Postsurgical Diagnosis Research Articles

Pediatric Renal Cell Carcinoma Associated With Xp11.2 Translocation/TFE3 Gene Fusion

Renal cell carcinoma (RCC) in children and young adults is rare and pathologically problematic. RCC can be either hereditary or sporadic and has a guarded prognosis because appropriate management has not been established. A case of RCC in an 11-year-old is reported. The clinical presentation was a right abdominal mass, hematuria, urinary tract infection, and wasting. Radio-logically, the mass was found within the right kidney with calcification and paraaortic lymphadenopathy. The postsurgical diagnosis was Wilms' tumor stage T4N2M0. On gross inspection, the tumor was ill defined, extending across Gerota's fascia and into the ureter lumina. Microscopically, the tumor consisted of malignant epithelial cells with clear and eosinophilic cytoplasm in nested, papillary, and alveolar configuration. Hyaline nodules, psammoma bodies, vascular invasion, capsular invasion, and extension into the ureter were also found. Immunohistochemically, the cells showed strong nuclear immunoreactivity for TFE3. We concluded that this case was an RCC associated with Xp11.2 translocation/TFE3 fusion, Fuhrman grade 3, stage IV.

Isolated metastasis of lung cancer to the thyroid gland

A 67-year-old man with lung cancer developed an isolated metastasis to the thyroid gland. The patient had undergone a right upper lobectomy, followed by chemotherapy consisting of cisplatin and etoposide based on post-surgical diagnosis of small cell lung cancer. Four years later, he had an isolated metastasis to the thyroid gland. The patient underwent a metastasectomy and adjuvant chemotherapy including cisplatin and irinotecan. The cancer cells in resected thyroid tumor had large nuclei and cytoplasm, and expressed the neuroendocrine markers, CD56 and chromogranin A. Retrospectively, the primary lung cancer consisted of both small cell and large cell cancer, and the latter was consistent with the pathological finding of the thyroid tumor. This is the first report to document an isolated recurrence of the lung cancer to the thyroid.

273. Immuno Gene Therapy of Feline Fibrosarcoma Using Intratumoral Magnetofection or Gene-Activated Matrices for Gene Delivery – Preliminary Results of a Veterinary Clinical Study

Feline fibrosarcoma is one of the most common feline tumors. It arises spontaneously, is rarely metastatic and relapses within 6 months after standard therapy (surgical resection) in 75 % of the cases. This makes it an ideal model for evaluating immunostimulatory therapeutic strategies. Moreover, besides aggressive surgical excision no effective and versatile treatment is available. Here we report preliminary results from a comparative clinical study where the genes for feline GM-CSF, IFN-g and IL-2 in combination, feline GM-CSF alone or human GM-CSF were administered. The study design is prospective, randomized, placebo- controlled (= standard therapy) and includes five arms: (1) standard therapy, i.e. surgery alone; (2) nonviral Magnetofection of the feline GM-CSF, IFN-g and IL-2 genes into the tumor before surgery or nonviral administration by Magnetofection of feline (3) or human GM-CSF (4) gene alone and (5) nonviral application of the feline GM-CSF, IFN-g and IL-2 genes by a gene-activated-matrix. The procedure included phase I dose finding studies for the gene therapy groups followed by a phase II. Preliminary clinical endpoint is relapse-free survival for one year. Magnetofection, which has been developed in our laboratory, is the association of vectors with magnetic particles (chemicell, Berlin, Germany) and gene delivery under the influence of a magnetic field (Scherer et al. 2002, Gene Ther., Plank et al. 2003, Biol. Chem). It was applied here in order to achieve improved retention of the injected vector dose in the tumor. Copolymer-protected gene vectors (Scherer et al. 2002, J. Gene Med. 4:634-643) were immobilized on a collagen sponge to achieve sustained localized matrix-mediated gene delivery. After tumor excision the gene-activated matrices were implanted in the tumor bed intrasurgically. Pre- and postsurgical diagnosis included complete clinical monitoring of the cats. All gene-therapeutic treatments were well tolerated and led to prolonged relapse-free survival (one year time points: 50 % for intrasurgical implantation of the vector-loaded collagen sponge in the tumor bed, and 52 % for presurgical Magnetofection with human GM-CSF versus 23 % for surgery alone). Additional patients have been admitted to the Magnetofection group such that long-term follow-up will warrant a profound assessment of the benefits of this treatment.

Peritoneal fluid leptin is associated with chronic pelvic pain but not infertility in endometriosis patients*

Leptin influences the proinflammatory immune responses and has angiogenic activity in vitro and in vivo. The objective of this study was to evaluate the peritoneal fluid levels of leptin in patients with endometriosis and idiopathic infertility and compare them with a control group of tubal ligation/reanastomosis patients. In this observational, prospective controlled study, peritoneal fluid from 108 women was obtained while they underwent laparoscopy for pelvic pain, infertility, tubal ligation or sterilization reversal. We measured the concentration of leptin in the peritoneal fluid and compared the levels among women who were divided into groups according to their post-surgical diagnosis. Sixty patients were diagnosed with endometriosis, 10 with idiopathic infertility and 38 had undergone tubal ligation or reanastomosis (control group). Peritoneal fluid leptin was significantly higher in endometriosis 14.62+/-9.79 (mean+/-SD) ng/ml compared to idiopathic infertility [0.92+/-1.57 ng/ml (P=0.0007)] and to controls [0.78+/-1.94 ng/ml (P<0.0001)]. Leptin levels were positively correlated with the stage of endometriosis (r=0.45; P=0.03), and with pelvic pain in endometriosis patients (r=0.49; P=0.001). Peritoneal fluid leptin levels in patients with idiopathic infertility were comparable to controls. Higher levels of leptin were observed in peritoneal fluid of patients with endometriosis compared to those without the disease. These data suggest that the proinflammatory and neoangiogenic action of leptin may contribute to the pathogenesis of endometriosis. Moreover, leptin may play a role in endometriosis-associated pain.

EUS: An Ideal Initial Test for Elderly Patients with Idiopathic Pancreatitis

Methods: We reviewed 67 cases of patients who underwent cholecystectomies and who also showed thickened gallbladder wall in their preoperative EUS. According to the post-surgical pathologic diagnosis, the cases were classified into malignant and benign diseases, and then they were statistically compared with several findings of EUS of thickened gallbladder wall such as thickness, extent of wall thickening, associations of gallstones, loss or preservation of layered structure of wall, internal echo pattern within thickened wall, associations of microcyst or echogenic nodule within thickened wall, and irregularity of inner surface of thickened wall. Results: Pathologic diagnoses included 10 cancers and 57 benign gallbladder diseases. The sensitivity and specificity of EUS examination for diagnosis of the gallbladder cancer were 90% and 98% respectively, and especially in the specificity, EUS was superior to that of abdominal ultrasonography or abdominal CT scan that were also performed to enrolled patients preoperatively. Through statistical analyses, EUS findings of thickened wall such as thickness, associations of gallstones, loss or preservation of layered structure, and irregularity of inner surface of thickened wall were turned out to be the statistically significant variables in the differential diagnosis between malignant and benign causes of thickened gallbladder wall. On the multivariate analyses, loss or preservation of layered structure, and irregularity of inner surface of thickened wall were finally remained as independent variables, odds ratio (OR) 12.10: 95% CI (1.2, 137.6), OR 15.80: 95% CI (1.5, 167.0). Conclusion: EUS is useful to diagnose gallbladder cancer when gallbladder shows thickened wall and EUS findings of thicker wall, absence of gall stones, loss of normal layered structure, and irregular internal surface of thickened wall are predictive factor of gallbladder cancer. *T1603 EUS: An Ideal Initial Test for Elderly Patients with Idiopathic Pancreatitis Karin M. Rettig, Allan G. Halline, Russell D. Brown, Rama P. Venu Background: Current standard of care for patients with idiopathic pancreatitis (IP) involves an extensive evaluation including ERCP with possible sphincter manometry to identify an etiology. ERCP carries a significant risk of pancreatitis in comparison to endoscopic ultrasound (EUS). Furthermore, EUS identifies malignancy, stones, sludge, and chronic pancreatitis as well as or better than ERCP. Older patients may have a higher risk of malignancy and a lower incidence of sphincter dysfunction (SD), making EUS an attractive method for initial endoscopic evaluation in this group. Aim: To determine if EUS should be used as the initial investigation of choice in older patients with IP. Methods: Patients >55 years old referred with IP were evaluated with history, physical, amylase, lipase, triglyceride, calcium, liver enzymes, ultrasound and CT. Patients in whom the etiology was unknown after noninvasive evaluation were included in this study. Each patient had EUS, followed by helical CT and ERCP +/sphincterotomy (ES). Radial array EUS was done first followed by linear array EUS with possible fine needle aspirate (FNA). CT, ERCP with brush cytology and/or SOM was performed in all patients. ES, stone extraction, stent placement, laparotomy, or Whipple operation was done based on ERCP results. Results: Of 20 patients, an etiology was identified in 7 (35%). Four of 20 patients had a malignancy (3 pancreas, 1 periampullary). One patient each had choledocholithiasis, pancreas divisum, SD, and early chronic pancreatitis. EUS demonstrated a mass in all 4 patients withmalignancy, andFNAof eachmasswas positive for adenocarcinoma in 3. ERCP showed PD stricture suggestive ofmalignancy in 3 patients, with brush cytology positive for adenocarcinoma in one. Both EUS and ERCP identified a common bile duct stone in one patient, while SD (1) and pancreas divisum (1) were diagnosed exclusively by ERCP. EUS established a diagnosis in 6/7 (84%), while ERCP did so in 4/7 (56%). CT scanning revealed a mass in only one of four cancer patients and an enlarged pancreas due to pancreatitis in 17/20 patients. Three of four patients with cancer underwent Whipple surgery, and all three were correctly staged by EUS. One patient had metastasis to the liver and was treated with endoprosthesis. Conclusion: EUS should be considered as the initial endoscopic study of choice in older patients with IP. EUS has an overall higher yield and can accurately establish a tissue diagnosis, enable staging of malignancy, and aid in appropriate planning for therapy.

Assessment of leptin levels in the peritoneal fluid of patients with pelvic endometriosis and idiopathic infertility

Objective: Pelvic endometriosis is an immune-related chronic inflammatory disease with increased secretion of proinflammatory cytokines and neoangiogenesis. Leptin, the adipocyte-derived hormone, has been shown to have a role in food intake, basal metabolism, and reproductive function. Leptin levels are dynamically regulated, being elevated by inflammatory mediators and reduced by starvation. Leptin can influence the proinflammatory immune responses of CD4+ T lymphocytes, and reports have also shown this hormone to be an angiogenic factor in vitro and in vivo. The objective of this study was to evaluate the peritoneal fluid (PF) levels of leptin in patients with endometriosis and idiopathic infertility and compare it to a control group of tubal ligation/reanastomosis patients. Design: Prospective controlled study. Materials/Methods: Peritoneal fluid (PF) from 91 women were obtained while they underwent laparoscopy for pain, infertility, tubal ligation or sterilization reversal. We measured the concentration of leptin in the peritoneal fluid (PF) and compared the levels among women, who were divided into groups according to their postsurgical diagnosis. Fifty-six patients were diagnosed with endometriosis, 8 with idiopathic infertility and 27 had undergone tubal ligation or reanastomosis (control group). Results: Peritoneal fluid leptin was significantly higher in endometriosis 14.62 ± 9.79 ng/mL compared to idiopathic infertility 0.92 ± 1.57 ng/mL (p = 0.0007) and to controls 0.78 ± 1.94 ng/mL (p <0.0001). Leptin levels were positively correlated with the stage of the disease in endometriosis patients (r = 0.4538; p = 0.03), and with pelvic pain in endometriosis patients (r = 0.4918; p = 0.001). Conclusions: Higher levels of leptin were observed in the PF of endometriosis as compared to non endometriosis. These data suggest that the proinflammatory and neoangiogenic actions of leptin may contribute to the pathogenesis of endometriosis. Supported by: Research grant from the Minimally Invasive Surgery Center (MISC) of the Cleveland Clinic Foundation (RPC#2156).

Evaluation of a Pregnancy-Testing Protocol in Adolescents Undergoing Surgery

Abstract Study Objective The purpose of this study was to determine the rate of unknown and nondisclosed pregnancies identified from a preoperative protocol for pregnancy testing of adolescents. Design A protocol was developed for pregnancy testing of all 12–21-year-old females presenting to the day surgery unit (DSU) at a large children’ s hospital. The charts of all patients identified with a positive urine ICON II human chorionic gonadotropin (uhCG) assay result were reviewed for demographic data, presurgical and postsurgical diagnosis, and proposed and actual procedure performed. Adolescents were asked the date of their last menstrual period (LMP), whether they were sexually active (SA) (engaged in vaginal intercourse), and whether they might be pregnant, and a uhCG was performed. Setting DSU at a large children's hospital in Boston, Massachusetts. Participants All 12–21-year-old females presenting to DSU. Main Outcome Measures Disclosure of sexual activity, date of LMP, and any possibility of pregnancy. The initial decision (continuation, abortion, or undecided) at the time of identification of the positive uhCG, compliance with follow-up referral appointments, outcome of the pregnancy, and subsequent choice of contraception were also documented. Results A total of 801 adolescent girls presented to the DSU for a surgical procedure between October 1994 and July 1996 and had a uhCG. Six of the 801 girls had a positive uhCG; 4 of 801 (0.49%) were pregnant. The remaining two had falsepositive uhCG tests associated with ovarian failure and elevated gonadotropins. An LMP was recorded for the four pregnant patients, but only two patients were able to identify an exact date. SA was admitted by two of four and denied by the other two. One of the two who disclosed SA admitted to the possibility of being pregnant in response to the question, the other denied the possibility of pregnancy. The two who denied SA also failed to disclose the possibility of pregnancy. After disclosure of a positive uhCG, the surgical procedure was postponed in all four individuals. Conclusions A routine preoperative uhCG testing program identified 4 of 801 (0.49%) patients with previously undiagnosed pregnancy. The current protocol has contributed to enhanced care and identifies pregnant adolescents who need counseling before surgical procedures are performed.

Evaluation of a Pregnancy-Testing Protocol in Adolescents Undergoing Surgery

Study ObjectiveThe purpose of this study was to determine the rate of unknown and nondisclosed pregnancies identified from a preoperative protocol for pregnancy testing of adolescents. DesignA protocol was developed for pregnancy testing of all 12–21-year-old females presenting to the day surgery unit (DSU) at a large children’ s hospital. The charts of all patients identified with a positive urine ICON II human chorionic gonadotropin (uhCG) assay result were reviewed for demographic data, presurgical and postsurgical diagnosis, and proposed and actual procedure performed. Adolescents were asked the date of their last menstrual period (LMP), whether they were sexually active (SA) (engaged in vaginal intercourse), and whether they might be pregnant, and a uhCG was performed. SettingDSU at a large children's hospital in Boston, Massachusetts. ParticipantsAll 12–21-year-old females presenting to DSU. Main Outcome MeasuresDisclosure of sexual activity, date of LMP, and any possibility of pregnancy. The initial decision (continuation, abortion, or undecided) at the time of identification of the positive uhCG, compliance with follow-up referral appointments, outcome of the pregnancy, and subsequent choice of contraception were also documented. ResultsA total of 801 adolescent girls presented to the DSU for a surgical procedure between October 1994 and July 1996 and had a uhCG. Six of the 801 girls had a positive uhCG; 4 of 801 (0.49%) were pregnant. The remaining two had falsepositive uhCG tests associated with ovarian failure and elevated gonadotropins. An LMP was recorded for the four pregnant patients, but only two patients were able to identify an exact date. SA was admitted by two of four and denied by the other two. One of the two who disclosed SA admitted to the possibility of being pregnant in response to the question, the other denied the possibility of pregnancy. The two who denied SA also failed to disclose the possibility of pregnancy. After disclosure of a positive uhCG, the surgical procedure was postponed in all four individuals. ConclusionsA routine preoperative uhCG testing program identified 4 of 801 (0.49%) patients with previously undiagnosed pregnancy. The current protocol has contributed to enhanced care and identifies pregnant adolescents who need counseling before surgical procedures are performed.

A Pregnancy Testing Protocol for Adolescents Undergoing Surgery

<h3>Background</h3> Unintended pregnancy is a common problem for United States teens. Many postmenarchal young women have irregular ovulation/menstrual cycles and may thus be unaware or in denial of the possibility of pregnancy. Previous studies have suggested that perioperative drugs and surgical manipulation can increase the risk of teratogenic effects and miscarriage. The purpose of this study was to review the findings from a pregnancy testing preoperative protocol for adolescents. <h3>Methods</h3> A protocol was developed for pregnancy testing of all 12–21year old female presenting to Day Surgery Unit (DSU) at a large pediatric hospital. Charts of all patients identified with a positive urine ICON II hCG (uhCG) assay result were reviewed for demographic data, pre and post surgical diagnosis, proposed and actual procedure perforrned. Adolescents were asked the date of their last menstrual period (LMP), whether they are sexually active(SA) or not, and if there is any chance of being pregnant. The initial decision (continuation, abortion, or undecided) at the time of identification of the positive hCG was documented. Compliance with follow up referral appointments (counseling, prenatal care, or abortion), outcome of the pregnancy (delivery, therapeutic or spontaneous abortion), and subsequent choice of contraception was also documented. <h3>Results</h3> 801 adolescent girls presented to the DSU for surgical procedure between October 1994 to July 1996 and had a uhCG. Of the 801 patients, 6 (0.75%) had a positive uhCG. Two of the 6 were false positive: one had bilateral streaked gonads and uterine hypoplasia and the other had Hodgkins Lymphoma and ovarian failure. The demographics of the remaining 4 patients revealed: mean age at presentation 16 years (range: 15–17); 1 Hispanic/Latino, 1 Caucasian, and 2 African-American. LMP was noted for all patients, but only 2 patients were able to identify an exact date. SA was admitted by 2/4, and denied by the other two. One of the 2 who disclosed SA admitted to being pregnant, the other denied the possibility of pregnancy. The 2 who denied SA also failed to disclose the possibility of pregnancy. After disclosure of a positive uhCG, the operation was postponed in all 4. Subsequently, 3 chose abortion and 1 continued to term. All 3 who chose abortion initiated contraception after the procedure. <h3>Conclusions</h3> Due to concerns of potential teratogenic and abortive effects of medications used during the perioperative period and surgical manipulations, our hospital initiated a policy for routine preoperative uhCG testing. Adolescents are often reluctant to disclose and are sometimes unaware of their pregnancy. We have found that the current protocol contributes to enhanced care and identifies pregnant adolescents who need counseling before surgical procedures are performed.

Comparison of two serologic methods for the diagnosis of hydatidosis

The sera of 176 patients with epidemiologic antecedents or radiologic and clinical signs of hydatidosis were tested by counterimmunoelectrophoresis (CIE) and enzyme-linked immunoassay (ELISA). A semipurified antigen from cysts of human origin was used for both techniques. The results were compared with those obtained from complementary radiologic studies and were confirmed by examination of excised cysts. Biopsy confirmed the diagnosis of hydatidosis in 65 patients (37%) and revealed the presence of other diseases in the remaining 111 (63%). Of the original 176 patients, 36 (20.4%) were positive by CIE and 62 (35.2%) by ELISA. Both techniques showed an excellent correlation with postsurgical diagnosis; neither produced any false positives, and the ELISA gave false negative results for only three patients (4.6%) with cysts that were infected, infertile, or calcified to some degree. The paper describes standardization of an inexpensive and easy-to-use microELISA.

Preoperative Evaluation of D-Dimer and CA 125 Levels in Differentiating Benign from Malignant Ovarian Masses

Plasma levels of D-dimer (DD) and CA 125 were measured preoperatively in 121 patients with ovarian masses submitted to laparotomy. DD and CA 125 levels were higher in the 56 patients with epithelial ovarian cancer than in the 65 patients with benign ovarian disease (P< 0.0001). The logistic regression procedure showed that both DD assay (cutoff 416 ng/ml) and CA 125 assay (cutoff 65 U/ml) were significant predictive variables for malignancy (P= 0.0001). The concordance between predicted probabilities and observed responses was 75.7% for DD, 72.1% for CA 125, and 90.8% for DD and CA 125. It is worth noting that DD was increased (>416 ng/ml) in 73% of FIGO stage I patients, whereas CA 125 was above 65 U/ml in only 33.3%. Sensitivity, specificity, positive predictive value, and negative predictive value of the tests in differentiating benign from malignant ovarian masses were as follows: 76.8, 93.8, 91.5, and 82.4%, respectively, for CA 125; 94.6, 76.9, 77.9, and 94.3%, respectively, for the combination CA 125 or DD; and 73.2, 100.0, 100.0, and 81.3%, respectively, for the combination CA 125 and DD. The combination CA 125 and DD seems to be a useful diagnostic tool to differentiate benign from malignant ovarian masses. Elevated preoperative levels of both antigens are invariably associated with a postsurgical diagnosis of epithelial ovarian cancer.