Laparoscopic adrenalectomy for large adrenal masses: a challenge or a routine?

AIM: The increased incidence of malignancy and the concern for higher rate of complications with laparoscopic resection of larger tumors typically limits laparoscopic adrenalectomy to small adrenal masses. We used our prospectively collected database to compare laparoscopic adrenalectomy outcomes between small and large adrenal tumors. METHODS: Operative details and outcomes were compared by adrenal mass size size: Group A≤4 cm and Group B>4 cm, for consecutive laparoscopic adrenalectomies performed between 2009 and 2013. RESULTS: Group A (N.=50) and Group B (N.=27) subjects had similar operative times (131 vs. 132 min, P=0.48). Group B subjects were older, had more adrenal malignancies, and had a higher blood loss with a slightly larger change in hemoglobin than Group A subjects; however, no subject required blood transfusion and complication rates were similar between groups (4% vs. 11%, P=0.34). One subject from each group required conversion to open adrenalectomy. CONCLUSION: Laparoscopic adrenalectomy can be performed safely for adrenal masses >4 cm and size is not a contraindication to the laparoscopic approach.

Current approaches, challenges and future directions for monitoring treatment response in prostate cancer.

Prostate cancer is the most commonly diagnosed non-cutaneous neoplasm in men in the United States and the second leading cause of cancer mortality. One in 7 men will be diagnosed with prostate cancer during their lifetime. As a result, monitoring treatment response is of vital importance. The cornerstone of current approaches in monitoring treatment response remains the prostate-specific antigen (PSA). However, with the limitations of PSA come challenges in our ability to monitor treatment success. Defining PSA response is different depending on the individual treatment rendered potentially making it difficult for those not trained in urologic oncology to understand. Furthermore, standard treatment response criteria do not apply to prostate cancer further complicating the issue of treatment response. Historically, prostate cancer has been difficult to image and no single modality has been consistently relied upon to measure treatment response. However, with newer imaging modalities and advances in our understanding and utilization of specific biomarkers, the future for monitoring treatment response in prostate cancer looks bright.

Distinctive stages and strain variations of A. baumannii biofilm development under shear flow.

OBJECTIVE: To examine and characterise the process of Acinetocbacter baumannii biofilm development under shear flow. METHOD: Using an automated flow-cell system with microfluidic channels connected to an imaging system, I 0 clinical wound isolates of A. baumannii were examined for their ability to form biofilms under shear flow, on the glass surface of the flow through device. Flow biofilm development by this organism was observed to comprise four stages: attachment, microcolony formation, maturation with three dimensional structures, and dispersion. RESULTS: A. baumannii adheres readily to glass surfaces and quickly forms biofilm. Significant variations were observed among these I 0 clinical strains in their ability to attach and form flow biofilms. CONCLUSION: These specific characteristics in biofilm formation may contribute to this organism's ability to disseminate within health-care environments.

Patients at risk for peritoneal surface malignancy of colorectal cancer origin: the role of second look laparotomy.

Peritoneal surface malignancy (PSM) is a frequent occurrence in the natural history of colorectal cancer (CRC). Although significant advances have been made in screening of CRC, similar progress has yet to be made in the early detection of PSM of colorectal cancer origin. The fact that advanced CRC can be confined to the peritoneal surface without distant dissemination forms the basis for aggressive multi-modality therapy consisting of cytoreductive surgery (CRS) plus hyperthermic intra-peritoneal chemotherapy (HIPEC), and neoadjuvant and/or adjuvant systemic therapy. Reported overall survival with complete CRS+HIPEC exceeds that of systemic therapy alone for the treatment of PSM from CRC, underscoring the advantage of this multi-modality therapeutic approach. Patients with limited peritoneal disease from CRC can undergo complete cytoreduction, which is associated with the best reported outcomes. As early or limited peritoneal carcinomatosis is undetectable by conventional imaging modalities, second look laparotomy is an important means to identify disease in high-risk patients at a stage most amenable to complete cytoreduction. This review focuses on the identification of patients at risk for PSM from CRC and discusses the role of second look laparotomy.

Multi-Parametric MRI-Directed Focal Salvage Permanent Interstitial Brachytherapy for Locally Recurrent Adenocarcinoma of the Prostate: A Novel Approach.

Even with the technological advances of dose-escalated IMRT with the addition of the latest image guidance technologies, local failures still occur. The combination of MRI-based imaging techniques can yield quantitative information that reflects on the biological properties of prostatic tissues. These techniques provide unique information that can be used for tumor detection in the treated gland. With the advent of these improved imaging modalities, it has become possible to more effectively image local recurrences within the prostate gland. With better imaging, these focal recurrences can be differentially targeted with salvage brachytherapy minimizing rectal and bladder toxicity. Here we report a novel use of MRI-directed focal brachytherapy after local recurrence. This technique offers a unique opportunity to safely and successfully treat recurrent prostate cancer, previously treated with definitive radiation therapy. The use of multi-parametric MRI-directed focal salvage permanent interstitial brachytherapy for locally recurrent adenocarcinoma of the prostate is a promising strategy to avoid more aggressive and expensive treatments that are associated with increased morbidity, potentially improving survival at potentially lower costs.

Primary anorectal melanoma: an update.

The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

Infiltrating lobular carcinoma of the breast presenting as gastrointestinal obstruction: a mini review.

One in twelve American women will develop breast cancer, with infiltrating lobular carcinoma (ILC) comprising approximately 15% of these cases. The incidence of ILC has been increasing over the last several decades. It has been hypothesized that this increase is associated with combined replacement hormonal therapy. Although pathologically distinct from infiltrating ductal carcinoma (IDC), ILC is treated in the same manner as IDC. However, ILC demonstrates significantly different patterns of late local recurrence and distant metastasis. The incidence of extra-hepatic gastrointestinal metastases is reported to be 6% to 18%, with stomach being most common. Herein, we present a brief review of the literature and a typical case involving ILC initially presenting as a small bowel obstruction. Evidence suggests that the late clinical patterns of ILC are distinctly separate from IDC and physicians need be cognizant of its late local recurrence and unique late metastatic pattern. Different follow up strategy should be entertained in patients with ILC.

An overview of biofilm and its detection in clinical samples.

In many instances, wound colonising-bacteria are thought to be capable of forming biofilms, a significant factor contributing to delays or failure in wound healing. This review summarises the accumulated knowledge of biofilm and addresses the unmet need of biofilm detection in clinical wound samples.

Current Practice Patterns Regarding the Conduct of Thyroidectomy and Parathyroidectomy amongst Surgeons - A Survey Study.

BACKGROUND: Heterogeneity of surgical care exists among surgeons regarding the conduct of thyroidectomy and parathyroidectomy. AIM: To identify the current patterns of technical conduct of operation amongst surgeons performing thyroidectomy or parathyroidectomy. METHODS: A survey was designed and beta-tested on five surgical oncologists for face validity and usability. The final version of this survey was constructed and disseminated using the professional version of the internet-based survey mechanism Survey Monkey and consisted of two eligibility questions and 22 questions regarding thyroidectomy/parathyroidectomy treatment patterns. The survey was disseminated electronically to American Association of Endocrine Surgeons (AAES) and American College of Surgeons (ACS) members. Survey results were collected, tabulated and analyzed. Responses among groups were compared using two sample T- tests. Significant responses were subsequently analyzed in generalized linear models to ascertain if significance remained with control of covariates. RESULTS: Of 420 initial web survey visits, 236 (56.2%) surveys were completed. The majority of respondents reported being 'fellowship trained', experienced and 'high-volume' surgeons. The most common fellowship trainings were endocrine (46%), oncology (22%), head & neck (13%), or combinations of the three fellowships (14%). Most surgeons reported that they dissect the course of the recurrent laryngeal nerve (RLN) without using neuromonitoring. Nearly a third of respondents reported routinely using the Harmonic scalpel during the conduct of the operations. Significant differences emerged regarding operative technique according to residency training type, fellowship training, surgeon volume, and practice setting, but only those associated with residency training type and annual surgeon surgical volume remained significant within generalized linear models. CONCLUSION: Most surgeons who responded to this survey do not routinely use RLN neuromonitoring and most dissect the RLN during thyroidectomy. There are multiple variations in technique according to surgical training, surgeon volume, experience, and practice setting; however, only differences by residency training type and surgeon volume remained correlated significantly to surgeons' approaches to thyroidectomy and parathyroidectomy in multivariate analysis. These data may be useful for surgeons reflecting upon their individual practice, as well as for further defining current standards of practice from a medico legal perspective.

Aberrant expression of chromogranin A, miR-146a, and miR-146b-5p in prostate structures with focally disrupted basal cell layers: an early sign of invasion and hormone-refractory cancer?

Our recent studies have suggested that prostate tumor invasion is triggered by autoimmunoreactions induced focal basal cell layer disruptions (FBCLD) that selectively favor monoclonal proliferation of the overlying progenitors or of a biologically more aggressive cell clone. As circulating chromogranin-A (CgA) levels are found to correlate with tumor progression and the status of hormone refractoriness, our current study attempted to assess whether CgA-positive cells would be preferentially distributed in epithelial structures with FBCLD. Paraffin-embedded specimens from 50 patients with organ-confined prostate cancer were subjected to double immunohistochemical analysis with monoclonal antibodies to basal cells and CgA. From each case, 3-5 randomly selected fields were digitally photographed and the photos were magnified 400% and the numbers of CgA-positive cells in epithelial structures with non-disrupted, focally disrupted, and lost basal cell layer were separately counted. The averaged number of cell for each category was statistically compared with the Pearson's Chi-square test. In addition, morphologically similar structures with and without CgA-positive cell clusters were microdissected from four selected cases and subjected to a comparison of differential micro-RNA expression levels. Our study revealed that, although isolated CgA-positive cells were seen in both the basal cell layer and the luminal cell population in all cases, only 8 cases (16%) harbored large clusters of CgA-positive cells that were concentrated in a given area, in which all or nearly all cells appeared to share a similar morphological and immunohistochemical profile. Microdissected epithelial structures with CgA-positive cell clusters exhibited a more than 5- and 7-fold lower expression of miR-146a and miR-146b-5p than their CgA-negative counterparts. As focal basal cell layer disruptions and the reduction or loss of miR-146a and miR-146b-5p has been documented to correlate with prostate tumor invasion and hormone refractoriness, our findings suggest that aberrant CgA expression in epithelial structures with FBCLD may represent an early sign of these events.

Novel model of peripheral tissue trauma-induced inflammation and gastrointestinal dysmotility.

BACKGROUND: Trauma is a leading cause of death and although the gut is recognized as the 'motor' of post-traumatic systemic inflammatory response syndrome and multiple organ failure, studies on the gastrointestinal (GI) tract are few. Our objectives were to create a precisely controllable tissue injury model in which GI motility, systemic inflammation and wound fluid can be analyzed. METHODS: A non-narcotic murine trauma model was developed by the subcutaneous dorsal trans-implantation of a devitalized donor syngeneic harvested tissue-bone matrix (TBX), which was precisely adjusted to % total body weight and studied after 21 h. Gastrointestinal transit histograms were plotted after the oral administration of non-digestible FITC-dextran and geometric centers calculated. Organ bath evaluated jejunal circular muscle contractility. Multiplex electrochemiluminescence measurements of serum and TBX wound fluid inflammatory mediators were performed. KEY RESULTS: Increasing TBX amounts progressively delayed transit, whereas TBX heat denaturation or decellularization prevented ileus and death. In the TBX(17.5%) model, jejunal muscle contractility was suppressed and a systemic inflammatory response developed as significant serum elevations in IL-6, keratinocyte cytokine and IL-10 compared to sham. In addition, inflammatory responses within the wound fluid showed elevated levels of preformed IL-1ß and TNF-α, whereas, 21 h after implantation IL-1ß, IL-6 and keratinocyte cytokine were significantly increased in the wound. CONCLUSIONS & INFERENCES: A novel donor tissue-bone matrix trauma model was developed that is precisely adjustable and recapitulates important clinical phenomena. The non-narcotic model demonstrated that increasing tissue injury progressively caused ileus, initiated a systemic inflammatory response and developed inflammatory changes within the wound.

Accuracy and clinical relevance of computed tomography scan interpretation of peritoneal cancer index in colorectal cancer peritoneal carcinomatosis: a multi-institutional study.

BACKGROUND: Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. METHODS: A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. RESULTS: Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P < 0.0005), RLQ (P = 0.003), distal jejunum (P = 0.004), and distal ileum (P < 0.0005). When CT-PCI was classified based on the extent of carcinomatosis, 17 cases (33%) were underestimations, of which, 11 cases (21%) were upstaged from low to moderate, 4 cases (8%) were upstaged from low to severe, and 2 cases (4%) were upstaged from moderate to severe. Relevant clinical discordance where an upstage occurred to severe carcinomatosis constituted a true inaccuracy and was observed in six cases (12%). CONCLUSIONS: The actual clinical impact of inaccuracies of CT-PCI was modest. CT-PCI will remain as a mandatory imaging tool and may be supplemented with other tools including positron emission tomography scan or diagnostic laparoscopy, in the patient selection for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Resistance carrying plasmid in a traumatic wound.

OBJECTIVE: To isolate and identify antibiotic-resistant bacteria from the exudate of a complex wound and determine if antibiotic resistance genes are chromosomal or plasmid borne. METHOD: Antibiotic resistant bacteria from wound exudate of a single clinical sample were selected on agar media with ampicillin. A single colony was further screened for resistance to kanamycin by antibiotic-supplemented agar and to other antibiotics by an automated Phoenix instrument. Identification of the isolate was carried out by biochemical profiling and by 16S rDNA analysis. RESULTS: Approximately 51% of total bacteria in the wound exudate with identical colony morphotype were resistant to 100 microg/ml of ampicillin. A single colony from this population also demonstrated resistance to 50 microg/ml of kanamycin on kanamycin-supplemented agar. Further antimicrobial sensitivity testing by the Phoenix instrument indicated resistance to inhibitory concentrations of amoxicillin-clavulanate, ampicillin-sulbactam, cefazolin, gentamicin, nitrofurantoin, tobramycin, and trimethoprim-sulfamethoxazole. Biochemical and 16S rDNA analysis identified this bacterial isolate as a member of genus Enterobacter. A plasmid preparation from this isolate successfully transferred ampicillin and kanamycin resistance to E. coli competent cells. E. coli transformants displayed two resistance phenotypes and the plasmids from these transformants displayed two different restriction type patterns, with one correlating to ampicillin and kanamycin resistance and the other only to ampicillin resistance. CONCLUSION: A multiple antibiotic-resistant Enterobacter spp. from the wound fluid of a clinical sample was found to carry an antibiotic-resistant plasmid in a closely related species E. coli. The presence of antibiotic resistance plasmid in Enterobacteria that are part of the normal microbial flora of the human gut and skin could lead to the spread of resistance phenotype and emergence of antibiotic resistant pathogens. This study suggests normal human microbial fl ora could be a potential reservoir for resistance genes.

Monitoring circulating tumor cells in cancer vaccine trials.

The presence of circulating tumor cells (CTC) from various cancers has provided a wealth of information and possibilities. As the role of CTC detection in the treatment assessment of metastatic breast cancer becomes standard, there is interest in applying this tool in cancer vaccine development and clinical trial monitoring. Since we lack a proven immunologic assay that correlates with clinical response, CTC detection, quantification and phenotypic characterization may be a useful surrogate for clinical outcome. The Cancer Vaccine Development Program is involved in the development of HER2/neu peptide based vaccine development for the prevention of recurrence in HER2/neu expressing cancers like breast cancer. The CellSearch System (Veridex, LLC Warren, NJ) has been used by our lab in conjunction with in vivo and/or in vitro immunologic measurements to define a monitoring tool that could predict clinical response. Once validated, this assay could significantly shorten clinical trials and lead to more efficient assessment of potentially promising cancer vaccines.

Continuous peripheral nerve block in combat casualties receiving low-molecular weight heparin.

BACKGROUND: Continuous peripheral nerve block (CPNB) is an important therapeutic tool in the anaesthetic and analgesic management of combat casualties at Walter Reed Army Medical Center (WRAMC). We describe our experience using CPNB techniques in combat trauma patients treated with low-molecular weight heparin (LMWH). Guidelines used at our institution for managing CPNB catheters in patients being treated with LMWH are introduced. METHODS: From March 2003 to April 2005, 187 combat casualties treated by the WRAMC regional anaesthesia/acute pain section using CPNB were evaluated retrospectively by electronic chart review. Patient characteristic data, CPNB type, duration of CPNB, indication for LMWH [enoxaparin sodium injection (Lovenox-Sanofi Aventis, Bridgewater, NJ, USA)], enoxaparin dose (mg) before and after catheter insertion and removal, time from CPNB placement and removal to enoxaparin dose, and complications were recorded. RESULTS: Median enoxaparin dose and time given before catheter insertion were 30 mg and 21 h, respectively. Median enoxaparin dose was also 30 mg given a median of 12 h after peripheral nerve catheter placement. Catheters remained in situ for a median of 8 days (range 1-33 days). Catheter specific complications were infrequent and identified in 7 (3.7%) patients (two catheter malfunction-kinking, catheter tip dislodgement in situ, two superficial catheter site infections and two catheter dislocations). There were no catheter-related bleeding complications evident in this study. CONCLUSIONS: Information regarding the safety of CPNB in patients treated with LMWH for perioperative venous thromboembolism prevention is scarce. Our initial experience with CPNB and concurrent LMWH has not been complicated by catheter-related bleeding.

The utility of a rapid parathyroid assay for uniglandular, multiglandular, and recurrent parathyroid disease.

The rapid parathyroid hormone assay (rPTH) is an effective tool in minimally invasive resections of parathyroid adenomas. However, there are relatively few reports examining its utility in the full spectrum of parathyroid disease. The purpose of this study was to examine the utility of the rapid parathyroid hormone assay in uniglandular, multiglandular, and recurrent hyperparathyroidism. A retrospective analysis of all patients undergoing parathyroid resection from June 2001 to March 2003 was undertaken. All patients underwent preoperative localization studies. Rapid parathyroid hormone (PTH) levels were drawn immediately prior to and 10 minutes following parathyroid resection. A decline of > or = 50 per cent rPTH qualified as a successful/complete resection. Additional intraoperative samples were drawn as needed for patients with multiglandular disease. Of 46 treated patients who were examined (average age, 54 years), 30 had single, 12 patients had multigland disease, and 4 had recurrent/persistent hyperparathyroidism. Thirty-seven patients had primary hyperparathyroidism (32 with single and 3 with double adenomas; 2 with hyperplasia), 4 patients had secondary hyperparathyroidism, and 5 tertiary hyperparathyroidism. All procedures were considered successful, as every patient exhibited a postresection decrement in rPTH exceeding 50 per cent (average decrement, 91%). Although 2 patients exhibited a postoperative PTH increase exceeding 50 per cent of the preoperative value, all remained asymptomatic and eucalcemic (median follow-up, 21.5 months). The rPTH assay is an effective tool in determining success of parathyroidectomy in patients with primary uni- and multiglandular as well as recurrent hyperparathyroidism. It can be used to achieve minimally invasive neck dissections or guide surgical decision-making in more complex cases.

Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma.

BACKGROUND: Immunohistochemical analysis of sentinel lymph nodes from patients with breast carcinoma and melanoma has been shown to increase the sensitivity for detecting lymph node metastases. To the authors' knowledge, this technique has not been described in patients with Merkel cell carcinoma. METHODS: Lymphatic mapping and sentinel lymph node biopsy was performed on 26 patients with Merkel cell carcinoma between 1997 and 1999. All sentinel lymph nodes were analyzed with conventional hematoxylin and eosin (H&E) staining and then analyzed with immunohistochemical staining to evaluate whether this additional technique would increase the number of patients found to have lymph node metastasis. RESULTS: The median age of the patients in the current study was 67 years and the median tumor size at the time of presentation was 2 cm. Lymph node metastases were identified in 5 of the 26 patients (19%). Three of these five lymph node positive patients were identified with H&E staining. The remaining two patients were identified only after immunohistochemical analysis. The median follow-up in this group of lymph node positive patients was 14 months, with 2 of the 5 lymph node positive patients developing a recurrence. The median follow-up in the 21 patients who were lymph node negative was 19 months, with only 1 patient having developed a recurrence at the time of last follow-up. CONCLUSIONS: Immunohistochemical analysis of sentinel lymph nodes from patients with Merkel cell carcinoma appears to increase the sensitivity of detecting clinically occult lymph node metastases.

High Ki-67 proliferative index predicts disease specific survival in patients with high-risk soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STSs) are heterogeneous neoplasms that have variable clinical outcome. Several clinical parameters and few molecular markers, including Ki-67 proliferative index, have been shown to correlate with patient prognosis. To the authors' knowledge, no definitive report exists to identify one molecular marker that can be analyzed easily in a clinical setting and that predicts survival in a cohort of patients with high-risk STS of identical clinical characteristics but variable outcome. METHODS: The influence of clinical prognostic factors was eliminated by selecting two patient groups with identical high-risk characteristics: large (> 10 cm), high-grade, deep, completely resected primary extremity STS (n = 47). Patients in the first group remained disease free (no evidence of disease [NED]) after primary tumor treatment (n = 19), whereas patients in the second group subsequently died of disease (DOD; n = 28). Triplicate 0.6-mm core biopsies from defined morphologic areas of paraffin embedded primary tumors were assembled on a tissue microarray and analyzed by immunohistochemistry with the MIB-1 antibody, and Ki-67 proliferative indices were correlated with patient outcome. RESULTS: High Ki-67 proliferative index, defined as greater than 30% tumor cells showing nuclear immunoreactivity, was significantly more frequent in the DOD group than in the NED group and was associated with tumor-related mortality (P = 0.02). This marker identifies an especially aggressive malignant phenotype within a cohort of high-risk tumors that is based on well established clinical and pathologic parameters alone and is easy to use in a clinical setting. CONCLUSIONS: On the basis of these data and previous reports, high Ki-67 proliferative index is suggested as a significant factor for predicting the prognosis of patients with high-risk STS and should be evaluated prospectively based on clinical trials.

Amputation for recurrent soft tissue sarcoma of the extremity: indications and outcome.

BACKGROUND: Limb salvage after primary site failure of extremity soft tissue sarcoma is a challenging problem. Amputation may be the most effective treatment option in selected patients with local recurrence. We compared the outcome of patients treated with amputation versus limb-sparing surgery (LSS) for locally recurrent extremity sarcoma. METHODS: From 1982 to 2000, 1178 patients with localized primary extremity sarcoma underwent LSS. Of these, 204 (17%) developed local recurrence. Eighteen (9%) required major amputation and the remainder underwent LSS, of which 34 were selected for matched-pair analysis according to established prognostic variables. Rates of recurrence or death were estimated by the Kaplan-Meier method. Following adjustment for prognostic variables, a Mantel-Haenszel test was used to compare the outcome between the two treatment groups. RESULTS: Patients in each group were well matched. All patients had high-grade tumors deep to the fascia. Median time to local recurrence was similar for both groups. Median follow-up was 95 months. Amputation was associated with a significant improvement in local control of disease (94% vs. 74%; P = .04). We observed no difference in disease-free (P = .48), disease-specific (P = .74), or overall survival (P = .93) between the two groups. Median postrecurrence survival was 20 months and 5-year OS was 36% for the entire study group. CONCLUSIONS: Limb-sparing treatment achieves local control in the majority of recurrent extremity sarcomas for which amputation is infrequently indicated. Amputation improves local disease control but not survival under these circumstances.

Hürthle cell carcinoma: a critical histopathologic appraisal.

PURPOSE: Controversy exists over the ability of morphology to predict the biologic behavior of Hürthle cell carcinoma. The aim of this study was to conduct a critical histopathologic review of Hürthle cell carcinoma and to correlate morphologic parameters with clinical outcome. PATIENTS AND METHODS: Patients with histologically confirmed Hürthle cell carcinoma treated between 1940 and 2000 form the basis of this study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB] n = 17) had solid growth pattern, incomplete capsular invasion (Ci), or both but no vascular invasion (Vi). Minimally invasive carcinomas ([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33) demonstrated more than one focus of Vi, more than one focus of Ci, or both. The primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Rates of recurrence/death were estimated by Kaplan-Meier method. The univariate influence of prognostic factors on end points was analyzed by log-rank test, and multivariate analysis was performed by Cox regression. RESULTS: Median follow-up was 8 years. No patients with UMB or MIC relapsed or died of disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and extent of resection did not influence outcome. Adverse predictors of RFS and DSS among WIC were extrathyroidal extension, nodal metastasis, positive margin, and solid growth pattern (P <.05). Both Ci and Vi were associated with worse DSS (P <.05). On multivariate analysis, extrathyroidal extension and nodal metastases were independent predictors of outcome (P <.05). CONCLUSION: Patients with Hürthle cell carcinoma have a prognosis that is predicted by well-defined histomorphologic characteristics. Unlike differentiated thyroid cancer, nodal metastases predict a worse outcome in widely invasive Hürthle cell carcinoma, as does extrathyroidal extension.