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Objectives: The objectives of this prospective series were to present our results in 106 sequential cases of lymphatic mapping and sentinel lymph node biopsy (SLNB) in the head and neck region and contrast the experience in oral cancer with that for cutaneous lesions. Hypotheses: SLNB has an acceptably low complication rate in the head and neck. Lymphatic mapping and gamma probe-guided lymphadenectomy can improve the management of malignancies of the head and neck by more accurate identification of the nodal basins at risk and more accurate staging of the lymphatics. For appropriately selected patients, radionuclide lymphatic mapping may safely allow for minimally invasive sentinel lymphadenectomy without formal completion selective lymphadenectomy. Methods: One hundred six patients underwent intralesional radionuclide injection and radiologic lymphoscintigraphy (LS) on Institutional Review Board-approved protocols and 103 of these underwent successful SLNB. These included 35 patients with malignant melanoma, 10 cutaneous squamous cell carcinomas, four lip cancers, eight Merkel cell carcinomas, two rare cutaneous lesions, and 43 oral cancers. Mean follow up was 24 months. Patients with oral cavity malignancy underwent concurrent selective neck dissection after narrow-exposure sentinel lymph node excision. In this group, the SLNB histopathology could be correlated with the completion neck specimen histopathology. Patients with cutaneous malignancy underwent SLNB alone and only received regional lymphadenectomy based on positive histology or clinical indications. Data were tabulated for anatomic drainage patterns, complications, histopathology, and patterns of cancer recurrence. Results: Surgical complications were rare. No temporary or permanent dysfunction of facial or spinal accessory nerves occurred with sentinel node biopsy. Lymphatic drainage to areas dramatically outside of the expected lymphatic basins occurred in 13.6%. Predictive value of a negative sentinel node was 98.2% for cutaneous malignancies (based on regional recurrence) and 92% with oral cancer (based on pathologic correlation). Gross tumor replacement of lymph nodes and redirection of lymphatic flow represented a significant technical issue in oral squamous cell carcinoma. Sixteen percent of patients with oral cancer were upstaged from N0 to N1 after extended sectioning and immunohistochemistry of the sentinel node. Conclusions: LS and SLNB can be performed with technical success in the head and neck region. Complications are minimal. More accurate staging and mapping of lymphatic drainage may improve the quality of standard lymphadenectomy. The potential for minimally invasive surgery based on this technology exists, but there is a small risk of missing positive disease. Whether the failure rate is greater than that of standard lymphadenectomy without gamma probe guidance is not known. New studies need to focus on refinements of technique and validation of accuracy as well as biologic correlates for the prediction of metastases. [ABSTRACT FROM AUTHOR]

The purpose of this study is to assess the consequences for breast cancer patients of the trend away from breast conservation in favor of bilateral and contralateral mastectomy. The methods are followed from the review of the literature from 1991 to 2015. Breast-conserving surgery and sentinel lymph node biopsy, introduced into mainstream practice in the 1980s and 1990s, respectively, are now the standard of care for early-stage breast cancer. Disruptive change has unexpectedly supervened in the guise of bilateral mastectomy for cancer or prophylaxis and contralateral prophylactic mastectomy. These operations are now being resorted to at a rate which cannot be explained by any of the biological imperatives related to breast cancer and related diseases. This phenomenon extends across the Western world and beyond, driven by patients' cancer concern, a misunderstanding of what surgery can and cannot achieve and preserve, and the current popular media/cultural environment. These developments and their consequences for patients are reviewed. Surgical complications, especially those related to reconstruction, are unusually common. Of equal or greater concern are the physical, esthetic, psychosocial, psychosexual morbidities, and other adverse sequelae of these operations.

The association between malignancy and thrombosis has long been appreciated but remains incompletely understood. This is the second of a two-part review of the complex, integral relationship between these two entities, and addresses the specifics of cancer outcomes, occult malignancy in the presence of thrombosis, and the possibilities of cancer suppression by modulating thrombogenesis., (Copyright © 2012 Wiley Periodicals, Inc.)

The association between malignancy and thrombosis has long been appreciated but remains incompletely understood. This is the first of a two-part review of the complex, integral relationship between these two entities, and addresses the mechanisms and pathogenesis of this relationship and the clinical risk factors for thromboembolism in cancer patients., (Copyright © 2011 Wiley-Liss, Inc.)

Breast cancer screening constitutes an integral part of surgical practice for many surgeons and is an important tool in the war against breast cancer. Among many modalities, mammography plays a central role, with MRI now being increasingly used for women with high risk for breast cancer. Current guidelines for screening are in the process of evolution as more scientific knowledge is gained. The challenge lies in developing cost-effective methods to reach the maximum number of the population at risk.

Localizing positron emission tomography (PET)/computed tomography (CT) findings in heavily scarred surgical fields can be challenging. A high energy gamma probe (PET probe) can be used to guide surgery in those difficult areas. We describe our experience localizing and removing fluorodeoxyglucose (FDG) avid lesions in different body areas. Between 2004 and 2007, we used the PET probe to localize and remove 12 lesions from 9 patients. The lesions were removed confirming ex vivo and tumor bed FDG activity. Five patients had lesions in previously operated and sometimes radiated fields. One patient had FDG avid spots in the retroperitoneum. Two lymphoma patients had been previously treated and had new FDG avid spots in a background of scarred nodes. The last patient had a core biopsy suspicious for lymphoma but a repeat CT was non-specific. One patient with gastric cancer patient, two patients with melanoma patients and two patients with breast cancer had 10 metastatic lesions easily identified and removed. After a median follow-up of 14 months all five patients are alive. The two patients with lymphoma had their FDG avid lymph nodes easily identified and biopsied. In one patient with melanoma and one patient with suspected lymphoma, the preoperative scan revealed no FDG avid lesions. The PET probe confirmed this finding in the operating room. Clinical applications of PET probe guided surgery include restaging for previously treated lymphoma patients, localization and resection of metastatic FDG avid nodules especially in previously operated or radiated fields and biopsy of PET findings difficult to localize.

Lumpectomy specimens are commonly divided into six sides: superficial, deep, superior, inferior, medial, and lateral. Orienting stitches are placed on the specimen during surgery to allow reorientation by pathology. Despite those efforts, specimen disorientation may occur. The aim of this study was to assess the correlation in orientation between surgeons and pathologists. Lumpectomy specimens were routinely oriented. An additional Prolene suture was randomly placed by the surgeon on one side to be localized by pathology. The results were recorded and the disorientation rate calculated. Specimen size and presence of skin and/or muscle were also recorded. There were 122 lumpectomy specimens prospectively entered. Average specimen volume was 95.5 cm(3). Twenty-four specimens had segments of skin or muscle. The additional sutures were evenly divided between the six sides. The overall disorientation rate was 31.1% (95% confidence interval, 23.1-40.2).The side-specific disorientation rates were 43%, 40%, 35%, 29%, 28%, and 14% for the deep, superficial, lateral, medial, superior, and inferior surfaces, respectively (no statistical difference). Presence of skin or muscle on the specimen did not contribute to better orientation. Specimen volumes, however, were highly associated with orientation. Specimens of <20 cm(3) had a disorientation rate of 78%, while larger specimen had a disorientation rate of 20% (p < .001). Specimen orientation with stitches placed on two surfaces is associated with a high disorientation rate. Better orientation techniques are necessary to minimize the specimen disorientation.

Background: Differences in cancer survival based on race, ethnicity, and socioeconomic status (SES) are a major issue. To identify points of intervention and improve survival, the authors sought to determine the impact of race, ethnicity, and socioeconomic status for patients with cancers of the head and neck (HN)., Methods: HN cancer patients diagnosed between 1998 and 2002 were examined using a linked Florida Cancer Data System and Florida Agency for Health Care Administration data set., Results: A total of 20,915 patients with HN cancers were identified, predominantly in the oral cavity and larynx. Overall, 72% of patients were male, 89.7% were white, 8.4% were African American (AA), and 10.6% were Hispanic. The median survival time (MST) was 37 months. MST varied significantly by race (white, 40 months vs AA, 21 months; P < .001), sex (men, 36 months vs women, 41 months; P = .001), and area poverty level (lowest, 27 months vs highest, 34 months; P < .0001). Only 32% of AA patients underwent surgery in comparison with 45% of white patients (P < .001). On multivariate analysis, independent predictors of poorer outcomes were race, poverty, age, sex, tumor site, stage, grade, treatment modality, and a history of smoking and alcohol consumption., Conclusions: Carcinomas of the HN have an overall high mortality with a disproportionate impact on AA patients and the poor. Dramatic disparities by race and SES are not explained completely by demographics, comorbid conditions, or undertreatment. Earlier diagnosis and greater access to surgery and adjuvant therapies in these patients would likely yield significant improvement in outcomes.

Background: The purpose of this study was to determine the value of lymphoscintigraphy (LS) for internal mammary sentinel node (IMSN) identification, the metastatic rate, and the change in staging and treatment., Methods: Between 2001 and 2007 a prospective database was obtained of all patients undergoing IMSN biopsies using an open or thoracoscopic approach. Radiotracer injection was peritumoral., Results: Thirty-four patients were included. There was one man. Three had ductal carcinoma in situ. LS showed IMSN in 47.1%. The IMSN biopsy success rate was 91.2%. Seven of the 28 successfully biopsied invasive cancer patients had metastatic IMSNs (25%). Positive IMSNs were associated with positive axillary nodes in 71.4% (P = .036). All patients with positive IMSNs were upstaged and received radiation to the internal mammary chain. In 4 of 28 patients (14%) the chemotherapy plans were probably altered. In univariate and multivariate analyses tumor size, location, nuclear grade, estrogen receptors, progesterone receptors, Her-2, and histology were not significant predictors of positivity., Conclusions: IMSNs were positive in 25% of the invasive cancer patients. All had treatment changes. LS identified less than 50% of IMSNs. There are no good tumor-related predictors of IMSN positivity.

Surgical gamma detection probes (GDPs) have become important in the surgical management of neoplastic disease in the past 20 years. Their history and radiophysics are discussed, with consideration of the overarching issue of tumor-to-background ratio (TBR). GDPs are currently most commonly used in sentinel node applications in a variety of tumors. Whether their role in clinical surgical practice can be extended to other applications will depend on the development of radiolabeled tumor marking agents which have much improved TBR, and parallel developments in oncology research which may overtake this technology.

Background and Objectives: To date, outcome reports for soft-tissue sarcoma (STS) have largely been limited to single or paired institutional series. To more accurately elucidate population-based outcomes and prognostic factors associated with STS, a large cancer registry was examined., Methods: STS arising in the Florida Cancer Data System were examined (1981-2004)., Results: A total of 8249 patients were identified, the calculated annual incidence of sarcoma being approximately 38 cases per million in 2003. The tumor histologies among these patients were leiomyosarcoma and gastrointestinal stromal tumor (LMS/GIST) (43.5%), malignant fibrous histiocytoma (MFH) (31.5%), liposarcoma (19.0%), and fibrosarcoma (6.0%). Tumors were situated in the extremities (30.7%), truncal or visceral locations (50.4%), retroperitoneum (11.7%), and head or neck (7.2%). Thirty-three percent of lesions were over 10 cm in greatest dimension, while 50.2% were classified as high grade. Median overall survival was 25 months. Superior survival was observed for liposarcomas and fibrosarcomas as compared to MFH and LMS/GIST (P < 0.001). Retroperitoneal and truncal sarcomas had a more ominous prognosis than did other sites (P < 0.001). Multivariate analysis of pretreatment variables demonstrated that increasing age, male gender, non-Caucasian race, advanced stage, and a truncal or retroperitoneal location were each independently associated with lower survival. Histological subtype was also an independent predictor of outcome. Surgical resection and radiation therapy were the only treatment variables shown to improve survival., Conclusions: Histological subtype, tumor site, and stage are independent prognostic factors in STS. Surgical resection and radiotherapy are unique among treatment modalities in association with a significant survival benefit.

Objective: : To define the prognostic significance of surgical center case volume on outcome for soft tissue sarcoma (STS)., Methods: : STS cases registered in the Florida Cancer Data System (FCDS) between 1981 and 2001 were analyzed. Medical facilities were ranked by STS operative volume. Facilities above the 67th percentile for volume were defined as high-volume centers (HVCs)., Results: : Of the 4205 operative cases of STS identified, 68.1% were treated at low-volume centers (LVCs) and 31.9% at HVCs. A larger proportion of high-grade tumors (53.8% vs. 44.3%) and lesions over 10 cm (40.7% vs. 28.7%) were resected at HVC (P < 0.001). The 30-day mortality was 0.7% for HVC and 1.5% for LVC (P = 0.028), and mortality rates at 90 days were 1.6% and 3.6%, respectively (P = 0.001). Median survival was 40 months at HVC and 37 months at LVC (P = 0.002). Univariate analysis demonstrated significantly improved survival at HVC for high-grade tumors (median 30 months vs. 24 months, P = 0.001), lesions over 10 cm (28 months vs. 19 months, P = 0.001) and truncal or retroperitoneal sarcomas (39 months vs. 31 months, P = 0.011). Limb amputation rate was lower (9.4% vs. 13.8%, P = 0.048) and radiation and chemotherapy were more frequently administered at HVC (OR = 1.54). On multivariate analysis, treatment at a HVC was a significant independent predictor of improved survival (OR = 1.292, P = 0.047)., Conclusions: : STS patients treated at HVC have significantly better survival and functional outcomes. Patients with either large (>10 cm), high-grade or truncal/retroperitoneal tumors should be treated exclusively at a high-volume center.

Background: Prognostication of truncal and retroperitoneal soft tissue sarcomas has traditionally been predicated on tumor location and grade., Objective: To compare outcomes for patients with retroperitoneal or truncal sarcomas., Methods: Retrospective analysis of a prospective cancer data registry from 1977 to 2004 was performed and outcomes were determined., Results: The study group numbered 312 patients (median age 58 years, 54% male, 56% Caucasian, 14% black, 29% Hispanic). The most common tumor types were liposarcoma (35.9%), leiomyosarcoma (30.1%), and malignant fibrous histiocytoma (MFH) (19.5%). Tumor distributions were retroperitoneal (38.9%), pelvic (24.7%), abdominal (18.6%) and thoracic (17.9%). Median overall survival was 74 months. Operative resection was undertaken in 89.4% of cases and multiple surgeries (range 2-5) in 42.2%. Negative resection margins were obtained in 72.7% of patients. Univariate analysis comparing retroperitoneal versus truncal location demonstrated no significant differences in survival. Survival was improved in lower grade tumors (P < 0.02). Liposarcoma and fibrosarcoma were associated with improved survival (P < 0.0001). Multivariate analysis of pre-treatment variables showed increasing age, grade, histopathology (leiomyosarcoma and MFH) and metastasis to be associated with worse outcomes. Multivariate analysis of the treatment variables showed that surgery and negative resection margins were associated with improved survival (P < 0.001). No advantage for chemoradiotherapy could be demonstrated., Conclusions: Successful operative resection can confer prolonged disease-free survival and cure for truncal and retroperitoneal sarcomas. Histological subtype, not location, is predictive of long-term survival. Future studies should focus on histological subtype rather than tumor location for truncal and retroperitoneal sarcomas.

Objective: To train surgeons in a standardized technique of sentinel lymph node biopsy and to prepare them for the requirements of a prospective randomized surgical trial., Summary Background Data: The NSABP B32 trial opened to accrual in May 1999. A significant component of this trial was a prerandomization training phase of surgeons performed by a group of core surgical trainers. The goals of this training phase were to expeditiously instruct surgeons in a standardized technique of sentinel lymph node biopsy and to educate those same surgeons in complete and accurate data collection and source documentation for the trial., Methods: This study is a description of the training data collected in a prospective fashion for the training component for surgeon entry into the B32 trial, evaluating the effectiveness of the training program in regards to surgical outcomes and protocol compliance., Results: Two hundred twenty-six registered surgeons underwent site visit training by a core surgical trainer and 187 completed training and were approved to randomize patients on the trial. The results of 815 training (nontrial) cases demonstrated a technical success rate for identifying sentinel nodes at 96.2% with a false negative rate of 6.7%. A protocol compliance analysis, which included the evaluation of 94 separate fields, showed mean protocol compliance of 98.6% for procedural fields, 95.5% for source documentation fields and 95.0% for data entry fields., Conclusions: This training and quality control program has resulted in a large number of surgeons capable of performing sentinel lymph node biopsy in a standardized fashion with a high degree of protocol compliance and pathologic accuracy. This will ensure optimal results for procedures performed on the randomized phase of the trial.

Background: Male breast cancer is rare, and little is known about state population-level patterns of incidence. The primary objective of this study was to determine the incidence of MBC in Florida in comparison with the Surveillance, Epidemiology, and End RESULTS (SEER) program data., Methods: Study data were obtained from the Florida Cancer Data System (FCDS). All males with pathologically confirmed invasive breast carcinoma diagnosed from 1985 to 2000 were included. Age-adjusted incidence rates, regional incidence rates, and descriptive statistics were calculated. Annual percent change (APC) for the study period was calculated with a linear model. Results were compared with the SEER data., Results: A total of 1396 cases of MBC were identified. Age-adjusted incidence rates increased from 0.9 cases per 100,000 in 1990 to 1.5 cases per 100,000 in 2000. In 2000, the highest rates were in the age groups of 70 to 75 years (7.9) and > or =85 years (12.5). Infiltrating ductal was the most common subtype (92%); less common subtypes included mucinous (2%) and papillary (2%). Localized disease accounted for 45% of all cases, with regional disease in 33%, distant metastases in 7%, and unstaged in 15%. Most incident cases were diagnosed in the Palm Beach-Broward region (23%). The number of cases increased from 56 in 1985 to 132 new cases in 2000. The APC for this 16-year period was 2.0% (95% confidence interval [CI], 1.05-3.01; P <.005). SEER data indicated no change in MBC incidence rates (APC, 0.5; NS)., Conclusions: The incidence of MBC in Florida increased significantly between 1985 and 2000. This finding is discordant with SEER incidence data. Further epidemiologic studies are warranted to investigate regional variation.

Primary sarcoma constitutes less than one per cent of breast malignancies. A retrospective review of this disease at our institution was undertaken to assess the effect of different treatment modalities on outcome. Over a 24-year period 28 patients were identified. Follow-up ranged from one to 228 months. Partial mastectomy was done in seven patients, whereas ten underwent total mastectomy and nine had modified radical mastectomy. Two refused surgery. All margins of resection were negative. In total ten axillary lymph node dissections were done with no positive nodes identified. Pathologic analysis of tumors revealed a variety of sarcomas including high-grade malignant cystosarcoma phyllodes in 13. Recurrence of disease occurred in two women, both with malignant cystosarcoma phyllodes. One was a local recurrence in a patient who had undergone partial mastectomy. This was successfully treated with a total mastectomy. The second recurrence involved a distant metastasis in a patient treated with modified radical mastectomy that eventually led to her death. For the entire group the disease-free survival was 75 per cent at 10 years whereas overall survival was 87.5 per cent. In conclusion an adequate margin of resection is the single most important determinant of long-term survival. Axillary lymph node dissection is not necessary for the treatment of these tumors.

Background: Dietary lipids enhance immune function and improve outcome from injury or infection in animal models. We tested the hypothesis that amount, type, or both, of dietary lipid increases intracellular calcium concentration, a surrogate for lymphocyte activation., Methods: Mice were fed 2 weeks on semipurified diets with 5% (by weight [w/w]), 10% (w/w), or 20% (w/w) dietary fat consisting of coconut, olive, safflower, or linseed oil. Changes in intracellular calcium concentration after mitogen stimulation of splenic lymphocytes was estimated by using flow cytometry., Results: Olive oil diets increase intracellular calcium concentration after concanavalin A, lipopolysaccharide, and CD3 stimulation. On the other hand, linseed oil (which is high in omega-3 fatty acids, which have been shown in other studies to enhance immune function) depresses intracellular calcium levels. The amount of dietary fat had no effect on intracellular calcium., Conclusion: Olive oil merits further study in the application of nutritional pharmacology to immunomodulation of the critically injured, because it may enhance lymphocyte function.

To determine the effects of dietary fats on surface antigen expression, we tested the effects of amount and type of dietary fat on murine lymphocytes. Mice were fed diets with 12 en%, 23 en%, or 47 en% fat containing coconut, olive, safflower, or linseed oil. After 2 wk of ad libitum feeding, the mice were killed and splenic lymphocytes were harvested. Lymphocytes were incubated with fluorescent-tagged monoclonal antibodies and assayed for mean and total surface expression using flow cytometry. Our results show that high-fat (47 en%) diets suppress expression of CD3 and CD25 antigens. We also found that linseed-oil diets suppress expression of CD11a but enhance expression of CD25 antigens. Both CD3 and CD25 are critical for lymphocyte activation, and we conclude that immunosuppression associated with high-fat diets may be associated with suppression of these surface antigens.

Introduction: Sentinel lymph node biopsy (SLNB) may prove superior to axillary node dissection (AND) for breast cancer staging. At issue is whether existing clinical data support performance of SLNB without AND at this time., Discussion: The various methods of SLNB are discussed in detail. SLNB using radiocolloids and surgical probes (with or without blue dye) yields superior SLN localization rates as compared to blue dye alone. However, the incidence of false-negative SLNB is variable with all methods and frequently 10% or higher (11.4% in the only published multicenter study)., Conclusions: Outside of a clinical trial, SLNB should be performed in addition to, not instead of, AND. The sensitivity of pathological staging is enhanced and nonaxillary SLNs are identified, while concomitant AND apprehends all false-negative SLNBs. Two prospective randomized cooperative trials provide excellent educational, training and research opportunities for North American breast surgeons as they gain experience with this new, promising staging procedure.

Background: There are few clinical data on technical limitations and radiocolloid kinetics related to sentinel lymph node (SLN) biopsy for breast cancer., Methods: In 70 clinical node-negative patients, unfiltered 99mTc sulfur-colloid was injected peritumorally and cutaneous hot spots were mapped with a gamma probe. SLN biopsy was performed followed by axillary lymph node dissection. Missed radioactive nodes (nodes not under hot spots) were removed from axillary lymph node dissection specimens and submitted separately., Results: At least one hot spot was mapped in 69 patients (98%) and SLNs were retrieved in 62 (89%). No radiolabeled nodes were found in five (7%) and only nodes not under hot spots were retrieved in three patients (4%). Residual nodes not under hot spots were retrieved in 17 patients (24%) in whom at least one SLN specimen had been found. Diffuse radioactivity around the radiocolloid injection site impeded identification of all radiolabeled nodes during SLN biopsy, and was responsible for one of two false negatives (20 node-positive patients; false-negative rate 10%). Hot spot radioactivity, number of radiolabeled nodes, and nodal radioactivity did not change with time interval from radiocolloid injection to surgery (0.75-6.25 hours)., Conclusions: Although SLN localization rate is high, intraparenchymal injection may predispose to failure of radiocolloid migration, failure to identify SLNs because of high radiation background, and false-negative outcomes. Alternative routes of radiocolloid administration should be explored.

The goal of this pilot study was to determine in patients with operable breast cancer the incidence of breast cancer cells present in the blood, the clearance rate after surgical resection of the primary tumor, and the incidence of patients with persistent cancer cells in the blood after the primary tumor was removed. Twenty-one patients with operable breast cancer had 15 ml venous blood obtained twice prior to surgery and after surgery at 2, 4, 8, 12, 24, and 48 hours and also on days 7 and 14. Immunomagnetic selection of malignant cells was performed on each sample. Cells were then fixed on slides and immunocytochemistry performed on the collected cells. Cells that had a rosette of magnetic beads, cytoplasmic staining for keratin, and malignant morphology were counted as breast cancer cells. Eighteen of 19 of patients had cancer cells detected in at least one of the two blood samples preceding surgical removal of the primary tumor. The incidence of cancer cells in the blood of patients rapidly declined during the 48 hours postsurgery. The incidence of cancer cells in the blood remained stable in approximately 30% of patients to 14 days. The majority of breast cancer patients in this pilot study (even with small tumors and negative nodes) had detectable cancer cells in the blood prior to resection of the primary tumor. These findings justify further investigation. Successful application of this methodology may serve as a powerful indicator of which patients need systemic adjuvant therapy, the effectiveness of systemic adjuvant therapy, tumor recurrence, and early detection of breast cancer.

The authors sought to examine the utility of resection in conjunction with adjuvant chemotherapy for treatment of metastases from breast cancer isolated to the liver or lungs. Limitations of regional therapy were examined and potential agents for systemic therapy were reviewed. As resection of metastases is a controversial therapeutic approach, no clinical trials are available for review. Rather, evidence for a potential role for surgery rests on retrospective studies of small series of patients. Technical advances have rendered resection of liver and lung metastases safe. Long-term results as reported by other investigators support the role of metastasectomy in selected patients. The site of failure following ablation of liver metastases is usually in the liver. Following resection of lung metastases, nonpulmonary and disseminated recurrences are most common. Adjuvant therapy with docetaxel or any other agent or combination with significant activity against visceral metastases might potentiate long-term results.

Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-111-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticuloendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m-labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunogenicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT) for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab'; CEA-Scan), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immunogenicity and toxicity, and a significant further improvement in the accuracy of clinical decision making in oncology patients.

CD44 isoforms belong to a family of cell adhesion molecules expressed on the cell surface of many tumor cells during human breast cancer progression. In this study we have analyzed the expression of CD44v3-containing isoforms [containing heparan sulfate addition sites for growth factor binding] in primary breast tumors, axillary nodal metastases and normal breast tissue. Using reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot, cloning, nucleotide sequencing and RT-in situ-PCR analyses, we have found that at least two CD44v3-containing isoforms, including one new species of CD44v2,deltav3-10 (deltav3 defined as a v3 exon lacking the first 24 base pairs) and another previously reported CD44v3,8-10 are preferentially expressed in human primary breast tumor and axillary nodal metastases but not in normal breast tissues. These finding suggest that these CD44v3-containing isoforms are closely associated with breast cancer metastasis.

Objectives: To determine the association of intratumoral thymidylate synthase (TS) gene expression with resistance to fluoropyrimidines and to study the association of TS gene expression with outcome in patients with liver metastases from colorectal cancer., Methods: Intratumoral TS gene expression was measured by reverse transcriptase and polymerase chain reaction in 33 patients with liver metastases from colorectal carcinoma. Fifteen patients underwent resection, and 18 were treated with chemotherapy only. Patients with high levels of TS gene expression were compared to those with low levels of TS gene expression., Results: All patients with a high level of TS gene expression were nonresponders to fluoropyrimidine chemotherapy. Median survival in patients with unresectable disease was shorter in those who had high levels of TS gene expression (7 months vs 15 months, P = 0.02). After hepatic resection, median disease-free interval was shorter in patients with high levels of TS gene expression (5 months vs 18 months; P = 0.004). Similarly, survival was shorter after resection in those with high TS gene expression (17 months vs 43 months, P = 0.0002)., Discussion: Increased TS gene expression is associated with a poor outcome in patients with liver metastases from colorectal carcinoma, whether resected or treated by chemotherapy only. This is related in part to reduced responsiveness to chemotherapeutic agents, but it also reflects inherently more aggressive behavior of metastases.

Methods: Thirty-two patients with clinical node-negative breast cancer underwent sentinel node localization study as part of a National Cancer Institute-sponsored multicenter trial. Anatomical and histopathologic characteristics of sentinel lymph node (SLN) and a kinetic analysis of nodal uptake were studied. Patients were injected with 1 mCi/4 ml unfiltered 99mTc-sulfur colloid in four divided doses around the palpable lesion or immediately adjacent to the excision cavity if prior biopsy was performed. SLN biopsy was performed 1.5-6 hr (mean = 3 hr) postinjection. Intraoperative localization was performed using a gamma probe. All patients underwent complete axillary dissection., Results: SLN was identified in 30 of 32 (94%) patients. There were no false-negative SLN biopsies., Conclusion: This study supports the clinical validity of SLN biopsy in breast cancer and confirms that, unlike the blue dye technique, the learning curve with unfiltered 99mTc-sulfur colloid and the gamma detection probe is short, and SLN localization is achievable in over 90% of cases by surgeons with modest experience. The use of unfiltered 99mTc-sulfur colloid (larger particle size) with larger injected volume permits effective localization of SLNs.

This study analyzes a single-institution experience by evaluating the impact on survival of increasing total dose of adjunctive irradiation in patients who had extremity soft-tissue sarcoma (ESTS). A retrospective review of the tumor registry at a university medical center from January 1984 through December 1992 yielded a total of 59 surgical patients of ESTS. With follow-up ranging from 30 to 135 months (median, 65 months), the 2-, 5-, and 8-year overall and disease-free survival for all patients was 86%, 71%, 58% and 76%, 70%, 56%, respectively. Multivariate analyses using the Cox proportional hazards model revealed that total radiation dose (p = 0.02), American Joint Committee on Cancer stage (p = 0.04), and tumor size (p = 0.006) were all significant prognostic factors of overall survival; however, only tumor size was predictive of disease-free survival (p = 0.02). When the effect of tumor size and disease stage were controlled in the Cox model, a dose-response curve between increasing total radiation dose and improved overall patient survival was indicated. This study demonstrates the significance of tumor size on predicting both overall and disease-free survival in patients who have soft-tissue sarcomas of the extremity. It also suggests, however, that a radiation dose-response relation may exist for overall survival. Future investigations should consider evaluating the minimal total radiation dose needed to optimize patient survival after limb-sparing surgery.

Objective: Several authors have suggested that patients adjust more poorly to breast cancer if they are heavily invested in body image as a source of their sense of self-worth. This prospective study examined this possibility, looking at two aspects of concern about body image as predictors of several indices of adjustment over the first postoperative year., Methods: At diagnosis (and again a year later) 66 women with early stage breast cancer reported how much they valued a) a sense of body integrity (or intactness) and b) a good physical appearance. The day before surgery, a week afterward, and at 3-month, 6-month, and 12-month follow ups, they reported on their mood. At presurgery and at follow ups they also rated their attractiveness and sexual desirability and reported on frequency of sexual interaction. At follow-ups they also indicated how much their illness and treatment were interfering with social and recreational activities., Results: Initial investment in appearance was related to distress across the postsurgical year. In contrast, investment in appearance made women more resilient against deterioration in their perceptions of attractiveness. Concern about body integrity did not strongly predict emotional distress, but it related to adverse impact on social and recreational activities in the follow-up period, to deterioration in feelings of sexual desirability, and to feelings of alienation from the self (feeling "not like yourself anymore")., Conclusions: Body image is often thought of in terms of physical appearance, but there is also a body image pertaining to integrity, wholeness, and normal functioning. People who are greatly concerned about either aspect of their body image are vulnerable to poorer psychosocial adjustment when confronting treatment for breast cancer. The poorer adjustment takes a different form, however, depending on the nature of the patient's body-image concern.

Somatostatin receptor expression, which was not a previously described marker for Hürthle cell cancer of the thyroid, was demonstrated by in vivo imaging with (111)In-pentetreotide in three patients. This phenomenon not only adds another imaging technique to the nuclear medicine armamentarium for detecting recurrent and metastatic cancer in patients with Hürthle cell cancer but also opens up an alternative therapeutic avenue with somatostatin analogs or their radiolabeled compounds.

In a small proportion of patients with extensive primary or locally recurrent rectal cancer, disease remains confined to the pelvis for a prolonged period. Symptoms are highly prejudicial to quality of life and often refractory to treatment short of extirpative surgery. Cure requires en bloc excision of all involved pelvic viscera with tumor-free margins. The pelvic exenterations (PE) are the most radical operations for rectal cancer. PE carries a high risk of perioperative morbidity and mortality, and has profound functional, psychological, and psychosexual implications for patients. Careful preoperative counseling regarding surgical risks and the impact of PE on body function and image is indispensable; the patient's consent must be truly informed. Patients with major medical or psychiatric/emotional comorbidity and those who are mentally incompetent are not candidates. Tenesmus and central pelvic/perineal pain are amenable to PE whereas radicular pain is not; sciatica and lower extremity lymphedema portend unresectability. Extrapelvic disease should be excluded preoperatively. While invaded sacrum can be resected en bloc with involved viscera (sacropelvic exenteration), fixity of tumor to the pelvic sidewall(s) in nonirradiated patients almost invariably implies unresectability. Other contraindications to PE include invasion of the proximal (S1 or higher) lumbosacral spine or lumbosacral plexus/sciatic nerves, ureteric obstruction proximal to the ureterovesical junctions, and encasement of the external or common iliac vessels by tumor. PE for advanced primary rectal carcinoma yields 5-year survival of over 40%; when performed for recurrent disease, long-term salvage rates are not as high. While radical surgery is rarely indicated for palliation, PE in carefully selected (good performance status and life expectancy, complete excision of all gross disease) incurable patients results in abrogation of disabling symptoms and reasonable intervals of high-quality survival.

Objective: The objective was to determine the role of arcitumomab (CEA-Scan; Immunomedics, Morris Plains, NJ), an anticarcinoembryonic antigen (CEA) Fab' labeled with technetium-99m, in the presurgical evaluation of patients with recurrent or metastatic colorectal carcinoma., Summary Background Data: Surgical resection is the only method known to cure recurrent or metastatic colorectal carcinoma. The location and extent of disease must be determined before surgery. The role of antibody imaging, a new cancer detection modality, in preoperative evaluation for resection of locally recurrent or metastatic colorectal cancer has not been established, either alone or in combination with standard diagnostic modalities., Methods: In a blinded analysis of 209 patients with known or suspected colorectal cancer, the accuracy of arcitumomab, alone and combined with computed tomography (CT), was compared to that of CT for predicting abdominopelvic tumor resectability by correlating the results with surgical and histopathologic findings., Results: Arcitumomab alone or combined with CT was found to be significantly more accurate for predicting surgical outcome than CT alone. When the results of CT and arcitumomab were concordant for abdominopelvic resectability, nonresectability, or absence of disease, the prediction was accurate in 67%, 100%, and 64%, respectively. Thus, the concordance for nonresectability (100% correct) may obviate the need for other diagnostic modalities or exploratory surgery. When the two tests were discordant, arcitumomab was correct substantially more often than CT. Because the liver is the most common site of distant metastasis in colorectal cancer, a subset of patients with hepatic disease was also analyzed; findings were similar to the overall resectability results. The product's safety profile was excellent: the incidence of induction of an immune response against arcitumomab was <1% and that of potentially adverse events was 1.2%., Conclusions: The accuracy of arcitumomab for assessing resectability status is greater than that of CT, both in all patients undergoing evaluation for curative abdominopelvic resection of colorectal cancer and in the subset of patients with suspected or proven liver metastases. The additional use of arcitumomab with CT potentially doubles the number of patients who could be saved the cost, morbidity, and mortality of unnecessary abdominopelvic surgery and increases those who are potentially resectable for cure by 40%.

Axillary lymph node status is the most important pathological determinant of prognosis in early breast cancer. Determination of axillary status is crucial in clinical decision-making. It is currently accepted that the total axillary lymphadenectomy is the most reliable staging procedure. However, routine axillary dissection does not benefit a majority of early breast cancer patients who are node-negative, and the patients sustain the potential morbidity and the economic cost of this procedure. There is substantial evidence that there is an orderly progression of breast cancer metastases in a lymphatic basin, sentinel node being the first node to receive lymphatic drainage from the tumor site. Sentinel lymph node biopsy may prove to be the optimal sampling technique for staging of breast cancer patients. A large multicenter trial to study the clinical validity of sentinel lymph node biopsy in breast cancer is underway. This paper addresses the rationale for sentinel lymph node biopsy and discusses the technical issues with regard to anatomy and physiology of breast lymphatics.

The leukocyte CD44 and CD45 cell surface receptors are associated via the linker proteins ankyrin and fodrin with the cytoskeleton, which itself is important in immune cell functions such as adherence, chemotaxis, and phagocytosis. The effects of rat antihuman CD44 and CD45 monoclonal antibodies on phagocytosis of fluoresceinated heat-killed Staphylococcus aureus 502A by normal human neutrophils (PMNs) during 2 hr incubation in RPMI-1640 was studied via flow cytometry and confocal microscopy. Flow cytometry was performed using an excitation wavelength of 488 nm, fluorescence being measured at 515-560 nm on 50,000 PMNs per sample. Confocal microscopy was performed on samples after further incubation with rhodamine-conjugated antiankyrin. Anti-CD44 resulted in an increase of 27-31% compared to control (P = 0.004) in the proportion of PMNs fluorescing, an increase of 17-24% (P = 0.001) in mean intracellular fluorescence per PMN, and an increase in total PMN fluorescence of 50-58% compared to control (P < 0.001). In contrast, anti-CD45 had little effect on phagocytosis. Colchicine (a microtubule-disrupting agent) enhanced, whereas cytochalasin-D (a microfilament inhibitor) inhibited bacterial phagocytosis; cytochalasin-D completely abrogated the effect of anti-CD44 on this PMN function. Hyaluronic acid augmented phagocytosis by an increment similar to that observed with anti-CD44. Two-color flow cytometry and confocal microscopy demonstrated that ankyrin always colocalized with ingested fluorescein isothiocyanate (FITC)-labeled bacteria. These data strongly suggest that CD44 is involved in bacterial phagocytosis, provide further evidence of CD44 receptor linkage to cytoskeletal elements in human leukocytes, and suggest that ankyrin has a significant role in the transport of phagosomes.

Purpose: To assess the performance and the potential clinical impact of a new antibody imaging agent, CEA-Scan (Immunomedics Inc, Morris Plains, NJ), in 210 presurgical patients with advanced recurrent or metastatic colorectal carcinomas., Methods: CEA-Scan, an anti-carcinoembryonic antigen (CEA) Fab antibody fragment labeled with technetium-99m-pertechnetate (99mTc), was injected intravenously (IV), and external scintigraphy was performed 2 to 5 and 18 to 24 hours later. Imaging with conventional diagnostic modalities (CDM) was also performed, and findings were confirmed by surgery and histology., Results: The sensitivity of CEA-Scan was superior to that of CDM in the extrahepatic abdomen (55% v 32%; P = .007) and pelvis (69% v 48%; P = .005), and CEA-Scan findings complemented those of CDM in the liver. Among 122 patients with known disease, the positive predictive value was significantly higher when both modalities were positive (98%) compared with each alone (68% to 70%), potentially obviating the need for histologic confirmation when both tests are positive. Imaging accuracy also was significantly improved by adding CEA-Scan to CDM. In 88 patients with occult cancer, imaging accuracy was enhanced significantly by CEA-Scan combined with CDM (61% v 33%). Potential clinical benefit from CEA-Scan was demonstrated in 89 of 210 patients. Only two patients developed human antimouse antibodies (HAMA) to CEA-Scan after a single injection, and none of 19 assessable patients after two injections., Conclusion: CEA-Scan affords high-quality, same-day imaging, uses an inexpensive and readily available radio-nuclide, adds clinically significant information in assessing extent and location of disease in colorectal cancer patients, and only rarely induces a HAMA response.

That L-arginine (L-Arg) augments the host response to acute bacterial sepsis suggests that this amino acid intervenes early in the immune response, perhaps via the nitric oxide synthetase (NOS) pathway. The effect of L-Arg supplementation on in vitro phagocytosis of fluorescein-labeled, heat-killed Staphylococcus aureus by peripheral blood neutrophils (PMNs) from 12 normal human volunteers was studied. Separated PMNs were incubated for 2 h with labeled bacteria, with and without supplemental L-Arg, D-arginine, glycine, and/or the NOS inhibitors L-canavanine, aminoguanidine, or L-NG-nitroarginine methyl ester. PMNs were fixed and extracellular fluorescence quenched with crystal violet. By flow cytometry and confocal microscopy, L-Arg supplementation was shown to result in a highly significant increase in PMN bacterial phagocytosis, the maximal effect being seen with L-Arg 380 microM and falling off with higher concentrations. This augmentation was completely abrogated by NOS inhibitors in molar excess, but inhibitors alone did not suppress phagocytosis below that of unsupplemented controls. Neither D-arginine nor glycine affected phagocytosis; the L-Arg effect was stereospecific and not related to utilization of L-Arg as an energy source. L-Arg supplementation significantly enhances bacterial phagocytosis in human neutrophils, perhaps by effects on cytoskeletal phenomena, and this appears to be mediated through NOS activity. Phagocytosis by nonspecific immune cells which intervene early in the response to sepsis is critically important, and beneficial effects of L-Arg on the clinical course of sepsis may be due at least in part to augmentation of phagocyte function.

Radioimmunoscintigraphy (RIS) using human monoclonal antibodies offers the important clinical advantage of repeated imaging over murine monoclonal antibodies by eliminating the cross-species antibody response. This article reports a Phase I-II clinical trial with Tc-99m-labeled, totally human monoclonal antibody 88BV59H21-2 in patients with colorectal carcinoma. The study population consisted of 34 patients with colorectal cancer (20 men and 14 women; age range, 44-81 years). Patients were administered 5-10 mg antibody labeled with 21-41 mCi Tc-99m by the i.v. route and imaged at 3-10 and 16-24 h after infusion using planar and single-photon emission computed tomographic (CT) techniques. Pathological confirmation was obtained in 25 patients who underwent surgery. Human antihuman antibody (HAHA) titers were checked prior to and 1 and 3 months after the infusion. RIS with Tc-99m-labeled 88BV59H21-2 revealed a better detection rate in the abdomen-pelvis region compared with axial CT. The combined use of both modalities increased the sensitivity in both the liver and abdomen-pelvis regions. Ten patients developed mild adverse reactions (chills and fever). No HAHA response was detected in this series. Tc-99m-labeled human monoclonal antibody 88BV59H21-2 RIS shows promise as a useful diagnostic modality in patients with colorectal cancer. RIS alone or in combination with CT is more sensitive than CT in detecting tumor within the abdomen and pelvis. Repeated RIS studies may be possible, due to the lack of a HAHA response.

Unlabelled: We report a pilot study of radioimmunoscintigraphy (RIS) and operative gamma probe scintimetry (OPS) using a 99mTc-labeled anti-cytokeratin human monoclonal antibody (MAb) (99mTc-88BV59) in patients with newly diagnosed, recurrent or metastatic colorectal cancer., Methods: Twelve presurgical patients with biopsy- or contrast radiographic-proven colorectal cancer or recurrent colorectal carcinoma were studied. After chest roentgenography and abdominopelvic CT, 99mTc-88BV59 was administered intravenously, planar and SPECT external imaging was performed 3 to 6 hr after injection and planar imaging was performed 18 to 24 hr after injection. Surgery was performed immediately after late planar imaging. OPS of a standardized list of sites to document background radiation activity and of tumor sites, resection margins and tumor beds was performed., Results: The patients had 23 histologically proven tumor sites. Overall sensitivity for CT, planar RIS, SPECT, surgery and OPS was 43%, 61%, 78%, 96% and 91%, respectively. SPECT was superior to CT for imaging extrahepatic abdominal and pelvic disease. OPS detected all liver and extrahepatic abdominal tumor sites and correctly predicted histological tumor-free margins and tumor beds in all cases. OPS did not identify tumor deposits that the surgeon could neither see nor feel. No patient demonstrated human anti-human immune responsiveness 1 and 3 mo after 99mTc-88BV59 infusion., Conclusion: Technetium-99m-88BV59 is a safe, effective radioimmunoconjugate for colorectal cancer imaging, with superior sensitivity as compared to CT.

Background: Recent studies indicate that breast cancer patients do not usually experience the devastating psychological consequences once viewed as inevitable. However, some adjust to the disease more poorly than others. This study examined the personality trait of optimism versus pessimism as a predictor of adjustment over the first year, postsurgery., Methods: Seventy women with early stage breast cancer reported on their general optimism-pessimism at diagnosis. One day before surgery, and at 3-month, 6-month, and 12-month follow-ups, they reported their subjective well-being (mood scales and a measure of satisfaction with life). At follow-ups, they also rated their sex lives, indicated how much physical discomfort was interfering with their daily activities, and reported on thought intrusion., Results: Pessimism displayed poorer adjustment at each time point by all measures except interference from pain. Even controlling for previous well-being, pessimism predicted poorer subsequent well-being, suggesting that pessimism represents a vulnerability to a negative change in adjustment. In contrast, effects of pessimism on quality of sex life and thought intrusion were not incremental over time. Additional analyses indicated that effects of the optimism-pessimism measure were captured relatively well by a single item from the scale., Conclusions: A sense of pessimism about one's life enhances a woman's risk for adverse psychological reactions to the diagnosis of, and treatment for, breast cancer. This finding suggests the potential desirability of assessing this quality informally in patients, to serve as a warning sign regarding the patient's well-being during the period surrounding and following surgery.

Background: Radioimmunodetection of cancer using monoclonal antibody fragments offers certain potential advantages over that with whole monoclonal antibodies, including the ability to image early (i.e., to provide images at an early time after injection of the radioantibody) while minimizing the incidence of human anti-mouse antibody response. This paper reports a prospective trial comparing radioimmunodetection with IMMU-4 (a murine anti-CEA monoclonal antibody) 99mTc-labeled Fab' fragments to conventional imaging in 35 colorectal cancer patients., Methods: All patients were investigated by conventional diagnostic methods (CDM) within 4 weeks of radioimmunodetection. Surgical corroboration of findings was obtained in 26 patients (15 with evidence of disease on CDM [CDM+] and 11 with abnormal serum CEA [CDM-] as the only evidence for recurrence). After 1 mg IMMU-4 99mTc-Fab' was injected (19.3 mCi on average), patients underwent planar/SPECT radioimmunodetection 2-5 hours later and planar radioimmunodetection 18-24 hours later. Three patients underwent a second radioimmunodetection study 16, 20 and 23 months after the first., Results: Radioimmunodetection was superior to CDM, accurately predicting disease distribution in six nonsurgical and ten CDM+ surgical patients, and was complementary to computed tomography in two nonsurgical and two CDM+ surgical patients. Radioimmunodetection would have directed or changed management decisions in 6 of the 15 (40%) CDM+ surgical patients. Radioimmunodetection correctly identified all recurrent tumor in 8 of 11 CDM- surgical patients and was negative in one patient with cirrhosis and no recurrence, representing a potential clinical benefit of 82%. Analyzed on a regional basis, radioimmunodetection was found to be superior to CDM in extrahepatic abdomen and pelvis imaging and was complementary to (although not as accurate as) CDM in the liver. Human anti-mouse antibody did not develop in any of the patients, including three who were injected twice., Conclusions: IMMU-4 99mTc-Fab' radioimmunodetection shows promise as a clinically useful diagnostic tool in patients with colorectal cancer, detecting disease often missed by conventional imaging. IMMU-4 99mTc-Fab' may prove useful for serial radioimmunodetection studies, because human anti-mouse antibody response does not appear to be a problem with this radioimmunoconjugate. It also has the advantage of permitting same-day imaging.

Pelvic recurrence following curative resection for colorectal carcinoma continues to pose a challenge to the oncologist despite current multimodality therapy. Pelvic exenteration with or without sacral resection may provide long-term disease-free survival and a chance of cure for a small subset of patients in whom the recurrent disease is confined to the pelvis and can be resected with "clear" margins. For others with residual disease, exenteration may offer good palliation for the intractable symptoms, but no survival advantage. The clinical decision to perform exenteration with palliative intent must be individualized. This is generally not advised because of the short life expectancy in the face of prolonged convalescence. This technically demanding procedure is associated with significant morbidity, especially in patients with prior pelvic radiation. Current advances in urinary diversion and methods of pelvic reconstruction may significantly reduce these problems. The surgeon's experience and careful patient selection remain the most important determinants of success with this operation.

Background: Local failure after curative surgery for colorectal adenocarcinoma remains a major source of morbidity and mortality. This retrospective analysis reviews the authors' experience with pelvic exenteration in the setting of recurrent and locally advanced colorectal cancer., Methods: Between 1979 and 1986, 50 pelvic exenterations were performed for recurrent (43) and primary (7) colorectal pelvic malignancies. Of these, 30 patients were operated on with curative intent, whereas 20 underwent operation for palliation of intractable pain, sepsis, fistula, bleeding, or bowel obstruction. Twenty-six patients had received radiation to 4000 cGy or more. Of the recurrent tumors, the median time from primary treatment to exenteration was 39.7 months., Results: Postoperative mortality included 7 in-hospital deaths (14%): 5 of 20 in the palliative group and 2 of 30 in the curative group. Complications were common (a total of 71 occurrences), but there has been a significant decrease with experience. The median survival was 19 months for the curative group and 10 months for the palliative group, excluding perioperative mortality. The 5-year survival was 6% overall, and 10% for the curative group. Eighty-nine percent of patients in the curative group had significant pain relief (71% complete, 18% partial), whereas 67% of those in the palliative group had complete or partial pain control., Conclusions: Long-term survival after pelvic exenteration for recurrent colorectal carcinoma is uncommon (2/43), but sustained palliation and local control can be achieved with acceptable morbidity and mortality in most patients with intractable pelvic symptoms.

Neoplasms of APUD cell origin are quite variable in their metastatic behavior. Whereas pituitary and parathyroid tumors almost never metastasize, all oat cell lung cancers, malignant melanomas, trabecular carcinomas of the skin and medullary thyroid cancers are capable of dissemination. The metastatic proclivity of individual carcinoids, pancreatic and extrapancreatic islet cell tumors, and paragangliomas is much less predictable. In particular, there are no reliable histological markers of risk for lymphatic or hematogenous dissemination. The behavior of many carcinoids, islet cell carcinomas and paragangliomas is relatively indolent, even when metastatic disease is already present. However, unresectable distant metastases, especially liver involvement, connote a poor prognosis. Mortality is more often related to uncontrolled tumor growth and metastasis than to associated endocrinopathies. Curative or debulking surgical resection should be aggressively pursued as recent data show that worthwhile clinical disease-free survival can be realized in at least some patients.

At diagnosis, 59 breast cancer patients reported on their overall optimism about life; 1 day presurgery, 10 days postsurgery, and at 3-, 6-, and 12-month follow-ups, they reported their recent coping responses and distress levels. Optimism related inversely to distress at each point, even controlling for prior distress. Acceptance, positive reframing, and use of religion were the most common coping reactions; denial and behavioral disengagement were the least common reactions. Acceptance and the use of humor prospectively predicted lower distress; denial and disengagement predicted more distress. Path analyses suggested that several coping reactions played mediating roles in the effect of optimism on distress. Discussion centers on the role of various coping reactions in the process of adjustment, the mechanisms by which dispositional optimism versus pessimism appears to operate, third variable issues, and applied implications.