serum of achalasia patients could reproduce the phenotype and functional changes that occur with disease progression in an ex vivo human model. Methods: Specimens of normal human fundus were maintained in culture in the presence of serum from patients with achalasia, gastro-oesophageal reflux disease (GORD), or healthy subjects (controls). Immunohistochemical detection of choline acetyltransferase (ChAT), neurone specific enolase (NSE), vasoactive intestinal polypeptide (VIP), nitric oxide synthase (NOS), and substance P was carried out in whole mounts of gastric fundus myenteric plexus. In addition, the effects of achalasia serum on electrical field stimulation (EFS) induced contractions were measured in circular muscle preparations. Results: Serum from achalasia patients did not affect the number of myenteric neurones. Tissues incubated with serum from achalasia patients showed a decrease in the proportion of NOS (- 26% of NSE positive neurones; p = 0.016) and VIP (- 54% ; p = 0.09) neurones, and a concomitant increase in ChAT neurones (+ 16% ; p< 0.001) compared with controls. In contrast, GORD serum did not modify the phenotype of myenteric neurones. Area under the curve of EFS induced relaxations (abolished by N-nitro-L-arginine methyl ester) was significantly decreased following incubation with serum from achalasia patients compared with controls (- 7.6 (2.6) v - 14.5 (5.0); p = 0.036). Conclusions: Serum from achalasia patients can induce phenotypic and functional changes which reproduce the characteristics of the disease. Further identification of putative seric factors and mechanisms involved could lead to the development of novel diagnostic and/or therapeutic strategies in achalasia.
文摘Background and aim: A genetically impaired intestinal barrier Function has long been suspected to be a predisposing factor for Crohn’s disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. Methods: We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC)were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. Results: Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% ofwild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. Conclusions: In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.
文摘PURPOSE:Differences in conventional outcomes such as functional results and the rate of complications have caused a controversy about whether the ileal pouch anal anastomosis or the ileorectal anastomosis is the preferred surgical treatment for patients with familial adenomatous polyposis. We therefore sought to ascertain not only the surgical results but also the perceptions of patients about their outcomes. METHODS: Between 1981 and 1998, 152 patients at our institution had an ileal pouch-anal anastomosis and 32 patients had an ileorectal anastomosis for familial adenomatous polyposis. Of these 184 patients, 173 were sent a study-specific quality-of-life questionnaire and the Short Form 36 health survey to determine their health-related quality of life. RESULTS: Ninety-four ileal pouch patients and 21 ileorectal patients returned the surveys. No difference was found in early postoperative complications, 5-year probability for complications, or functional results after either procedure. On the Short Form 36 health survey, the ileorectal patients had a lower mental health summary score compared with that of the ileal pouch patients but a similar physical health summary score. The study-specific questionnaire found both groups to have a comparable quality of life. CONCLUSION: Because ileal pouch-anal anastomosis has the advantage of removing as much at-risk tissue as possible with similar functional results and better mental health, it may be considered the preferred operation for most patients with familial adenomatous polyposis.
文摘PURPOSE: The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 80 years old compared with open colectomy. METHODS: Sixty-one patients undergoing laparoscopic colectomy for colorectal cancer were matched to 61 open colectomy patients for gender, age, year of surgery, site of cancer, and comorbidity on admission. Independence status on admission and at discharge from the hospital was also evaluated. RESULTS: Mean (standard deviation) age was 82.3 (3.5) years in the laparoscopy group and 83.1 (3.3) years in the open group. Conversion rate was 6.1 percent. Operative time was 49 minutes longer in the laparoscopy group (P = 0.001 ). The overall mortality rate was 2.4 percent. The morbidity rate was 21.5 percent in the laparoscopy group and 31.1 percent in the open group (P = 0.30). Patients in the laparoscopy group had a faster recovery of bowel function (P = 0.01) and a significant reduction of the mean length of hospital stay (9.8 vs. 12.9 days for the open group, P = 0.001). Laparoscopy allowed a better preservation of postoperative independence status compared with the that of the open group (P = 0.02). CONCLUSION: Laparoscopic colectomy for cancer in octogenarians is safe and beneficial including preservation of postoperative independence and a reduction of length of hospital stay.
文摘A 25-year-old Japanese man was admitted to our hospital with a history of recurrent pancreatitis and a pseudocyst of the pancreas. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) revealed an encapsulated multilocular cystic mass 5 cm in diameter in the pancreatic tail. Endoscopic ultrasonography demonstrated a mural nodule, and endoscopic retrograde pancreatography showed a communication of the lesion with the main pancreatic duct. A neoplastic cystic tumor was suspected, and a resection of the body tail of the pancreas was performed. The lesion was a multilocular cyst having a common fibrous capsule and viscous content. Histologically, the cystic lesion was lined with a single layer of columnar cells with low-grade atypia. Ovarian-type stroma (OS) was confirmed, and it showed positive for antiestrogen receptor and antiprogesteron receptor staining. Based on these findings, the lesion was diagnosed as mucinous cystic neoplasm (MCN), an adenoma that shows extraordinarily high prevalence in women. Further study on the pathogenesis of MCN in male patients should be undertaken to elucidate the process of development.
文摘PURPOSE: This study was designed to elicit patient’s preferences with regard to adjuvant postoperative chemoradiation therapy in rectal cancer. METHODS: Forty-seven previously treated colorectal cancer patients underwent a structured interview and were presented with two scenarios involving surgery for rectal cancer: surgery alone, or surgery followed by postoperative chemoradiation therapy. Acute and long-term health states for each options were described. Their willingness to trade-off side-effects for treatment efficacy was evaluated by using the probability trade-off method. RESULTS: The age and gender distribution of the cohort were comparable with the general colon cancer population. Rectal cancer had been diagnosed in 20 individuals. The majority of patients valued their disease-free status in light of the anticipated long-term effects on their quality of life. The median point at which patients switched their preference was 5 percent, a value reflecting the critical local recurrence rate acceptable. The important items that influenced decisions were the effects on bowel function and fear of recurrence. CONCLUSIONS: This small study demonstrates a substantial variation in patient’s preferences with regard to postoperative chemoradiation for rectal cancer. Further studies in the preoperative setting are warranted.
文摘PURPOSE: The proportion of colorectal cancers located proximal to the splenic flexure increases with age. Colorectal cancers of the microsatellite instability phenotype are preferentially located in the proximal colon. We investigated the location of colorectal cancer with this phenotype in different age groups to determine whether different molecular mechanisms could account for the changes in distribution of colorectal cancers. METHODS: A representative sample of 230 colorectal cancers from three age groups (< 45 years, 60-70 years, >87 years)was selected from a subset of The Upper Midwest Oncology Medical Registries database. Microsatellite instability was determined by polymerase chain reaction using a panel of five microsatellite markers. The presence of new microsatellite alleles at two or more loci was scored as microsatellite instability. Tumors were otherwise considered microsatellite stable. MLH1 and MSH2 expression was determined by immunohistochemistry. Methylation of the MLH1 gene promotor was determined by methylation-specific polymerase chain reaction assay. RESULTS: The proportion of tumors of the microsatellite instability phenotype was 21 percent in the young group, 15 percent in the middle group, and 33 percent in the old group. More tumors of the microsatellite instability phenotype were proximal compared with microsatellite-stable tumors in all three age groups, but the differences were significant only for the old group. Tumors of the microsatellite instability phenotype in the older group were associated with MLH1 inactivation (24/29 or 83 percent), MLH1 promoter methylation (18/29 or 62 percent), and proximal location (25/29 or 86 percent), while tumors in the young group were associated with MSH2 inactivation (8/18 or 44 percent) and distal location (11/18 or 62 percent). CONCLUSION: The age-related proximal shift of colorectal cancers is associated with the microsatellite instability phenotype, MLH1 inactivation, and MLH1 promoter hypermethylation.
