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Philip H Gordon

Publications and source records attributed to Philip H Gordon.

11 recordsLinked to original sources
PubMed2006

Distinct patterns of germ-line deletions in MLH1 and MSH2: the implication of Alu repetitive element in the genetic etiology of Lynch syndrome (HNPCC).

A relatively high frequency of germ-line genomic rearrangements in MLH1 and MSH2 has been reported among Lynch Syndrome (HNPCC) patients from different ethnic populations. To investigate the underlying molecular mechanisms, we characterized the DNA breakpoints of 11 germ-line deletions, six for MLH1 and five for MSH2. Distinct deletion patterns were found for the two genes. The five cases of MSH2 deletions result exclusively from intragenic unequal recombination mediated by repetitive Alu sequences. In contrast, five out of the six MLH1 deletions are due to recombinations involving sequences of no significant homology (P=0.015). A detailed analysis of the DNA breakpoints in the two genes, previously characterized by other groups, validated the observation that Alu-mediated unequal recombination is the main type of deletion in MSH2 (n=34), but not in MLH1 (n=21) (P<0.0001). Plotting the distribution of known DNA breakpoints among the introns of the two genes showed that, the highest breakpoint density is co-localized with the highest Alu density. Our study suggests that Alu is a promoting factor for the genomic recombinations in both MLH1 and MSH2, and the local Alu density may be involved in shaping the deletion pattern.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Ileocecal hobnail hemangioendothelioma: report of a case and review of the literature.

Hobnail hemangioendothelioma is a rare vascular neoplasm that belongs to the category of vascular neoplasms of borderline (or low-grade) malignancy, defined by a significant potential for local recurrence but very low numbers of metastatic or fatal events. It is typically found in the skin, and rarely in the oral mucosa of children and young adults. We report the first case of hobnail hemangioendothelioma located in the intestine (ileocecal valve).

Adult↗
PubMed2006

The value of multi-modal gene screening in HNPCC in Quebec: three mutations in mismatch repair genes that would have not been correctly identified by genomic DNA sequencing alone.

Hereditary non-polyposis colorectal cancer (HNPCC) is a dominantly inherited cancer syndrome caused by a mutation in one of the mismatch repair genes, most frequently MLH1 or MSH2. The rate of mutation detection is influenced by many factors, including the diagnostic methods used. Large deletions, which occur frequently in MLH1 and MSH2, are not detected by exon-by-exon screening methods. Here, we describe three mutations in mismatch repair genes detected using a screening protocol that combines protein truncation test (PTT) analysis and multiplex ligation-dependent probe amplification (MLPA) with genomic and cDNA sequencing. Two of these mutations consist of large deletions in MLH1 that were detected by both MLPA and PTT but that would have been missed by genomic DNA sequencing. The third is a large deletion in MSH2 that could not be detected by PTT because of its location relative to the primers used to amplify the cDNA, or by sequencing. This mutation was detected by MLPA.

Base Pair Mismatch↗
PubMed2004

Outcome of local excision of rectal carcinoma.

PURPOSE: This study was designed to determine the results of patients with rectal adenocarcinoma treated with local excision. METHODS: A retrospective, chart review was conducted for all patients treated with local excision for rectal adenocarcinoma from 1984 to 1998. RESULTS: Sixty-four patients were retained for analysis. The median follow-up was 37 (range, 9-125) months. There were 15 local failures with a median time to local failure of 12 months. Seven patients were salvaged with further operation (4 by repeat local excision, 4 by abdominoperineal resection, and 1 by low anterior resection). The incidence of local recurrence increased with advancing stage of the carcinoma (T1, 13 percent; T2, 24 percent; T3, 71 percent), histologic grade of differentiation, (well, 12 percent; moderately, 24 percent; poorly, 44 percent), and margin status (negative, 16 percent; close (within 2 mm), 33 percent; positive, 50 percent). Sixteen percent of carcinomas < or = 3 cm failed compared with 47 percent for carcinomas > 3 cm. Nine percent (1/11) of T2 patients treated with adjuvant radiation therapy recurred locally compared with 36 percent (5/14) without radiation therapy. Three of four T3 patients who received radiation therapy failed locally compared with two of three who did not. Using the Kaplan-Meier method, the overall survival at five years was 71 percent, and disease-free survival was 83 percent. Actuarial local failure was 27 percent and freedom from distant metastasis was 86 percent. The sphincter preservation rate was 90 percent at five years. CONCLUSIONS: Local excision alone is an acceptable option for well-differentiated, T1 carcinomas, < or = 3 cm. Adjuvant radiation is recommended for T2 lesions. The high local recurrence rate in patients after local excision of T3 lesions with or without adjuvant radiotherapy would mandate a radical resection.

Adenocarcinoma↗
PubMed2004

Surgical considerations in anal cancer.

SCC of the anus is rare; however, the surgeon is bound to encounter some of these patients during his or her career. It is important that the anatomic location and the histology be defined because the initial treatment may initially differ. Multimodality therapy is the treatment of choice in SCC of the anal canal, with surgery reserved for persistent or recurrent tumors. Multimodality therapy can be used selectively in SCC of the perianal skin, especially in large bulky tumors, followed by definitive surgery. Nevertheless, the initial treatment of perianal neoplasms is surgical therapy. In general, inguinal node metastases are treated with chemoradiation. In highly selected patients, groin dissections are performed, but this procedure is not routine.

Anus Neoplasms↗
PubMed2002

Investigative modalities for massive lower gastrointestinal bleeding.

The objective of this study was to evaluate the efficacy of various diagnostic modalities in the assessment of patients with massive lower gastrointestinal bleeding. The charts of all patients admitted to a McGill University affiliated teaching hospital with the diagnosis of lower gastrointestinal bleeding over a 25-year period were reviewed. There were 136 patients who underwent 202 admissions. The information documented included demographics on age, gender, co-morbid disease, prescribed medications, requirements for blood transfusions, orthostatic change in blood pressure, acute drop in hematocrit (to <30%), and exclusion of upper gastrointestinal bleeding. Among the 202 admitted patients there were 116 men and 86 women), with an average age of 70 years (range 16-95 years). At least one significant medical disease was found in 93% of these patients; and 20% were on aspirin and 5% on anticoagulants at the time of diagnosis. Rigid or flexible sigmoidoscopy was performed in 68 and 18 patients, respectively, with a definitive diagnosis made in 2.9% and 11.0%, respectively. Colonoscopy was performed in 152 cases, 20 of which were incomplete; a specific diagnosis was made for 59 admissions (45%). A red blood cell or colloid scan was performed on 53 patients, with extravasation noted in 13 (24.5%); a localized site of bleeding was identified in 9 cases (17%). Angiography was performed on 31 patients with bleeding sites localized in 6 (19%). Barium enemas were completed in 85 of 92 patients, and the presumptive cause of bleeding was identified in 72% of those with a complete examination. The most common causes identified were diverticulosis in 52 patients and angiodysplasia in 14. The cause of bleeding was not detected in 48 (35%). Bleeding stopped in most patients spontaneously, with only 7 requiring operation. The average number of units transfused was 3 (range 0-26). Scintigraphy and angiography were less efficacious than colonoscopy for localizing the site and etiology of the bleeding. Despite the combination of investigative modalities, a definitive diagnosis was not made in 35% of the admitted patients. The need for operative intervention in our study was lower than in most previous reports.

Adolescent↗
PubMed2002

Polymorphisms and HNPCC: PMS2-MLH1 protein interactions diminished by single nucleotide polymorphisms.

Hereditary nonpolyposis colorectal cancer (HNPCC) is one of the most common autosomal dominant inherited diseases. Mutations in the human mismatch repair (MMR) proteins MLH1, MSH2, MSH6, PMS1, and PMS2 have been found to co-segregate with HNPCC. The MLH1 and MSH2 proteins have been demonstrated to interact with PMS1, PMS2, and MSH6 proteins. A previous study reported that missense mutations in specific regions of MLH1 can lead to defects in protein-protein interactions with PMS2. Here we report that three missense alterations previously identified as single nucleotide polymorphisms (SNPs) in PMS2 (P511K, T597S, and M622I) cause defective protein-protein interactions with MLH1, even though the alterations are not in the previously reported interaction domain. These results suggest that an additional domain in PMS2 affects MLH1-PMS2 interaction. This study also demonstrates that SNPs can result in gene alterations that indeed have a functional effect on protein phenotype. Thus, these three SNPs may ultimately represent variants with an increased risk factor for tumorgenesis in HNPCC. This study is one of the first to use a functional assay to appraise the role of SNPs and suggests that traditional definitions of polymorphisms and mutations are in need of reconsideration.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Cancer prevention in inflammatory bowel disease and the chemoprophylactic potential of 5-aminosalicylic acid.

The risk of colorectal cancer is increased in ulcerative colitis and Crohn's colitis. Regular dysplasia surveillance colonoscopy in chronic colitis generally has been adopted as a strategy to prevent colorectal cancer or at least to diagnose it in an earlier stage. This has not been proven to reduce mortality, but it does provide the clinician and the patient with some confidence that they are participating in an active strategy to deal with the problem of colorectal cancer in chronic colitis. Disease extent and duration have long been held to be risk factors for colorectal cancer in chronic colitis, and recently some special risk groups have been identified which may require either more intensive surveillance or alternative approaches to cancer prevention. These include patients with primary sclerosing cholangitis, patients with first-degree relatives with sporadic colon cancer, and possibly, patients with backwash ileitis. There is an emerging interest in potential chemopreventative strategies in both sporadic and colitis-associated colorectal cancer. There also have been suggestive data that chronic maintenance 5-aminosalicylate use might reduce the risk of developing colorectal cancer. Recent data have suggested some potential preventative benefit of using ursodeoxycholic acid in patients with ulcerative colitis and primary sclerosing cholangitis. The scientific rationale for using these agents is sound but clinical data are lacking to fully support these approaches as chemoprevention in chronic colitis at present.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Readmission for small-bowel obstruction in the early postoperative period: etiology and outcome.

OBJECTIVES: To determine the frequency of readmission for early postoperative small-bowel obstruction (SBO), to highlight factors that may predispose to this condition, to define the risks of strangulation and to compare the immediate and long-term risks and benefits of operative versus nonoperative treatment. DESIGN: A chart review. SETTING: The Sir Mortimer B. Davis-Jewish General Hospital, a university-affiliated teaching hospital in Montreal. PATIENTS: Out of a total of 1001 cases of SBO in 552 patients, 30 patients were readmitted within 50 days of a previous laparotomy with the diagnosis of SBO. INTERVENTION: Selective nonoperative management and exploratory laparotomy. MAIN OUTCOME MEASURES: The value of nonoperative management and need for operation. RESULTS: Adhesions were the cause of the obstruction in most cases (24); other causes were Crohn's disease (2), hernia (1), malignant neoplasm (1) and a combination of adhesions and malignant disease (2). Thirteen (43%) of the procedures preceding the obstruction were primary small-bowel operations. There was only 1 episode of strangulated bowel. Of the patients readmitted for SBO, 7 (23%) were treated operatively with a long-term recurrence rate of 57% compared with 63% for those treated nonoperatively for the SBO. The median time to recurrence was 0.1 years (range from 0.02-6 yr) for those whose SBO was managed operatively, compared with 0.7 years (range from 0.08-5 yr) for those managed nonoperatively for the SBO. The median length of stay for patients managed operatively for SBO was 12 days (range from 9-17 d) compared with 6 days (range from 2-33 d) for those managed nonoperatively. CONCLUSIONS: Readmission for SBO within 50 days of a previous laparotomy represents a small percentage of all cases of SBO. They frequently follow small-bowel operations. Cases of strangulation are no more common than in general cases of SBO. Patients treated nonoperatively for SBO did not experience less favourable outcomes with respect to resolution of symptoms, length of stay, risk of recurrence and reoperation. Thus, operative intervention is not necessary in an otherwise stable patient.

Causality↗
PubMed2002

Immediate postlaparotomy small bowel obstruction: a 16-year retrospective analysis.

Small bowel obstruction (SBO) is a particularly vexing problem in the postoperative period. The goal of this study was to compare the results of operative versus nonoperative treatment. A secondary goal was to explore risk factors for necessitating reoperation in the immediate postoperative period. We conducted a historical cohort retrospective chart review at a university-affiliated hospital. The medical records of patients treated between 1985 and 2000 at the Sir Mortimer B. Davis Jewish General Hospital (Montreal, Quebec, Canada) who developed SBO after undergoing a laparotomy during that admission were reviewed. Postoperative SBO was defined as cessation of flatus or bowel movements after their resumption following operation. To compare operative versus nonoperative management of early postoperative mechanical SBO we used the following outcome measures: Reoperation rate, time to return of function, length of stay, and mortality. Of 52 patients who developed SBO in the immediate postoperative period 37 were male, 25 had colorectal surgery, and nine had a gastrectomy as the initial operation on admission; five had inflammatory bowel disease, six had a previous SBO, 22 had virgin abdomens before the current operation, and 11 had adhesions noted at the initial operation. The median time to the development of obstructive symptoms was 8 days (range 1-33). The reoperation rate was 42 per cent overall (67% in women and 32% in men, P = 0.02). For operatively treated patients the median time between onset of symptoms and surgery was 5 days [range 1-23, interquartile range (IQR) = 5]. The median time to the return of bowel function was greater in the operatively treated patients compared with nonoperatively treated patients [11.5 days (range 4-37, IQR = 11) vs 6 days (range 1-28, IQR = 7), P < 0.0001] as was median length of stay from onset of obstruction [23 days (range 6-60, IQR = 14) vs 12 days (range 2-45, IQR = 16), P < 0.009]. Operatively treated patients also stayed longer after their obstruction was relieved although not significantly longer [8 days (range 1-35, IQR = 11) vs 4.5 days (range 0-40, IQR = 10), P = 0.15]. There were 11 complications in nine of 22 patients who underwent operative treatment of their SBO. Immediate postoperative SBO can be treated nonoperatively in stable patients resulting in significantly quicker return of bowel function and shorter lengths of hospital stay. Definitive risk factors for immediate SBO could not be identified.

Aged↗