Effects of preceding endoscopic mucosal resection on the efficacy and safety of radiofrequency ablation for treatment of Barrett's esophagus: results from the United States Radiofrequency Ablation Registry.

The effects of preceding endoscopic mucosal resection (EMR) on the efficacy and safety of radiofrequency ablation (RFA) for treatment of nodular Barrett's esophagus (BE) is poorly understood. Prior studies have been limited to case series from individual tertiary care centers. We report the results of a large, multicenter registry. We assessed the effects of preceding EMR on the efficacy and safety of RFA for nodular BE with advanced neoplasia (high-grade dysplasia or intramucosal carcinoma) using the US RFA Registry, a nationwide study of BE patients treated with RFA at 148 institutions. Safety outcomes included stricture, gastrointestinal bleeding, and hospitalization. Efficacy outcomes included complete eradication of intestinal metaplasia (CEIM), complete eradication of dysplasia (CED), and number of RFA treatments needed to achieve CEIM. Analyses comparing patients with EMR before RFA to patients undergoing RFA alone were performed with Student's t-test, Chi-square test, logistic regression, and Kaplan-Meier analysis. Four hundred six patients were treated with EMR before RFA for nodular BE, and 857 patients were treated with RFA only for non-nodular BE. The total complication rates were 8.4% in the EMR-before-RFA group and 7.2% in the RFA-only group (P = 0.48). Rates of stricture, bleeding, and hospitalization were not significantly different between patients treated with EMR before RFA and patients treated with RFA alone. CEIM was achieved in 84% of patients treated with EMR before RFA, and 84% of patients treated with RFA only (P = 0.96). CED was achieved in 94% and 92% of patients in EMR-before-RFA and RFA-only group, respectively (P = 0.17). Durability of eradication did not differ between the groups. EMR-before-RFA for nodular BE with advanced neoplasia is effective and safe. The preceding EMR neither diminished the efficacy nor increased complication rate of RFA treatment compared to patients with advanced neoplasia who had RFA with no preceding EMR. Preceding EMR is not associated with poorer outcomes in RFA.

Evaluation of the safety and pharmacokinetics of the multi-targeted receptor tyrosine kinase inhibitor sunitinib during embryo-fetal development in rats and rabbits.

BACKGROUND: Angiogenesis plays a key role in embryo-fetal development and, based on nonclinical safety data, the majority of vascular endothelial growth factor (VEGF)-targeted antiangiogenic agents used in cancer therapy are not recommended during pregnancy. We investigated the effects of sunitinib (an oral inhibitor of multiple receptor tyrosine kinases [RTKs] including VEGF-receptors) on embryo-fetal development. METHODS: Presumed-pregnant Sprague-Dawley rats and New Zealand White rabbits received repeated daily oral doses of sunitinib (0-30 mg/kg/day), during the major period of organogenesis. Clinical/physical examinations were performed throughout the gestation phase, and blood samples were collected to determine systemic exposure. Necropsy (including uterine examination) was performed on all animals and fetal morphology was examined. RESULTS: The no-observed-adverse-effect level was 1-5 mg/kg/day for maternal toxicity and 3 mg/kg/day for developmental toxicity in rats; 1 and 0.5 mg/kg/day, respectively, in rabbits. Embryo-fetal toxicity included decreases in the number of live fetuses and increases in the numbers of resorptions and post-implantation/complete litter losses; these were observed at doses of > or =5 mg/kg/day in rats and 5 mg/kg/day in rabbits. Malformations included fetal skeletal malformations (generally thoracic/lumbar vertebral alterations) in rats and cleft lip/palate in rabbits. These developmental effects were observed at approximately 5.5- (rats) and approximately 0.3-times (rabbits) the human systemic exposure at the approved sunitinib dose (50 mg/day). CONCLUSIONS: Similar effects have been reported with the prototype monoclonal antibody bevacizumab. As is typically observed for potent inhibitors of RTKs involved in angiogenesis, sunitinib was associated with embryo-fetal developmental toxicity in rats and rabbits at clinically relevant dose levels.

Patterns of abnormal FDG uptake by various histological types of non-small cell lung cancer at initial staging by PET.

The aim of this study was to identify useful patterns of abnormal fluorine-18 fluorodeoxyglucose (FDG) uptake by different types of non-small cell (NSC) lung cancer and to assess their clinical implications. One hundred and three sequential patients with newly diagnosed, pathology-proven NSC lung cancer were included. FDG positron emission tomography (PET) images were acquired using a dedicated PET scanner. There were 35 squamous cell carcinomas (SQC), 17 large cell cancers (LGC), 38 adenocarcinomas (ADC), 1 bronchioloalveolar carcinoma (BAC) and 12 non-classified NSC cancers. PET images were categorized into detectable patterns of necrotic center in the primary tumor, satellite lesions (T4), hilar lymph nodes (N1), and N2, N3, and M1 lesions by visual interpretation of PET images for SQC, LGC, and ADC (n=90; BAC and non-classified NSC cancers were excluded). The PET lesions were correlated with surgical pathology and with CT findings in inoperable cases. Necrosis was more commonly present in the primary tumors of LGC (53%) and SQC (43%) than in those of ADC (26%) (P<0.0001 and <0.01, respectively). The frequencies of nodal uptake in ADC, SQC and LGC were similar (71%, 60%, and 59%, respectively). However, M1 lesions were present significantly more often in LGC (41%) and ADC (34%) than in SQC (3%) (both P<0.0001). Significantly more surgically inoperable cases were found by PET (T4, N3, M1) in ADC (50%) and LGC (41%) than in SQC (26%) (P<0.001 and <0.02, respectively). Our results suggest a wide variation of PET findings for different types of NSC lung cancer. Identification of these patterns is useful in clinical PET interpretation, in that knowledge of the most probable association between the PET patterns and the histological types will facilitate initial staging and planning of management.

Incidence and significance of lobar atelectasis in thoracic surgical patients.

Lobar atelectasis, defined by complete lobar collapse and mediastinal shift on chest roentgenogram, represents one extreme form of postoperative atelectasis. We have evaluated the incidence and clinical significance of lobar atelectasis in a thoracic surgical patient group. A retrospective review was done of patients who underwent pulmonary resection over a 2-year period to determine patient characteristics, contributing comorbidities, and associated perioperative care factors. Lung resections were performed for both benign and malignant disease through open or video-assisted techniques. One hundred eighty patients had pulmonary resection, 101 males and 79 females, and they were divided into three groups: I, no complications (112 patients, 62%); II, complications unrelated to lobar atelectasis (60 patients, 33%); and III, complications of lobar atelectasis (8 patients, 5%). There was one death in the series, in the lobar atelectasis group (III). Mean age for the entire group was 64.5 +/- 12.5 years; however, patients in Groups II (67.3 years) and III (69.6 years) were significantly older than in Group I (P < 0.02). Mean hospital length of stay in Group I was 6 +/- 3 days, whereas that in Group II was 13 +/- 12 days (P < 0.001), and in Group III it was 27 +/- 31 days (P < 0.001). In addition, patients who developed lobar atelectasis were more likely to be male (88% vs 48%, P = 0.034), had a longer ICU length of stay (P < 0.001), were more likely to have two or more comorbidities (P < 0.05), and had a lower forced expiratory volume in 1 second (2.34 +/- 0.90 vs 1.96 +/- 0.63). All patients in the lobar atelectasis group were operated on for malignancy, but this was not significantly different from the other groups. None of the 16 patients who had thoracoscopy developed lobar atelectasis, but this also was not a significant finding. We conclude that severe postoperative atelectasis occurs as lobar atelectasis in approximately 5 per cent of patients who undergo pulmonary resection and significantly adds to the intensive care unit and hospital length of stay. The etiology of lobar atelectasis appears to be multifactorial and warrants further study to define mechanisms of occurrence and their prevention.

Immunohistochemically detected micrometastases in peribronchial and mediastinal lymph nodes from patients with T1, N0, M0 pulmonary adenocarcinomas.

The T1, N0, M0 subset of stage I lung adenocarcinoma is a tumor that has a 5-year disease-free survival rate of 66% to 85%. To date, there has not been a rigorous immunohistochemically detected lymph node micrometastasis study composed of patients with identical stage and type of tumors, and in which standard histologic features were incorporated into multivariate analyses. We immunohistochemically examined the peribronchial and mediastinal lymph nodes from 80 consecutively accrued patients with T1, N0, M0 adenocarcinomas and bronchioloalveolar carcinomas unselected for distant metastasis, and an additional 39 patients with similar stage and type neoplasms who were selected for their development of metastases to evaluate the prevalence of micrometastases, their association with distant metastases, and their relationship with other pathologic prognostic features. All slides were stained with keratin AE1/3. Micrometastases were confirmed with Ber-Ep4. Three immunohistochemically detected lymph node micrometastases were identified in three of 80 consecutively accrued patients (4%). These three positive stains constituted 0.5% of the 573 stains required to immunohistochemically screen all of the lymph node blocks from these patients. Among the 39 patients who were selected because they developed distant metastases, three immunohistochemically detected lymph node micrometastases from three patients were identified, which constituted 8% of patients in this group and 1% of the 280 stains required to screen all of these patients' lymph nodes. Small vessel invasion, maximum tumor dimension, and immunohistochemically detected lymph node micrometastases were independently associated with metastases on multivariate analysis. Among patients who developed metastases, there was no significant difference in the disease-free survival rate between those with and those without immunohistochemically detected lymph node micrometastases. Given the low sensitivity in terms of the number of immunohistochemical stains performed, and the prognostic significance of standard histologic features, the use of immunohistochemical screening lymph nodes from all patients with T1, N0, M0 adenocarcinomas is questionable.

Prognostic factors in T1 NO MO adenocarcinomas and bronchioloalveolar carcinomas of the lung.

There are few prognostic factors for patients with T1 N0 M0 pulmonary conventional and bronchioloalveolar adenocarcinomas (BACs), despite a 25% to 35% failure rate. To identify prognostic factors related to disease-free survival, we retrospectively studied the histologic features of 218 cases of T1 NO MO adenocarcinomas. The mean overall follow-up was 5.9 years, and the 5-year disease-free survival was 72%; 148 patients (67.9%) were disease-free, and in 57 (26.1%), nonpulmonary metastases developed. Features significantly associated with decreased 5-year disease-free survival were larger tumor size, increasing central fibrosis, most common and highest nuclear grade, lymphatic vascular space invasion, and more than 50% tumor necrosis. Patients with lymphatic vascular space invasion had a 35% 5-year metastases-free survival. A tumor size of 2 to 3 cm, lymphatic vascular space invasion, highest nuclear grade 3, and increased central fibrosis were associated with metastases. Lymphatic vascular space invasion had the strongest odds ratio of 5.4. These histologic features can stratify patients with T1 N0 M0 neoplasms who have an increased risk of metastases. Future studies are needed to address the usefulness of adjuvant therapy for patients with neoplasms that display these negative factors.

Nonoperative management of gunshot wounds of the abdomen.

Nonoperative management of stab wounds of the abdomen is currently practiced in many trauma centers; this report examines the role of expectant management of gunshot wounds to the abdomen in a select patient population. Patients presenting to a single trauma service from 5/91 to 1/94 at Detroit Receiving Hospital with a gunshot wound (GSW) to the abdomen fulfilling the following criteria were observed: 1) single GSW to the right upper quadrant, 2) stable vital signs, 3) reliable examination with minimal abdominal tenderness and available team/operating room, and 4) minimal or no abdominal tenderness. There were 12 patients fulfilling the study criteria; all were successfully observed. One nontherapeutic laparotomy was done due to abdominal tenderness. The role of expectant therapy of abdominal gunshot wounds is cautiously advanced. With appropriate criteria, this technique appears safe and efficacious.

Fibrin gel limits intra-abdominal adhesion formation.

Autologous fibrin gel (FG) has recently been reported efficacious in hepatic injury; the effects of fibrin compounds on intra-abdominal adhesion formation is controversial. This study evaluated intra-abdominal adhesion formation in a rabbit devascularization model. Seventeen New Zealand rabbits were anesthetized and laparotomy was done. The uterine horns were abraded to punctate bleeding followed by bilateral uterine devascularization. Treatment consisted of 10 cc saline control (c) or FG applied to the uterine horns. Peritoneal lavage was done at 15 minutes for red blood cell (RBC) analysis. Autopsy was performed at 1 week. Adhesions were graded from grade 0 (no adhesions) to grade III (dense adhesions). Adhesion grading revealed no difference in average adhesion grade between FG and C with small bowel (1.0 +/- 1.3 vs 0.5 +/- 1.0); bladder (2.1 +/- 1.1 vs 2.4 +/- 1.2); or uterus (1.2 +/- vs 2.0 +/- 1.2). Adhesion grade was significantly less in FG compared to C for the colon and the abdominal incision (0.4 +/- 0.5 vs 1.7 +/- 1.1 and 1.2 +/- 1.1 vs 3.0 +/- 1.2; P less than 0.05 by t-test). There were no differences in lavage RBC count between FG and C (13.1 x 106 +/- 4.1 x 10(6) vs 8.7 x 106 +/- 3.2 x 10(6)). Fibrin gel significantly decreased incisional and colonic adhesions and reduced other abdominal adhesion formation by a nonhemostatic dependent mechanism.

[Disseminated lymphangioleiomyomatosis]. / Disseminierte Lymphangioleiomyomatose.

Clinical and histological findings of generalised lymphangioleiomyomatosis are demonstrated. A 40-year old woman died within a few weeks because of massive pulmonary involvement. Tumour mass in the area of the left ovary together with enlarged lymph nodes suggested a metastasising ovarian cancer.

[Schwannoma of the larynx in Recklinghausen disease. Differential diagnostic considerations and immunohistochemical detection]. / Schwannom des Larynx bei Morbus Recklinghausen. Differentialdiagnostische Erwägungen und immunhistochemischer Nachweis.

A case of schwannoma of the larynx in a 29-year-old woman with Recklinghausen's disease is reported. The tumor was located in the arytenoid region. The patient complained of disturbed swallowing, aphonia, and dyspnea. The tumor was endoscopically removed. The light-microscopic and immunohistochemical findings are presented.

A comparative study on in vitro invasion rates by melanoma cells in the human amniotic basement membrane model versus in vivo tumor nodule formation in C57BL6 mice.

Invasion by murine B16-F10 melanoma cells was studied using the human amniotic basement membrane (HABM) assay. B16-F10 cells were collected after a single passage through the amnion and grown to near confluency. The cycle of plating, passaging, collecting, and culturing B16-F10 cells was repeated five times. The invasion rate for B16-F10 cells remained relatively unchanged after six passages through the amnion. Injection of first-passage B16-F10 cells into C57BL6 mice resulted in 29 lung tumors per animal whereas sixth-passage cells resulted in 300+ lung tumors. While there exists no correlation of the number of cells penetrating the amnion with colonization number, lung colonization appears correlated with increased number of passages through the amnion.

Effect of hyperthermia, radiation and adriamycin combinations on tumor vascular function.

Pathophysiologic studies of tumor vascular responses to hyperthermia, radiation or adriamycin given alone or in specific combinations have been made in the cervical carcinoma grown in the transparent cheek pouch chamber of the Syrian hamster. A specially designed chamber containing a compartment for flowing water enabled controlled heating of the tumor and pouch to within 0.2 degrees C; the desired temperatures were achieved within one minute. Heating at 42 degrees C for 30 minutes was followed, at 1, 5 or 24 hours, by a second heating for 30 minutes at 42 degrees C. In addition, the same period of heating was preceded or followed, at 1, 5 or 24 hour intervals, by a single exposure to 2000R or a single intravenous injection of adriamycin given at a rate of 0.45mg/100gm body weight. Of the three modalities, heat appeared to have the greatest acute effect on the tumor vascular system. A single dose of heat produced a rapid but transient constriction followed by a prominent dilation of vessels. Two heating periods given at a 1 hour interval caused persistent stasis in the tumor which progressed to coagulation necrosis. Although heating prior to irradiation or adriamycin, in general, increased the vascular responses to these agents, this sequence gave no tumor control. Radiation or adriamycin given prior to heating had relatively little effect on the vascular response to heating and produced no tumor control except when heat was applied shortly after irradiation. These studies indicate that changes in the microvasculature and perfusion in tumors, in response to hyperthermia alone or combined in specific sequences with radiation, can alter the internal environment of the tumor to produce a greater degree of tumor control than can be attributed to direct cell killing by these agents.