[Surgical treatment of well differentiated neuroendocrine tumours of the lung]. / Terapia chirurgica dei tumori neuroendocrini ben differenziati del polmone.

The bronchial tree represents the most frequent site of origin of carcinoids (around 25% of the total). The spectrum of differentiation of lung neuroendocrine tumors ranges from low-malignancy (carcinoids) to highly aggressive forms (small cell lung carcinoma) Diagnostic and therapeutic strategies therefore vary greatly. In well differentiated tumors (carcinoids) signs and symptoms are related to the airways obstruction in central forms, while peripheral forms are mostly discovered accidentally if asymptomatic. Clinical or subclinical paraneoplastic syndromes are associated in a minority of cases. Diagnostic work-up includes CT multislice, bronchial endoscopy and Octreoscan with chest Single Photon Emission Computed Tomography (SPECT). Further contribute may be added by the (68), Ga-DOTA-D-Phe(1)-Tyr(3)-ocreotide (DOTATOC) and 5-hydroxytryptophan (5-HTP) PET-CT, at present available only in a few centres, and by endobronchial ultrasound (EBUS), fluorescence bronchoscopy and virtual bronchoscopy. Surgery is the treatment of choice, while medical therapy is useful to treat the hypersecretion in paraneoplastic syndromes and to control tumor proliferation in metastatic or/and inoperable disease.

Thymic neuroendocrine carcinoma (carcinoid) in multiple endocrine neoplasia type 1 syndrome: the Italian series.

Neuroendocrine tumors may occur in the setting of multiple endocrine neoplasia type 1 (MEN1) syndrome. Among these, a probably underestimated prevalence of well differentiated neuroendocrine thymic carcinoma (carcinoid), a neoplasm characterized by very aggressive behavior, has been described. We report characterization of the seven Italian cases in which this association occurred among a series of 221 MEN1 patients (41 sporadic and 180 familial cases; prevalence, 3.1%). All of the patients were male, and six of seven (85%) were heavy smokers. No associated hormonal hypersecretion was detected. The first diagnosis was between the second and fifth decades. Familial clusters were present in three of seven (42.8%). No genotype-phenotype correlation was found. All seven cases were associated with hyperparathyroidism. In one patient, prophylactic thymectomy revealed a small nodular lesion suggestive of a thymic carcinoid, providing evidence that preventive thymectomy might prevent additional growth of an occult thymic carcinoid. These findings confirm that thymic carcinoids are associated with a very high lethality, with a near-total prevalence in smoker males. Therefore, prophylactic thymectomy should be considered at neck surgery for primary hyperparathyroidism in MEN1 male patients, especially for smokers, and, due to the frequent familial clusters distribution of this pathology, in subjects with affected relatives presenting this feature. Thus, we recommend screening every patient affected with a neuroendocrine thymic neoplasm for MEN1 syndrome.

Adjuvant radiochemotherapy in high-risk rectal cancer results of a prospective non-randomized study.

AIMS AND BACKGROUND: In 1990 the National Institutes of Health Consensus Conference recommended adjuvant combined therapy for patients with radically resected rectal cancer at high risk for relapse (ie, stage II-III). The purpose of our prospective non-randomized study was to verify the feasibility and effectiveness of postoperative radiochemotherapy in terms of improvement in disease-free and overall survival in this patient subgroup. STUDY DESIGN: From January 1990 to October 1998, 191 consecutive patients with radically resected stage II-III rectal cancer were treated. A total of 159 patients with a 24-month follow-up were assessable for toxicity and survival. Anterior resection was performed in 129 (81%) and abdomino-perineal resection in 30 (19%) patients. Fifty-four (34%) stage II and 105 (66%) stage III patients entered the study. Within 45-60 days of surgery, all patients received 5-fluorouracil chemotherapy at the dose of 500 mg/m2 as an i.v. bolus on days 1-5, every 4 weeks, for 6 cycles. Chemotherapy cycles III and IV were administered at the same daily dose on radiotherapy days 1-3 and 29-31. Radiotherapy consisted of 45 Gy/25 fractions plus a boost dose of 5.4 Gy. RESULTS: After a median follow-up of 57 months (range, 25-123), overall recurrent disease was reported in 58 (36%) patients: local, systemic, and both local and systemic relapses in 12 (8%), 37 (23%) and 9 (6%) cases, respectively. According to local extension, recurrence rates were 15% and 48% in stage II and III, respectively. Five-year overall and disease-free survival were 71% and 66%, respectively. Overall survival was 87% in stage II and 62% in stage III patients, and disease-free survival was 84% and 56% in stage II and III disease, respectively. According to univariate and multivariate analyses, significant prognostic factors for better tumor control were: stage (II vs III, P <0.001), the number of involved nodes (< or = 3 vs > 3, P <0.0001), and no extracapsular node invasion (P <0.0001). The recommended dose of the combined radiochemotherapy regimen was generally well tolerated. The incidence of any > or = grade 3 acute toxicity (according to the WHO scale) was 13% diarrhea, 11% proctitis, 5% perineal dermatitis and 4% myelosuppression. Four (3%) patients had radiotherapy-related severe late toxicity which required surgery. CONCLUSIONS: The study provided recurrence rates and survival similar to other adjuvant radiochemotherapy regimens published in the literature. However, in view of the low 5-year survival rate recorded in stage III patients, a different approach should be investigated.

Selective trophic effect of L-carnitine in type I and IIa skeletal muscle fibers.

Biopsies were taken from the vastus lateralis muscle of 26 chronic uremic patients before and after a 24-week treatment with L-carnitine given at the dose of 2 g i.v. at the end of hemodialysis, or in dialysis solution, or per os twice daily. The aim of the study was to evaluate both the muscle morphology in dialyzed subjects and the modification provoked by the therapy. All patients manifested a significant, even if variable, degree of muscular atrophy which involved all types of muscle fibers. After the treatment there was an increase of about 7% in the diameter of type I and type IIa fibers, which can utilize carnitine for fatty acid oxidation to produce energy, and a reduction in the atrophic fibers. No noteworthy changes were documented in type IIb fibers, which depend on glycolysis for energy production.

[Echography and integrated imaging in the diagnosis of hyperparathyroidism]. / Ecografia e imaging integrato nella diagnosi dell'iperparatiroidismo.

The authors report their personal experience with US, CT, biopsy and, lately, MRI, to localize enlarged parathyroid glands in primary and secondary hyperparathyroidism. December 1986 through December 1993, sixty-four primary and 55 secondary hyperparathyroidism patients were examined--119 in all. At biopsy and surgery, US sensitivity appeared to be 72%, with 0.94 positive predictive value; CT sensitivity was 80% with 0.91 positive predictive value. The two methods combined had 87% sensitivity in all. In the authors' experience, US proved to be a sensitive, accurate and cost-effective technique, as well as the best method to guide biopsy thanks to its multiplanar capabilities. Even though it requires great operator's experience, US is the method of choice in the localization of abnormal parathyroid glands. Its combination with CT increased overall sensitivity mainly in ectopic localizations and postoperative recurrences. Finally, technologic progress and increased MR sensitivity are likely to make MRI the imaging technique of choice, replacing CT, in the diagnostic protocol of hyperparathyroidism.

Giardia lamblia infestation reveals underlying Whipple's disease in a patient with longstanding constipation.

Whipple's disease is an uncommon disorder, generally associated with gastrointestinal symptoms; of these, diarrhea is a common feature. We report a case of Whipple's disease associated with chronic constipation which was not diagnosed until after Giardia lamblia infestation had caused diarrhea. To the best of our knowledge this association has not previously been reported. The clinical, laboratory, endoscopic, and manometric aspects are described and discussed.

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis). Morphological and immunohistochemical study of eight cases.

Eight examples of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi's lymphadenitis) are described. They occurred in young or middle-aged women who usually complained of latero-cervical lymphadenopathy. Serology revealed significant titres for Epstein-Barr virus and Yersinia enterocolitica serogroup 9 in one of eight and one of six tested. All patients fully recovered within 2 months. On histological examination of the lymph nodes large foci of infiltration were observed in the cortex and/or paracortex: they consisted of variable numbers of small lymphocytes, immunoblasts, macrophages and so-called plasmacytoid T-cells; granulocytes were absent. Necrotic changes varied from single pyknotic cells to extensive areas of necrosis. Immunohistochemistry showed that within the lesion the number of macrophages was inversely proportional to the number of peripheral T-lymphocytes and 'plasmacytoid T-cells'. The latter displayed a phenotype (CD4+, CD10+, CD45+) which, in the absence of macrophage-associated antigens, seemed in keeping with their supposed lymphoid nature. In seven cases peripheral T-lymphocytes predominantly expressed the cytotoxic/suppressor phenotype, while in one remaining case a mild predominance of the helper/inducer subset was observed. In the areas with less extensive tissue necrosis, numerous T-immunoblasts expressed both markers of activation and the proliferation-associated nuclear antigen Ki-67. The results of the present study expand the spectrum of our knowledge and allow speculation as to the biology of this disease.

Relationship between the efficiency of muscular work during jumping and the energetics of running.

The running economy of seventeen athletes was studied during running at a low speed (3.3 m X s-1) on a motor-driven treadmill. The net energetic cost during running expressed in kJ X kg-1 X km-1 was on average 4.06. As expected, a positive relationship was found between the energetic cost and the percentage of fast twitch fibres (r = 0.60, n = 17, p less than 0.01). In addition, the mechanical efficiency during two different series of jumps performed with and without prestretch was measured in thirteen subjects. The effect of prestretch on muscle economy was represented by the ratio between the efficiency of muscular work performed during prestretch jumps and the corresponding value calculated in no prestretch conditions. This ratio demonstrated a statistically significant relationship with energy expenditure during running (r = -0.66, n = 13, P less than 0.01), suggesting that the elastic behaviour of leg extensor muscles is similar in running and jumping if the speeds of muscular contraction during eccentric and concentric work are of similar magnitudes.