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Martin J Heslin

Publications and source records attributed to Martin J Heslin.

At least 19 recordsLinked to original sources

Urine PGE-M: A metabolite of prostaglandin E2 as a potential biomarker of advanced colorectal neoplasia.

BACKGROUND & AIMS: The enzyme cyclooxygenase-2 is expressed in a majority of colorectal carcinomas (CRCs) and is important in prostaglandin production. We have developed an accurate method to measure the urinary metabolite of prostaglandin E(2) (PGE-M) using recently developed mass spectrometric techniques. The purpose of this pre-validation study was to determine if urinary PGE-M levels can be used as a biomarker to discriminate between healthy patients and those with colorectal disease. METHODS: Urine PGE-M was assessed in a total of 228 patients with CRC, colonic adenomatous polyps, Crohn's disease, and in subjects with no endoscopically detectable disease. Thirteen rectal carcinoma patients were treated with celecoxib and urinary PGE-M was measured before and after treatment. RESULTS: Urine PGE-M levels were increased among healthy men compared with healthy women (median, 8.59 [interquartile range (IQR), 5.67-22.3] vs 4.25 [IQR, 2.35-6.03], P = .0027). Urine PGE-M levels among patients with Crohn's disease (median, 19.85 [IQR, 6.89-90.2]), CRC (median, 14.65 [IQR, 5.94-92.1]), or large adenomas greater than 1 cm in size (median, 18.85 [IQR, 11.9-25.6]) were significantly increased when compared with patients who had either small polyps less than 1 cm in size (median, 9.69 [IQR, 6.41-22.2]), or no polyps (median, 7.05 [IQR, 2.35-24.7]) (P = .0001). PGE-M levels decreased significantly after celecoxib treatment in patients with rectal cancer (median, 21.7 [IQR, 16.2-29.9] vs 9.14 [IQR, 7.14-13.2], P = .009). CONCLUSIONS: The increase in urinary PGE-M in patients with colorectal cancers and large adenomas suggests that urinary PGE-M is a potentially useful biomarker for the detection of advanced colorectal neoplasia.

Adenoma↗

Preoperative radiation therapy with selective dose escalation to the margin at risk for retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPSs) are rare tumors with poor survival rates due to difficult resectability and high local and distant recurrence rates. Preoperative radiation therapy appears to have dosimetric advantages to utilize the tumor as a tissue expander to limit exposure of small bowel to higher radiation doses. METHODS: Between June 1999 and December 2003, 16 consecutive patients with biopsy-proven RPS were treated with preoperative radiation with selective dose escalation. This included 45 grays (Gy) in 25 fractions to the entire tumor plus margin and a boost dose of 57.5 Gy to the volume predicted as high risk for positive surgical margins. Treatment toxicity and local control were evaluated prospectively as primary endpoints. The secondary goal was the theoretical calculation of future dose escalation and feasibility. Each patient underwent laparotomy. Tumor response was judged using computed tomography (CT) scan and by necrosis on final pathology. Theoretical treatment plans evaluated the potential for additional radiation dose escalation. RESULTS: All patients completed the radiation protocol. The most common acute side effects were nausea/vomiting, which affected 4 patients (25%), with only 1 patient requiring inpatient intravenous hydration. There was no severe late postoperative morbidity or mortality. Twelve tumors (75%) decreased in maximum dimension, with a median decrease of 9.4%. Fourteen of 16 patients (88%) underwent complete macroscopic resection. With a median follow-up of 28 months (range, 7-52 months), there were only 2 local recurrences. The actuarial 2-year local control rate was 80%. Theoretical treatment plans suggest that significant dose escalation (up to 80 Gy) may be possible. CONCLUSIONS: Preoperative radiation therapy with selective dose escalation to the margin at risk is tolerable and allows higher radiation dose to the volume judged to be at greatest risk for local tumor recurrence.

Adult↗

Trends in hospital and surgeon volume and operative mortality for cancer surgery.

BACKGROUND: We measured 13-year trends in operative mortality for six cancer resections. We then examined whether these trends are driven by changes in hospital and surgeon volume or by changes that occurred among all providers, regardless of volume. METHODS: We analyzed administrative discharge data on patients who received one of six cancer resections in Florida, New Jersey, and New York for three time periods: 1988 to 1991, 1992 to 1996, and 1997 to 2000. Descriptive statistics and nested regression models were used to test for changes in the association between inpatient mortality and annual hospital and annual surgeon volume over time, adjusting for patient and hospital characteristics. RESULTS: Unadjusted inpatient mortality rates for the six cancer resections declined between .8 and 4.0 percentage points between the time periods 1988 to 1991 and 1997 to 2000. Over this time period, annual hospital and surgeon volumes for the six cancer operations increased an average of 24.3% and 24.2%, respectively. The logistic regressions indicated a relatively stable relationship over time between both increased hospital and surgeon volume and lower inpatient mortality. Simulations suggest that increases in hospital and surgeon procedure volume over time led to a reduction in inpatient mortality ranging from .1 percentage points for rectal cancer to 2.3 percentage points for pneumonectomy. CONCLUSIONS: Persistence of the volume-outcome relation and increasing hospital and surgeon volumes explain much of the decline over time in inpatient mortality for five of the six cancer operations studied. Concentrating cancer resections among high-volume providers should lead to further reduced inpatient mortality.

Aged↗

Radiation therapy for retroperitoneal sarcoma.

Retroperitoneal soft-tissue sarcoma is an uncommon cancer of mesodermal origin, which is difficult to treat owing to its location and proximity to vital structures. Complete gross resection, often involving en bloc resection, is the standard of care as it represents the only treatment that improves overall survival. Unlike extremity sarcoma, retroperitoneal soft-tissue sarcoma tumor mortality is from local recurrence. Radiation therapy is the only adjuvant treatment that has improved local control in several institutional series. However, there remains no definitive prospective, randomized trial that establishes the role of adjuvant radiation versus no radiation. Owing to significant radiation morbidity with adjacent organs, especially the small bowel, there exists no consensus on radiation timing, delivery method or dosing. Recent and current protocols use preoperative external-beam radiation with or without a method of focal boost dosing. Methods of boost dosing include brachytherapy, intraoperative radiation therapy and intensity-modulated radiation therapy. Further studies are needed to definitively include radiation therapy in the standard treatment of retroperitoneal soft-tissue sarcoma and to find the optimal balance between acceptable radiation toxicity and effective local control in treatment protocols.

Clinical Trials as Topic↗

Analysis of KIT mutations in sporadic and familial gastrointestinal stromal tumors: therapeutic implications through protein modeling.

PURPOSE: Gastrointestinal stromal tumors (GIST) are characterized by expressing a gain-of-function mutation in KIT, and to a lesser extent, PDGFR. Imatinib mesylate, a tyrosine kinase inhibitor, has activity against GISTs that contain oncogenic mutations of KIT. In this study, KIT and PDGFRalpha mutation status was analyzed and protein modeling approaches were used to assess the potential effect of KIT mutations in response to imatinib therapy. EXPERIMENTAL DESIGN: Genomic DNA was isolated from GIST tumors. Exons 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRalpha were evaluated for oncogenic mutations. Protein modeling was used to assess mutations within the juxtamembrane region and the kinase domain of KIT. RESULTS: Mutations in KIT exons 9, 11, and 13 were identified in GISTs with the majority of changes involving the juxtamembrane region of KIT. Molecular modeling indicates that mutations in this region result in disruption of the KIT autoinhibited conformation, and lead to gain-of-function activation of the kinase. Furthermore, a novel germ-line mutation in KIT was identified that is associated with an autosomal dominant predisposition to the development of GIST. CONCLUSIONS: We have used protein modeling and structural analyses to elucidate why patients with GIST tumors containing exon 11 mutations are the most responsive to imatinib mesylate treatment. Importantly, mutations detected in this exon and others displayed constitutive activation of KIT. Furthermore, we have found tumors that are both KIT and PDGFRalpha mutation negative, suggesting that additional, yet unidentified, abnormalities may contribute to GIST tumorigenesis.

Adult↗

E1A-F is overexpressed early in human colorectal neoplasia and associated with cyclooxygenase-2 and matrix metalloproteinase-7.

Studies suggest the expression of cyclooxygenase-2 (COX-2) and matrilysin (MMP-7) increase in the early stages of colorectal carcinogenesis, however their interaction with other molecular markers is poorly understood. Results from cell line studies and mouse models suggest polyomavirus enhancer activator 3 (PEA3) may play a role in the activation of COX-2 and MMP-7 promoters. However, the role of E1A-F, the human homolog of murine PEA3, in colorectal cancer (CRC) development has not been elucidated. In this study, we used real-time reverse transcription (RT)-polymerase chain reaction (PCR) to measure the levels of E1A-F, COX-2, and MMP-7 in matched normal mucosa, adenomas, and/or carcinomas from 128 patients. Our results demonstrate significant overexpression of E1A-F and MMP-7 in adenomas and E1A-F, COX-2, and MMP-7 in carcinomas. In carcinomas, E1A-F expression was significantly associated with both COX-2 and MMP-7 overexpression. These results suggest E1A-F is overexpressed in early stages of human CRC development and may be an important factor in the overexpression of COX-2 and MMP-7.

Adenovirus E1A Proteins↗

Leiomyosarcoma of the inferior vena cava: three case reports and review of the literature.

We describe 3 cases of leiomyosarcoma of the inferior vena cava (IVC) and review the literature describing clinicopathologic features of 211 cases and the outcome. Of these, 74% of the cases affected women with median age of 52 years. The most common symptoms were abdominal pain or mass (57%), Budd-Chiari syndrome (17%), and deep vein thrombosis (4%). The most frequent site of tumor origin is the middle segment of the IVC (33%). Tumor size ranged from 2 to 38 cm (mean, 12 cm). Of the tumors with an assigned grade, 46% were high grade, 17% were intermediate grade, and 36% were low grade. Of all patients, 47% underwent complete resection, 24% had complete resection with preoperative or postoperative chemotherapy and/or radiation, and 5% had palliative surgery. Tumor recurrence occurred in 40% of the patients (11% had local recurrence and 29% had metastasis). Perioperative mortality occurred in 4% of the cases. Of those patients who died, 42% died of the disease, 2% died of other causes, 26% were alive and free of the disease, 14% were alive with recurrent disease, and 11% were lost to follow-up. Tumors involving level 2 of the IVC have the best prognosis and tumors of level 1 have the worse prognosis. Although there is no standardized criteria for the grading of extrauterine leiomyosarcoma, we propose to grade based on mitotic activity as follows: high grade, 10 or more mitoses per 10 high-power field (HPF); intermediate grade, 5 to 9 mitoses per 10 HPF; and low grade, 1 to 4 mitoses per 10 HPF.

Aged↗

Tumor-associated down-regulation of 15-lipoxygenase-1 is reversed by celecoxib in colorectal cancer.

OBJECTIVE: To evaluate the role of celecoxib on 15-lipoxygenase-1 (15-LOX-1) expression, protein levels, and rates of apoptosis in colorectal cancer cell lines. Also, to evaluate the expression of 15-LOX-1 in human normal mucosa, adenoma, and carcinoma with correlation to overall survival. SUMMARY BACKGROUND DATA: The function of 15-LOX-1 is to maintain normal rates of apoptosis (programmed cell death). Decreased apoptosis is one mechanism of cancer growth and dissemination. It is our hypothesis that expression of 15-LOX-1 is reduced in human colorectal cancer (CRC) and the administration of celecoxib can reverse this process and induce apoptosis. METHODS: Effect of celecoxib in cell culture: The effect of 40 micromol/L celecoxib was compared with untreated controls in tissue culture utilizing HT-29 and DLD-1 CRC cell lines. Expression of 15-LOX-1 protein was measured by immunoblot. Induction of apoptosis was evaluated by annexin V staining. All data are presented as mean +/- SEM, with significance defined as P < 0.05. 15-LOX-1 in human CRC: From February 1998 to January 2002, 126 patients underwent surgical resection of either colorectal adenomas (n = 24) or carcinomas (n = 102), or both (n = 25). Tissue was macrodissected, snap frozen, and stored at -80 degrees C. After tissue processing, RNA was extracted and gene expression of 15-LOX-1 was quantified utilizing ABI prism real-time quantitative RT-PCR. Significance evaluated by the Wilcoxon signed rank test. RESULTS: Effect of celecoxib in cell culture: After 72 hours of treatment with celecoxib, immunoblot demonstrated a 1.5- to 2-fold increase in 15-LOX-1 protein expression in HT-29 and DLD-1 cells, respectively. Celecoxib produced greater than a 2-fold increase in the rate of apoptosis compared with control cells in both cell lines (P < 0.05). 15-LOX-1 in human CRC: The mean age of the patients was 62 +/- 1 years; 78% were white and 48% were female. The mean size of the polyps and cancers were 3.0 +/- 0.4 and 5.0 +/- 0.1 cm, respectively. Expression of 15-LOX-1 relative to S9 was 30 in normal mucosa and significantly down-regulated to 11 in adenomas and 16 in carcinomas (P < 0.05). CONCLUSIONS: 15-LOX-1 gene expression is significantly reduced in both human colorectal adenomas and carcinomas and associated with decreased survival. Administration of celecoxib restores 15-LOX-1 protein expression and induces apoptosis. Down-regulation of 15-LOX-1 is an early event in the adenoma to carcinoma sequence, and reversal with celecoxib may represent one mechanism for chemoprevention of polyps or treatment of carcinomas.

Adenoma↗

Adrenocortical carcinoma: a single institution experience.

Adrenocortical carcinoma (ADCC) ranks among the least common malignant endocrine tumors. Surgical resection is considered the most important treatment for this neoplasm. Medical records of patients with the diagnosis of ADCC between 1990 and 2000 were reviewed. Patient and pathologic factors were analyzed with overall survival as the primary endpoint. Statistical analysis was performed by the method of Kaplan-Meier. There were a total of 17 patients, with a mean age of 56 years. Twelve per cent presented as an asymptomatic mass, 41 per cent as a functional tumor, and 47 per cent as a nonfunctioning tumor. Primary treatment was surgical resection in 71 per cent. There was no operative mortality and one complication. Seven patients presented with stage II, five with stage III, four with stage IV, and in one could not be determined. Median follow-up was 12.8 months, median survival 67, 13, and 3 months for stages II, III, and IV, respectively. Older age, distant metastasis, nonoperative management, positive margins, advanced tumor stage, and venous invasion were significantly associated with worse overall actuarial survival. Survival for ADCC is poor. Factors associated with a worse prognosis were stage of disease, nonoperative management, positive surgical margins, vascular invasion, and older age.

Adrenal Cortex Neoplasms↗

An empirical bayes adjustment to increase the sensitivity of detecting differentially expressed genes in microarray experiments.

MOTIVATION: Detection of differentially expressed genes is one of the major goals of microarray experiments. Pairwise comparison for each gene is not appropriate without controlling the overall (experimentwise) type 1 error rate. Dudoit et al. have advocated use of permutation-based step-down P-value adjustments to correct the observed significance levels for the individual (i.e. for each gene) two sample t-tests. RESULTS: In this paper, we consider an ANOVA formulation of the gene expression levels corresponding to multiple tissue types. We provide resampling-based step-down adjustments to correct the observed significance levels for the individual ANOVA t-tests for each gene and for each pair of tissue type comparisons. More importantly, we introduce a novel empirical Bayes adjustment to the t-test statistics that can be incorporated into the step-down procedure. Using simulated data, we show that the empirical Bayes adjustment improved the sensitivity of detecting differentially expressed genes up to 16%, while maintaining a high level of specificity. This adjustment also reduces the false non-discovery rate to some degree at the cost of a modest increase in the false discovery rate. We illustrate our approach using a human colon cancer dataset consisting of oligonucleotide arrays of normal, adenoma and carcinoma cells. The number of genes with differential expression level declared statistically significant was about 50 when comparing normal to adenoma cells and about five when comparing adenoma to carcinoma cells. This list includes genes previously known to be associated with colon cancer as well as some novel genes. AVAILABILITY: R code for the empirical Bayes adjustment and step-down P-value calculation via resampling are available from the supplementary web-site. SUPPLEMENTARY INFORMATION: http://www.mathstat.gsu.edu/~matsnd/EB/supp.htm

Algorithms↗

Dihydropyrimidine dehydrogenase (DPD) rapidly regenerates after inactivation by eniluracil (GW776C85) in primary and metastatic colorectal cancer.

PURPOSE: Catabolism of 5-fluorouracil (5-FU) is primarily regulated by DPD. Inactivation of DPD using eniluracil is advantageous in that it renders 5-FU orally bioavailable with more predictable pharmacokinetics and blocks one of the major potential mechanisms of 5-FU chemoresistance. The purpose of this study was to initially document inactivation of DPD by eniluracil in primary and metastatic colorectal cancer (CRC) and then to assess the time-course of the regeneration of DPD activity in peripheral blood (and where possible, additional tissues). METHODS: Of 28 patients entered, 23 were randomized to preoperative oral eniluracil (20 mg orally twice daily) or placebo prior to definitive resection of primary or metastatic CRC. Three patients were replaced, two because they had no residual tumor on pathologic evaluation and one for not taking the study drug. Patients received eniluracil 48, 36, 24 and approximately 12 h prior to surgical resection. In a second part of the study to document tissue regeneration of DPD, the additional five patients received eniluracil 144, 132, 120 and 108 h prior to surgical resection. DPD activity was measured in normal tissues, tumors and peripheral blood mononuclear cells (PBMC). Serum eniluracil and plasma uracil concentrations were determined before and through 28 days after eniluracil dosing. Data are presented as means+/-SEM, and significance defined as P<0.05. RESULTS: Eniluracil inactivated DPD below the level of detection in primary and metastatic CRC as well as in normal tissues (0.0 pmol/min per mg protein) compared to primary tumor, metastatic tumor, PBMC, normal mucosa, and normal liver of patients receiving placebo (57+/-12, 119+/-19, 157+/-22, 77+/-12, 243+/-24 pmol/min/mg protein, respectively; P<0.05). At the time of surgery, serum eniluracil and uracil concentrations were 207+/-36 ng/ml and 2700+/-170 ng/ml in drug-treated patients. Within 6 days following treatment with eniluracil, serum eniluracil and uracil concentrations were undetectable, while DPD activity in PBMC had returned to baseline. The second group of patients (n=5) were given eniluracil 8 and 7 days prior to surgery to evaluate DPD regeneration in normal tissues and primary CRC tissue. In samples of these tissues, collected 6 days after the last eniluracil dose, DPD activity approached baseline in normal mucosa, normal liver and primary tumor (28+/-12, 94+/-23 and 20+/-8 pmol/min per mg protein, respectively). CONCLUSIONS: These results demonstrate that oral administration of eniluracil inactivated DPD below the level of detection in normal tissues as well as in primary and metastatic CRC. After discontinuation of eniluracil, DPD rapidly returned toward baseline within 6 days in PBMC, normal intestinal mucosa and normal liver.

Aged↗

Effect of hospital volume and experience on in-hospital mortality for pancreaticoduodenectomy.

OBJECTIVE: To examine the relative impact of procedure volume versus years of hospital experience on inpatient death rates after pancreaticoduodenectomy. SUMMARY BACKGROUND DATA: Past studies have identified a significant volume-outcome relation for hospitals performing pancreaticoduodenectomy (the Whipple procedure). METHODS: Administrative discharge data were examined for 6,652 patients who underwent the procedure between 1988 and 1998 in California and Florida. Patients were divided into approximate quartiles according to each hospital's annual procedure volume: very low (1), low (2 or 3), medium (4-9), and high (10+). Logistic regression analysis was used to examine differences in inpatient mortality among hospitals with different procedure volume and years of experience, while adjusting for patient characteristics. RESULTS: Medium- and high-volume hospitals had lower rates of inpatient mortality after pancreaticoduodenectomy relative to very-low-volume facilities. Greater years of hospital experience also reduced the odds of inpatient death. Predictions based on the regression estimates indicate that within volume categories, increased hospital experience did not lead to significant reductions in inpatient mortality. However, high-volume hospitals had significantly lower inpatient mortality rates than very-low-volume facilities with the same amount of experience. CONCLUSIONS: Hospitals with more years of experience with pancreaticoduodenectomy had lower rates of inpatient mortality. However, higher procedure volume has played a larger role than increased experience in reducing inpatient death rates.

Aged↗

Recent insights into angiogenesis, apoptosis, invasion, and metastasis in colorectal carcinoma.

The numerous studies profiling mechanisms in colorectal carcinoma have implicated multiple pathways in the malignant progression of a colorectal epithelial cell. Such pathways as aberrations in the cell cycle, deviation from apoptosis, neovascularization of tumors, and invasion and metastasis of malignant epithelial cells have been shown to occur in the progression of a normal epithelial cell to an adenoma and carcinoma. Today, we continue to search for communications or connections between these pathways as we try to get a more global picture of the events responsible for the adenoma-carcinoma sequence. This review focuses on the latest developments of three well-characterized pathways implicated in colorectal carcinoma: angiogenesis, apoptosis, and invasion and metastasis. We will attempt to highlight clinical correlates, when available, with some of the more interesting molecules.

Apoptosis↗

Expression of p53 and proliferation index as prognostic factors in gastrointestinal sarcomas.

BACKGROUND: Sarcomas arising in the gastrointestinal (GI) tract are rare tumors. Molecular markers could be associated with prognosis in these types of tumors. METHODS: We performed a retrospective analysis of adult patients with sarcomas arising in the GI tract at the National Institute of Medical Sciences in Mexico City and the University of Alabama at Birmingham Hospital. All histological types were included. Patient, tumor, and treatment factors were analyzed, with overall survival as the main outcome variable. Expression of p53 and cellular proliferation antigen Ki-67 was also analyzed. Statistical analysis was performed by log-rank test and Cox regression. Significance was defined as P <.05. RESULTS: Forty-seven patients were analyzed. The median patient age was 53 years (range, 16-82 years). Twenty-five patients (53%) were women. The stomach was the most common site of presentation. The mean tumor size was 14 cm (2-45 cm). A complete resection was achieved in 40 patients. With a median follow-up of 30 months, the actuarial 3-year survival was 68%. Univariate analysis identified overexpression of p53 and Ki-67, high tumor grade, tumor size >10 cm, and incomplete resection as significant negative prognostic factors. Hispanic race and good performance status were significantly associated with prolonged survival. On multivariate analysis, overexpression of p53 was the only independent negative prognostic factor. CONCLUSIONS: Overexpression of p53 is the strongest predictor of poor prognosis in patients with sarcomas of the GI tract.

Adolescent↗

Laparoscopic adrenalectomy and splenectomy are safe and reduce hospital stay and charges.

The proposed benefits of laparoscopy for certain surgical procedures have been decreased post-operative pain and hospital stay balanced against the proposed deficits of increased costs. We have reviewed our data to evaluate factors associated with patient, procedure, and hospital charges for patients undergoing open versus laparoscopic adrenalectomy and splenectomy during the same time period. Eighty-seven patients underwent adrenalectomy (n = 47) or splenectomy (n = 40) from October 30, 1995 to June 6, 2001 and were retrospectively reviewed. Patient and operative factors were analyzed by intent to treat; the major endpoints were operating room (OR) time in minutes, blood loss in cm3, length of hospital stay in days, and charges broken down by anesthesia/operation [OR/recovery room (RR)] and total charges in dollars x 1000. Comparisons of means were analyzed by unpaired t test; data are presented as mean +/- SEM, and significance is defined as P < 0.05. Median age of the group was 47 years (range 20-77). Forty-five patients underwent a laparoscopic approach of which two were converted to open (4%) as compared with 42 undergoing an open operation; one patient from each group was excluded from outcome analyses because of prolonged hospitalization (>3 weeks). Operative mortality of the whole group was one per cent. There were no differences between the groups with respect to age, gender, or comorbidity. The laparoscopic group had significantly longer operative times and OR/RR charges. However, the length of hospital stay and the total charges for the patient undergoing a laparoscopic approach were significantly less (P < 0.05). We conclude that a laparoscopic approach for adrenalectomy or splenectomy can be accomplished in approximately 95 per cent of patients selected for this procedure. Despite prolonged OR time and increased OR/RR charges the laparoscopic procedures resulted in significantly decreased length of hospital stay and overall patient charges. Laparoscopy is a safe and cost-effective approach and should be strongly considered in patients requiring adrenalectomy or splenectomy.

Adrenalectomy↗

Results of long-term follow-up for transanal excision for rectal cancer.

Low anterior resection and abdominoperineal resection are the surgical techniques used most frequently in the treatment of rectal cancer. It is our hypothesis that selected patients with early T stage, well or moderate grade of differentiation, and small tumor size are good candidates for transanal excision in terms of minimal morbidity, low recurrence rate, and sphincter preservation. From January 1993 until August 2001 30 patients underwent transanal excision; three patients were excluded because they had histology other than adenocarcinoma. Factors analyzed included those related to the patient [age (years), gender, race, body mass index, and anal tone], tumor [size (cm), distance from the anal verge (cm), differentiation, and American Joint Committee on Cancer stage], and additional treatment. Median follow-up of the group was 40.7 months (range 0.6-99) and the primary end points were local and distant recurrence. Data are presented as mean (range). The median age of the group was 58.9 years (range 27-94); 52 per cent were female and 48 per cent were male. The mean body mass index was 25.9 (range 22.7-36.7). Preoperatively 81, 11, and 4 per cent of the patients had stage I, II, and III/IV cancer, respectively. Preoperative size of the tumor was 2.0 cm (1-3 cm), and distance from the anal verge was 5.0 cm (3-15 cm). Blood loss was 50 cm3 (5-200 cm3), and there were no operative complications. Tumor differentiation levels were well (37%) and moderate (63%). All patients had negative margins. Additional treatment consisted of radiation therapy in seven patients (six postoperative and one preoperative). Chemotherapy was given to seven patients (six postoperative and one preoperative). The local recurrence rate was 7.4 per cent (two patients), and 3.7 per cent recurred distantly (one patient). Transanal excision of low rectal cancer in selected patients is an acceptable alternative to formal resection. Important selection criteria include early T stage, well or moderate differentiation, relatively small tumor size, and negative microscopic margins. The roles of radiation and chemotherapy remain controversial.

Adenocarcinoma↗

Endoscopic ultrasound-guided fine-needle aspiration biopsy: a study of 103 cases.

BACKGROUND: Endoscopic ultrasound (EUS) provides detailed imaging of both intramural and extramural structures within the abdomen and mediastinum. However, EUS is limited in its ability to differentiate an inflammatory/reactive process from a malignancy. Fine-needle aspiration biopsy (FNAB), coupled with EUS, allows for the sampling of the target lesion under ultrasound guidance in real time. To better evaluate the clinical utility and efficiency of EUS-FNAB, a retrospective analysis of the first 103 EUS-FNABs performed at our institute was undertaken. METHODS: EUS-FNABs was performed in 80 patients with 103 lesions. Both air-dried and alcohol-fixed smears were prepared and stained with Diff-Quik (American Scientific Products, McGraw Park, IL) and Papanicolaou stains, respectively. In addition, ThinPrep slides (Cytyc, Boxborough, MA) and cell blocks, when additional material was available, were also prepared. Immunohistochemical stains were performed on cell blocks wherever required. Cytologic diagnoses were then correlated with the final diagnoses. The latter was based on histologic examination of biopsies/resected pathology materials (n = 54) and clinical follow up (n = 48). Follow-up information was not available for one lesion. RESULTS: Of 103 EUS-FNABs, 42 FNABs were from the pancreas, 38 from the lymph nodes (10 mediastinal and 28 intraabdominal), 10 from the gastrointestinal tract, 7 from the liver, 4 from the adrenal gland, 1 from the biliary tract, and 1 from a retroperitoneal mass. The mean number of passes to obtain diagnostic materials was 3.3. Of 103 EUS-FNABs, 45, 9, 6, and 37 were reported as malignant, suspicious, atypical, and benign, respectively. Six FNABs were nondiagnostic. The authors did not encounter any false-positive cases. There were three false-negative cases (two pancreatic carcinomas and one gastrointestinal stromal tumor of the stomach). No complications were encountered. The sensitivity, specificity, and accuracy were 71%, 100%, and 81%, respectively. If the FNABs that were classified as suspicious were considered as malignant, the sensitivity, specificity, and accuracy were 86%, 100%, and 91%, respectively. CONCLUSIONS: EUS-FNAB is a safe and accurate diagnostic procedure for the evaluation of intramural and extramural lesions of the gastrointestinal tract. In the majority of cases, it obviates the need for more invasive diagnostic procedures to obtain a tissue diagnosis.

Adult↗