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Biomedical subjects

David P Jaques

Publications and source records attributed to David P Jaques.

26 records · Page 2Linked to original sources

Adrenocortical carcinoma: clinical, morphologic, and molecular characterization.

PURPOSE: To define multimolecular phenotypes of adrenocortical carcinoma (ACC) and to correlate outcome with morphologic and molecular parameters. PATIENTS AND METHODS: Clinical data were analyzed for 124 patients, histopathologic slides for 67 primary tumors, and tissue specimens for 74 patients (38 primary and 36 metastatic tumors) with ACC and for 38 normal adrenal tissue samples. Molecular expression profiles were investigated by immunohistochemistry. The prognostic significance of 12 gross and histologic parameters in 67 primary ACCs was evaluated. Morphologic and protein expression patterns were correlated with disease-specific survival (DSS). Univariate influence of prognostic factors on DSS was analyzed by log-rank test and multivariate analysis by Cox regression. RESULTS: The median follow-up period was 4.7 years. Significant predictors of DSS included distant metastasis at time of initial presentation; venous, capsular, and adjacent organ invasion; tumor necrosis, mitotic rate, atypical mitosis, and mdm-2 overexpression. Five-year DSS by number (one to six) of adverse histologic parameters was as follows: one to two, 84%; three to four, 37%; more than four, 9% (P =.005). The phenotype Ki-67(-)p53(-)mdm-2(+)cyclinD1(-)Bcl-2(-)p21(-)p27(+) was observed in 83% of normal and 3% of malignant adrenal tissue (P =.01). Molecular phenotypic expression was more heterogeneous in malignant than in normal (10 v five phenotypes) adrenal tissue. CONCLUSION: Meticulous morphologic evaluation, mitotic count, and tumor stage are essential in determining prognosis for patients with ACC. Multimolecular phenotyping demonstrates that the molecular complexity and heterogeneity of these neoplasms are such that targeted therapy needs to be patient specific.

Adolescent↗

A prospective evaluation of patients undergoing surgery for the palliation of an advanced malignancy.

BACKGROUND: Decisions regarding the use of surgical procedures for the palliation of symptoms caused by advanced malignancies require the highest level of surgical judgment. Prospective analysis of palliative surgical care may facilitate a more effective and representative evaluation of these patients. METHODS: Patients requiring surgery planned solely for the palliation of an advanced malignancy were offered entry onto this study. Outcome measurements were made before surgery and monthly thereafter until the patient's death. Accepted techniques of pain assessment, quality of life, and functional status were used. RESULTS: Between May 1997 and December 1999, 26 patients were enrolled. Although 46% (12 of 26) of patients demonstrated improvement in pain control or quality of life after palliative surgery, these benefits lasted a median of only 3.4 months. Palliative surgery was associated with significant postoperative complications in 35% (9 of 26) patients. CONCLUSIONS: Although many patients had no apparent demonstrable benefit from surgery, surgeons were able to identify a group of patients who experienced significant benefits after a palliative procedure. The relationships between the patient and family members and the surgeon play an important role in decision-making throughout the palliative phase of cancer treatment.

District of Columbia↗

Randomized clinical trials in soft tissue sarcoma.

What has been learned thus far from the very best prospective randomized controlled clinical trials for soft tissue sarcoma that will guide physicians in the quest for evidence-based treatment decision making? Based on the evidence provided in the following articles, we have learned that limb-sparing surgery with adjuvant radiation is equivalent (and therefore preferable) to a radical amputation in controlling local disease. We also learned that adding radiation therapy (both external beam and brachytherapy) to a complete surgical resection of extremity soft tissue sarcoma significantly improves local control over surgery alone. This is true for high-grade lesions and may be true (external beam) for larger low-grade lesions also. Local control, however, does not govern overall survival as most patients who die from this disease do so from systemic (not local) manifestations. Finally, further studies are required to identify the role of adjuvant chemotherapy in the treatment of soft tissue sarcoma as no single study has demonstrated a consistent long-term survival benefit with the use of any chemotherapeutic regimen. Based on a recent large meta-analysis, however, if there is any benefit to adjuvant doxorubicin based chemotherapy, it must be a very small one.

Evidence-Based Medicine↗

Achieving RO resection for locally advanced gastric cancer: is it worth the risk of multiorgan resection?

BACKGROUND: In gastric adenocarcinoma, only complete resection (R0) translates into survival benefit. Given the potential for increased morbidity and mortality from multiple organ resection we asked the question as to whether extended (multiple organ) resection was justified for advanced gastric cancer. STUDY DESIGN: From July 1985 to July 2000, 1,283 patients underwent gastric resection for adenocarcinoma at Memorial Sloan-Kettering Cancer Center, and were entered and followed in a prospectively recorded database. Four hundred eighteen patients (33%) underwent primary resection and had one or more organs resected in addition to the stomach. Eight hundred twenty-six patients (64%) underwent gastrectomy alone, with 39 patients (3%) not undergoing gastrectomy. Clinicopathologic, operative, and morbidity data were evaluated in this group. Complications were categorized by severity on a scale from 0 to 5, 0 being no complication to 5 being death. Chi-square analysis and the logistic regression method were used to compare and estimate factors significantly associated with having a complication. RESULTS: Three hundred thirty-seven patients had a single additional organ resected, 63 had two organs, and 18 had three organs. Five hundred eighty complications occurred in 33% of patients (404 of 1,283). The perioperative mortality was 4% (48 patients). Logistic regression identified the number of organs resected, two or greater, to be predictive of complications (RR 2.0), as well as age greater than 70 years old (RR 1.57). When excluding minor complications (values 1 and 2), only the number of organs resected (RR 3.8) was a major factor for severe complications (values 3, 4, and 5). CONCLUSIONS: Resection of two or more adjacent organs in advanced gastric adenocarcinoma is associated with a greater risk of developing a complication. The use of a graded surgical complication scale is needed for better reporting and comparison of complications. Achieving an R0 resection should still be considered the goal, even in locally advanced gastric cancer, but resection of additional organs should be performed judiciously.

Adenocarcinoma↗

Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas.

OBJECTIVE: To define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. METHODS: The authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. CONCLUSIONS: Positive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.

Adolescent↗

Quality of complication reporting in the surgical literature.

OBJECTIVE: To identify 10 critical elements of accurate and comprehensive reports of surgical complications. SUMMARY BACKGROUND DATA: Despite a venerable tradition of weekly morbidity and mortality conferences, inconsistent complication reporting is common in the surgical literature. METHODS: An analysis of articles reporting short-term outcomes after pancreatectomy, esophagectomy, and hepatectomy was performed. Randomized clinical trials (RCTs) published from 1975 to 2001 and retrospective series of more than 100 patients published from 1990 to 2001 were reviewed. RESULTS: A total of 119 articles reporting outcomes in 22,530 patients were analyzed. This included 42 RCTs and 77 retrospective series. Of the 10 criteria developed, no articles met all criteria; 2% met 9 criteria, 38% 7 or 8, 34% 5 or 6, 40% 3 or 4, and 12% 1 or 2. Outpatient information (22% of articles), definitions of complications provided (34% of articles), severity grade used (20% of articles), and risk factors included in analysis (29% of articles) were the most commonly unmet quality reporting criteria. Type of study (RCT vs. retrospective), site of institution (U.S. vs. non-U.S.) and journal (U.S. vs. non-U.S.) did not influence the quality of complication reporting. CONCLUSIONS: Short-term surgical outcomes are routinely included in the data reported in the surgical literature. This is often used to show improvements over time or to assess the impact of therapeutic changes on patient outcome. The inconsistency of reporting and the lack of accepted principles of accrual, display, and analysis of complication data argue strongly for the creation and generalized use of standards for reporting this information.

Digestive System Surgical Procedures↗

Extended local resection for advanced gastric cancer: increased survival versus increased morbidity.

OBJECTIVE: To characterize factors predictive of improved survival following gastrectomy with additional organ resection for the treatment of gastric cancer. SUMMARY BACKGROUND DATA: Recent large series have reported significant survival disadvantages to patients who have undergone gastrectomy with splenectomy or pancreaticosplenectomy, and yet gastrectomy with additional organ resection is needed to accomplish an R0 resection in some cases. Gastrectomy with splenectomy and other organ resections has been associated with advanced T-stage, positive resection margins, and higher postoperative morbidity and mortality rather than an absolute predictor of survival. METHODS: The authors reviewed the Department of Surgery prospective gastric database at Memorial Sloan-Kettering Cancer Center from July 1985 to July 2000. During this period, of the 2,112 patients with primary gastric cancer, 1,133 underwent an R0 resection. The R0 resection group included 865 patients who underwent gastrectomy alone and 268 patients who underwent gastrectomy with another organ resection. Clinicopathologic, operative, complication, and survival data were compared between these two groups. Chi-square analysis and the Kaplan-Meier method were used to compare and estimate median survival. RESULTS: The most common organs resected were the spleen and pancreas, with an even distribution of other organs. Pathologic factors revealed that the gastrectomy with organ resection group had significantly larger lesions, greater T-stage, and a higher incidence of advanced nodal disease than the group who did not undergo additional organ resection. The incidence of pathologically confirmed T4 cancers in the additional organ resection group was only 14%. The overall 5-year survival rate for patients with T3/T4 disease was 27% with additional organ resection. The overall 5-year survival rate for the gastrectomy with organ resection group (32%, median 32 months) was significantly less than the group that did not undergo additional resection (50%, median 63 months) on univariate analysis. However, additional organ resection was not a predictor of survival on multivariate analysis. Multivariate analysis identified advanced T-stage (T3 or greater) and nodal stage (N1 or greater) as adverse predictors of survival in this group. CONCLUSIONS: Long-term survival following gastrectomy with additional organ resection is possible. Depth of invasion and the extent of lymph node metastasis are the most important predictors of survival following gastrectomy with additional organ resection, and a R0 resection has been achieved. Judicious use of additional organ resection for the treatment of advanced gastric cancer must be emphasized, given the increased overall morbidity and infrequent finding of actual T4 disease. Additional organ resection can be performed with minimal morbidity and can improve the chance of overall survival in patients with advanced T-stage disease.

Adult↗

Symptom control in patients with locally recurrent rectal cancer.

BACKGROUND: Although resection of locally recurrent rectal cancer has been associated with improved survival, clinical outcomes after such repeat surgery have been incompletely characterized. METHODS: From 1997 to 1999, 105 consecutive patients requiring repeat surgery for locally recurrent rectal cancer were identified. Patients were observed for a minimum of 2 years or until death. RESULTS: An operation was performed with palliative intent in 23% of patients. Before repeat surgery, 79% of the palliative-intent patients had symptoms: 21% bleeding, 42% obstruction, and 21% pain. After repeat surgery with palliative intent, improvement was noted in 40% with bleeding, 70% with obstruction, and 20% with pain. Additional or recurrent symptoms were noted in 87% during follow-up. Seventy-seven percent of patients had an operation with nonpalliative intent. Before repeat surgery, 57% of nonpalliative patients had symptoms, with 32% experiencing bleeding, 11% obstruction, and 19% pain. After repeat surgery with nonpalliative intent, initial improvement was noted in 88% with bleeding, 78% with obstruction, and 40% with pain. During follow-up, symptoms arose in 37% of the initially asymptomatic patients, and additional or recurrent symptoms were seen in 63% of those previously symptomatic. CONCLUSIONS: Although symptomatic relief is associated with repeat surgery, the recurrence or development of alternate symptoms makes a completely asymptomatic clinical course uncommon.

Adult↗