18F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: a pilot study / 18F-FDG PET/TC, cirugía citorreductora y quimiohipertermia intraperitoneal para el tratamiento terapéutico de la carcinomatosis peritoneal: estudio piloto

Aim. Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal18F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. Methods. Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery 18F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. Results. 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by 18F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased 18F-FDG uptake, were recognized. Conclusions. PP + IPCH of patients selected by 18F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients (AU)

Objetivo. La carcinomatosis peritoneal es una evolución común de las neoplasias y constituye el estadio terminal de la enfermedad. Se ha desarrollado una nueva técnica, basada en la extirpación quirúrgica de las lesiones peritoneales (procedimiento de peritonectomía - PP), combinada con quimiohipertermia intraperitoneal (IPCH). La adecuada selección de los pacientes es primordial, a fin de optimizar los resultados del tratamiento. El objetivo de este estudio fue investigar el papel de la tomografía de emisión de positrones con [(18)F]fluoro-2-deoxy-d-glucosa/tomografía computarizada (18F-FDG PET/TC) en pacientes con carcinomatosis peritoneal, seleccionados para someterse a PP e IPCH. Además, tratamos de identificar los patrones característicos de la captación abdominal de 18F-FDG y correlacionar dichos patrones con los hallazgos anatómicos disponibles tras la cirugía. Métodos. Se realizaron exámenes 18F-FDG PET/TC de manera prospectiva, y previamente a la cirugía, a los pacientes con carcinomatosis peritoneal histológicamente confirmada, o sospechada mediante seguimiento clínico y/o hallazgos de imagen. Solo puede tratarse con PP y IPCH a aquellos pacientes que no reflejen evidencia de metástasis extraperitoneales en los exámenes PET/TC. Resultados. Se seleccionó para el estudio a 11 pacientes con carcinomatosis peritoneal (5 colorrectales, 4 ováricas, una pancreática) y un cáncer primitivo desconocido. En todos los casos, el examen PET/TC reflejó múltiples implantes peritoneales. En 6 de los 11 casos (54%) las metástasis fueron evidenciadas mediante 18F-FDG PET/TC: 2 casos con metástasis hepáticas, un caso con metástasis óseas, y 3 pacientes con lesiones ganglionares. Se reconocieron 2 patrones de imagen distintos, con aumento de captación focal o difusa de 18F-FDG. Conclusiones. La combinación PP + IPCH de los pacientes seleccionados mediante 18F-FDG PET/TC parece ser una técnica segura y factible. La PET/TC se revela como una herramienta fiable para la detección y caracterización de los implantes peritoneales, con un impacto potencial sobre el tratamiento terapéutico de dichos pacientes (AU)

(18)F-FDG PET/CT, cytoreductive surgery and intraperitoneal chemohyperthermia for the therapeutic management in peritoneal carcinomatosis: A pilot study.

AIM: Peritoneal carcinomatosis is a common evolution of neoplasms and the terminal stage of disease. A new therapeutic technique, based on the total surgical removal of peritoneal lesions (peritonectomy procedure - PP) combined with the intraperitoneal chemohyperthermia (IPCH), has been developed. Proper patient selection is mandatory for optimizing the results of treatment. The aim of this study was to investigate the role of [(18)F]fluoro-2-deoxy-d-glucose Positron Emission Tomography/Computed Tomography ((18)F-FDG PET/CT) in patients with peritoneal carcinosis selected to undergo PP and IPCH. Furthermore, we aimed to identify characteristic patterns of abdominal(18)F-FDG uptake and to correlate these patterns with available anatomic findings after surgery. METHODS: Patients with either histologically confirmed peritoneal carcinosis or suspected upon clinical follow-up and/or imaging findings were prospectively submitted to pre-surgery (18)F-FDG PET/CT scan. Only those patients without evidence of extra-peritoneal metastases at PET/CT scan were treated with PP and IPCH. RESULTS: 11 patients with peritoneal carcinomatosis (5 colorectal, 4 ovarian, 1 pancreatic) and 1 unknown primitive cancer, were eligible for the study. In all cases PET/CT scan showed multiple peritoneal implants. In 6 out of 11 cases (54%) metastases were evidenced by (18)F-FDG PET/CT: 2 cases with liver metastases; 1 case with bone metastases; 3 patients with lymph-node lesions. Two distinct imaging patterns, with focal or diffuse increased (18)F-FDG uptake, were recognized. CONCLUSIONS: PP+IPCH of patients selected by (18)F-FDG PET/CT seems to be safe and feasible. PET/CT scan appears as a reliable tool for the detection, characterization of peritoneal implants with potential impact in the therapeutic management of these patients.

Class II-specific histone deacetylase inhibitors MC1568 and MC1575 suppress IL-8 expression in human melanoma cells.

Here, we explored the effects of the novel class II-specific histone deacetylase inhibitors (HDACis) MC1568 and MC1575 on interleukin-8 (IL-8) expression and cell proliferation in cutaneous melanoma cell line GR-M and uveal melanoma cell line OCM-3 upon stimulation with phorbol 12-myristate 13-acetate (PMA). We found that PMA upregulated IL-8 transcription via the AP-1 binding site and identified c-Jun as the transcription factor involved in this eventS. MC1568 and MC1575 inhibited IL-8 levels and cell proliferation in either unstimulated or PMA-stimulated melanoma cells. They acted by suppressing (i) c-Jun binding to the IL-8 promoter, (ii) recruitment of histones 3 and 4, RNA polymerase II and TFIIB to the c-Jun promoter, and (iii) c-Jun expression. Our findings provide new insights into mechanisms underlying anti-tumoral activities of class II-specific HDACis in human melanoma and suggest that they may constitute a novel therapeutic strategy for improving the treatment of this cancer.

Unexpected histological findings of lesions diagnosed in the adrenal region in a series of 420 patients submitted to adrenal surgery. Review of our experience.

INTRODUCTION: The incidence of adrenal incidentalomas is reported to be up to 30% in the current literature; nevertheless, in some patients undergoing surgery, a final diagnosis of non-adrenal origin of the mass is performed. In this paper we present our experience of 13 patients with unexpected histological findings of lesions diagnosed in the adrenal region. PATIENTS AND METHODS: From June 1986 to December 2004, 420 patients underwent adrenalectomy in our Department. Since the introduction of videolaparoscopic technique in 1993, 228 adrenalectomies have been performed videolaparoscopically. Pre-operative diagnosis was: incidentaloma (34.0% of patients), Conn's adenoma (29.0%), Cushing's adenoma (13.9%), pheochromocytoma (8.8%), suspicious metastasis (7.3%), Cushing's disease (6.0%), other (1.0%). RESULTS: Final histology revealed an unexpected diagnosis of non-adrenal origin of the mass in 13 patients (3.1%). Histology demonstrated a benign neurogenic tumor in 10 patients. In the other 3 patients diagnosis was respectively of lymphnode, hemangioma and a gastric metastasis of melanoma. Five patients out of 7 had a successful laparoscopic resection of the lesion. Mean operative time in this group was higher compared to laparoscopic resection for adrenal lesion (95.3 min vs 73.2 min). CONCLUSION: A small percentage of our patients (3.1%) demonstrated unexpected findings of the lesion pre-operatively misinterpreted as an adrenal mass. Despite a complete pre-operative assessment, adrenal lesions might reveal a different origin, increasing the surgical challenge as well as the morbidity for the patient.