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Biomedical subjects

M J Heslin

Publications and source records attributed to M J Heslin.

At least 19 recordsLinked to original sources

Radio-frequency ablation in cirrhotic patients with hepatocellular carcinoma.

Current surgical treatments for hepatocellular carcinoma (HCC) include radio-frequency ablation (RFA), resection, and orthotropic liver transplant (OLT). RFA is particularly attractive in these high-risk patients because surgery is associated with high mortality and there is a relative scarcity of organs available for those in need of transplants. This study was performed to evaluate the management of cirrhotic patients with HCC undergoing RFA at a single Western institution. A retrospective study from March 1999 to June 2002 was performed to evaluate the clinicopathologic and treatment-related variables in cirrhotic patients with HCC. Forty-nine lesions in 26 patients with HCC and cirrhosis underwent RFA. Data was analyzed for safety and overall survival as the main endpoints. The mean age was 60.4 +/- 11 years, 19 patients were male, 5 had hepatitis B virus, and 19 had hepatitis C virus. The Child classification was 26 per cent, 39 per cent, and 35 per cent for A, B, and C; the number of lesions was 1 in 62 per cent, 2 in 23 per cent, and more than 2 in 15 per cent. The approach was laparoscopic in 58 per cent, percutaneous in 15 per cent, and open in 27 per cent. There were no mortalities and only 1 complication. Average hospital stay was 2.7 +/- 2 days. Subsequent to RFA, 9 patients underwent an OLT within a median of 4.1 months. The median follow-up of the whole group was 13 months and the disease-free survival 9.3 months. Tumor recurrence was identified in 3 previously ablated lesions, nonablated liver in 11, and as pulmonary metastases in 3. Overall survival (P = 0.03) was prolonged for those treated with RFA + OLT over RFA alone. We conclude that RFA is a safe ablative technique in high-risk cirrhotic patients with HCC. This technique may provide a bridge to OLT; however, it remains to be proven whether it prolongs survival in those who do not undergo OLT.

Adult↗

Reducing the cost of diagnosis of breast carcinoma: impact of ultrasound and imaging-guided biopsies on a clinical breast practice.

BACKGROUND: The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen-detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas. METHOD: Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies. RESULTS: The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm. CONCLUSIONS: Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.

Biopsy, Needle↗

Colorectal hepatic metastases: resection, local ablation, and hepatic artery infusion pump are associated with prolonged survival.

BACKGROUND: Treatment of metastatic colorectal cancer to the liver is not uniform. We describe the management of metastatic colorectal cancer of the liver at a single institution during a 10-year period. METHODS: From January 1, 1990, through December 31, 1999, 174 patients were identified from the tumor registry at the University of Alabama at Birmingham with a diagnosis of metastatic colorectal cancer to the liver. Patient, tumor, laboratory, operative, and adjuvant therapy factors were analyzed, with overall survival as the endpoint. Log-rank tests were used for univariate analysis, Cox-proportional hazards model for multivariate analysis, and Kaplan-Meier curves were used for graphical representation of survival. Significance was defined as P<.05. RESULTS: Median age was 60 years (age range, 18-92 years). Seventy-nine percent of patients had synchronous liver metastases at the time of diagnosis of the primary colorectal tumor. The primary tumor was in the colon and rectum 75% and 25% of the time, respectively. Of the 89 patients who underwent operation, 73 received definitive surgical treatment for their liver metastases. Fifty-two patients underwent lobectomy or wedge resection, 5 underwent cryotherapy, and 16 had a hepatic artery infusion pump (HAIP) inserted. Median follow-up duration of surgically treated patients was 26 months. Operative mortality was 1.3%. The 3-year actuarial survivals for patients who underwent resection, HAIP, or those with unresectable disease were 70 months, 32 months, and 3 months, respectively (P<.001). By multivariate analysis, surgical intervention, a carcinoembryonic antigen level less than 200 microg/L, or a low T stage of the primary tumor were associated with prolongation of survival. CONCLUSIONS: Surgical resection should be attempted for hepatic colorectal metastases, as this is associated with prolonged overall survival. Hepatic artery infusion pump insertion seems to prolong overall survival for those with unresectable hepatic metastases, but it is not equal to resection. Aggressive surgical management of patients with hepatic colorectal metastases is safe, may prolong overall survival, and therefore should be considered in all patients with metastases confined to the liver.

Adolescent↗

Multimodality treatment of Merkel cell carcinoma: case series and literature review of 1024 cases.

BACKGROUND: Merkel cell carcinoma (MCC) is an unusual and potentially aggressive cancer of the skin. There is no consensus regarding the optimal therapeutic approach, and the relative roles of surgery, radiotherapy, and chemotherapy still are controversial The aim of this study is to analyze the roles of these therapeutic options. METHODS: The medical records of 16 patients with a diagnosis of localized, primary MCC treated at the University of Alabama at Birmingham were reviewed. An extensive review of the English-language literature also was performed. The Kaplan-Meier method was used to develop the survival curves. Comparisons were made using Fisher's exact test. Significance was defined as P < .05. RESULTS: MCC presented primarily in Caucasians (98.3%) with a median age of 69 years. Immunosuppressive therapy appeared to play a role in the development of this cancer. In the UAB experience, 3-year actuarial survival was 31%. The only factor significantly associated with overall survival was the stage of disease at presentation: median survivals were 97 vs. 15 months for stages I and II, respectively (log-rank, P = .02). From the literature review, adjuvant radiotherapy was associated with a reduced risk of local recurrence (P < .00001). CONCLUSIONS: MCC is an aggressive cancer, with a high tendency for local recurrence and distant spread. Surgery and adjuvant radiotherapy appear to provide optimal local control. The role of chemotherapy remains to be defined.

Adult↗

Sentinel node biopsy for cutaneous melanoma in the head and neck.

BACKGROUND: Selective sentinel lymphadenectomy has gained widespread acceptance for staging of melanomas arising in the trunk and extremities, but the complex lymphatic drainage of the head and neck area has limited its application in this area. METHODS: We performed a retrospective analysis of patients who underwent selective sentinel lymphadenectomy for cutaneous melanoma of the head and neck at the University of Alabama at Birmingham from 1997 through 2000, by using a standard technique of preoperative lymphoscintigram and biopsy guided with blue dye injection and a handheld gamma probe. Complete lymph node dissection was recommended only for tumor-positive sentinel lymph nodes (SLNs). Survival curves were constructed with the Kaplan-Meier method. Fisher's exact test was used for comparisons. Significance was defined as P < .05. RESULTS: Thirty-eight patients underwent selective sentinel lymphadenectomy with the standard technique during the study period. A majority (82%) of patients were men with a median age of 55 years. The most common site of the primary tumor was the face (44%), followed by the scalp (24%). Mean tumor thickness was 2.5 mm. The sentinel node was identified during surgery in 35 patients (92%). Before the use of the handheld gamma probe, the identification rate of the SLN was only 56%. A single SLN was identified in 53% of cases. The incidence of metastases in SLN was 11.4%. With a mean follow-up of 17 months, the actuarial 3-year overall survival was 92%. The accuracy of the selective sentinel lymphadenectomy in this series was 80%. CONCLUSIONS: Selective sentinel lymphadenectomy in the head and neck region is a technically demanding procedure, but the combined use of blue dye and gamma-probe radiolocalization can be a reliable method of staging regional lymph nodes and determining the need for elective lymphadenectomy.

Adult↗

Role of matrix metalloproteinases in colorectal carcinogenesis.

OBJECTIVE: To measure coexpression of matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9 genes by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in benign and malignant phases of colorectal carcinogenesis. SUMMARY BACKGROUND DATA: Matrix metalloproteinases degrade and remodel the extracellular matrix and have been implicated in facilitating carcinoma cells to invade and metastasize. MMP-2, MMP-7, and MMP-9 have been shown to be overexpressed in various carcinomas; however, simultaneous examination of these enzymes in human normal mucosa, adenoma, and carcinoma has not been performed to date. METHODS: Between January 1, 1998, and June 15, 2000, 40 patients underwent colectomy and harvest and snap-freezing of normal mucosa, adenoma, and carcinoma. Five patients had adenoma and carcinoma in the same specimen; 35 had either adenoma (n = 6) or carcinoma (n = 29). Taqman qRT-PCR methodology was used to measure MMP gene copy number and normalized to beta-actin RNA expression. RESULTS: The mean age was 62 +/- 4 years, with 22 men and 18 women. One fifth of the adenomas exhibited severe dysplasia. MMP-7 gene expression was significantly increased in adenomas (43 times normal mucosa) but did not increase further in carcinomas (50 times normal mucosa). MMP-2 and MMP-9 were not different in adenomas (1.8 and 1.4 times normal mucosa, respectively) but were elevated in carcinomas (2.2 and 1.8 times normal mucosa, respectively). There was no correlation between size or dysplasia in adenomas or AJCC stage in carcinomas and MMP gene expression. CONCLUSIONS: Overexpression of MMP-7 is an early event in the adenoma-to-carcinoma pathway, and expression does not appear to increase further in carcinomas. MMP-2 and MMP-9 appear to be primarily overexpressed in carcinomas. This may be one mechanism by which adenoma cells gain the ability to invade and carcinoma cells to metastasize.

Adenoma↗

Quantitation of dihydropyrimidine dehydrogenase expression by real-time reverse transcription polymerase chain reaction.

Several recent studies have reported a correlation between intratumor dihydropyrimidine dehydrogenase (DPD) messenger RNA (mRNA) levels and sensitivity to 5-fluorouracil (5-FU). However, significant tissue requirements and labor-intensive methodology have limited the large-scale studies necessary for statistical validation. In addition, the semiquantitative results obtained by these methods further limit their application. We have developed a real-time reverse transcription-PCR (RT-PCR) assay, based on TaqMan fluorescence methodology, capable of rapid and accurate quantitation of DPD mRNA levels in biopsy-sized tissue samples. Results obtained with this approach indicate a linear dynamic range of 10(8)-10(3) DPD mRNA copies, with an intra-assay variation of <5%. We evaluated the data using three different methods (absolute standard curve, relative standard curve, and comparative C(T)) and show them to be equivalent. This RT-PCR assay was validated by quantitative comparison to Northern blot analysis in five tissues. In addition, analysis of 18 colorectal tumor and liver tissue specimens demonstrated a significant correlation (r(2) = 0.90) between DPD enzyme activity and mRNA levels. This method provides the first high-throughput, reproducible, and sensitive technique capable of determining DPD mRNA expression levels in nanogram amounts of total RNA.

Dihydrouracil Dehydrogenase (NADP)↗

Advances in perioperative nutrition: cancer.

The role of perioperative nutritional support in the management of cancer patients remains controversial. The benefit of supplemental calories is not the only current issue: in fact, the route of delivery, composition of basic nutrients (carbohydrate, protein, fat), and the role of supplemental additives (arginine, glutamine, omega-3 fatty acids, nucleotides) in improving immune status and ultimate outcome have been the focus of much discussion. Emerging data suggest that the use of supplemental agents is associated with improvement in immune status in these patients, although there is little clear evidence that this improves outcome. Ongoing studies are aimed at defining the group of patients who would most benefit from nutritional interventions during the perioperative period.

Dietary Supplements↗

Clinicopathological characteristics of gastric carcinoma in young and elderly patients: a comparative study.

BACKGROUND: Gastric cancer is one of the most common gastrointestinal malignancies world-wide. Some studies have suggested that it has a worse prognosis in young than in elderly patients. METHODS: All young and elderly patients treated for gastric adenocarcinoma during the period 1988 to 1994 in a tertiary referral center in Mexico City were included. Demographic, clinical, and pathologic features of young patients (less than 40 years of age) with gastric cancer were compared with those of elderly patients (70 years of age or older) with the same diagnosis. Overall survival was the main outcome measure. RESULTS: There were 38 patients in each group. The mean age of the young and elderly groups was 33 and 77 years, respectively. Family history of gastric cancer was reported by 6 patients of the younger group and by 1 patient in the older group (P < .05). Most patients in both groups were symptomatic and had an advanced stage of the disease. With a mean follow-up of 17 months, the overall median survival for all patients was 12 months. By group, the median survival was 13 and 12 months for the young and elderly patients, respectively (P = .38). Variables with significant impact on survival were the stage of the disease, possibility of surgical resection, location of the tumor, and a family history of gastric cancer. CONCLUSIONS: Young patients represent a significant proportion of patients with gastric cancer in Hispanic populations. There were no significant differences in clinicopathological characteristics and outcome of gastric adenocarcinoma between young and elderly patients. Survival was determined by the stage of the tumor and the possibility of complete surgical resection.

Adenocarcinoma↗

Primary gastrointestinal sarcomas.

Gastrointestinal (GI) sarcomas are uncommon tumors with the majority of previous studies performed over long time intervals. The purpose of this review is to analyze our single-institution experience with primary GI sarcomas. Between January 1990 and June 1998, 27 adult patients with primary GI sarcomas were identified in the tumor registry at the University Hospital, School of Medicine of University of Alabama at Birmingham and retrospectively reviewed. Patient, tumor, and treatment factors as well as expression of p53 and Ki-67 were analyzed with overall survival as the main outcome variable. Statistical analysis was performed by log rank test and Cox regression. Significance was defined as P < 0.05. Median age was 55 years (range 36-80 years). The stomach was the most common site of presentation (59%) followed by small bowel (29%). The average tumor size was 15 cm (range 2-46 cm). A complete resection was performed in 22 patients (81.5%). Fifteen tumors were classified as low grade (55.5%). Actuarial 3-year survival was 43 per cent with a median follow-up of 16 months. Overexpression of p53 and Ki-67 correlated with a trend to decreased survival but it did not reach statistical significance. Multivariate analysis found incomplete resection (P = 0.00001) and high grade (P = 0.003) to be significant negative prognostic factors. We conclude that GI sarcomas tend to be large tumors with most arising in the stomach and proximal GI tract. Complete surgical resection is associated with prolonged survival and despite the large size of these tumors should be attempted whenever possible.

Actuarial Analysis↗

Surgical oncology fellowship: viable pathway to academic surgery?

BACKGROUND: Data that document academic status after surgical oncology fellowship are sparse. This study was done to report the academic status and clinical practice of graduates of a major surgical oncology program. METHODS: During the 10 years that ended in 1994, 68 fellows graduated. Each was surveyed about current academic status, number of jobs, job satisfaction, hours worked per week, and clinical practice. During 1995 and 1996, 11 fellows graduated. From this group, data were available on clinical practice while in fellowship (n = 6) and from the most recent year (ending July 1997) in a new position (n = 8). RESULTS: Sixty-seven of the 68 (99%) who were fellows from 1985 to 1994 returned surveys. Most (69%) are in "academic full-time" positions. Of those who listed an academic rank, 51% and 27% are assistant or associate professors, respectively. Job satisfaction was reported at a mean of 4.2, median of 5, on a scale from 1 to 5, with 5 being the best. Seventy-one percent remain at their first job, whereas 26% have had one previous position. The median number of hours worked per week was 70 (range, 45-100). Time allocation was patient care--60%; research--20%; education--10%; and administration--10%. CONCLUSIONS: Surgical oncology fellowship results in the majority placed in academic surgery, satisfied with their positions. Graduates are prepared for current practice patterns, and surgical oncology fellowship training should be suggested to residents interested in academic medicine.

Academic Medical Centers↗

The role of pancreaticoduodenectomy in the treatment of severe chronic pancreatitis.

Chronic pancreatitis remains a debilitating disease with few definitive options for treatment. The purpose of this study was to evaluate the benefit of pancreaticoduodenectomy in the treatment of chronic pancreatitis. The results were evaluated by standard descriptive statistics. In a retrospective study, we reviewed the patients at a single institution undergoing pancreaticoduodenectomy between 1994 and 1997 for complications of chronic pancreatitis. Patients were evaluated for preoperative indication for surgery and perioperative morbidity and mortality, as well as long-term results. Thirty-two patients underwent pancreaticoduodenectomy for chronic pancreatitis; 56 per cent (18) underwent pylorus-preserving and 44 per cent (14) underwent classic pancreaticoduodenectomy. The mean age of these patients was 56+/-14.7 years (range, 23-79). All patients underwent preoperative CT scan and endoscopic retrograde cholangiopancreatography. The preoperative indication for surgery in 81 per cent (26) of these patients was intractable pain in the setting of a nondilated pancreatic duct. The other 19 per cent were treated for biliary/pancreatic duct stricture and pancreatic head fibrosis (mass suspicious of malignancy). Fifty-three per cent of the patients had a history of previous abdominal surgery. There were no perioperative deaths. The mean postoperative stay was 12.2+/-7.4 days. The postoperative morbidity rate was 31 per cent (10), consisting of 25 per cent with delayed gastric emptying, 3 per cent with pneumonia, and 3 per cent with wound infections. There was no occurrence of pancreatic fistulas. With a mean follow-up of 40 months (range, 10-52 months), 85 per cent reported a significant improvement in pain with 71 per cent being pain free and not requiring narcotics. Twenty per cent developed new-onset diabetes. The overall event survival rate at 5 years was 97 per cent. Thus, in a selected group of patients with severe chronic pancreatitis, resection of the head of the pancreas achieved relief of symptoms and was a safe and effective treatment for chronic pancreatitis.

Adult↗

Imaging of soft tissue sarcomas.

Imaging of soft tissue sarcomas is critically important in the management of these patients. Whether CT scanning or MR imaging is the best test remains controversial; studies to support either modality exist and are reviewed. An integrated approach using clinical algorithms and radiologic studies to preoperatively stage and follow these patients seems to provide optimal care.

Abdominal Neoplasms↗

Ki-67 detected by MIB-1 predicts distant metastasis and tumor mortality in primary, high grade extremity soft tissue sarcoma.

BACKGROUND: Preoperative staging of localized extremely soft tissue sarcoma (STS) includes tumor grade, size, and depth. A positive microscopic margin (PMM) adds prognostic information postoperatively, which is not helpful for preoperative stratification into low and high risk groups. This study was undertaken to identify molecular markers associated with poor outcome that could be used to refine the preoperative staging of high grade extremity STS. METHODS: Between January 1, 1983, and December 31, 1989, 1416 patients were entered into the STS prospective data base at the Memorial Sloan-Kettering Cancer Center. Of 232 patients identified with primary, high grade extremity lesions, 121 had tissue available for immunohistochemical (IHC) analysis. The clinicopathologic variables and molecular markers for the original 232 patients were correlated with those for the 121 patients analyzed in the current study. Overexpression of Ki-67, p53, and mdm2 and deletion of Rb were determined via standard IHC techniques on serial paraffin sections. Categoric overexpression was defined as > or = 20% nuclear staining. Continuous determination of the percentage of nuclear staining was also used for correlation with distant metastasis (DM) and tumor mortality (TM). Univariate and multivariate analyses were conducted with log rank and Wilcoxon tests and Cox regression analyses, respectively. RESULTS: The median follow-up was 64 months. Fifty-four of the 121 patients (45%) developed DM. Fifty-one of the 121 patients (42%) died of their disease. Factors found to be significant in univariate and multivariate analyses for both DM and TM were Ki-67 score, size, and PMM (all P values <0.05). Five year freedom from DM with a Ki-67 score of <20 was 70% versus 50% for a score. Overexpression of p53 of mdm2 or deletion of Rb did not correlate with increased risk of DM or TM alone or in combination with a Ki-67 score of > or = 20. CONCLUSIONS: In addition to standard preoperative criteria, Ki-67 score is an independent prognostic molecular marker that predicts DM and TM in high grade extremity STS. Selecting patients with high grade tumors for preoperative investigational treatment may be further refined according to whether the patients have Ki-67 score of > or = 20 and large tumor size.

Adult↗

A preoperative biliary stent is associated with increased complications after pancreatoduodenectomy.

BACKGROUND: A preoperative biliary stent is commonly used after the initial evaluation of the patient with a periampullary mass. OBJECTIVE: To evaluate the effect of a preoperative biliary stent on operative difficulty, postoperative complications, and length of hospital stay after a pancreatoduodenectomy. DESIGN: A retrospective review of a prospectively collected consecutive series. SETTING: The Memorial Sloan-Kettering Cancer Center's Surgical Service, New York, NY. PATIENTS AND METHODS: Seventy-four patients underwent pancreatoduodenectomy between March 1, 1994, and February 15, 1996. Thirty-five did not receive a biliary stent, and 39 received a biliary stent prior to medical evaluation. We analyzed patient, nutritional, laboratory, and operating room factors. Univariate analysis was by Student t test, chi2 test, and Fisher exact test; multivariate analysis was by logistic regression. Significance was defined at P<.05. MAIN OUTCOME MEASURES: Operative time, amount of blood loss, complications, and length of hospital stay. Wound complications were defined as cellulitis, superficial infections, and deep infections. Intra-abdominal complications were defined as intra-abdominal abscesses and pancreatic or biliary fistula. RESULTS: Groups were equivalent for tumor size, risk of comorbidity, time spent in the operating room, and amount of blood loss. There was 1 perioperative death. Patients with a stent had significantly lower bilirubin (P<.03) and aspartate aminotransferase (P<.04) levels and a significantly increased risk of nodal positivity (P<.05). The patients with a biliary stent had an increased risk of wound or abdominal complications on univariate (P<.003) and multivariate (P<.02) analysis and tended toward a prolonged hospital stay (P<.04, Wilcoxon signed rank test). CONCLUSIONS: A preoperative biliary stent was associated with an increased risk of wound or intra-abdominal complications; a stent may prolong the length of hospital stay. However, length of time under anesthesia, amount of blood loss, and transfusion requirements were not altered. A biliary stent should be used with a high degree of selectivity in the management of patients with resectable periampullary masses.

Aged↗

Preoperative identification and operative management of intraatrial extension of lung tumors.

Preoperative identification of intraatrial tumor is uncommon. A 23-year-old woman presented with local recurrence and pulmonary metastases after previous resection of a clavicular sarcoma. Evaluation by computed tomography revealed bilateral pulmonary masses. Due to the size and proximal location, magnetic resonance imaging and transesophageal echocardiography were performed, revealing a large intraatrial mass. She then underwent staged surgical excision without intraoperative complications. We summarize this case and review risk factors for intracardiac extension and prevention of tumor emboli.

Adult↗