Edward F. Hollinger

Hematopoietic cytokine-mediated FDG uptake simulates the appearance of diffuse metastatic disease on whole-body PET imaging

FDG-PET is increasingly being used to assess malignant tumors. However, leukocyte colony-stimulating factors (CSFs), which promote the expansion of hematopoietic bone marrow, have also been demonstrated to cause increased bone-marrow FDG uptake. Three hundred FDG-PET studies conducted over a 1-year period were reviewed for diffuse bone-marrow uptake. Elevated bone-marrow uptake on PET was correlated with pathological findings and courses of granulocyte-CSF (G-CSF) therapy. These results demonstrate that G-CSF mediated FDG uptake in bone marrow is often indistinguishable from that caused by disseminated metastatic disease. However, the bone-marrow response to G-CSF decreases rapidly following the last CSF administration. Therefore, FDG-PET in patients receiving G-CSF should be delayed, when possible, until 5 days after the end of G-CSF therapy.

Human heparanase-1 gene expression in pancreatic adenocarcinoma

Extracellular matrix degradation is an essential step that allows tumor cells to penetrate a tissue barrier and become metastatic. Heparanase-1 (HPR1) is an endoglycosidase that specifically degrades heparan sulfate proteoglycans, a chief component of the extracellular matrix. HPR1 is not expressed in normal epithelial cells but can be detected in a variety of malignancies. In the present study, we examined HPR1 expression in pancreatic cancer by using in situ hybridization and tested whether HPR1 expression correlated with any clinicopathlogic parameters. HPR1 was not detected in the ductal cells of normal pancreas samples obtained from 10 patients at autopsy. However, HPR1 was detected in 77 (78%) of 99 panceatic adenocarcinomas. Among them, 69 (78%) of 89 primary pancreatic adenocarcinomas and 8 (80%) of the 10 metastases were HPR1 positive. Age, sex, tumor stage, and lymph node status were not predictive of HPR1 expression. Log-rank test of the Kaplan-Meier survival curves revealed that HPR1 expression in early-stage tumors was associated with decreased survival. HPR1 expression was frequent in pancreatic adenocarcinomas and was associated with decreased survival in early-stage tumors. This suggests that HPR1 may contribute to the highly invasive and early metastatic behavior of pancreatic cancer.

Response of Osteosarcoma to Chemotherapy: Evaluation with F-18 FDG-PET Scans

Objective: Positron emission tomography (PET) using fluorine-18-fluoro-2-D-deoxyglucose (FDG) is increasingly being used to evaluate and manage oncology patients. Several reports have documented its utility in diagnosis, staging, response to treatment, and tumor viability assessment. There is, however, a paucity of literature on PET scanning in patients with osteosarcoma. We report results of serial F-18 FDG-PET scans in 16 untreated patients with osteosarcoma who underwent chemotherapy prior to surgical resection of the primary tumor site.Procedure: Changes in tumor fluoro-2-D-deoxyglucose (FDG) uptake were correlated with percent tumor necrosis on histopathology. PET studies were analyzed by visual assessment of tumor uptake of FDG by 3 independent observers, calculating a tumor to normal background activity ratio (TBR) by drawing regions of interest (ROIs) around the tumor and background activity in the contralateral normal limb, and percent change in TBR values between baseline and presurgical study.Results: All patients had positive baseline scans. Baseline TBRs ranged between 2.5-8.7 and visual assessment of intensity of FDG uptake was 2-3 on a scale of 0-3. At histopathologic examination, 8 patients were classified as good responses with more than 90% tumor necrosis and 8 patients as poor responses with less than 90% necrosis. Tumor necrosis was accurately predicted on PET scan in 15/16 patients by visual assessment, 14/15 patients by final TBR value on presurgery scans, and 7/15 patients using percent change of TBR on serial scans.Conclusions: The results of this small series suggest that FDG-PET scanning is fairly accurate in evaluating the response of osteosarcoma to chemotherapy. Visual assessment and TBR are more accurate in predicting tumor necrosis than percent change in TBR on serial scans.

The case for pancreas after kidney transplantation

Abstract:  Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti‐thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One‐yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus‐based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

Normal thymic uptake of 2-deoxy-2[F-18]fluoro-D-glucose.

Whole-body 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) positron emission tomography (PET) of a 54-year-old woman with a history of recurrent thyroid follicular cancer and an elevated thyroglobulin level showed significant FDG uptake in the thyroid bed and anterior mediastinum. A previous scan after high-dose I-131 therapy also showed iodine uptake in these regions. Because of a lack of response to iodine therapy, the patient had surgery. Recurrent thyroid cancer was found in the neck, but the mediastinal lesion was shown to consist of normal thymus tissue. In repeated examinations performed after surgery, there was no uptake of FDG or I-131 in the anterior mediastinum. Previous treatment with a high dose of radioiodine may have contributed to visualization of a normal adult thymus with FDG PET.

Mechanical, histologic, and biochemical effects of canine rectal formalin instillation

Instillation of 4 percent formalin effectively treats radiation hemorrhagic proctitis; however, little is known regarding its side effects. PURPOSE: The study contained herein was undertaken to determine rectal compliance and collagen content, mucosal and vascular histologic changes, and kinetics of formalin absorption following instillation. METHODS: Fifteen mongrel dogs (50–60 pounds) were randomized into five experimental groups according to time elapsed from formalin treatment: control, acute, one week, two weeks, and four weeks. Formalin was instilled in 30-ml aliquots to a total volume of 400 ml. Rectal compliance (closed manometry system) was assessed pre-formalin and post-formalin at the designated time interval. Serum formalin metabolites were determined at time 0, 0.5, 1, and 3 hours. A segment of rectal wall was analyzed for collagen content, mucosal injury, and blood vessel density. RESULTS: Serum formalin levels peaked within 30 minutes, returning to normal by 3 hours. With the exception of one dog, toxic levels were not reached at any time during the study. No dogs experienced sepsis, fever, or altered gastrointestinal function. Acute and one-week dogs showed mild diffuse proctitis and mucosal slough, which healed within two weeks. Rectal compliance and collagen content were unchanged. Mucosal blood vessels decreased in number early (P=0.03). CONCLUSIONS: Instillation of 4 percent formalin in sequential aliquots of a small volume that is kept in contact for a short period of time is safe. Serum formalin levels generally do not reach toxic levels, and the slight elevation in formalin concentration that was seen returns to normal within three hours. Formalin-induced proctitis heals within two weeks, and no long-term changes in rectal compliance or collagen content were seen.

Immediate Retransplantation for Pancreas Allograft Thrombosis

Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1–16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin‐induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76–1137 days (mean 572 days). One‐year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first‐time pancreas transplantation.

No Difference in Transplant Outcomes for Local and Import Pancreas Allografts

Background. In the United States, pancreas allograft allocation is strictly regulated. Local centers have the first option to accept an organ, followed by regional and national allocation for those not accepted locally. For a pancreas to be imported, many centers must have previously rejected the organ for transplantation. This study reviews the outcomes of all pancreas allografts transplanted at a single center between January 2003 and November 2007. Early graft function and graft survival were stratified by geographic source of the donor pancreas. Methods. The records of 247 pancreas recipients and the donors of 11 imported and discarded pancreas allografts were reviewed. Pancreas allograft survival is represented using a Kaplan-Meier survival curve comparing (1) locally procured and imported pancreas grafts and (2) grafts procured by a team from our own center with the grafts procured by another team. Results. Of the 247 grafts, 184 (74%) were local and 63 (26%) were imported. There were no differences between the two geographic groups in 1-year graft survival (local 91%, import 90%, P=0.76). Similarly, graft survival was similar regardless of whether the organ was procured by our own team or by another center (local team 91%, another team 90%, P=0.96). Conclusions. Pancreas allografts refused by a large number of centers may still be imported and successfully transplanted without affecting survival results.

The utility of mock oral examinations in preparation for the American Board of Surgery certifying examination.

BACKGROUND Determine the utility of mock oral examinations in preparation for the American Board of Surgery certifying examination (ABS CE). METHODS Between 2002 and 2012, blinded data were collected on 63 general surgery residents: 4th and 5th-year mock oral examination scores, first-time pass rates on ABS CE, and an online survey. RESULTS Fifty-seven residents took the 4th-year mock oral examination: 30 (52.6%) passed and 27 (47.4%) failed, with first-time ABS CE pass rates 93.3% and 81.5% (P = .238). Fifty-nine residents took the 5th-year mock oral examination: 28 (47.5%) passed and 31 (52.5%) failed, with first-time ABS CE pass rates 82.1% and 93.5% (P = .240). Thirty-eight responded to the online survey, 77.1% ranked mock oral examinations as very or extremely helpful with ABS CE preparation. CONCLUSIONS Although mock oral examinations and ABS CE passing rates do not directly correlate, residents perceive the mock oral examinations to be helpful.

Outcomes after combined liver-kidney transplant vs. kidney transplant followed by liver transplant

The decision for isolated kidney transplant (KT) vs. combined liver–kidney transplant (CLKT) in patients with end‐stage renal disease (ESRD) with compensated cirrhosis remains controversial. We sought to determine outcomes of patients requiring listing for a liver transplant (LT) following either a cadaveric or living donor KT and compare these outcomes to similar patients receiving a CLKT.