Pulmonary blastoma after liver transplant: a case report

There is an increased risk of cancer after organ transplantation mainly due to the immunosuppressive therapy required in these patients. We report a case of biphasic pulmonary blastoma in an adult male who underwent liver transplant for hepatocellular carcinoma in March 1999, followed by immunosuppressive treatment and adjuvant chemotherapy with epirubicin. Disease-free survival lasted 18 months, then a diagnosis of biphasic pulmonary blastoma was made and the patient underwent a lung lobectomy. Five months after surgical resection a recurrence of this rare tumor was recorded and two cycles of cisplatin + etoposide and ifosfamide + etoposide and one cycle of second-line chemotherapy with vinorelbine were administered. The tolerability and the efficacy of this treatment were poor. The patient died less than one year after diagnosis. To our knowledge this is the first reported case of pulmonary blastoma in a transplant patient. Our findings confirm that organ transplant recipients deserve long-term medical surveillance also in the absence of graft complications, and that pulmonary blastoma is an aggressive tumor with a poor prognosis.     

Real-time in vivo dosimetry using micro-MOSFET detectors during intraoperative electron beam radiation therapy in early-stage breast cancer.

PURPOSE: In a previous paper we reported the results of off-line in vivo measurements using radiochromic films in IOERT. In the present study, a further step was made, aiming at the improvement of the effectiveness of in vivo dosimetry, based on a real-time check of the dose. MATERIALS AND METHODS: Entrance dose was determined using micro-MOSFET detectors placed inside a thin, sterile, transparent catheter. The epoxy side of the detector was faced towards the beam to minimize the anisotropy. Each detector was plugged into a bias supply (standard sensitivity) and calibrated at 5 Gy using 6 MeV electrons produced by a conventional linac. Detectors were characterized in terms of linearity, precision and dose per pulse dependence. No energy and temperature dependence was found. The sensitivity change of detectors was about 1% per 20 Gy accumulated dose. Correction factors to convert surface to entrance dose were determined for each combination of energy and applicator. From November 2004 to May 2005, in vivo dosimetry was performed on 45 patients affected by early-stage breast cancer, who underwent IOERT to the tumour bed. IOERT was delivered using electrons (4-10 MeV) at high dose per pulse, produced by either a Novac7 or a Liac mobile linac. RESULTS: The mean ratio between measured and expected dose was 1.006+/-0.035 (1 SD), in the range 0.92-1.1. The procedure uncertainty was 3.6%. Micro-MOSFETs appeared suitable for in vivo dosimetry in IOERT, although some unfavourable aspects, like the limited lifetime and the anisotropy with no build-up, were found. Prospectively, a real-time action level (+/-6%) on dose discrepancy was defined. CONCLUSIONS: Excellent agreement between measured and expected doses was found. Real-time in vivo dosimetry appeared feasible, reliable and more effective than the method previously published.     

Interleukin-2 and 13-cis retinoic acid as maintenance therapy in advanced ovarian cancer

The primary objective was to assess whether low-dose Interleukin-2 (IL-2) and 13-cis-retinoic acid (RA) could decrease serum vascular endothelial growth factor (VEGF) and improve the immune function of patients with advanced ovarian cancer (AOC) responsive to chemotherapy. The secondary end-point was to compare the response of these patients with that of a group of control patients, treated with standard care. Forty-four patients with AOC, responding to chemotherapy and with elevated serum levels of VEGF, were entered into the study from 04/98 to 12/02. After chemotherapy, patients received self-administered subcutaneous IL-2, 1.8x10(6) IU and oral RA, 0.5 mg/kg for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week rest, for 1 year and with intermittent schedules for up to 5 years. Eighty-two well-matched controls were selected from a large cohort of patients of similar disease status, treated with standard therapies. A statistically significant decrease of VEGF was observed amongst the 44 evaluable patients. Lymphocyte NK counts and CD4+/CD8+ ratio improved with respect to both baseline values and controls. The progression-free survival (PFS) and overall survival (OS) curves showed a statistically significant improvement in IL-2/RA-treated patients. These preliminary data show that, after chemotherapy for AOC, the administration of low-dose subcutaneous IL-2 and oral RA is feasible, has low toxicity, is cost-effective and improves both PFS and OS.     

Expression of cortistatin and MrgX2, a specific cortistatin receptor, in human neuroendocrine tissues and related tumours

Cortistatin (CST), a novel hormone originally described in the rat, mouse, and human cerebral cortex, displays structural and functional similarities to somatostatin (SRIF). CST binds to all five somatostatin receptors and, differently from SRIF, also binds to MrgX2, which has recently been identified as its specific receptor. Little is known about the distribution of CST and MrgX2 in peripheral non-tumour and neoplastic tissues. The aim of the present study was therefore to determine by immunohistochemistry and mRNA analysis (RT-PCR) the distribution of CST and MrgX2 in 56 human non-tumour and 108 tumour tissues, with special reference to neuroendocrine tissue types. Despite the high level of CST mRNA expression in non-tumour and tumour (both neuroendocrine and non-neuroendocrine) tissues, the presence of immunoreactive CST was confirmed in a subset of gastroenteropancreatic, parathyroid, and pituitary non-tumour cells only, and showed a predominantly focal pattern in most neuroendocrine tumours. Co-localization experiments in the gastroenteropancreatic system demonstrated that the normal CST-producing cells are delta cells, while in the adenohypophysis no preferential co-localization of CST with any of the pituitary hormones was observed. MrgX2 mRNA was variably detected in the hypothalamus, pituitary, thyroid, lung, gastroenteropancreatic tract, testis, and ovary, and was negative in the cerebral cortex, parathyroid, and adrenal, as well as in a variety of tumour types. Conversely, immunolocalization of MrgX2 protein was restricted to neurohypophysis and testis, whilst all tumours analysed were negative. A possible explanation for the discrepancy between RT-PCR and immunohistochemistry is that MrgX2 protein was widely detected in blood vessels, scattered lymphocytes, and gastrointestinal ganglia in both normal and neoplastic samples. The findings demonstrate a selective distribution of CST in normal and neoplastic neuroendocrine tissues, suggesting that CST might have a broader functional role than previously assumed, whereas possible autocrine/paracrine actions via its recently described specific receptor MrgX2 are restricted to selected tissues.     

Hysteroscopic metroplasty under laparoscopic guidance in infertile women with septate uteri: follow-up of reproductive outcome

OBJECTIVE: To evaluate the effectiveness of hysteroscopic metroplasty under laparoscopic guidance in the treatment of infertile women with a diagnosis of septate uterus and the impact of this surgical procedure on reproductive outcome. STUDY DESIGN: From January 1996 to December 2000, 36 women referred to our endoscopy center underwent hysteroscopic metroplasty. Follow-up covered the incidence of pregnancy, term pregnancies and mode of delivery. RESULTS: The mean age of the patients was 31.9 +/- 3.9 years (range, 23-39). One patient (3%) dropped out during follow-up. There were no intraoperative or postoperative complications. The mean interval from metroplasty to conception was 11.3 +/- 9.2 months (range, 2.0-35.5). Twenty of 35 (57%) women had a history of > or = 1 spontaneous abortions, and 18 of the 20 (90%) achieved pregnancy, with 15 of 18 (83%) term deliveries (10 vaginal deliveries and 5 cesarean sections). Fifteen of 35 patients (43%) were nulliparous, and 8 of 15 (53.3%) had term deliveries (1 cesarean section). CONCLUSION: Hysteroscopic metroplasty under laparoscopic guidance is safe, allows spontaneous delivery and short-term pregnancy planning, is particularly successful in infertile women with a history of > or = 1 spontaneous abortions.     

Histologic assessment of biliary obstruction with different percutaneous endoluminal techniques

BACKGROUND: Despite the sophisticated cross sectional image techniques currently available, a number of biliary stenosis or obstructions remain of an uncertain nature. In these pathological conditions, an "intrinsic" parietal alteration is the cause of biliary obstruction and it is very difficult to differentiate benign from malignant lesions using cross-sectional imaging procedures alone. We evaluated the efficacy of different endoluminal techniques to achieve a definitive pathological diagnosis in these situations. METHODS: Eighty patients underwent brushing, and or biopsy of the biliary tree through an existing transhepatic biliary drainage route. A subcoort of 12 patients needed balloon-dilatation of the bile duct and the material covering the balloon surface was also sent for pathological examination (balloon surface sampling). Pathological results were compared with surgical findings or with long-term clinical and instrumental follow-ups. Success rates, sensitivity, specificity, accuracy, confidential intervals, positive predictive value and negative predictive value of the three percutaneous techniques in differentiating benign from malignant disease were assessed.The agreement coefficient of biopsy and brushing with final diagnosis was calculated using the Cohen's "K" value. RESULTS: Fifty-six patients had malignant strictures confirmed by surgery, histology, and by clinical follow-ups. Success rates of brushing, balloon surface sampling, and biopsy were 90.7, 100, and 100%, respectively. The comparative efficacy of brushing, balloon-surface sampling, and biopsy resulted as follows: sensitivity of 47.8, 87.5, and 92.1%, respectively; specificity of 100% for all the techniques; accuracy of 69.2, 91.7 and 93.6%, Positive Predictive Value of 100% for all the procedures and Negative Predictive Value of 55, 80, and 75%, respectively. CONCLUSIONS: Percutaneous endoluminal biopsy is more accurate and sensitive than percutaneous bile duct brushing in the detection of malignant diseases (p < 0.01).     

Trunk muscular strength in pre-pubertal children with and without back pain

OBJECTIVE: While in adulthood there is no proven relationship between back pain and trunk muscle strength, in pre-pubertal subjects this topic has been poorly studied. The aim of the study was to evaluate isometric and isokinetic trunk muscle strength in children with or without previous back pain. METHODS: The recent occurrence of back pain (last 6 months) among 144 children (77 males, 67 females, age 11.9 +/- 0.3 years) was assessed using a questionnaire. Extensor and flexor trunk muscle strength was measured through isometric and isokinetic (60, 90, 120 degrees/s) tests. Peak torque (PT), PT angle, PT flexor/PT extensor ratio and intra-session coefficient of variation (COV) were determined. RESULTS: Flexor and extensor muscle PT, but not PT angle, were significantly higher in males than in females, irrespective of back pain occurrence. PT flexor/PT extensor ratio at 90 degrees angular velocities increased significantly only in males with back pain, compared with males without back pain. The COV trend was similar for flexor and extensor muscles. CONCLUSIONS: Isometric and isokinetic trunk muscle strength probably play a minor role in back pain occurrence in children. The isokinetic testing velocity may be important in determining trunk strength differences between children with and without back pain.     

Hemolytic effects of water-soluble fullerene derivatives

A series of water-soluble fullerene C(60) derivatives has been investigated for their cytotoxic and hemolytic properties, with the aim to correlate structure with toxicity. We observed that cationic chains induce significant toxicity while the presence of neutral or anionic moieties did not produce any response in our model. A validation of these experimental observations has been performed by theoretical studies in which hydrophilic and hydrophobic surface areas were correlated quantitatively with hemolytic properties.