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Richard F Heitmiller

Publications and source records attributed to Richard F Heitmiller.

17 recordsLinked to original sources
PubMed2006

Phase II, parallel-design study of preoperative combined modality therapy and the matrix metalloprotease (mmp) inhibitor prinomastat in patients with esophageal adenocarcinoma.

PURPOSE: This randomized phase II, parallel-design study evaluated preoperative combined modality therapy and the matrix metalloprotease (MMP) inhibitor prinomastat in patients with resectable adenocarcinoma of the esophagus that were stage II or greater. The objectives of the trial were to determine pathologic complete response rate (pCR), overall response rate, progression-free survival, pattern of disease relapse, and two-year and overall survival. PATIENTS AND METHODS: Preoperative staging included computed tomography, endoscopic ultrasound, and, when feasible, laparoscopy. Eligible patients were randomized to preoperative prinomastat or placebo, plus continuous infusion 5-FU, cisplatin, paclitaxel, and concurrent radiotherapy. Esophagectomy was performed on day 71. Adjuvant paclitaxel and prinomastat were available to all study patients. RESULTS: Between August 2000 and June 2001, 15 of a planned 78 patients were randomized into the trial. One patient after randomization withdrew consent. Fourteen patients, 7 in each arm, completed preoperative treatment and surgery. pCR was achieved in 5 patients; 1/ 7 prinomastat and 4/ 7 placebo. Disease improvement was achieved in 7 patients; 5 /7 prinomastat and 2 /7 placebo. At a median follow-up of 28 months, 7 patients (2 prinomastat, 5 placebo) are alive with no evidence of disease. The primary prinomastat related toxicity was moderate to severe musculoskeletal toxicity interfering with daily function. This toxicity was managed with treatment rest, dose reduction, or discontinuation. Five patients (3 prinomastat and 2 placebo) had life-threatening thrombo-embolic events, which led to early evaluation of safety and efficacy, and subsequent termination of the study. CONCLUSIONS: All patients, regardless of treatment arm, were able to successfully undergo neoadjuvant combined modality therapy and esophagectomy. However, early closure of the study due to unexpected thrombo-embolic events precluded any conclusions regarding clinical activity of prinomastat in locally advanced esophageal cancer patients.

Adenocarcinoma↗
PubMed2006

Esophageal conduit necrosis.

A cumulative review of the prevalence of esophageal conduit necrosis is summarized in Table 4. The spectrum of conduit ischemia is broad and includes cases in which there is anastomotic leak or stricture as well as cases in which there is frank graft necrosis. Many of the studies that the authors reviewed do not specify the exact nature of postoperative ischemic complications or how they are defined. Therefore, postoperative conduit ischemia is reported globally. Based on the authors' review, average rates of ischemic complications for stomach, colon, and jejunum are 3.2%, 5.1%, and 4.2%, respectively. Results for colon and jejunum include results for both long- and short-segment grafting. Most reports that compare outcomes using different esophageal conduits demonstrate findings similar to the authors'. Davis and colleagues compared results with colon versus gastric conduit esophageal reconstruction. They found that operative mortality, anastomotic leaks, and conduit ischemia rates were all lower for the stomach than for the colon. Specifically, ischemia of the stomach conduit was 0.5%, compared with 2.4% for the colon conduit. Moorehead and Wong, in a large series of 760 esophagectomy patients in whom the stomach, colon, or jejunum was used for reconstruction, demonstrated that the stomach had the lowest incidence of conduit ischemia (1%), followed by jejunum (11.3%), then colon (13.3%). Some of the factors they identified as correlating with the risk of ischemia include length of conduit, technique of stomach graft preparation, whether anastomosis is in the neck or chest, and route of passage of the conduit. Mansour and colleagues compared their results using bowel interposition (either colon or jejunum) to reconstruct the resected esophagus. The authors report an overall mortality of 5.9%, and 3% conduit ischemia. All ischemia was noted in the colon conduits harvested from the left side. No ischemic complications were noted from jejunal segments. Briel and colleagues compared stomach versus colon conduit use after esophagectomy. They note an overall incidence of ischemia of 9.2%. In their series, the incidence of ischemia for stomach and colon was 10.4% and 7.4%, respectively. Anastomotic leak and stricture rates, both thought to be sequelae of ischemia, also were lower for colon conduit use than for stomach conduit. Multivariate analysis identified patient comorbidities as the only independent risk factor for conduit ischemia. The authors use their findings to support the preferential use of colon conduits rather than stomach conduits. The incidence of colon conduit ischemia (7.4%) is directly in line with all other published results, including the cumulative review by the authors of this article, whereas the rate of stomach conduit ischemia (10.4%) is considerable higher than in most other studies. Esophageal conduit necrosis is an uncommon but disastrous complication of esophageal surgery. Careful selection of patients for surgery, preoperative evaluation of the proposed conduit, and meticulous operative technique are the best defenses against conduit ischemia. Postoperatively, surgeons should have a high index of suspicion for this complication. Unexplained tachycardia, respiratory failure, leukocytosis, or any evidence for graft or anastomotic leak should prompt a search for conduit ischemia. The diagnosis is made by contrast esophagography, endoscopy, or direct operative inspection. There is no documented salvage technique once ischemia is identified. Treatment for mild cases may be supportive, with or without management of anastomotic leak. More severe cases of necrosis require débridement and conduit take-down with proximal esophageal diversion and placement of enteral feeding tubes. Reconstruction can be planned for later if possible. The majority of the data demonstrates that risk of ischemia is related to conduit type, length of conduit, comorbidities, and operative technique. The stomach has the lowest reported incidence of conduit ischemia, followed by the jejunum, and colon. In the future, methods to predict conduit ischemia more accurately at the time of surgery may further reduce the incidence of this disastrous complication.

Anastomosis, Surgical↗
PubMed2006

Delayed diagnosis and elevated mortality in an urban population with HIV and lung cancer: implications for patient care.

OBJECTIVE: Lung cancer is more common in HIV-infected patients than in the general population. We examined how effectively lung cancer was being diagnosed in our HIV-infected patients. METHODS: Retrospective study assessing clinical diagnosis of lung cancer in HIV-infected patients at Johns Hopkins Hospital between 1986 and 2004. RESULTS: Ninety-two patients were identified. Compared to HIV-indeterminate patients (n=4973), HIV-infected individuals were younger with more advanced cancer. CD4 counts and HIV-1 RNA levels indicated preserved immune function. Mortality was higher in HIV-infected patients, with 92% dying of lung cancer (hazard ratio, 1.57; 95% confidence interval, 1.25-1.96), compared to HIV-uninfected patients. Advanced stage and black race were associated with worse survival. After adjustment for these factors, HIV infection was not associated with increased mortality (hazard ratio, 1.04; 95% confidence interval, 0.83-1.32). Of 32 patients followed in our HIV clinic, 60% of chest radiographs had no evidence of neoplasm within 1 year of diagnosis compared to only 1 (4%) of 28 chest computed tomography scans. Nonspecific infiltrates were observed in 9 patients in the same area that cancer was subsequently diagnosed. CONCLUSIONS: HIV-infected lung cancer patients have shortened survival mainly due to advanced stage. Low clinical suspicion and overreliance on chest radiographs hindered earlier detection. Aggressive follow-up of nonspecific pulmonary infiltrates in these patients is warranted.

Adult↗
PubMed2003

Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy.

PURPOSE: Despite the availability of cellular markers associated with cell cycle, apoptosis, and DNA repair, predictive factors for pathological complete response (CR) and overall survival (OS) are few in patients with locally advanced esophageal cancer. This study evaluates the role of clinical and cellular markers in predicting CR and OS in patients with esophageal cancer. EXPERIMENTAL DESIGN: Patients were treated with infusional cisplatin and 5-fluorouracil combined with daily radiotherapy followed by esophagectomy. Pretreatment tumors (n = 54) were analyzed for epidermal growth factor receptor (EGF-R), bax, and bcl-2 expression by immunohistochemistry and for p53 mutations by direct DNA sequencing of exons 5-8. Clinical covariates included patients' age at enrollment; gender; Barrett's metaplasia; and tumor location, histology, and differentiation. Logistic regression and survival analyses were used to evaluate the predictors. RESULTS: Age ranged from 32 to 75 years; most patients were male (45 male; 9 female); and tumors were distal (47 distal; 7 mid), adenocarcinoma (41 adenocarcinomas; 13 squamous cell carcinomas), and moderately differentiated (33 moderate; 6 well; 15 poor). Female gender predicted CR (odds ratio 7.5; 95% confidence interval, 1.4-41). The OS was 43% at 5 years. Presence of CR (P < 0.001 log rank) and p53 mutation (P = 0.051 log rank) correlated with increased OS, whereas increased EGF-R expression predicted poor OS (P = 0.009 log rank). EGF-R remained significant when adjusted for clinical covariates. There was a trend toward increased OS related to better tumor differentiation and decreased bcl-2. CONCLUSIONS: These data suggest that EGF-R and p53 mutation may be used as both outcome predictors and targets for molecular therapy for esophageal cancer.

Adenocarcinoma↗
PubMed2003

Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma.

PURPOSE: We investigated aberrant methylation patterns in esophageal adenocarcinoma and correlated the findings to patient survival and tumor recurrence. EXPERIMENTAL DESIGN: Gene promoter methylation was performed in 82 samples from 41 esophagectomy patients consisting of 41 adenocarcinoma samples, each with its adjacent nonmalignant tissue, which included one sample with Barretts metaplasia. The methylation status of seven genes was determined. Epigenetic silencing was confirmed using immunohistochemical staining. Kaplan-Meier plots were constructed using disease-specific survival as the primary end point and the interval from surgery to tumor recurrence as the secondary end point. The association of clinicopathological and biomolecular risk factors to survival and recurrence was performed using the Log-rank test and Cox proportional hazards model for multivariate analysis. RESULTS: Methylation frequencies of the genes analyzed were APC, 68%; E-cadherin, 66%; O(6)-methylguanine DNA methyltransferase, 56%; ER, 51%; p16, 39%; DAP-kinase, 19%; and TIMP3, 19%. DNA methylation of some genes individually showed only trends toward diminished survival, whereas patients whose tumors had >50% of their gene profile methylated had both significantly poorer survival (P = 0.04) and earlier tumor recurrence (P = 0.05) than those without positive methylation. By multivariate analysis, the hazard ratios (HRs) with positive methylation status were more powerful predictors of survival [HR 2.7 (1.14-6.45; 95% confidence interval)] and tumor recurrence [HR 2.5 (1.11-5.6)] than age (HR 2.03 and 1.96, respectively) or stage (HR 1.48 and 1.67, respectively). CONCLUSIONS: Our data suggest that positive methylation status for multiple genes in esophageal adenocarcinoma is a predictor of poor prognosis.

Adenocarcinoma↗
PubMed2003

Prophylactic esophagectomy in Barrett esophagus with high-grade dysplasia.

OBJECTIVES: We review the significance of Barrett mucosa with high-grade dysplasia, management options, rationale for prophylactic esophagectomy, and results of surgical treatment. PATIENTS AND METHODS: The surgical results of prophylactic esophagectomy are presented from two previous studies, involving 60 patients over 1982-2001 at a single institution. These results are compared with nonsurgical treatment options. RESULTS: The transhiatal esophagectomy technique was the most commonly used surgical approach (81.7% of patients). Operative mortality was 1.7%. The incidence of occult adenocarcinoma for 1982-1994 and 1994-2001 was 43% and 16.7%, respectively. The overall incidence of occult adenocarcinoma for the entire study period was 30%. CONCLUSIONS: Prophylactic esophagectomy for patients with Barrett esophagus and high-grade dysplasia, performed at a center of high volume and experience, can be accomplished with low mortality and excellent long-term survival. Incidence of occult adenocarcinoma is decreasing, but still 16.7-30%.

Adenocarcinoma↗
PubMed2003

Tracheal release maneuvers.

Careful preoperative trachea "mapping" with accurate measurements should make an unexpected shortfall in remaining tracheal length and mobility uncommon. Bronchoscopy is the most accurate means of "mapping" the pathologic tracheal anatomy. Rigid bronchoscopy using the ventilating bronchoscope is preferred over flexible bronchoscopy because it provides the most accurate means of measuring the length of stenotic trachea (especially when used in conjunction with rigid fiberoptic telescopes), it can be used to dilate a tracheal stenosis before operative repair, and it establishes a safe airway under direct vision. When the anatomy of the tracheal pathology is accurately defined, specific plans for tracheal resection can be established to accomplish a well-vascularized, low-tension tracheal anastomosis.

Humans↗
PubMed2003

Barrett's esophagus with high grade dysplasia: surgical results and long-term outcome--an update.

We updated our surgical results and long-term outcome for prophylactic esophagectomy in patients with Barrett's esophagus and high-grade dysplasia (HGD) and determined the incidence of occult adenocarcinoma. Sixty consecutive patients with HGD who underwent esophagectomy had pre- and postoperative pathology examined at our institution from 1982 to 2001. We reviewed medical records to determine patient characteristics, surgical approach, operative morbidity and mortality, pathology, and length of stay. Patients and/or referring physicians were contacted to determine long-term outcome. Fifty-three men (88%) and 7 women (12%) were followed up for a median of 4.6 years. Transhiatal esophagectomy was performed in the majority of patients (82%). There was one operative death (1.7%) and 15 complications (29%). Median length of stay was 9 days. In 18 patients (30%), invasive adenocarcinoma was detected in the resected specimen. When examined by time periods, 43% (13/30) of patients were diagnosed with occult cancer from 1982-1994, whereas 17% (5/30) harbored occult malignancy from 1994-2001. All patients with adenocarcinoma in the recent interval had stage I disease, as opposed to only 61.5% of patients from the earlier study. Operative mortality declined from 3.3% to 0% over the two intervals as did mean length of stay from 14 days to 10 days. Five-year survival was excellent at 88%. Age and amount of preoperative weight loss were preoperative predictors of survival, whereas major postoperative complications and stage were postoperative predictors of outcome. Barrett's esophagus with high-grade dysplasia continues to be an indication for prophylactic esophagectomy. Overall prevalence of occult adenocarcinoma remains high. We have demonstrated a declining incidence of occult cancer and treatment of earlier stage adenocarcinoma when found in this population of patients treated with esophagectomy.

Adenocarcinoma↗
PubMed2002

Postesophagectomy morbidity, mortality, and length of hospital stay after preoperative chemoradiation therapy.

BACKGROUND: Data suggest that preoperative chemoradiation improves survival in patients with stage II and III esophageal tumors. Whether preoperative therapy increases postesophagectomy morbidity and mortality has not been determined. This study evaluates our postoperative results after chemoradiation therapy. METHODS: From 1989 through 1998, 120 consecutive patients underwent chemoradiation therapy followed by esophagectomy at our institution. The medical records for these patients were reviewed to determine patient age, sex, race, cell type, operative technique, complications, deaths, and length of hospital stay (LOS). RESULTS: There were 106 (88%) men and 14 (12%) women with a mean age of 58 (32 to 77) years. White patients predominated (114 of 120, 95%); 98 (82%) had adenocarcinoma and 22 (18%) had squamous cell carcinoma. Operative technique was transhiatal in 91 (76%) patients, three-incision in 23 (19%), Ivor-Lewis in 4 (3%), and thoracoabdominal in 2 (2%). There was 1 death. Complications developed in 44 (37%) patients; 59% (13 of 22) of squamous cell carcinoma patients and 32% (31 of 98) of adenocarcinoma patients developed complications. Respiratory complications occurred in 32% (7 of 22) of squamous cell carcinoma patients and in 3% (3 of 98) of adenocarcinoma patients. Mean length of stay after surgery was 15 days (range 7 to 163). CONCLUSIONS: Postesophagectomy results after chemoradiation therapy are comparable to those reported after esophagectomy alone. Squamous cell carcinoma patients are nearly twice as likely to develop postoperative complications and are more likely to have respiratory complications than adenocarcinoma patients.

Adenocarcinoma↗
PubMed2002

Molecular assessment of lymph nodes in patients with resected stage I non-small cell lung cancer: preliminary results of a prospective study.

OBJECTIVES: Routine histologic examination of resected lymph nodes in patients with stage I non-small cell lung cancer may underestimate the incidence of advanced disease. The presence of occult lymph node metastases may predict a higher risk of recurrence after intended curative resection. The purpose of this study was to determine the prognostic significance of TP53 and K-ras mutations in histologically determined negative lymph nodes from patients with stage I non-small cell lung cancer who underwent intended curative surgical resection. METHODS: Between July 1995 and March 1998, clinical data and tissue samples of primary tumors and lymph nodes were collected in a prospective fashion from 102 patients undergoing resection for non-small cell lung cancer (stage I, n = 55; stage II, n = 32; stage IIIA, n = 15). TP53 and K-ras mutations were detected by direct sequencing. If molecular alterations were found in the primary tumor, the corresponding lymph nodes were examined for these same TP53 (by oligonucleotide hybridization) and K-ras (by allele-specific ligation) mutations. RESULTS: TP53 mutations were found in 47 of 94 primary tumors (50%), and K-ras mutations were present in 26 of 55 adenocarcinomas (47%). A total of 134 lymph nodes from 32 patients with stage I disease were analyzed. In 9 cases (28%) the same TP53 or K-ras mutations were found in tumor and lymph node specimens, suggesting occult metastasis. On the basis of nodal location, 7 patients had their disease upstaged by a single stage and 2 patients by two stages. All 28 patients with stage II or III disease had pathologically determined positive nodes that were confirmed as positive by molecular analysis. Standard histopathologic assessment of regional lymph nodes failed to detect metastases at levels below 0.9% tumor-specific mutant TP53 clones per node. No statistically significant difference in disease-specific or overall survival was observed between patients with stage I disease with and without molecular lymph node metastases. CONCLUSIONS: Occult lymph node metastases are present in a significant percentage of patients with stage I non-small cell lung cancer. These data suggest that molecular analysis allows a more accurate assessment of staging. However, larger studies are needed to determine the clinical role of molecular staging.

Adult↗
PubMed2002

Mediastinal abscess due to passage of a broncholith.

We report a case of a 32-year-old woman who, after passage of broncholiths, developed a mediastinal abscess that required surgical drainage for treatment. Previously reported infectious complications resulting from broncholiths include obstructive pneumonitis and recurrent aspiration pneumonitis secondary to bronchoesophageal fistulas. Because radiographic evidence of abnormal calcification in the chest is common, but rarely is associated with broncholithiasis, the patient's history of lithoptysis was crucial to determining the underlying etiology of her abscess.

Adult↗
PubMedDate not supplied

Polypoid esophageal adenocarcinoma--a clinicopathological variant of esophageal cancer?

PURPOSE: Neoplastic polyps are common in the colon, but not elsewhere in the gastrointestinal tract. They are rare at the gastroesophageal junction, especially associated with Barrett's dysplasia or adenocarcinoma. We identify a subset of early esophageal adenocarcinomas that present as symptomatic polyps with gastrointestinal bleeding, reflux, and even dysphagia. Because little is known about polypoid esophageal adenocarcinomas, we examine the clinical presentation, pathological features, and postoperative outcomes of these lesions. METHODS: We defined esophageal polyps as macroscopic, well-demarcated projections above the mucosa that project the greater percentage of their mass into the lumen without central ulceration. From a consecutive series of 400 patients who underwent esophagectomies for adenocarcinoma (1988 to 2000), 14 (4%) had polyps on presentation. Clinical records, pathology reports, photographs, and original slides of these resected specimens were reviewed. RESULTS: All patients with polyps had early staged esophageal adenocarcinomas. Lymph node involvement was found in only 4 patients, and no patients with distant metastases were found. All but 1 patient (13 of 14; 93%) were symptomatic at diagnosis. Most presented either with gastrointestinal bleeding or gastroesophageal reflux (11 of 14; 79%). Only 2 patients complained of mild dysphagia, and mean weight loss of the series was minimal at 1.3 +/- 4.0 kg (range, 0 to 15 kg). Barrett's was present in 10 patients (71%), and in 80% of these cases, high-grade dysplasia was found. The polyps were small 3.4 +/- 1.1 cm, and most contained poorly differentiated adenocarcinomas. No postoperative mortalities occurred, and follow-up was complete at 100%. Actuarial 2-year survival was 88%, with a mean survival of 61.3 months. Recurrent disease was identified in 4 patients. CONCLUSIONS: Polypoid adenocarcinomas of the distal esophagus are a subset of esophageal cancer that produce clear symptoms at an early tumor stage, which allows prompt detection and favorable prognosis. Their pathological features and demographics suggest an origin via the Barrett's esophagus-dysplasia-carcinoma sequence.

Journal Article↗