The Safety and Efficacy of Laparoscopic Surgical Staging and Debulking of Apparent Advanced Stage Ovarian, Fallopian Tube, and Primary Peritoneal Cancers

Objectives:

To describe our experience with laparoscopic primary or interval tumor debulking in patients with presumed advanced ovarian, fallopian tube, or peritoneal cancers.

Methods:

This is a retrospective analysis of a prospective case series. Women with presumed advanced (FIGO stage IIC or greater) ovarian, fallopian tube, or primary peritoneal cancers deemed appropriate candidates for laparoscopic debulking by the primary surgeon(s) were recruited.

Results:

The study comprised 32 patients who underwent laparoscopic evaluation. Seventeen underwent total laparoscopic primary or interval cytoreduction, with 88.2% optimal cytoreduction. Eleven underwent diagnostic laparoscopy and conversion to laparotomy for cytoreduction, with 72.7% optimal cytoreduction. Four patients had biopsies, limited cytoreduction, or both. In the laparoscopy group, 9 patients have no evidence of disease (NED), 6 are alive with disease (AWD), and 2 have died of disease (DOD), with mean follow-up time of 19.7 months. In the laparotomy group, 3 patients are NED, 5 are AWD, and 3 are DOD, with mean follow-up of 25.8 months. Estimated blood loss and length of hospital stay were less for the laparoscopy group (P=0.008 and P=0.03), while operating time and complication rates were not different. Median time to recurrence was 31.7 months for the laparoscopy group and 21.5 months for the laparotomy group (P=0.3).

Conclusions:

Laparoscopy can be used for diagnosis, triage, and debulking of patients with advanced ovarian, fallopian tube, or primary peritoneal cancer and is technically feasible in a well-selected population.     

18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor

[(18)F]MK-9470 is a selective, high-affinity, inverse agonist (human IC(50), 0.7 nM) for the cannabinoid CB1 receptor (CB1R) that has been developed for use in human brain imaging. Autoradiographic studies in rhesus monkey brain showed that [(18)F]MK-9470 binding is aligned with the reported distribution of CB1 receptors with high specific binding in the cerebral cortex, cerebellum, caudate/putamen, globus pallidus, substantia nigra, and hippocampus. Positron emission tomography (PET) imaging studies in rhesus monkeys showed high brain uptake and a distribution pattern generally consistent with that seen in the autoradiographic studies. Uptake was blocked by pretreatment with a potent CB1 inverse agonist, MK-0364. The ratio of total to nonspecific binding in putamen was 4-5:1, indicative of a strong specific signal that was confirmed to be reversible via displacement studies with MK-0364. Baseline PET imaging studies in human research subject demonstrated behavior of [(18)F]MK-9470 very similar to that seen in monkeys, with very good test-retest variability (7%). Proof of concept studies in healthy young male human subjects showed that MK-0364, given orally, produced a dose-related reduction in [(18)F]MK-9470 binding reflecting CB1R receptor occupancy by the drug. Thus, [(18)F]MK-9470 has the potential to be a valuable, noninvasive research tool for the in vivo study of CB1R biology and pharmacology in a variety of neuropsychiatric disorders in humans. In addition, it allows demonstration of target engagement and noninvasive dose-occupancy studies to aid in dose selection for clinical trials of CB1R inverse agonists.     

Epidemiologische Daten zur Nahrungsmittelallergie in Europa

The interpretation of epidemiological data on food hypersensitivities should clearly separate two issues: the disposition to respond symptomatically to certain foods and the actual reactions occurring, which can be observed only when there is sufficient consumption or targeted exposure/provocation.     

Potential role of Jun activation domain-binding protein 1 as a negative regulator of p27kip1 in pancreatic adenocarcinoma

Reduced expression of p27 has been associated with poor prognosis in most human cancers, including pancreatic adenocarcinoma. Jun activation domain-binding protein 1 (JAB1), an activator protein (AP-1) coactivator, previously implicated in p27 degradation, is overexpressed in various tumors and correlates with low p27 expression. We examined JAB1 and p27 in normal and neoplastic pancreatic tissues. Increased JAB1 expression was seen in pancreatic carcinoma samples but not in paired normal pancreatic tissues. Immunohistochemical analysis using tissue microarrays showed that JAB1 was overexpressed in all 32 (100%) pancreatic adenocarcinoma samples tested, predominantly nuclear in 23 (72%) samples and predominantly cytoplasmic in 9 (28%) tumors. When 10% was used as a cutoff for p27 positivity, p27 was expressed in 11 (34%) of tumors; however, p27 expression was localized in the nuclei of tumor cells in only 4 (13%) of the samples. Overexpression of the JAB1 in the pancreatic carcinoma cell lines Panc-1, Mia PaCa-2, and Panc-28 resulted in decreased p27 expression. Conversely, down-regulation of JAB1 by short interfering RNA substantially increased p27 expression and inhibited progression from G(1) to S phase of the cell cycle. Interestingly, JAB1-mediated p27 degradation was not impaired when S-phase kinase-interacting protein 2 (Skp2), an F-box protein required for the ubiquitination and consequent degradation of p27, was silenced. Thus, JAB1 may have an Skp2-independent p27 degradation mechanism in pancreatic cancer cells. These findings suggest that JAB1 overexpression is involved in the pathogenesis of pancreatic cancer through JAB1-mediated p27 degradation and that control of JAB1 expression is a novel therapeutic target in patients with pancreatic adenocarcinomas.     

Dose-response relationship in locoregional control for patients with stage II-III esophageal cancer treated with concurrent chemotherapy and radiotherapy

PURPOSE: To evaluate the correlation between radiation dose and locoregional control (LRC) for patients with Stage II-III unresectable esophageal cancer treated with concurrent chemotherapy and radiotherapy. METHODS AND MATERIALS: The medical records of 69 consecutive patients with clinical Stage II or III esophageal cancer treated with definitive chemoradiotherapy at the University of Texas M. D. Anderson Cancer Center between 1990 and 1998 were retrospectively reviewed. Of the 69 patients, 43 had received < or =51 Gy (lower dose group) and 26 >51 Gy (higher dose group). The median dose in the lower and higher dose groups was 30 Gy (range, 30-51 Gy) and 59.4 Gy (range, 54-64.8 Gy), respectively. Two fractionation schedules were used: rapid fractionation, delivering 30 Gy at 3 Gy/fraction within 2 weeks, and standard fractionation, delivering > or =45 Gy at 1.8-2 Gy/fraction daily. Total doses of <50 Gy were usually given with rapid fractionation. Cisplatin and 5-fluorouracil were administrated to 93% of the patients. RESULTS: The patient characteristic that differed between the two groups was that patients in the lower dose group were more likely to have had weight loss >5% (46.2% vs. 23.3%). The lower dose group had more N1 tumors, but the tumor classification and stage grouping were similar in the two groups. The median follow-up time for all patients was 22 months (range, 2-56 months). Patients in the higher dose group had a statistically significant better 3-year local control rate (36% vs. 19%, p = 0.011), disease-free survival rate (25% vs. 10%, p = 0.004), and overall survival rate (13% vs. 3%, p = 0.054). A trend toward a better distant-metastasis-free survival rate was noted in the higher dose group (72% vs. 59%, p = 0.12). The complete clinical response rate was significantly greater in the higher dose group (46% vs. 23%, p = 0.048). In both groups, the most common type of first failure was persistence of the primary tumor. Significantly fewer patients in the higher dose group had tumor persistence after treatment (p = 0.02). No statistically significant difference was found between the two groups in the pattern of locoregional or distant failure. The long-term side effects of chemoradiotherapy were similar in the two groups, although it was difficult to assess the side effects accurately in a retrospective fashion. On multivariate analysis, Stage II (vs. III) disease and radiation dose >51 Gy were independent predictors of improved LRC, and locoregional failure was an independent predictor of worse overall survival. CONCLUSION: Our data suggested a positive correlation between radiation dose and LRC in the population studied. A higher radiation dose was associated with increased LRC and survival in the dose range studied. The data also suggested that better LRC was associated with a lower rate of distant metastasis. A threshold of tumor response to radiation dose might be present, as suggested by the flattened slope in the high-dose area on the dose-response curve. A carefully designed dose-escalation study is required to confirm this assumption.     

Pharmacoeconomics of cholinesterase inhibitors in the treatment of Alzheimer's disease

Cholinesterase inhibitors constitute one of few treatment options available for Alzheimer's disease, the most common cause of dementia. The modest effects and relatively high acquisition costs of these drugs make the health economics of dementia an important subject of study. Simulation models can be used to bring together existing data and make predictions of the long-term cost effectiveness of treatment. Most models have been built around cognitive function as a key parameter based on the observed relationship between cognitive function and costs of care. Patients with more severe disease attain higher total costs of care. Also, these patients have a higher share of formal care costs than do patients with mild disease, who are usually looked after by informal caregivers. The valuation of unpaid care is controversial, and the choice of method may affect results considerably. Another important issue is the measurement of health-related QOL in patients with Alzheimer's disease. The few existing studies have used proxy respondents to elicit utility weights in different disease states; however, this methodology has not been validated. It is likely that the increased drug costs incurred by the use of cholinesterase inhibitors will be offset (at least partly) by savings in other healthcare costs. However, these results should be viewed as preliminary, since we are still awaiting data from long-term follow-up studies. Also, the value of treatment for patients and caregivers in terms of QOL improvements has yet to be established.     

Leiomyosarcoma of the esophagus metastatic to the eyelid: a clinicopathologic report

PURPOSE: To report a case of gastrointestinal sarcoma with leiomyosarcomatous differentiation metastatic to the eyelid. METHODS: Clinical data including a comprehensive ophthalmologic examination, histologic findings, a bone scan, and hospital records were reviewed. RESULTS: A 56-year-old woman with a history of esophageal cancer had a rapidly growing lesion on her right upper eyelid that was initially treated as a chalazion. A biopsy specimen of the lesion was consistent with a gastrointestinal sarcoma with leiomyosarcomatous differentiation. The esophageal tumor was reclassified after histopathologic evaluation of the eyelid specimen. Bony metastasis developed soon after excision of the eyelid lesion. The patient died 3 months after proper diagnosis of the eyelid lesion. CONCLUSIONS: This is a rare case of a metastatic leiomyosarcoma of the eyelid. To our knowledge, only two other cases of eyelid leiomyosarcoma have been described in the literature. The importance of correct histopathologic diagnosis of eyelid lesions is underscored in this case report.