Biomedical subjects

José G Guillem

Publications and source records attributed to José G Guillem.

12 recordsLinked to original sources

PubMed2007

Combined CT colonography and 18F-FDG PET of colon polyps: potential technique for selective detection of cancer and precancerous lesions.

OBJECTIVE: The purpose of this study was to determine the feasibility of imaging the colon with fused CT colonography (CTC) and 18F-FDG PET and to correlate the findings with the histologic features of polyps. SUBJECTS AND METHODS: Eighteen patients with suspected colorectal polyps enrolled in this prospective study. Before colonoscopy, 17 of the patients underwent a combination of FDG PET and CTC. CTC consisted of 4-MDCT merged with PET. PET of the abdomen and pelvis was performed after each CTC scan. One radiologist and one nuclear medicine physician in consensus analyzed PET and CTC fusion data. PET standard uptake value was correlated with the findings at histologic examination of polyps. Patient feasibility was defined as the ability to tolerate prolonged scanning with good colonic distention. Technical feasibility was determined by how closely anatomically matched polyps overlapped on fusion images. RESULTS: Seventeen of 18 patients tolerated scanning. Eighty-five percent of colon segments were optimally distended. Twenty-three of 27 FDG-avid polyps measuring 10 mm or more had excellent overlap at fusion imaging. PET depicted 23 of 39 premalignant polyps and even showed increased tracer activity associated with four small tubular adenomas (4-6 mm). Sixteen benign polyps (10-25 mm) were not depicted on PET. All nine cases of cancer (tumors measuring 11-60 mm) were detected with both PET and CTC. The standard uptake value of malignant tumors ranged from 4 to 20 (mean, 9). However, six benign flat polyps did not exhibit FDG avidity. CONCLUSION: The novel combination of CTC and PET was feasible in 17 of 18 patients and allowed excellent image correlation in 23 of 27 proven polyps measuring 10 mm or more on PET-CTC fusion. This technique shows promise in accurate anatomic correlation of both malignant and premalignant lesions evaluated with FDG PET.

Adolescent↗

PubMed2006

ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes.

Although the etiology of solid cancers is multifactorial, with environmental and genetic factors playing a variable role, a significant portion of the burden of cancer is accounted for by a heritable component. Increasingly, the heritable component of cancer predispositions has been linked to mutations in specific genes, and clinical interventions have been formulated for mutation carriers within affected families. The primary interventions for mutations carriers for highly penetrant syndromes such as multiple endocrine neoplasias, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and hereditary breast and ovarian cancer syndromes are primarily surgical. For that reason, the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) have undertaken an educational effort within the oncology community. A joint ASCO/SSO Task Force was charged with presenting an educational symposium on the surgical management of hereditary cancer syndromes at the annual ASCO and SSO meetings, resulting in an educational position article on this topic. Both the content of the symposium and the article were developed as a consensus statement by the Task Force, with the intent of summarizing the current standard of care. This article is divided into four sections addressing breast, colorectal, ovarian and endometrial cancers, and multiple endocrine neoplasia. For each, a brief introduction on the genetics and natural history of the disease is provided, followed by a detailed description of modern surgical approaches, including a description of the clinical and genetic indications and timing of prophylactic surgery, and the efficacy of prophylactic surgery when known. Although a number of recent reviews have addressed the role of genetic testing for cancer susceptibility, including the richly illustrated Cancer Genetics and Cancer Predisposition Testing curriculum by the ASCO Cancer Genetics Working Group (available through http://www.asco.org), this article focuses on the issues surrounding the why, how, and when of surgical prophylaxis for inherited forms of cancer. This is a complex process, which requires a clear understanding of the natural history of the disease and variance of penetrance, a realistic appreciation of the potential benefit and risk of a risk-reducing procedure in a potentially otherwise healthy individual, the long-term sequelae of such surgical intervention, as well as the individual patient and family's perception of surgical risk and anticipated benefit.

Female↗

PubMed2006

Sacral resection for recurrent rectal cancer: analysis of morbidity and treatment results.

PURPOSE: Composite sacropelvic resection for locally advanced recurrent rectal cancer is a high-risk procedure that benefits select patients. We reviewed our recent institutional experience to evaluate case selection, morbidity, and outcomes. METHODS: Between 1987 and 2004, 29 patients underwent composite resection for recurrent locoregional rectal cancer (17 females; median age, 60 years). Clinicopathologic indicators were evaluated as indicators of survival by log-rank test and Cox proportional hazards model. RESULTS: Of 29 total patients, 27 (93 percent) received radiotherapy with their previous surgery (n = 10; 34 percent) or before sacrectomy (n = 17; 59 percent), and 12 (41 percent) received intraoperative therapy. Sacral resections were performed at S2/S3 (55 percent) or S4/S5 (45 percent) using anterior (41 percent) or combined anterior-posterior approach (59 percent), with adherence to (62 percent) or cortical invasion in (38 percent) the sacrum. A majority of those who had undergone previous abdominoperineal resection had total exenteration (9/13), whereas most patients who had undergone a previous sphincter-preserving procedure had abdominoperineal resection (12/16) and none had exenteration. Pedicle flaps (omental, 11; abdominal rectus, 7) often were used. A median of five (range, 1-33) units of blood was given intraoperatively. Transfusions were associated with previous abdominoperineal resection (P < 0.03), correlating strongly with postoperative morbidity (P < 0.02). There were 33 complications in 17 (59 percent) patients, most commonly perineal wound breakdown (9 (31 percent)) and pelvic abscess (5 (17 percent)). Median hospital stay was 18 (range, 7-56) days, significantly longer in patients with previous abdominoperineal resection (P < 0.02) or postoperative morbidity (P < 0.03). The only postoperative death was from pelvic sepsis. Resection was complete (R0) in 18 patients (62 percent), with microscopically positive margins (R1) in 10 (34 percent) and grossly positive margins (R2) in 1 (3 percent). Two-year and five-year recurrence rates were 47 and 85 percent, respectively; disease-specific survival was 63 and 20 percent, respectively. Less transfusion (P = 0.03), R0 resection (P = 0.005), lack of anterior organ involvement (P = 0.02), and absence of cortical bone invasion (P < 0.001) were associated with better survival on univariate analysis; original colorectal cancer stage was not. CONCLUSIONS: Sacrectomy for rectal cancer is a high-risk procedure that can achieve clear resection margins with low mortality in select patients. This procedure has a low cure rate but may provide local disease control with acceptable morbidity.

Adenocarcinoma↗

PubMed2006

ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes.

BACKGROUND: A significant portion of cancers are accounted for by a heritable component, which has increasingly been linked to mutations in specific genes. Clinical interventions have been formulated for mutation carriers within affected families. The primary interventions for mutation carriers of highly penetrant syndromes are surgical. METHODS: The American Society of Clinical Oncology and the Society of Surgical Oncology formed a task force charged with presenting an educational symposium on surgical management of hereditary cancer syndromes at annual society meetings, and this resulted in a position paper on this topic. The content of both the symposium and the position paper was developed as a consensus statement. RESULTS: This article addresses hereditary breast, colorectal, ovarian/endometrial, and multiple endocrine neoplasias. A brief introduction on the genetics and natural history of each disease is provided, followed by detailed descriptions of modern surgical approaches, clinical and genetic indications, timing of prophylactic surgery, and the efficacy of surgery (when known). Although several recent reviews have addressed the role of genetic testing for cancer susceptibility, this article focuses on the issues surrounding surgical technique, timing, and indications for surgical prophylaxis. CONCLUSIONS: Risk-reducing surgical treatment of hereditary cancer is a complex undertaking. It requires a clear understanding of the natural history of the disease, realistic appreciation of the potential benefits and risks of these procedures in potentially otherwise healthy individuals, and the long-term sequelae of such interventions, as well as the individual patient's and family's perceptions of surgical risk and anticipated benefit.

Female↗

PubMed2005

Surgical salvage of recurrent rectal cancer after transanal excision.

PURPOSE: This study examines surgical salvage of locally recurrent rectal cancer following transanal excision of early tumors. METHODS: Through retrospective review of a colorectal database we identified 50 patients who underwent attempted surgical salvage for local recurrence following initial transanal excision of T1 or T2 rectal cancer. Eight patients had resectable synchronous distant disease. Clinicopathologic variables were associated with extent of surgery required for salvage and outcome. RESULTS: Salvage procedures included abdominoperineal resection (31), low anterior resection (11), total pelvic exenteration (4), and transanal excision (3). One patient had unresectable disease at exploration, requiring diverting ostomy. Of the 49 patients who underwent successful salvage, 27 (55 percent) required an extended pelvic dissection with en bloc resection of one or more of the following structures: pelvic sidewall and autonomic nerves (18); coccyx or portion of sacrum (6); prostate (5); seminal vesicle (5); bladder (4); portion of the vagina (3); ureter (2); ovary (1); and uterus (1). Complete pathologic resection (R0) was accomplished in 47 of 49 patients. Of the eight patients with distant and local recurrence, two underwent synchronous resection and six had delayed metastasectomy. With a median follow-up of 33 months, 29 patients had recurred or died of disease at the time of this analysis. Five-year disease-specific survival was 53 percent. Factors predictive of survival included evidence of any mucosal recurrence on endoscopy, low presalvage carcinoembryonic antigen, and absence of poor pathologic features (lymphovascular and perineural invasion). Patients who required an extended pelvic resection had a worse survival rate. CONCLUSION: Pelvic recurrence following transanal excision of early rectal cancer is often locally advanced, requiring an extended pelvic dissection with en bloc resection of adjacent pelvic organs to achieve salvage. The long-term outcome in patients undergoing resection is less than expected, considering the early stage of their initial disease. When contemplating local excision for early rectal cancer, the risk of local recurrence, the extent and morbidity of surgery required for salvage, and the modest cure rate following salvage should be considered.

Adult↗

PubMed2005

The development of a validated instrument to evaluate bowel function after sphincter-preserving surgery for rectal cancer.

PURPOSE: Sphincter-preserving surgery is technically feasible for many rectal cancers, but functional results are not well understood. Therefore, the purpose of this study was to develop an instrument to evaluate bowel function after sphincter-preserving surgery. METHODS: A 41-item bowel function survey was developed from a literature review, expert opinions, and 59 patient interviews. An additional 184 patients who underwent sphincter-preserving surgery between 1997 and 2001 were asked to complete the survey and quality-of-life instruments (Fecal Incontinence Quality of Life, European Organization for Research and Treatment of Cancer QLQ 30/Colorectal Cancer 38). A factor analysis of variance was performed. Test-retest reliability was evaluated, with 20 patients completing two surveys within a mean of 11 days. Validity testing was done with clinical variables (gender, age, radiation, length of time from surgery), surgical variables (procedure: local excision, low anterior resection, coloanal anastomosis), reconstruction (J-pouch, straight), anastomosis (handsewn, stapled), and quality-of-life instruments. RESULTS: The survey response rate was 70.1 percent (129/184). Among the 127 patients with usable data, 67 percent were male, the median age was 64 (range, 38-87) years, and the mean time for restoration of bowel continuity after sphincter-preserving surgery was 22.9 months. Patients had a median of 3.5 stools/day (range, 0-30), and 37 percent were dissatisfied with their bowel function. Patients experienced a median of 22 symptoms (range, 7-32), with 27 percent reported as severe, 37 percent as moderate, and 36 percent as mild. The five most common symptoms were incomplete evacuation (96.8 percent), clustering (94.4 percent), food affecting frequency (93.2 percent), unformed stool (92.8 percent), and gas incontinence (91.8 percent). The factor analysis identified 14 items that collapsed into three subscales: FREQUENCY (alpha = 0.75), DIETARY (alpha = 0.78), and SOILAGE (alpha = 0.79), with acceptable test-retest reliability for the three subscales and total score (0.62-0.87). The instrument detected differences between patients with preoperative radiation (n = 67) vs. postoperative radiation (n = 15) vs. no radiation (n = 45) (P = 0.02); local excision (n = 10) vs. low anterior resection (n = 55) vs. coloanal anastomosis (n = 62) (P = 0.002); and handsewn (n = 18) vs. stapled anastomosis (n = 99) (P = 0.006). The total score correlated with 4 of 4 Fecal Incontinence Quality of Life (P < 0.01) and 9 of 17 European Organization for Research and Treatment of Cancer subscales (all P < 0.01). CONCLUSIONS: Patients undergoing sphincter-preserving surgery for rectal cancer have impaired bowel function, and those treated with radiation, coloanal anastomoses, or handsewn anastomoses have significantly worse function. This reliable and valid instrument should be used to prospectively evaluate bowel function after sphincter-preserving surgery in patients undergoing rectal cancer therapy.

Adult↗

PubMed2004

Lymph node metastasis in T1 adenocarcinoma of the colon and rectum.

The biology of colorectal cancer differs according to location within the large intestine. To evaluate the clinical significance of tumor location as a risk factor for lymph node metastasis (LNM), we performed a detailed pathological review of T1 adenocarcinomas of the colon and rectum. T1 adenocarcinomas of the colon and rectum treated by radical resection (n=428) were identified from prospective clinical databases at two institutions. Tumor location was assigned as right colon (cecum to transverse), left colon (splenic flexure to sigmoid), or rectum (0-18 cm from AV). Pathology slides were reviewed, extent of submucosal invasion (sm width, sm depth) was quantified using an optical micrometer, and morphologic features of the cancer and its infiltrating margin were recorded. The overall rate of LNM was 10%. On univariate analysis, LNM was significantly more common in the rectum (27/176, 15%) compared to the left colon (13/160, 8%, p=.04) or right colon (3/92, 3%, p=.003). However, on multivariate analysis, deep submucosal invasion and lymphovascular invasion were independent and significant risk factors, whereas tumor location was not. T1 colorectal cancers have a progressively higher risk of LNM as their location becomes more distal. However, the increasing rate of LNM observed in cancers of the left colon and rectum is explained by a higher prevalence of high-risk pathologic features. In early colorectal cancers, tumor morphology is the strongest clinical predictor of metastatic behavior.

Adenocarcinoma↗

PubMed2003

MSH6 germline mutations are rare in colorectal cancer families.

Germline mutations in MSH6 can cause HNPCC, which is associated with a tumor phenotype featuring MSI. However, tumors arising in persons with disease-causing mutations of MSH6 may or may not exhibit MSI. We used D-HPLC to screen for germline mutations in the promoter region, the coding region and the 3'-UTR of MSH6. Eighty-four families, enrolled on the basis of Amsterdam I and II criteria (HNPCC families) and less stringent criteria (HNPCC-like families), were tested for MMR gene mutations; 27 families had a disease-causing mutation in MLH1 or MSH2, and the remaining 57 families were tested for mutations in MSH6. Two protein-truncating mutations were identified in each of 2 families fulfilling the Amsterdam I criteria, being present in persons affected with early-onset colorectal cancers exhibiting MSI. Immunohistochemical analysis showed that expression of both MSH2 and MSH6 proteins was lost in the cancer cells of the 2 mutation carriers but only MSH6 protein expression was lost in 2 adenomatous polyps. A third possibly disease-causing mutation was found in a person affected with a tumor that did not exhibit MSI. In addition, we found 4 new polymorphisms and determined that neither of the 2 studied by association analysis conferred susceptibility to colorectal or endometrial cancer. Altogether, our results indicate that disease-causing germline mutations of MSH6 are rare in HNPCC and HNPCC-like families.

Adult↗

PubMed2003

A636P is associated with early-onset colon cancer in Ashkenazi Jews.

BACKGROUND: Hereditary predisposition to colorectal cancer most often manifests itself as familial adenomatous polyposis from mutations of APC, or hereditary nonpolyposis colorectal cancer, resulting from mutations of MSH2, MLH1, MSH6, or other genes. Previously, we described a rare founder mutation MSH2*1906C > G in Ashkenazi Jews that was found in 8 of 1,345 individuals (0.6%) of Ashkenazi descent with colorectal cancer. This study seeks to characterize the proportion of individuals of Ashkenazi heritage with very early-onset colon cancer (diagnosed at age 40 or younger) that could be attributed to MSH2*1906C>G. STUDY DESIGN: We analyzed the carrier frequency of MSH2*1906C>G in paraffin samples from 31 Jewish patients age 40 or less, diagnosed with colorectal cancer at Memorial Sloan-Kettering and lymphocyte-derived DNA from 10 patients. We did not select for family history. Genotyping for MSH2*1906C>G was performed by polymerase chain reaction and restriction enzyme digestion methods. RESULTS: We detected the MSH2*1906G>C mutation in 3 of the 41 samples (7.14%) of patients who had colorectal cancer diagnosed at age 40 or younger. This incidence is significantly greater than the 8 in 1,345 (0.6%) we observed for cases of colorectal cancer in Ashkenazi Jews not selected for age (p = 0.004). CONCLUSION: Although very rare in the population, MSH2*1906G>C is found at an increased frequency in young Jewish patients with colorectal cancer. These results suggest that testing for the MSH2*1906G>C mutation should be included in the evaluation of Ashkenazi Jewish individuals diagnosed with early-onset colon cancer.

Adult↗

PubMed2002

Local therapy for rectal cancer.

Local procedures for carefully selected distal rectal cancer offer significant advantages such as sphincter preservation and avoidance of radical surgery. However, since preoperative selection criteria including current imaging modalities are unable to definitively stage regional lymph node status, local therapies for rectal cancer have the inherent potential disadvantage of undertreating a fraction of patients due to unresected mesorectal/regional lymph node disease. Current available data suggests that the local approach may be appropriate only for carefully selected T1 tumors with favorable pathologic features. Inferior local control and survival reported for T2 tumors and T1 tumors with unfavorable features, despite the addition of chemoradiation, outweigh the advantages of the local approach. Patients with unfavorable tumors who are unable to tolerate radical resection or who refuse surgery may be treated with local excision with or without adjuvant chemoradiation. Other modalities, such as electrocoagulation and endocavitary radiation, may also be valuable in this setting, as well as preoperative chemoradiation followed by local excision. Regardless of the approach used, all patients undergoing local therapy of a rectal cancer require careful long-term follow-up, because these patients remain at significant risk for local recurrence and distant failure.

Electrocoagulation↗

PubMed2002

Anal neoplasms.

A common theme in most anal neoplasms appears to be a delay in diagnosis due to confusion with more common, benign conditions. Thus, the clinician must maintain a high index of suspicion when evaluating lesions of the anal canal and margin. The use of primary chemoradiation for SCC of the anal canal has resulted in equivalent, if not superior, local control and survival compared with radical surgery, and results in sphincter preservation in over two thirds of cases. Nevertheless, abdominoperineal resection still plays an important role in salvage of treatment failures, and also for patients who are unlikely to tolerate chemoradiation or have pre-existing impaired continence. Recent studies indicate that variations in chemotherapeutic agents and radiation technique might potentially produce even better results. The prognosis for anorectal melanoma, as well as for small cell and undifferentiated tumors, continues to be poor. Fortunately, these are relatively rare tumors.

Anus Neoplasms↗

PubMed2002

Matrix metalloproteinase-7 expression in colorectal cancer liver metastases: evidence for involvement of MMP-7 activation in human cancer metastases.

PURPOSE: Matrix metalloproteinase-7 (MMP-7) is a member of the MMP family, which is overexpressed by some tumor cells and is thought to enhance the tumor metastatic potential. The aim of this study is to examine the MMP-7 expression in the human colorectal cancer (CRC) liver metastases and normal liver tissue using multiple techniques and to determine its association with liver metastases formation. EXPERIMENTAL DESIGN: MMP-7 mRNA, protein, and enzymatic levels were determined by reverse transcription-PCR, Western blot analysis, and casein zymography in the specimens of human CRC liver metastases and paired normal liver tissue from 44 patients. The cellular localization of MMP-7 was analyzed by immunohistochemistry. RESULTS: Our data reveal that all of the investigated liver metastases samples overexpressed MMP-7 mRNA and protein compared with the normal liver tissue. By zymogram, higher levels of the latent form of MMP-7 were found in 88.6% (39 of 44) liver metastases samples, whereas normal liver tissue exhibited only trace amounts. The activated form of MMP-7 was only found in those in which the pro-MMP-7 was present (n = 39); in contrast, it was not detected in the normal liver tissues. Immunohistochemically, MMP-7 is localized to the cytoplasm of tumor cells, and the strong signal is concentrated in the tumor front areas. CONCLUSIONS: Our observations emphasize the important role of MMP-7 production and activation in human CRC liver metastases formation.

Blotting, Western↗