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Douglas S Tyler

Publications and source records attributed to Douglas S Tyler.

At least 19 recordsLinked to original sources
PubMed2007

Improved survival with pulmonary metastasectomy: an analysis of 1720 patients with pulmonary metastatic melanoma.

OBJECTIVES: The outcomes of patients with metastatic melanoma are poor. Although prognostic models have been developed to predict the occurrence of pulmonary metastasis from cutaneous melanoma, few data exist to define the outcomes of these patients once metastasis has occurred. The objective of this study was to discriminate predictors of survival for patients with pulmonary metastatic melanoma. METHODS: We found 1720 patients with pulmonary metastasis listed in a prospective comprehensive cancer center database of 14,057 consecutive patients with melanoma (Jan 1, 1970-June 1, 2004). Demographic and histopathologic data, time and location of recurrences, number of pulmonary nodules, and subsequent therapies were collected. Univariate and multivariate Cox proportional hazards models were used to identify predictors of survival for patients with pulmonary metastatic melanoma. RESULTS: The median survival was 7.3 months after development of pulmonary metastasis. Significant predictors of survival from the multivariate model included nodular histologic type (P = .033), disease-free interval (P < .001), number of pulmonary metastases (P = .012), presence of extrathoracic metastasis (P < .001), and performance of pulmonary metastasectomy (P < .001). Interactions were identified between metastasectomy and disease-free interval and presence of extrathoracic metastasis. Surgery was associated with a survival advantage of 12 months for patients with a disease-free interval longer than 5 years (19 vs 7 months, P < .01) and of 10 months for patients without extrathoracic metastasis (18 vs 8 months, P < .01). CONCLUSIONS: When all other identified risk factors were controlled for mathematically, metastasectomy maintained a significant survival advantage for patients with pulmonary metastatic melanoma. These data support the role of surgery for a select subset of patients with pulmonary metastasis.

Disease-Free Survival↗
PubMed2006

Evaluation of preoperative therapy for pancreatic cancer using a prognostic nomogram.

BACKGROUND: Theoretical benefits of preoperative chemoradiation therapy (preop CRT) for pancreatic cancer include improved efficacy, resectability, and patient selection. The goal of this study was to evaluate the applicability of a nomogram, which was developed for patients undergoing resection without preop CRT and which incorporates several post-resection pathological factors, to a population of patients who received preop CRT prior to resection. METHODS: From 1994 to 2004, 82 patients with biopsy-proven, radiographically localized adenocarcinoma of the pancreatic head underwent preop CRT followed by pancreaticoduodenectomy (PD); 50 concurrent patients underwent PD without preop CRT. Mean nomogram-predicted disease-specific survival (DSS) rates were compared with observed DSS rates from the time of resection. RESULTS: Despite having more locally advanced tumors on initial staging (21 vs. 8%; P < .05), patients who received preop CRT had smaller resected tumors (mean 2.3 vs. 3.1 cm; P < .01), were less likely to have T3 tumors (54 vs. 80%, P < .01), were less likely to have positive lymph nodes (29 vs. 58%, P < .01), and had fewer positive lymph nodes (mean .4 vs. 1.9, P < .01), all factors that imply treatment effect and favorably impact on nomogram-predicted DSS. Observed DSS was similar to predicted DSS in both groups. CONCLUSIONS: The similarity in observed and predicted DSS following resection in patients who received preop CRT suggests that the effects of preop CRT-whether treatment, selection, or no effect-are reflected by the nomogram. The ability of the nomogram to evaluate the effects of preop CRT on survival is limited by the potential effects of preop CRT on factors within the nomogram.

Adenocarcinoma↗
PubMed2006

The Kraske procedure: a critical analysis of a surgical approach for mid-rectal lesions.

BACKGROUND AND OBJECTIVES: To analyze the Kraske procedure as an approach to mid-rectal disease. METHODS: Twenty-two patients underwent a Kraske procedure at either Duke University Medical Center, the Durham Veterans Administration Medical Center, or the Durham Regional Hospital between 1992 and 1997. The clinical and pathologic characteristics of these patients were retrospectively analyzed and compared with previous published series. RESULTS: Of the 22 patients, 13 underwent resection of an adenocarcinoma and 9 underwent resection of a villous adenoma. Post-operative complications included four fecal fistulas (two of which required a temporary diverting colostomy), two wound infections, two cases of urinary retention, and one case of transient fecal incontinence. CONCLUSIONS: The Kraske procedure minimizes exposure of mid-rectal lesions without the morbidity of a major laparotomy. However, it does carry a moderate complication rate and thus should be utilized selectively in managing patients with mid-rectal tumors not amenable to other treatment options.

Adenocarcinoma↗
PubMed2006

Randomized multicenter trial of hyperthermic isolated limb perfusion with melphalan alone compared with melphalan plus tumor necrosis factor: American College of Surgeons Oncology Group Trial Z0020.

PURPOSE: To determine in a randomized prospective multi-institutional trial whether the addition of tumor necrosis factor alpha (TNF-alpha) to a melphalan-based hyperthermic isolated limb perfusion (HILP) treatment would improve the complete response rate for locally advanced extremity melanoma. PATIENTS AND METHODS: Patients with locally advanced extremity melanoma were randomly assigned to receive melphalan or melphalan plus TNF-alpha during standard HILP. Patient randomization was stratified according to disease/treatment status and regional nodal disease status. RESULTS: The intervention was completed in 124 patients of the 133 enrolled. Grade 4 adverse events were observed in 14 (12%) of 129 patients, with three (4%) of 64 in the melphalan-alone arm and 11 (16%) of 65 in the melphalan-plus-TNF-alpha arm (P = .0436). There were two toxicity-related lower extremity amputations in the melphalan-plus-TNF-alpha arm, and one disease progression-related upper extremity amputation in the melphalan-alone arm. There was no treatment-related mortality in either arm of the study. One hundred sixteen patients were assessable at 3 months postoperatively. Sixty-four percent of patients (36 of 58) in the melphalan-alone arm and 69% of patients (40 of 58) in the melphalan-plus-TNF-alpha arm showed a response to treatment at 3 months, with a complete response rate of 25% (14 of 58 patients) in the melphalan-alone arm and 26% (15 of 58 patients) in the melphalan-plus-TNF-alpha arm (P = .435 and P = .890, respectively). CONCLUSION: In locally advanced extremity melanoma treated with HILP, the addition of TNF-alpha to melphalan did not demonstrate a significant enhancement of short-term response rates over melphalan alone by the 3-month follow-up, and TNF-alpha plus melphalan was associated with a higher complication rate.

Adult↗
PubMed2006

Melanoma patients with positive sentinel nodes who did not undergo completion lymphadenectomy: a multi-institutional study.

BACKGROUND: Completion lymph node dissection (CLND) is considered the standard of care in melanoma patients found to have sentinel lymph node (SLN) metastasis. However, the therapeutic utility of CLND is not known. The natural history of patients with positive SLNs who do not undergo CLND is undefined. This multi-institutional study was undertaken to characterize patterns of failure and survival rates in these patients and to compare results with those of positive-SLN patients who underwent CLND. METHODS: Surgeons from 16 centers contributed data on 134 positive-SLN patients who did not undergo CLND. SLN biopsy was performed by using each institution's established protocols. Patients were followed up for recurrence and survival. RESULTS: In this study population, the median age was 59 years, and 62% were male. The median tumor thickness was 2.6 mm, 77% of tumors had invasion to Clark level IV/V, and 33% of lesions were ulcerated. The primary melanoma was located on the extremities, trunk, and head/neck in 45%, 43%, and 12%, respectively. The median follow-up was 20 months. The median time to recurrence was 11 months. Nodal recurrence was a component of the first site of recurrence in 20 patients (15%). Nodal recurrence-free survival was statistically insignificantly worse than that seen in a contemporary cohort of patients who underwent CLND. Disease-specific survival for positive-SLN patients who did not undergo CLND was 80% at 36 months, which was not significantly different from that of patients who underwent CLND. CONCLUSIONS: This study underscores the importance of ongoing prospective randomized trials in determining the therapeutic value of CLND after positive SLN biopsy in melanoma patients.

Cohort Studies↗
PubMed2006

Histopathologic characteristics, recurrence patterns, and survival of 129 patients with desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) has been associated with higher local recurrence rates than other types of cutaneous melanoma. Current controversies regarding locoregional treatment strategies warrant further investigation. METHODS: Retrospective review of a prospectively maintained melanoma database identified 129 patients with DM out of >12,500 melanoma patients referred for treatment from 1980 to 2003. Clinical and histopathologic characteristics, recurrence, and survival were analyzed. RESULTS: The median follow-up was 4.0 years. Of the 129 patients identified, 82 (63.6%) were male, and the median age was 55.2 years. American Joint Committee on Cancer staging was I, II, and III in 25.6%, 68.0%, and 6.4% of patients, respectively, and the mean tumor thickness was 4.42 mm. Overall survival was 76% at 5 years and 64% at 10 years; median survival was 13.0 years. A total of 51 patients (39.5%) experienced disease recurrence, with a median time to recurrence of 1.3 years. The first recurrence was local in 18 patients (14.0%), nodal in 18 patients (14.0%), and distant in 15 patients (11.6%), with median survivals of 6.7, 7.8, and 1.8 years, respectively. Statistically significant predictors of recurrence were a final positive margin status and stage, and predictors of overall survival were patient age and stage. CONCLUSIONS: Compared with other types of melanoma, DMs do demonstrate a tendency toward local recurrence, thus suggesting that narrower excision margins may not be appropriate in this population. Scrutiny of final surgical margins is critical to the local management of DM. In addition, the potential for regional nodal involvement must be considered at the time of diagnosis and during surveillance for disease recurrence.

Adult↗
PubMed2006

Increased toxicity with gefitinib, capecitabine, and radiation therapy in pancreatic and rectal cancer: phase I trial results.

PURPOSE: Overexpression of epidermal growth factor receptor (EGFR) has been associated with aggressive tumor phenotypes, chemotherapy, and radiation resistance, as well as poor survival in preclinical and clinical models. The EGFR inhibitor gefitinib potentiates chemotherapy and radiation tumor cytotoxicity in preclinical models, including pancreatic and colorectal cancer. We initiated two phase I trials assessing the combination of gefitinib, capecitabine, and radiation in patients with localized pancreatic and rectal cancer. PATIENTS AND METHODS: Patients with pathologically confirmed adenocarcinoma of the pancreas and rectum were eligible. Pretreatment staging included computed tomography, endoscopic ultrasound, and surgical evaluation. Patients received 50.4 Gy of external-beam radiation therapy to the tumor in 28 fractions. Capecitabine and gefitinib were administered throughout the radiation course. Following completion, patients were restaged and considered for resection. Primary end points included determination of dose-limiting toxicity (DLT) and a phase II dose; secondary end points included determination of non-DLTs and preliminary radiographic and pathologic response rates. RESULTS: Ten patients were entered in the pancreatic study and six in the rectal study. DLT was seen in six of 10 patients in the pancreatic study and two of six patients in the rectal study. The primary DLT in both studies was diarrhea. Two patients developed arterial thrombi. CONCLUSION: The combination of gefitinib, capecitabine, and radiation in pancreatic and rectal cancer patients resulted in significant toxicity. A recommended phase II dose was not determined in either of our studies. Further investigation with this combination should be approached with caution.

Adenocarcinoma↗
PubMed2006

Pathologic nodal status predicts disease-free survival after neoadjuvant chemoradiation for gastroesophageal junction carcinoma.

BACKGROUND: The incidence of carcinoma of the gastroesophageal junction (GEJ) is rapidly increasing, and the prognosis remains poor. We examined outcomes in patients who received neoadjuvant chemoradiation for GEJ tumors to identify factors that predict disease-free (DFS) and overall (OS) survival. METHODS: A retrospective analysis was performed of 101 consecutive patients who received chemoradiation and surgery for GEJ carcinoma between 1992 and 2001. RESULTS: The median DFS and OS of all patients were 16 and 25 months, respectively. Twenty-eight patients with a complete histological response (T0N0) experienced greater DFS compared with all others (P = .02). Node-negative patients, regardless of T stage, experienced improved median DFS (24 months) compared with N1 patients (9 months; P = .01). Preoperative stage, age, tumor location, or Barrett's esophagus did not independently predict OS by univariate analysis. Multivariate analysis demonstrated that only posttreatment nodal status (P = .03)-not the degree of primary tumor response-predicted DFS. CONCLUSIONS: The nodal status of patients with GEJ tumors after neoadjuvant therapy is predictive of DFS after resection. The poor outcome in node-positive patients supports postneoadjuvant therapy nodal staging, because surgical aggressiveness should be tempered by the realization that cure is unlikely and median survival is short.

Adult↗
PubMed2006

Optimizing a novel regional chemotherapeutic agent against melanoma: hyperthermia-induced enhancement of temozolomide cytotoxicity.

PURPOSE: Previous preclinical studies have shown that regional temozolomide therapy via isolated limb infusion is more effective than melphalan, the current drug of choice for regional chemotherapy for advanced extremity melanoma. The aim of this study was to determine whether hyperthermia could further augment the efficacy of temozolomide, an alkylating agent, against melanoma and improve its therapeutic index in a rat model of isolated limb infusion. EXPERIMENTAL DESIGN: Athymic rats bearing s.c. human melanoma xenografts (DM6) in their hind limbs were randomized to a 15-minute isolated limb infusion procedure with or without temozolomide at room temperature, normothermic (37.5 degrees C), or hyperthermic (43 degrees C) conditions. RESULTS: The concomitant administration of hyperthermia during an infusion with temozolomide led to the greatest increase in tumor growth delay, decreased proliferative index, and increased cell death. Isolated limb infusion treatment with a low dose (350 mg/kg) of temozolomide was ineffective at producing tumor growth delay (P = 0.07). Similarly, temozolomide infusion under normothermia yielded minimal tumor growth delay (P = 0.08). In contrast, the combination of hyperthermia plus temozolomide treatment produced marked tumor growth delay of 10.4 days (P = 0.02) with minimal toxicity. The addition of heat to temozolomide treatment yielded the smallest proliferative index (P = 0.001), while markedly increasing the level of apoptosis 48 hours after isolated limb infusion. CONCLUSION: This study, the first to examine the interaction between hyperthermia and temozolomide, shows a strong, synergistic antitumor effect when hyperthermia is combined with temozolomide for regional treatment of melanoma confined to an extremity. The mechanism of this synergy seems to be through an augmentation, by hyperthermia, of the antiproliferative and proapoptotic effects of temozolomide.

Animals↗
PubMed2006

Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy.

BACKGROUND: Neoadjuvant chemoradiotherapy (neo-CRT) is being used with increasing frequency for periampullary tumors, but how it alters the complication rate of pancreaticoduodenectomy (PD) is unclear. METHODS: A retrospective analysis was conducted of 79 patients with periampullary malignancies who received 5-fluorouracil-based neo-CRT followed by PD. RESULTS: There was no difference in mortality between PD after neo-CRT (3.8%) and conventional PD for either malignant (4.5%) or benign (2.2%) disease. Focusing only on patients with malignancy, the neo-CRT group had a significantly lower pancreatic leak rate than the conventional group (10% vs. 43%; P < .001). Intra-abdominal abscesses were less common in the neo-CRT group (8.8% vs. 21%; P = .019), and there was one (1.2%) amylase-rich abscess in neo-CRT group, compared with eight (12%) in the conventional group. In addition, two patients in the conventional group died of leak-associated sepsis, compared with none in the neo-CRT group. Multivariate analysis revealed that neoadjuvant chemoradiation (odds ratio, .15) was the most significant factor associated with a reduced risk of pancreatic leak. CONCLUSIONS: Neo-CRT does not increase the mortality or morbidity of PD. In contrast, neo-CRT was associated with a marked reduction in the incidence of pancreatic leak, as well as leak-associated morbidity and mortality.

Adult↗
PubMed2006

A phase I study of eniluracil/5-FU in combination with radiation therapy for potentially resectable and/or unresectable cancer of the pancreas and distal biliary tract.

PURPOSE: Eniluracil is an effective inactivator of dihydropyrimidine dehydrogenase (DPD). It allows for oral dosing of 5-fluorouracil (5-FU), which may potentially improve the antitumor activity of 5-FU when delivered concurrently with radiotherapy while avoiding the inconvenience and morbidity of continuous infusion (CI) 5-FU. We addressed the safety of oral eniluracil/5-FU combined with radiation therapy and determined the profile of dose-limiting toxicities and recommended Phase II dose (RPTD) in patients with pancreatic and hepatobiliary cancers. METHODS AND MATERIALS: Patients with resectable or locally advanced pancreatic and biliary cancer received eniluracil (starting at 6.0 mg/m(2) q12h)/5-FU (starting at 0.6 mg/m(2) q12h). Eniluracil/5-FU were given concurrently with preoperative radiation to 4500 cGy followed by 540 cGy by reduced fields. Surgery was considered 4 weeks after completion of therapy. RESULTS: Thirteen patients were enrolled. Chemoradiotherapy was completed in all patients. The MTD was not reached and, thus, the RPTD of eniluracil/5-FU was determined to be 10 mg/m(2) q12h/1 mg/m(2) q12h. Two patients with locally advanced disease had a 30-45 percent cross-sectional tumor reduction, one of which underwent margin-negative resection. Two of 5 patients with pancreatic cancer, and 1 of 3 patients with cholangiocarcinoma, with underwent exploratory surgery had margin-negative resections. One patient had a pathologic complete response (pCR). Patient 5-FU plasma exposure increased slightly from Day 8 to Day 31. CONCLUSION: Preoperative chemoradiation with oral eniluracil/5-FU is feasible, well tolerated, and potentially effective in the neoadjuvant setting. Further investigation of oral fluoropyrimidines as radiosensitizers for pancreaticobiliary malignancies is warranted.

Aged↗
PubMed2006

Effect of the Veterans Affairs Medical System on plastic surgery residency training.

BACKGROUND: Teaching hospitals within the Veterans Affairs Health System perform the majority of complex and high-risk surgical procedures in the veteran patient population. Residency positions in the Veterans Affairs Medical System are usually part of a rotational educational system within a university-based residency, and plastic surgeons in training are a major work force and health care provider. The purpose of this study was to evaluate the current effect of the Veterans Affairs Medical System on plastic surgery residency training. METHODS: A 6-year (January of 1998 to December of 2003) review was performed of procedures completed at the Durham Veterans Affairs Medical Center, Section of Plastic Surgery. Procedures were divided into the following categories: extremities and trunk; breast and cosmetic; head and neck, including excision of skin lesions; hand surgery; craniomaxillofacial surgery; and other. Only procedures performed in the main operating room were reviewed and analyzed. In addition, a detailed review was performed of major head and neck reconstructions with free tissue transfer. RESULTS: A total of 1655 operative procedures were performed in 1290 patients. The ratio of men to women was 6:1 (1112 men and 178 women). Patients ranged in age from 26 to 97 years (average age, 62.7 years). Procedures in the extremities and trunk (n = 193, 11.7 percent), breast and cosmetic (n = 228, 13.8 percent), hand surgery (n = 155, 9.4 percent), and other (n = 275, 16.6 percent) categories were comparably distributed. Although the head and neck category accounted for the highest number of procedures (n = 766, 46.3 percent), the majority of these procedures were simple excisions of skin tumors (n = 612). There were significantly fewer major craniomaxillofacial cases (n = 38, 2.3 percent). CONCLUSIONS: Data from the retrospective analysis reveal that a broad spectrum of plastic surgical procedures is performed within the Veterans Affairs Health System, serving as a tremendous resource for resident training. The fact that approximately 260 procedures per year are performed demonstrates an active service. Craniomaxillofacial surgery is currently underrepresented compared with other categories at the authors' particular institution. By their definition, nonspecific plastic surgical procedures ("other") account for 275 (16.6 percent) of all 1655 procedures performed. This demonstrates that plastic surgery "overlaps" with other specialties, such as dermatology. The Veterans Affairs Health System will continue to play a significant role in the future training of plastic surgeons. Now, more than ever, a strong Veterans Affairs surgical service, including plastic surgery and its modern techniques, will be needed.

Adult↗
PubMed2006

Modulation of chemotherapy resistance in regional therapy: a novel therapeutic approach to advanced extremity melanoma using intra-arterial temozolomide in combination with systemic O6-benzylguanine.

This study investigated whether the therapeutic index of regional melanoma therapy using parenteral temozolomide could be improved by chemomodulation with O6-benzylguanine (O6BG), an inhibitor of the DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AGT). Using a nude rat s.c. human melanoma xenograft model of the extremity, tumors were analyzed for AGT level 2 to 3 hours after the i.p. injection of 3.5 to 70.0 mg/kg O6BG to inhibit AGT activity. Survival studies were conducted using animals that were treated with a 15-minute isolated limb infusion with 10% DMSO in PBS (control), temozolomide alone, or temozolomide in conjunction with single or multiple doses of i.p. O6BG. Tumor volume and toxicity level were monitored every other day. Administration of 3.5 mg/kg O6BG depleted tumor AGT activity by 93.5% (P < 0.01). Groups treated with regional temozolomide alone (350 mg/kg), systemic temozolomide with O6BG, or vehicle combined with O6BG showed no significant tumor responses compared with controls. Whereas use of regional temozolomide alone at a higher dose (750 mg/kg) showed some degree of tumor response, regional temozolomide given in conjunction with multiple dosages of O6BG showed a marked (P < 0.01) reduction in tumor growth with minimal toxicity. Our findings suggest that AGT modulation by the administration of O6BG in combination with temozolomide regional chemotherapy leads to a significant improvement in melanoma antitumor responses. Clinical trials using chemotherapy modulation may improve response rates in future regional infusion and perfusion drug trials.

Animals↗
PubMed2006

Utilizing quantitative polymerase chain reaction to evaluate prostate stem cell antigen as a tumor marker in pancreatic cancer.

BACKGROUND: Real-time quantitative polymerase chain reaction (qPCR) may prove to be a sensitive technique by which to evaluate potential tumor markers in pancreatic cancer. METHODS: The prostate stem cell antigen (PSCA) gene was identified as a marker highly expressed in pancreatic adenocarcinoma and not normal pancreas. RNA from pancreatic and nonpancreatic cancer cell lines as well as tissue and blood from pancreatic cancer and control patients was reverse-transcribed and PSCA quantified by qPCR. RESULTS: Individual operator experience affects the results of qPCR, with significantly different copy numbers at experiment numbers 5, 15, and 40. Five of six pancreatic cell lines had PSCA/actin ratios 10-fold greater than nonpancreatic cancer lines. Mean PSCA expression in pancreatic tumor tissue was significantly higher (P < 0.05, Student's t-test) than in the tissue of benign pancreatic processes. The close correlation of PSCA/actin copy number with number of tumor cells in the blood was demonstrated by regression analysis (r = 0.768, P = 0.0001). PSCA copy number was significantly higher in the blood of patients with metastatic pancreatic cancer than in that of normal patients (P < 0.05, Student's t-test). CONCLUSIONS: Such trends suggest that PSCA may prove to be a valuable pancreatic cancer tumor marker. More generally, the technique of qPCR is shown to provide a sensitive method of evaluating markers in cancer patients.

Adenocarcinoma↗
PubMed2005

Adjuvant external-beam radiotherapy with concurrent chemotherapy after resection of primary gallbladder carcinoma: a 23-year experience.

PURPOSE: Primary adenocarcinoma of the gallbladder is a rare malignancy. To better define the role of adjuvant radiation therapy and chemotherapy, a retrospective analysis of the outcome of patients undergoing surgery and adjuvant therapy was undertaken. METHODS AND MATERIALS: Twenty-two patients with primary and nonmetastatic gallbladder cancer were treated with radiation therapy after surgical resection. Median radiation dose was 45 Gy. Eighteen patients received concurrent 5-fluorouracil (5-FU) chemotherapy. Median follow-up was 1.7 years in all patients and 3.9 years in survivors. RESULTS: The 5-year actuarial overall survival, disease-free survival, metastases-free survival, and local-regional control of all 22 patients were 37%, 33%, 36%, and 59%, respectively. Median survival for all patients was 1.9 years. CONCLUSION: Our series suggests that an approach of radical resection followed by external-beam radiation therapy with radiosensitizing 5-FU in patients with locally advanced, nonmetastatic carcinoma of the gallbladder may improve survival. This regimen should be considered in patients with resectable gallbladder carcinoma.

Adult↗
PubMed2005

Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer.

BACKGROUND: Neoadjuvant (preoperative) chemoradiotherapy (CRT) for pancreatic cancer offers theoretical advantages over the standard approach of surgery followed by adjuvant CRT. We hypothesized that histological responses to CRT would be significant prognostic factors in patients undergoing neoadjuvant CRT followed by resection. METHODS: Since 1994, 193 patients with biopsy-proven pancreatic adenocarcinoma have completed neoadjuvant CRT, and 70 patients have undergone resection. Specimens were retrospectively examined by an individual pathologist for histological responses (tumor necrosis, tumor fibrosis, and residual tumor load) and immunohistochemical staining for p53 and epidermal growth factor receptor. Factors influencing overall survival were analyzed with the Kaplan-Meier (univariate) and Cox proportional hazards (multivariate) methods. RESULTS: The estimated overall survival (median +/- SE) in the entire group of patients undergoing resection was 23 +/- 4.2 months, with an estimated 3-year survival of 37% +/- 6.6% and a median follow-up of 28 months. Complete histological responses occurred in 6% of patients. Overexpression of p53 was more common in patients with large residual tumor loads. Tumor necrosis was an independent negative prognostic factor, as were positive lymph nodes, a large residual tumor load, and poor tumor differentiation. CONCLUSIONS: Histological response to neoadjuvant CRT--as measured by residual tumor load--may be useful as a surrogate marker for treatment efficacy. Characterization of the tumor cells that survive neoadjuvant CRT may help us to identify new or more appropriate targets for systemic therapy.

Adenocarcinoma↗
PubMed2005

Predictors of outcome after hyperthermic isolated limb perfusion: role of tumor response.

HYPOTHESIS: Analysis of multiple clinical and pathological factors in patients undergoing therapeutic hyperthermic isolated limb perfusion for extremity melanoma can identify variables with prognostic significance. DESIGN: Retrospective review of a prospectively collected limb perfusion database with a median follow-up interval of 32.2 months. SETTING: Single-institution tertiary care surgical oncology unit. PATIENTS: We report a series of 59 consecutive therapeutic hyperthermic isolated limb perfusion treatments (14 upper extremity and 45 lower extremity) in 54 patients with melanoma from January 1, 1995, through December 31, 2002, using a standard melphalan dosing protocol. At the time of perfusion, 31 cases had fewer than 10 lesions, with none greater than 3 cm in diameter. The remaining 28 cases had 10 or more lesions or at least 1 lesion greater than 3 cm in diameter. MAIN OUTCOME MEASURES: Response, recurrence, and survival were assessed in relation to multiple demographic, clinical, and technical variables using chi2, log-rank, and Kaplan-Meier survival analyses. RESULTS: The 3-year survival for the entire cohort was 54%. Thirty-three (56%) of the 59 perfusion treatments resulted in a persistent complete response of at least 6 months' duration. Statistical analysis showed that patients with no evidence of regional nodal involvement had a significantly lower incidence of distant recurrence (P = .02). Those patients achieving a complete response to therapy had a survival advantage (P = .03). CONCLUSION: In patients undergoing therapeutic hyperthermic isolated limb perfusion for in-transit melanoma, the ability to achieve a complete response following treatment, independent of regional nodal status, was the strongest predictor of long-term survival.

Aged↗