Jeffrey E. Lee

Multi-Institutional Melanoma Lymphatic Mapping Experience: The Prognostic Value of Sentinel Lymph Node Status in 612 Stage I or II Melanoma Patients

PURPOSE To compare the effect of pathologic sentinel lymph node (SLN) status with that of other known prognostic factors on recurrence and survival in patients with stage I or II cutaneous melanoma. PATIENTS AND METHODS We reviewed the records of 612 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between January 1991 and May 1995 to determine the effects of tumor thickness, ulceration, Clark level, location, sex, and SLN pathologic status on disease-free and disease-specific survival. RESULTS In the 580 patients in whom lymphatic mapping and SLN biopsy were successful, the SLN was positive by conventional histology in 85 patients (15%) but negative in 495 patients (85%). SLN status was the most significant prognostic factor with respect to disease-free and disease-specific survival by univariate and multiple covariate analyses. Although tumor thickness and ulceration influenced survival in SLN-negative patients, they provided no additional prognostic information in SLN-positive patients. CONCLUSION Lymphatic mapping and SLN biopsy is highly accurate in staging nodal basins at risk for regional metastases in primary melanoma patients and identifies those who may benefit from earlier lymphadenectomy. Furthermore, pathologic status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for recurrence. The information from SLN biopsy is particularly helpful in establishing stratification criteria for future adjuvant trials.

Borderline Resectable Pancreatic Cancer: Definitions, Management, and Role of Preoperative Therapy

With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of “borderline resectability.” In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180° of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome.

Patterns of recurrence following a negative sentinel lymph node biopsy in 243 patients with stage I or II melanoma.

PURPOSE To determine the patterns of recurrence and causes of regional nodal basin failure in stage I or II melanoma patients who had a histologically negative sentinel lymph node (SLN) and whose regional nodal basins were not dissected following lymphatic mapping and SLN biopsy. PATIENTS AND METHODS The records of 344 patients with primary cutaneous melanoma who underwent lymphatic mapping and SLN biopsy between 1991 and 1995 at The University of Texas M.D. Anderson Cancer Center were reviewed. Of 322 patients who underwent successful lymphatic mapping procedures, 270 had histologically negative SLNs; mapped nodal basins were observed without further surgical intervention in 243 of these 270 patients. Recurrence patterns were analyzed from this cohort and a histologic reevaluation of all previously identified SLNs on which a biopsy had been taken was performed in patients who developed recurrent disease. RESULTS Of 243 patients with a histologically negative SLN, 27 (11%) developed local, in-transit, regional nodal, and/or distant metastases after a median follow-up time of 35 months. Ten patients (4.1%) developed a nodal recurrence in the previously mapped basin, either solely or as a component of the first site of recurrence. Detailed analysis of the SLNs in these 10 patients demonstrated evidence of occult metastases in 80% by serial sectioning or immunohistochemical staining. CONCLUSION Regional nodal failures in melanoma patients following a negative SLN biopsy are infrequent and to date have most commonly occurred because conventional histologic evaluation was unable to identify occult metastatic disease. These data provide further evidence that lymphatic mapping and SLN biopsy accurately reflect the status of the regional nodal basin. Specialized pathologic techniques are necessary to reduce further the already low false-negative rates and to improve disease staging.

Borderline Resectable Pancreatic Cancer: The Importance of This Emerging Stage of Disease

BACKGROUND Patients with borderline resectable pancreatic adenocarcinoma (PA) include those with localized disease who have tumor or patient characteristics that preclude immediate surgery. There is no optimal treatment schema for this distinct stage of disease, so the role of surgery is undefined. STUDY DESIGN We defined patients with borderline resectable PA as fitting into one of three distinct groups. Group A comprised patients with tumor abutment of the visceral arteries or short-segment occlusion of the Superior Mesenteric Vein. In group B, patients had findings suggestive but not diagnostic of metastasis. Group C patients were of marginal performance status. Patients were treated initially with chemotherapy, chemoradiation, or both; those of sufficient performance status who completed preoperative therapy without disease progression were considered for surgery. RESULTS Between October 1999 and August 2006, 160 (7%) of 2,454 patients with PA were classified as borderline resectable. Of these, 125 (78%) completed preoperative therapy and restaging, and 66 (41%) underwent pancreatectomy. Vascular resection was required in 18 (27%) of 66 patients, and 62 (94%) underwent a margin-negative pancreatectomy. A partial pathologic response to induction therapy (< 50% viable tumor) was seen in 37 (56%) of 66 patients. Median survival was 40 months for the 66 patients who completed all therapy and 13 months for the 94 patients who did not undergo pancreatectomy (p < 0.001). CONCLUSIONS This is the first large report of borderline resectable PA and includes objective definitions for this stage of disease. Our neoadjuvant approach allowed for identification of the marked subset of patients that was most likely to benefit from surgery, as evidenced by the favorable median survival in this group.

Pancreaticoduodenectomy With Vascular Resection: Margin Status and Survival Duration

Major vascular resection performed at the time of pancreaticoduodenectomy (PD) for adenocarcinoma remains controversial. We analyzed all patients who underwent vascular resection (VR) at the time of PD for any histology at a single institution between 1990 and 2002. Preoperative imaging criteria for PD included the absence of tumor extension to the celiac axis or superior mesenteric artery (SMA). Tangential or segmental resection of the superior mesenteric or portal veins was performed when the tumor could not be separated from the vein. As a separate analysis, all patients who underwent PD with VR for pancreatic adenocarcinoma were compared to all patients who underwent standard PD for pancreatic adenocarcinoma. A total of 141 patients underwent VR with PD. Superior mesenteric-portal vein resections included tangential resection with vein patch (n = 36), segmental resection with primary anastomosis (n = 35), and segmental resection with autologous interposition graft (n = 55). Hepatic arterial resections were performed in 10 patients, and resections of the anterior surface of the inferior vena cava were performed in 5 patients. PD was performed for pancreatic adenocarcinoma in 291 patients; standard PD was performed in 181 and VR in 110. Median survival was 23.4 months in the group that required VR and 26.5 months in the group that underwent standard PD (P = 0.177). A Cox proportional hazards model was constructed to analyze the effects of potential prognostic factors (VR, tumor size, T stage, N status, margin status) on survival. The need for VR had no impact on survival duration. In conclusion, properly selected patients with adenocarcinoma of the pancreatic head who require VR have a median survival of approximately 2 years, which does not differ from those who undergo standard PD and is superior to historical patients believed to have locally advanced disease treated nonoperatively.

Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma

Objective:To better understand the impact of a microscopically positive margin (R1) on patterns of disease recurrence and survival after pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma. Summary Background Data:A positive resection margin after PD is considered to be a poor prognostic factor, and some have proposed that an R1 margin may be a biologic predictor of more aggressive disease. The natural history of patients treated with contemporary multimodality therapy who underwent a positive margin PD has not been described. Methods:We analyzed our experience from 1990 to 2004, which included the prospective use of a standardized system for pathologic analysis of all PD specimens. All patients who underwent PD met objective computed tomographic criteria for resection. Standard pathologic evaluation of the PD specimen included permanent section analysis of the final bile duct, pancreatic, and superior mesenteric artery (SMA) margins. First recurrences (all sites) were defined as local, regional, or distant. Survival and follow-up were calculated from the date of initial histologic diagnosis to the dates of first recurrence or death and last contact, respectively. Results:PD was performed on 360 consecutive patients with pancreatic adenocarcinoma. Minimum follow-up was 12 months (median, 51.9 months). The resection margins were negative (R0) in 300 patients (83.3%) and positive (R1) in 60 (16.7%); no patients had macroscopically positive (R2) margins. By multivariate analysis (MVA), high mean operative blood loss and large tumor size were independent predictors of an R1 resection. Patients who underwent an R1 resection had a median overall survival of 21.5 months compared with 27.8 months in patients who underwent an R0 resection. After controlling for other variables on MVA, resection status did not independently affect survival. By MVA, only lymph node metastases, major perioperative complications, and blood loss adversely affected survival. Conclusions:There was no statistically significant difference in patient survival or recurrence based on R status. However, this series is unique in the incorporation of a standardized surgical technique for the SMA dissection, the prospective use of a reproducible system for pathologic evaluation of resection margins, the absence of R2 resections, and the frequent use of multimodality therapy.

Role of preoperative ultrasonography in the surgical management of patients with thyroid cancer.

BACKGROUND Cervical recurrence occurs in up to 30% of patients with differentiated thyroid carcinoma. We retrospectively compared preoperative transcutaneous ultrasonography and physical examination (PE) results in the detection of local-regional metastases (lymph node and soft tissue) in patients with thyroid cancer. METHODS Data were collected retrospectively from the medical records of patients with thyroid carcinoma who underwent preoperative ultrasonography. Patients were divided into 3 groups: group 1, those undergoing primary thyroid/neck surgery; group 2, those undergoing reoperation for persistent disease; and group 3, those undergoing reoperation for recurrent thyroid carcinoma. For each group, we recorded the frequencies with which ultrasonography detected disease in a neck compartment (central or lateral) that was normal on PE. RESULTS Two hundred twelve patients underwent operation for primary, persistent, or recurrent papillary (n=130), medullary (n=61), or follicular/Hürthle cell (n=21) carcinoma. Ultrasonography detected additional sites of metastatic disease not appreciated on PE in 21 (20%) of 107 group 1 patients, 9 (32%) of 28 group 2 patients, and 52 (68%) of 77 group 3 patients. The surgical procedure performed was altered by the information obtained from preoperative ultrasonography in 82 (39%) of the 212 patients. Of the 107 group 1 patients, cervical recurrence has been detected in only 6 (6%) at a median follow-up of 36 months, in spite of 67 (63%) having tumors larger than 2 cm or lymph node metastases. CONCLUSIONS Preoperative high-quality ultrasonography detected lymph node or soft-tissue metastases in neck compartments believed to be uninvolved by PE in 39% of patients. Ultrasound findings altered the operative procedure in these patients, facilitating complete resection of disease and potentially minimizing local-regional recurrence.

Adrenal cortical carcinoma

Adrenal cortical carcinoma is a rare endocrine tumor for which complete surgical resection is the only potentially curative treatment. Accurate preoperative evaluation (biochemical and radiographic) of the patient who presents with an adrenal mass maximizes the opportunity for the patient to undergo a complete, margin-negative resection of the primary tumor, which is the most powerful prognostic variable for long-term survival. The response to chemotherapy or mitotane is modest in patients with advanced disease. Hopefully, an improved understanding of the molecular pathogenesis of this challenging tumor will lead to the development of more effective therapies in the future.RésuméLe cancer de la corticosurrénale est une tumeur endocrine rare pour laquelle seule la résection chirurgicale complète offre la possibilité de guérison. C’est par une évaluation préopératoire précise (biochimique et radiographique) d’un patient présentant une masse de la surrénale qu’on s’assure d’une résection complète, avec des marges libres, ce qui est le facteur pronostique le plus puissant pour évaluer la survie à long terme. La réponse à la chimiothérapie ou au mitotane est modeste chez la plupart de patients ayant une maladie avancée. On espère que grâce à une compréhension de la pathogenèse moléculaire de cette tumeur, on pourra développer de nouvelles thérapies plus efficaces dans l’avenir.ResumenEl carcinoma adrenocortical es un tumor endocrino raro para el cual la resección quirúrgica total es la única modalidad terapéutica potencialmente curativa. La debida evaluación preoperatoria (bioquímica y radiográfica) del paciente que presenta una masa suprarrenal maximiza la posibilidad de lograr la resección completa del tumor primario con márgenes libres, que es la variable pronóstica de mayor importancia en lo relativo a supervivencia a largo plazo. La respuesta a la quimioterapia o al mitotane es modesta en los casos de enfermedad avanzada. Se guarda la esperanza de que una mejor comprensión de la patogénesis molecular de este tumor lleve al desarrollo de nuevas y más efkaces formas de tratamiento.

Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence

OBJECTIVE Tumor invasion of the superior mesenteric-portal vein (SMPV) confluence is often considered a contraindication to pancreaticoduodenectomy for patients with malignant tumors of the pancreas or periampullary region. The authors sought to determine whether pancreaticoduodenectomy with en bloc resection of the SMPV confluence could be safely performed and whether tumors involving the SMPV confluence were associated with pathologic parameters suggesting poor prognosis. SUMMARY BACKGROUND DATA Several centers have reported high rates of retroperitoneal margin positivity after pancreaticoduodenectomy for tumors of the pancreatic head and periampullary region. Positive-margin or incomplete resection is associated with early tumor recurrence and no survival benefit compared with palliative therapy. Tumor adherence to the lateral of posterior wall of the SMPV confluence often represents the only barrier to complete tumor resection at the time of pancreaticoduodenectomy. METHODS Data on all patients undergoing pancreaticoduodenectomy for adenocarcinoma of the pancreas or periampullary region over a 3.5-year period were entered prospectively in a pancreatic tumor database. To be considered for surgery, patients were required to fulfill the following computed tomography criteria for resectability: 1) the absence of extrapancreatic disease, 2) no tumor encasement of the superior mesenteric artery or celiac axis, and 3) a patent SMPV confluence. Tumor adherence to the superior mesenteric vein or SMPV confluence was assessed intraoperatively, and en bloc venous resection was performed when necessary to achieve complete tumor extirpation. Data on operative characteristics, morbidity, mortality, tumor size, nodal metastases, margin positivity, perineural invasion, and tumor DNA content were compared for patients who did and did not receive venous resection. RESULTS Fifty-nine patients underwent pancreaticoduodenectomy, 36 without venous resection and 23 with en bloc resection of the SMPV confluence. No differences in median hospital stay, morbidity, mortality, tumor size, margin positivity, nodal positivity, or tumor DNA content were observed between groups. CONCLUSIONS When necessary, segmental resection of the SMPV confluence may be performed safely during pancreaticoduodenectomy for periampullary malignant tumors. Tumors invading the SMPV confluence are not associated with histologic parameters suggesting a poor prognosis. Our data suggest that venous involvement is a function of tumor location rather than an indicator of aggressive tumor biology.

Frequent Detection of Pancreatic Lesions in Asymptomatic High-Risk Individuals

BACKGROUND & AIMS The risk of pancreatic cancer is increased in patients with a strong family history of pancreatic cancer or a predisposing germline mutation. Screening can detect curable, noninvasive pancreatic neoplasms, but the optimal imaging approach is not known. We determined the baseline prevalence and characteristics of pancreatic abnormalities using 3 imaging tests to screen asymptomatic, high-risk individuals (HRIs). METHODS We screened 225 asymptomatic adult HRIs at 5 academic US medical centers once, using computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasonography (EUS). We compared results in a blinded, independent fashion. RESULTS Ninety-two of 216 HRIs (42%) were found to have at least 1 pancreatic mass (84 cystic, 3 solid) or a dilated pancreatic duct (n = 5) by any of the imaging modalities. Fifty-one of the 84 HRIs with a cyst (60.7%) had multiple lesions, typically small (mean, 0.55 cm; range, 2-39 mm), in multiple locations. The prevalence of pancreatic lesions increased with age; they were detected in 14% of subjects younger than 50 years old, 34% of subjects 50-59 years old, and 53% of subjects 60-69 years old (P < .0001). CT, MRI, and EUS detected a pancreatic abnormality in 11%, 33.3%, and 42.6% of the HRIs, respectively. Among these abnormalities, proven or suspected neoplasms were identified in 85 HRIs (82 intraductal papillary mucinous neoplasms and 3 pancreatic endocrine tumors). Three of 5 HRIs who underwent pancreatic resection had high-grade dysplasia in less than 3 cm intraductal papillary mucinous neoplasms and in multiple intraepithelial neoplasias. CONCLUSIONS Screening of asymptomatic HRIs frequently detects small pancreatic cysts, including curable, noninvasive high-grade neoplasms. EUS and MRI detect pancreatic lesions better than CT.