Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion in the treatment of recurrent epithelial ovarian cancer: a phase II clinical study.

AIMS AND BACKGROUND: The optimal salvage therapy for recurrent ovarian carcinoma has not been clearly established. Response to second-line chemotherapy is low, with a short median survival (8.8-15 months). We investigated the effect of an aggressive approach consisting of surgery followed by intraperitoneal drug delivery and local hyperthermia. PATIENTS AND METHODS: In a phase II clinical study, 27 patients with advanced/recurrent ovarian carcinoma were treated with cytoreductive surgery and intraperitoneal hyperthermic perfusion. Median patient age was 53 years (range, 30-67) and mean follow-up was 17.4 months (range, 0.3-36.0). Patients had been surgically staged and heavily pretreated with cisplatin-based, taxol-based or taxol/platinum-containing regimens. Nineteen (70%) patients were cytoreduced to minimal residual disease <2.5 mm. The intraperitoneal hyperthermic perfusion was performed with the closed abdomen technique, using a preheated polysaline perfusate containing cisplatin (25 mg/m2/L) + mitomycin C (3.3 mg/m2/L) through a heart-lung pump (mean flow of 700 mL/min) for 60 min in the hyperthermic phase (42.5 degrees C). RESULTS: Two-year overall survival was 55%. Median times to overall progression and local progression were 16 months and 21.8 months, respectively. Variables that affected the overall survival or time to progression were as follows: residual disease (P = 0.00025), patient age (P = 0.04), and lag time between diagnosis and cytoreductive surgery + intraperitoneal hyperthermic perfusion (P = 0.04). Treatment-related morbidity, mortality and acute toxicity (grade II-III) rates were 11%, 4% and 11%, respectively. Eight (89%) of 9 patients had ascites resolution. CONCLUSION: Our results suggest that cytoreductive surgery + intraperitoneal hyperthermic perfusion is a well-tolerated, feasible and promising alternative in the management of selected patients with recurrent ovarian cancer, but further randomized controlled studies are needed in order to confirm our findings.

Peritoneal carcinomatosis: feature of dissemination. A review.

Peritoneal carcinomatosis is a common event that develops in the natural history of many neoplastic diseases, representing a major problem encountered in cancer, management. Peritoneal seedings are often associated with neoplastic ascites resulting in a source of significant discomfort to the patient. Considered in the past as a terminal condition, peritoneal carcinomatosis was approached during the last two decades as a curable disease. The introduction of cytoreductive surgery or peritonectomy in the treatment of peritoneal neoplastic diseases drastically changed the natural history of peritoneal carcinomatosis. Another technique that showed an important impact on disease control is intraperitoneal hyperthermic perfusion, one of the most fascinating treatments of peritoneal carcinomatosis that results in an impressive increase in overall survival and quality of life in treated patients with low morbidity. This review illustrates the modality of dissemination of peritoneal carcinomatosis in relation to the primary tumor site and grade of malignancy. Peritoneal carcinomatosis is a term used to define an advanced stage of many abdominal neoplastic diseases that differ in biologic aggressiveness and prognosis. The different presentation of peritoneal carcinomatosis in relation to a different primary tumor and different grade of malignancy strongly influences the potentially therapeutic radical approaches using new and advanced modalities like cytoreductive surgery and intraperitoneal hyperthermic perfusion.

Functional MRI reveals spatially specific attentional modulation in human primary visual cortex.

Selective visual attention can strongly influence perceptual processing, even for apparently low-level visual stimuli. Although it is largely accepted that attention modulates neural activity in extrastriate visual cortex, the extent to which attention operates in the first cortical stage, striate visual cortex (area V1), remains controversial. Here, functional MRI was used at high field strength (3 T) to study humans during attentionally demanding visual discriminations. Similar, robust attentional modulations were observed in both striate and extrastriate cortical areas. Functional mapping of cortical retinotopy demonstrates that attentional modulations were spatially specific, enhancing responses to attended stimuli and suppressing responses when attention was directed elsewhere. The spatial pattern of modulation reveals a complex attentional window that is consistent with object-based attention but is inconsistent with a simple attentional spotlight. These data suggest that neural processing in V1 is not governed simply by sensory stimulation, but, like extrastriate regions, V1 can be strongly and specifically influenced by attention.

A local circuit approach to understanding integration of long-range inputs in primary visual cortex.

Integration of inputs by cortical neurons provides the basis for the complex information processing performed in the cerebral cortex. Here, we have examined how primary visual cortical neurons integrate classical and nonclassical receptive field inputs. The effect of nonclassical receptive field stimuli and, correspondingly, of long-range intracortical inputs is known to be context-dependent: the same long-range stimulus can either facilitate or suppress responses, depending on the level of local activation. By constructing a large-scale model of primary visual cortex, we demonstrate that this effect can be understood in terms of the local cortical circuitry. Each receptive field position contributes both excitatory and inhibitory inputs; however, the inhibitory inputs have greater influence when overall receptive field drive is greater. This mechanism also explains contrast-dependent modulations within the classical receptive field, which similarly switch between excitatory and inhibitory. In order to simplify analysis and to explain the fundamental mechanisms of the model, self-contained modules that capture nonlinear local circuit interactions are constructed. This work supports the notion that receptive field integration is the result of local processing within small groups of neurons rather than in single neurons.

An emergent model of orientation selectivity in cat visual cortical simple cells.

It is well known that visual cortical neurons respond vigorously to a limited range of stimulus orientations, while their primary afferent inputs, neurons in the lateral geniculate nucleus (LGN), respond well to all orientations. Mechanisms based on intracortical inhibition and/or converging thalamocortical afferents have previously been suggested to underlie the generation of cortical orientation selectivity; however, these models conflict with experimental data. Here, a 1:4 scale model of a 1700 microns by 200 microms region of layer IV of cat primary visual cortex (area 17) is presented to demonstrate that local intracortical excitation may provide the dominant source of orientation-selective input. In agreement with experiment, model cortical cells exhibit sharp orientation selectivity despite receiving strong iso-orientation inhibition, weak cross-orientation inhibition, no shunting inhibition, and weakly tuned thalamocortical excitation. Sharp tuning is provided by recurrent cortical excitation. As this tuning signal arises from the same pool of neurons that it excites, orientation selectivity in the model is shown to be an emergent property of the cortical feedback circuitry. In the model, as in experiment, sharpness of orientation tuning is independent of stimulus contrast and persists with silencing of ON-type subfields. The model also provides a unified account of intracellular and extracellular inhibitory blockade experiments that had previously appeared to conflict over the role of inhibition. It is suggested that intracortical inhibition acts nonspecifically and indirectly to maintain the selectivity of individual neurons by balancing strong intracortical excitation at the columnar level.