Chemotherapy-Induced Neurotoxicity: Evidence of a Protective Role of CC Homozygosis in the Interleukin-1ß Gene-511 C>T Polymorphism.

We hypothesized that the IL-1ß-511 C>T polymorphism could be associated with the development of neurotoxicity and that it could be a possible biomarker to rate the risk of occurrence of neurotoxicity in cancer patients. Genomic DNA was extracted from 85 cancer patients: 49 received systemic chemotherapeutic treatment (CHT) and 36 patients did not receive it (No-CHT). All subjects were genotyped for the functionally active polymorphisms of IL-1ß-511 C>T. We estimated neurotoxicity with the evaluation of neurological deficits. CHT patients showed erythrocytopenia, neurological deficit and a slight lowering of cognitive performance. The subgroup of patients carrying the CC genotype of the IL-1ß-511 C>T gene showed lesser neurological deficits. In the context of cancer treatment, we suggested the potential value of IL-1ß-511 C>T as genetic biomarkers to identify patients with higher risk to develop neurological deficits.

The Neurobiological Basis of the Distress Thermometer: A PET Study in Cancer Patients.

The objective of this study was to investigate the possible associations between the Distress Thermometer (DT) scores and the brain metabolism of structures involved in stress response. Twenty-one cancer patients were assessed using the DT, Problem Checklist and Hospital Anxiety and Depression Scale (HADS). The psychological measures were correlated with [18 F]PET-FDG brain glucose metabolism. Multiple and linear regression and binary logistic regression were run to analyse data. The DT and HADS scores illustrated that 48% of patients were distressed, 19% were depressed and 48% were anxious. Results showed that some subcortical areas activity, such as part of midbrain and of hypothalamus, was correlated with the DT scores. The Problem Checklist scores correlated with the activity of the same areas and included more regions in the limbic forebrain and brainstem. Compared with the DT and Problem Checklist, HADS-Depression scores showed a more extensive pattern of correlation with brain activity, including limbic and cortical areas. The results highlighted that the DT scores correlated with the activity of brain areas typically involved in stress response. Indeed, hypothalamus metabolism was found to be the best predictor of distressed patients.

The chemotherapy long-term effect on cognitive functions and brain metabolism in lymphoma patients.

AIM: A growing number of neuropsychological studies reported that chemotherapy may impair brain functions, inducing persistent cognitive changes in a subset of cancer survivors. The aim of this paper was to investigate the neural basis of the chemotherapy induced neurobehavioral changes by means of metabolic imaging and neuropsychological testing. METHODS: We studied the resting brain [¹8F]FDG-PET/CT images of 50 adult cancer patients with diagnosis of lymphoma: 18 patients were studied prior and 32 after to chemotherapy. All patients underwent to a neuropsychological examination assessing cognitive impairment (tests for shifting attention, verbal memory, phonemic fluency), depression, anxiety and distress. RESULTS: Compared to no chemotherapy patients, the treated group showed significant bilateral lower rate of glucose metabolism in prefrontal cortices, cerebellum, medial cortices and limbic brain areas. The metabolism of these regions negatively correlated with number of cycles and positively with post-chemotherapy time. The treated group showed a poorer performance in many frontal functions, but similar level of depression, anxiety and distress. CONCLUSIONS: Chemotherapy induced significant long-term changes in metabolism of multiple regions with a prevailing involvement of the prefrontal cortex. The observed cognitive dysfunctions could be explained by these changes. The recovery from chemotherapy is probably affected by treatment duration and by the time elapsed after its end. We speculated that the mechanism could be an accelerating ageing / oxidative stress that, in some patients at risk, could result in an early and persistent cognitive impairment.

Pre-operative lymphatic mapping and intra-operative sentinel lymph node detection in early stage endometrial cancer.

Lymphatic mapping and sentinel lymph node (SLN) biopsy are becoming increasingly useful for the identification of tumour lymphatic spread in a wide variety of neoplasms, such as breast cancer and melanoma, reducing unnecessary radical lymph node resection. The aim of our study was to determine the feasibility of lymphatic mapping with both labelled colloid and patent blue violet in patients with early stage endometrial cancer. Sixteen consecutive patients with endometrial cancer, stage International Federation of Gynecology and Obstetrics (FIGO Ib), were included in the study. Lymphoscintigraphy and laparoscopically assisted intra-operative SLN detection were performed in all patients. In addition, to verify the prognostic role of this method, 12 of 16 patients were followed up for a period of at least 1 year. In 15 of 16 patients, 24 SLNs (all internal iliac lymph nodes) were detected at lymphoscintigraphy (six monolateral and nine bilateral). At histological analysis, three of the 24 were positive for micrometastases, whereas the remaining 21 were negative. No other surgically dissected lymph nodes presented metastases. At 1 year of follow-up, none of the 12 patients presented relapse of their disease. In conclusion, in endometrial cancer, both pre-operative lymphoscintigraphy and intra-operative gamma-probe detection of SLNs represent promising tools for the visualization of SLNs. The status of the latter may yield a correct representation of pelvic lymph node involvement, providing important information for further treatment.

Sentinel node detection in breast carcinoma.

AIMS AND BACKGROUND: The standard procedure for the evaluation of axillary nodal involvement in patients with breast cancer is still complete lymph node dissection. However, about 70% of patients are found to be free of metastatic disease while axillary node dissection may cause significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. METHODS AND STUDY DESIGN: In a period of 18 months we studied 201 patients with breast cancer, excluding patients with palpable axillary nodes, tumors > 2.5 cm in diameter, multifocal or multicentric cancer, pregnant patients and patients over 80 years of age. Before surgery 99mTc-labeled colloid and vital blue dye were injected into the breast to identify the SLN. In lymph nodes dissected during surgery the metastatic status was examined by sections at reduced intervals. Only patients with SLNs that were histologically positive for metastases underwent axillary dissection. RESULTS: We localized one or more SLNs in 194 of 201 (96.5%) patients; when both techniques were utilized the success rate was 100%. Histologically, 21% of patient showed SLN metastases (7.8% micrometastases) and 68% of these had metastases also in other axillary nodes. None of the patients with negative SLNs developed metastases during follow-up. CONCLUSIONS: At present there is no definite evidence that negative SLN biopsy is invariably correlated with negative axillary status; however, our study and those of others demonstrate that SLN biopsy is an accurate method of axillary staging.

Preliminary study of sentinel node identification with 99mTc colloid and blue dye in patients with endometrial cancer.

AIMS AND BACKGROUND: Intraoperative lymphatic mapping and sentinel node (SLN) biopsy have generated a tremendous amount of interest and are already established as part of the standard practice in the surgical management of breast cancer and melanoma. To reduce extensive radical procedures and decrease the morbidity in the treatment of gynecologic malignancies, much effort is being made to use less aggressive interventions. The purpose of our study was to determine the feasibility of SLN mapping in a group of patients with endometrial cancer at early stages. METHOD AND STUDY DESIGN: Between September 2000 and May 2001 11 patients with endometrial cancer FIGO stage Ib (n = 10) and IIa (n = 1) underwent laparoscopic SNL detection during laparoscopy-assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and bilateral systematic pelvic lymphadenectomy. Radioactive isotope injection was performed 24 hours before surgery and blue dye injection was performed just before surgery in the cervix at 3,6, 9 and 12 hours. A 350 mm laparoscopic gamma scintyprobe MR 100 type 11, 99mTc settled (Pol Hi Tech), was used intraoperatively for SLN detection. RESULTS: Seventeen (17) SLNs were detected with lymphoscintigraphy (six bilateral and five unilateral). At laparoscopic surgery we found the same locations belonging at internal iliac lymph nodes (the so-called Lebeuf-Godard area, lateral to the inferior vesical artery, ventral to the origin of the uterine artery and medial or caudal to the external iliac vein). Fourteen (14) SLNs were negative on histological analysis and three were positive for micrometastases (mean SLN sections = 60). All other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with the gamma scintyprobe were observed at laparoscopy after patent blue dye injection. CONCLUSIONS: Our preliminary data suggest that combined 99mTc-labeled colloid and vital blue-dye techniques are feasible for SLA detection in endometrial cancer; they represent a very promising tool to transform the management of early-stage endometrial cancer. The clinical validity of this combined technique should be evaluated prospectively.