John C. Kairys

Immunopharmacologic Analysis of an Autologous, Hapten-Modified Human Melanoma Vaccine

PURPOSE We have previously reported a clinical trial of a human cancer vaccine consisting of autologous tumor cells modified with the hapten, dinitrophenyl (DNP), in patients with clinical stage III melanoma. Here we present a follow-up report expanded to 214 patients with 5-year follow-up. PATIENTS AND METHODS Two hundred fourteen patients with clinical stage III melanoma (117 patients with stage IIIC and 97 patients with stage IIIB) who were melanoma-free after standard lymphadenectomy were treated with multiple intradermal injections of autologous, DNP-modified vaccine mixed with bacille Calmette-Guérin. Four vaccine dosage schedules were tested sequentially, all of which included low-dose cyclophosphamide. Patients were tested for delayed-type hypersensitivity (DTH) to autologous melanoma cells, both DNP-modified and unmodified, and to control materials. RESULTS The 5-year overall survival (OS) rate of the 214 patients was 44%. DTH responses to unmodified autologous melanoma were induced in 47% of patients. The OS of this DTH-positive group was double that of DTH-negative patients (59.3% v 29.3%; P <.001). In contrast, positive DTH responses to DNP-modified autologous melanoma cells and to purified protein derivative developed in almost all patients but did not affect OS. Surprisingly, the OS after relapse was also significantly longer in patients who developed positive DTH to unmodified tumor cells (25.2% v 12.3%; P <.001). Finally, the development of DTH was dependent on the schedule of administration of the vaccine, specifically, the timing of an induction dose administered at the beginning of the treatment program. CONCLUSION This study underscores the importance of the immunopharmacology of the autologous, DNP-modified vaccine and may be relevant to other cancer vaccine technologies.

Have Endovascular Procedures Negatively Impacted General Surgery Training

Objective:Technological advances in vascular surgery have changed the field dramatically over the past 10 years. Herein, we evaluate the impact of endovascular procedures on general surgery training. Methods:National operative data from the Residency Review Committee for Surgery were examined from 1997 through 2006. Total major vascular operations, traditional open vascular operations and endovascular procedures were evaluated for mean number of cases per graduating chief general surgery resident (GSR) and vascular surgery fellow (VSF). Results:As endovascular surgical therapies became widespread, GSR vascular case volume decreased 34% over 10 years, but VSF total cases increased 78%. GSR experience in open vascular operations decreased significantly, as evidenced by a 52% decrease (P < 0.0001) in elective open AAA repair. VSFs have also seen significant decreases in open vascular procedures. Experience in endovascular procedures has increased for both general surgery and vascular residents, but the increase has been much larger in absolute number for VSFs. Conclusions:GSR experience in open vascular procedures has significantly decreased as technology has advanced within the field. Unlike VSFs, this loss has not been replaced by direct experience with endovascular training. These data demonstrate the impact technology can have on how we currently train general surgeons. New educational paradigms may be necessary in which either vascular surgery as an essential component is abandoned or training in catheter-based interventions becomes required.

Lymphoscintigraphy in Cutaneous Melanoma: An Updated Total Body Atlas of Sentinel Node Mapping

Lymphoscintigraphy has become part of the standard of care for patients with a new or recurrent diagnosis of melanoma, in helping determine the status of regional lymph nodes. Correct identification of sentinel lymph nodes enables the surgeon to further delineate the extent of malignancy by allowing sampling of the appropriate nodal group. Performing the lymphoscintigraphy prior to the planned operation allows limited surgery with less extensive postoperative morbidity. For this reason, a thorough knowledge of the lymph node drainage patterns from the different primary tumor locations, as well as of proper lymphoscintigraphic techniques and radiopharmaceuticals, constitutes an important armamentarium in the hands of surgeons, radiologists, and nuclear medicine physicians.

Surgeon-Performed Ultrasound for Preoperative Localization of Abnormal Parathyroid Glands in Patients with Primary Hyperparathyroidism

BackgroundThe introduction of portable ultrasound equipment enables surgeons to perform ultrasound examinations in a clinic setting. This study was undertaken to evaluate surgeon-performed ultrasound (SP-US) in patients with primary hyperparathyroidism (PHPT).MethodsBetween July 2003 and March 2004, 65 patients with PHPT were evaluated with SP-US and 48 of these patients underwent parathyroid surgery. Among this group of 48 evaluable patients, 47 had preoperative imaging with technetium-99m sestamibi scanning (MIBI), and 12 had an additional ultrasound examination at an external radiology department (RP-US).ResultsAll patients were cured of PHPT and the operative findings were used to determine the true status of the parathyroid glands of each patient. Twenty-four (50%) patients had concomitant thyroid nodules which were identified by SP-US, and 4 (8.3%) patients had simultaneous thyroid operations, 2 of which were for thyroid cancer. Considering data for all patients, SP-US had significantly higher sensitivity than MIBI or RP-US (60% vs. 46%, P = 0.013, and 60% vs. 11%, P = 0.004 respectively). Among the patients with a single adenoma, SP-US, MIBI, and RP-US had sensitivities of 83%, 63%, and 13% respectively. The specificities of all three imaging techniques were uniformly high and were not significantly different from each other.ConclusionsSurgeon-performed ultrasound is an accurate modality for localizing abnormal parathyroid glands in patients with PHPT, with results that compare favorably with other parathyroid imaging modalities.

Use of critical incidents to develop a rating form for resident evaluation of faculty teaching

Context  Monitoring the teaching effectiveness of attending physicians is important to enhancing the quality of graduate medical education.

Radioembolization for Treatment of Salvage Patients with Colorectal Cancer Liver Metastases: A Systematic Review

Currently, there is no consensus on the use of 90Y radioembolization for salvage patients with colorectal cancer liver metastases. The purpose of this study was to provide a comprehensive overview of the available data on tumor response and survival after 90Y radioembolization for this group of patients. Methods: A systematic literature search was conducted in PubMed (Medline), Excerpta Medica (EMBASE), and the Cochrane Library (September 2012) with synonyms for “radioembolization” and “colorectal cancer liver metastases.” Results were described separately for patient cohorts treated with 90Y radioembolization as monotherapy and with 90Y radioembolization in combination with chemotherapy. Results: The search yielded 13 relevant articles for systematic review on 90Y radioembolization as monotherapy and 13 relevant articles on 90Y radioembolization combined with chemotherapy. Disease control rates (i.e., complete response, partial response, and stable disease) ranged from 29% to 90% for 90Y radioembolization as monotherapy and from 59% to 100% for 90Y radioembolization combined with chemotherapy. Heterogeneity in the data prohibited pooling of response rates. Survival proportions at 12 mo ranged from 37% to 59% for 90Y radioembolization as monotherapy and from 43% to 74% for 90Y radioembolization combined with chemotherapy. Conclusion: In the studies included in this systematic review, approximately 50% of salvage patients with colorectal cancer liver metastases survive more than 12 mo after treatment with 90Y radioembolization, either as monotherapy or in combination with chemotherapy. Heterogeneity between studies has unfortunately prohibited pooling of data. Future research will discern the precise role of 90Y radioembolization in general clinical practice in comparison with chemotherapy.

Lymph node ratio is an important and independent prognostic factor for patients with stage III melanoma

The incidence of melanoma is dramatically increasing worldwide. We hypothesized that the ratio of metastatic to examined lymph node ratio (LNR) would be the most important prognostic factor for stage III patients.

Supernumerary parathyroid tissue hidden by high uptake in the submandibular gland.

A 63-year-old woman with chronic renal failure after subtotal parathyroidectomy was hospitalized for recurrent hyperparathyroidism, with a serum parathyroid hormone (PTH) level of 1,012 pg/ml (normal, 10 to 55 pg/ml). A presurgical Tc-99m sestamibi (925 MBq; 25 mCi) parathyroid scan revealed a left superior parathyroid remnant. After the remnant was surgically removed, the PTH level decreased to 164 pg/ml. Two days after surgery, however, the PTH level was elevated at 579 pg/ml. Another Tc-99m sestamibi parathyroid scan revealed a left supernumerary parathyroid gland. This finding was hidden on the previous study by overlying uptake by the left submandibular gland.

Consistent Surgeon Evaluations of Three-Dimensional Rendering of PET/CT Scans of the Abdomen of a Patient with a Ductal Pancreatic Mass

Two-dimensional (2D) positron emission tomography (PET) and computed tomography (CT) are used for diagnosis and evaluation of cancer patients, requiring surgeons to look through multiple planar images to comprehend the tumor and surrounding tissues. We hypothesized that experienced surgeons would consistently evaluate three-dimensional (3D) presentation of CT images overlaid with PET images when preparing for a procedure. We recruited six Jefferson surgeons to evaluate the accuracy, usefulness, and applicability of 3D renderings of the organs surrounding a malignant pancreas prior to surgery. PET/CT and contrast-enhanced CT abdominal scans of a patient with a ductal pancreatic mass were segmented into 3D surface renderings, followed by co-registration. Version A used only the PET/CT image, while version B used the contrast-enhanced CT scans co-registered with the PET images. The six surgeons answered 15 questions covering a) the ease of use and accuracy of models, b) how these models, with/without PET, changed their understanding of the tumor, and c) what are the best applications of the 3D visualization, on a scale of 1 to 5. The six evaluations revealed a statistically significant improvement from version A (score 3.6±0.5) to version B (score 4.4±0.4). A paired-samples t-test yielded t(14) = −8.964, p<0.001. Across the surgeon cohort, contrast-enhanced CT fused with PET provided a more lifelike presentation than standard CT, increasing the usefulness of the presentation. The experienced surgeons consistently reported positive reactions to 3D surface renderings of fused PET and contrast-enhanced CT scans of a pancreatic cancer and surrounding organs. Thus, the 3D presentation could be a useful preparative tool for surgeons prior to making the first incision. This result supports proceeding to a larger surgeon cohort, viewing prospective 3D images from multiple types of cancer.