Body composition in subjects with anorexia nervosa: bioelectrical impedance analysis and dual-energy X-ray absorptiometry.

OBJECTIVE: To evaluate the applicability and validity of bioelectrical impedance analysis (BIA) compared with dual-energy X-ray absorptiometry (DXA) in a population of girls with restrictive anorexia nervosa (AN). METHODS: A total of 30 girls (11-19 years old) with AN were enrolled. DXA and BIA (BIA software and the Deurenberg equations) were used to estimate the body composition. The correlation between the methods was assessed by Pearson's correlation coefficient and the Bland-Altman method. RESULTS: The mean FFM estimates were 33.2 kg (BIA software), 32.8 kg (BIA, Deurenberg equation) and 33.1 kg (DXA). The mean FM values were 5.6 kg (BIA software), 6.2 kg (BIA, Deurenberg equation) and 6.4 kg (DXA). There was a high correlation between the FFM values estimated with the two methods (BIA software vs DXA r=0.917, p<0.001; Deurenberg equation vs DXA r=0.931, p<0.001). For the FFM, the limits of agreement were equal to ±3.34 kg for the BIA software and ±2.96 kg for the Deurenberg equation. For the FM, the limits of agreement were equal to ±4.60 kg for the BIA software and ±3.82 kg for the Deurenberg equation. CONCLUSION: The results show a good correlation between DXA and BIA. BIA seems to be a valid alternative for epidemiological and clinical evaluations.

Practical management of pleural empyema.

Empyema is defined as pus in the thoracic cavity due to pleural space infection and has a multifactorial underlying cause, although the majority of cases are post-bacterial pneumonia. Despite treatment with antibiotics, patients with empyema have a considerable morbidity and mortality due at least in part to inappropriate management of the effusion. Timely diagnosis of pleural space infection and rapid initiation of effective pleural drainage represent fundamental principles for managing patients with empyema. Ultrasound is particularly useful to identify early fibrin membranes and septations in the pleural cavity conditioning treatment strategy. Empyema and large or loculated effusion with a pH < 7.20 need to be drained. Thoracoscopy has largely been used in pleural effusion due to lung infection. Whereas the efficacy of video-assisted thoracic surgery (VATS) in empyema management has been evaluated in several retrospective studies showing favourable results, less is known about the role of medical thoracoscopy (MT) in pleural infection. MT, appears to be safe and successful in multiloculated empyema treatment. It is also lower in cost and in frail patients is better tolerated than VATS which requires tracheal intubation.

A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study.

BACKGROUND: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control. PATIENTS AND METHODS: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response. RESULTS: Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP. CONCLUSION: TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.

Behavior of borderline tumors with particular interest to persistence, recurrence, and progression to invasive carcinoma: a prospective study.

PURPOSE: Borderline tumors account for 10% to 20% of epithelial ovarian tumors, and their prognosis is outstanding; nevertheless, a mortality of up to 20% has been reported, particularly in earlier reports. There is a lack of information about the actual mortality and the rate of progression into invasive carcinoma in large and prospectively accrued populations. PATIENTS AND METHODS: All women with borderline ovarian tumors undergoing primary surgery in our department or referred within 3 months from surgery performed elsewhere from 1982 to 1997 were prospectively accrued and observed. RESULTS: We studied 339 women (83.4% stage I, 7.9% stage II, and 8.5% stage III). The median age at diagnosis was 39 years. A total of 150 women underwent radical surgery, and 189 underwent fertility-sparing surgery. After surgery, 13 women had macroscopic residual disease. With a median follow-up of 70 months, 317 women are alive with no clinical disease (eight with documented subclinical persistence of implants), three are alive with clinical disease, two died of disease, 10 died of other reasons, and seven women have been lost to follow-up. The recurrence of disease was higher after fertility-sparing surgery (35 of 189 cases) than after radical surgery (seven of 150 cases); nevertheless, all but one woman with recurrence of borderline tumor or progression to carcinoma after conservative surgery were salvaged. We observed seven progressions (2.0%) into invasive carcinoma, five in serous tumors (2.4%), and two in mucinous tumors (1.6%). The disease-free survival is 99.6% in stage I patients, 95.8% in stage II, and 89% in stage III. CONCLUSION: The survival of patients with borderline tumors is higher than previously described in some retrospective studies. Conservative surgery is safe and may be proposed to several patients with early and disseminated disease after thorough discussion of all therapeutic options. Progression to carcinoma is approximately 2% and may be observed in both mucinous and serous tumors.

Batimastat, a synthetic inhibitor of matrix metalloproteinases, potentiates the antitumor activity of cisplatin in ovarian carcinoma xenografts.

Batimastat (also known as BB-94) is a synthetic matrix metalloproteinase inhibitor that has shown antineoplastic and antiangiogenic activity in various tumor models. In this study, two human ovarian carcinoma (HOC) xenografts (HOC22 and HOC8) were used to investigate the effect of batimastat on the antineoplastic activity of cisplatin. Both xenografts produced ascites and solid lesions in the peritoneal cavity of nude mice. HOC cells were inoculated i.p. in nude mice, and treatment was started at different stages of the disease. Batimastat was administered alone or concurrently with or subsequent to cisplatin therapy. In all of the protocols, the response of HOC xenografts was confirmed by cytological analysis of ascites and histological examination of the organs in the peritoneal cavity. Treatment of nude mice bearing early-stage (3 days after tumor implantation) HOC22 or HOC8 with cisplatin or batimastat alone delayed tumor growth and increased the survival time of the mice, although all animals eventually died. In contrast, treatment with batimastat (60 mg/kg i.p. every other day, for a total of eight injections) concomitantly with cisplatin (4 mg/kg i.v., every 7 days for a total of three injections) completely prevented growth and spread of both xenografts, and all animals were alive and healthy on day 200. The potentiation of cisplatin's activity by batimastat was dose dependent and was observed in the treatment of both advanced (7 days after tumor inoculation) and late-stage (20 days after inoculation) tumor. The administration of batimastat following cisplatin therapy also led to significant improvement in the survival of mice compared to treatment with cisplatin alone. These results suggest a potentiation of the antineoplastic activity of cisplatin by batimastat and support the use of the two agents in combination in the treatment of ovarian cancer patients.

Risk factors for epithelial ovarian tumours of borderline malignancy.

A case-control study was conducted on 91 cases with histologically-confirmed borderline ovarian tumours and 237 control subjects in hospital for acute non-gynaecological, hormonal or neoplastic disease. Women reporting three or more births, compared to nulliparae, had a relative risk (RR) estimate of 0.6, but this finding was not statistically significant (95% confidence interval (CI): 0.2-1.4). The risk of borderline tumours increased, although not significantly, with later age at first birth: compared to women reporting first birth at age 24 or before, the RRs were 1.3 and 1.7 in those reporting respectively their first birth at age 25-29 and 30 years or more. No significant relationship emerged between borderline ovarian cancer and age at menarche, menopausal status and lifelong menstrual pattern. Cases tended to report a later age at menopause than controls, but the trend in risk was not statistically significant. Nine cases (9.9%) and 68 controls (24.9%) reported oral contraceptive use: compared with never users the multivariate RR for ever users was 0.3, and the risk dropped with duration of use to 0.2 in users for two years or more (chi 2 (1) trend = 12.70, p less than 0.001). This study provides epidemiological evidence of a pathogenetic continuum between borderline and invasive ovarian tumours.

PIP: Researchers compared 91 women with histologically confirmed borderline ovarian tumors at the University of Milan with 237 women (controls) admitted to Ospedale Maggiore in Milan, Italy for acute nongynecological, nonhormonal and nonneoplastic conditions to learn more about the epidemiology of borderline ovarian tumors. Oral contraceptives (OC) users had about a 70% lower risk of borderline ovarian tumors than nonOC users (relative risk ¿RR¿=0.3). In fact, the RR fell significantly to 0.2 for women who used OCs for at least 2 years (p.001). Further the risk of borderline ovarian tumors increased significantly as the age of women at the time of 1st birth increased (RR=1.8 for 25-29 year olds and RR=2.5 for =or 30 year olds; p=.02 [Mantel-Haenszel technique]). Women who experienced at least 1 induced abortion were less likely to have borderline ovarian tumors than those who had never experienced an induced abortion (RR=0.2). This may be because these women were of high fertility which agreed with the finding of lower risk in women of parity =or 3 (RR=0.7; p=0.23 insignificant). A higher risk was associated with late age at menopause, but the association was insignificant (RR=around 50 years old). Since the sample size was small due to the rarity of borderline ovarian tumors, one should interpret these results which caution. Nevertheless they supported the incessant ovulation hypothesis in ovarian carcinogenesis where the more exposure to ovulation or ovulatory cycles the greater the chance of ovarian neoplasms. Therefore they suggested an epidemiological continuum between various grades of malignancy of epithelial ovarian neoplasms.

Surgical management of malignant ovarian germ-cell tumors: 10 years' experience of 129 patients.

OBJECTIVE: To evaluate the surgical management of ovarian germ-cell tumors treated at a single institution during the last decade. METHODS: One hundred twenty-nine patients affected by ovarian germ-cell tumors were studied retrospectively for their surgical management. Fifty-seven patients were affected by dysgerminoma, 39 by non-dysgerminoma, and 33 by pure immature teratoma. Seventy-nine patients were stage I according to International Federation of Gynecology and Obstetrics criteria, with five first referred at recurrence, 11 at stage II, 35 at stage III, and four at stage IV. RESULTS: Fertility-sparing surgery was performed in 108 of 129 patients. Eighty-five of 100 referred patients underwent surgical or radiologic restaging, with an increase in staging in 16 cases. Three patients with immature teratoma underwent second laparotomy for a growing mass. Thirty-one patients underwent second-look surgery, with positive findings in four cases. Three patients did not respond to chemotherapy, and ten had a recurrence after complete response or surveillance. Six patients died of tumor, with an overall survival of 96% (mean follow-up time 55 months). CONCLUSION: Fertility-sparing surgery is warranted in all ovarian germ-cell tumors because it does not affect recurrence rate or survival. Extensive tumor-reductive surgery is advisable only in immature teratoma patients and is not necessary for other histologic types. Restaging can be useful in selected cases, but the administration of effective chemotherapy, when needed, seems to be more important. The usefulness of second-look surgery is marginal.

Neuro- and ototoxicity of high-dose carboplatin treatment in poor prognosis ovarian cancer patients.

BACKGROUND: Hematopoietic toxicity of high-dose carboplatin (HD-CBDCA) chemotherapy can be managed effectively with autologous blood cell support, but no conclusive data are available on its neuro- and ototoxicity. PATIENTS AND METHODS: We determined the neuro- and ototoxicity of HD-CBDCA in 10 patients affected by advanced ovarian cancer. HD-CBDCA was delivered as 24-hour continuous infusion or as 5-day schedules. Each patient underwent an extended clinical and instrumental neurological and otological evaluation before, during and after treatment. RESULTS: After HD-CBDCA only 1 patient had a clinically-evident peripheral neuropathy, while 3 additional patients had only distal paresthesias. Neurophysiological examination evidenced mild, although diffuse, sensory nerve impairment. Motor nerve impairment was also occasionally observed. All the sensory and motor pathological changes had a favorable course during the follow-up period. Ototoxicity was more severe than neurotoxicity and, in one case it was dose-limiting and audiologic impairment tended to remain constant also in the follow-up period. CONCLUSIONS: HD-CBDCA treatment can be tolerated by most of the patients, but careful monitoring of neuro- and, especially, ototoxicity should be planned.

Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors of borderline malignancy.

Rota SM, Zanetta G, Ieda N, Rossi R, Chiari S, Perego P, Mangioni C. Clinical relevance of retroperitoneal involvement from epithelial ovarian tumors of borderline malignancy. Ovarian tumors of borderline malignancy have an outstanding prognosis. The need for aggressive surgical staging is questionable and the need for retroperitoneal node sampling is debated. From 1982 to 1996, 81 women underwent surgical staging including retroperitoneal sampling. Three patients (3.7%) with serous tumor had microscopic nodal involvement. Retroperitoneal metastases were found in two intraperitoneal stage I tumors and in one stage IIIA tumor. Positive nodes were found in 1/31 (3.2%) women undergoing sampling of para-aortic nodes and in 2/69 (2.8%) women undergoing sampling of pelvic nodes. With a median follow-up of 79 months we observed five recurrences, but none involved the retroperitoneum. The three patients with positive nodes remain alive without disease. Among 236 patients with diagnosis of borderline tumor but without sampling of the nodes, we observed one retroperitoneal recurrence (0.4%) in a serous tumor. There are no indications for retroperitoneal sampling of mucinous borderline tumors. For serous tumors this procedure should only be performed as a part of prospective trials. The clinical relevance of retroperitoneal involvement in borderline tumors appears minimal and does not justify routine aggressive surgery.

Limited invasiveness to assess retroperitoneal spread in stage I-II ovarian carcinoma.

OBJECTIVE: To evaluate the incidence of retroperitoneal metastases, survival rate and site of recurrence in early ovarian tumors undergoing limited retroperitoneal surgery. METHOD: Three hundred seventy-three consecutive patients underwent assessment of the retroperitoneum consisting of intraoperative palpation with or without biopsies. RESULTS: Retroperitoneal metastases were detected in 10 stage-I tumors (3.2%) and in 10 stage-II tumors (16%). The risk was inversely related to tumor differentiation. Palpation revealed metastases in 10 cases. During follow-up, none of the borderline tumors (1.9% of stage-I grade-1 node-negative, 2.7% of grade-2 and 7.0% of grade-3 tumors) recurred in the retroperitoneum. In stage II, two recurrences were observed in grade-2 tumors (11%) and one in grade 3 (4.5%). CONCLUSION: Limited retroperitoneal surgery enables satisfactory outcome in early ovarian cancers. Risk of retroperitoneal recurrence is minimal in grade 1 and non-existent in borderline tumors. Less differentiated tumors have low risk but further investigation of the therapeutic role of lymphadenectomy is justified.

[An unusual case of post-traumatic adult complex foot deformity]. / Un caso atípico de fractura de pie compleja postraumática en un adulto.

A peculiar clinical presentation of post-traumatic complex left foot fracture deformity is presented in this report as the result of a motorbike accident. Notwithstanding the significant deformity following forefoot fractures, the patient complained only of the recent onset of metatarsalgia. Of particular interest, is that this severe foot injury as well following deformity was overlooked, probably because patient had sustained head injury that was the main problem to treat due to life risk.

Frequency and clinical significance of human beta-herpesviruses in cervical samples from Italian women.

Human papillomaviruses (HPVs) are necessary, but not sufficient, for the development of cervical cancer (CC). Human beta-herpesviruses (beta-HHVs) have been suggested as possible cofactors in the oncogenesis of CC. In this cross-sectional study, the prevalence and possible association of cytomegalovirus (CMV), HHV-6 and -7 with HPV presence was investigated by quantitative real-time PCR assays in cervical samples obtained from 208 italian women. The two most common high-risk HPV types found were 31 and 16. Overall, the positive rates for CMV, HHV-6 and HHV-7 were 66%, 25%, and 6%, respectively. In particular, the prevalence of CMV was found to be extremely high irrespective of either the cytological category or HPV positivity. The prevalence of HHV-6 DNA was significantly higher in high-grade squamous intraepithelial lesions (HSIL) respect to normal women (P < 0.017); by contrast, the prevalence HHV-7 DNA was generally low and not associated with SIL. Copresence of CMV and HHV-6 DNA was found to be significantly higher in patients with SIL respect to normal women (P < 0.05). No correlation was demonstrated between the viral load of all three beta-HHVs and the different cytological stages or with the HPV presence. A few patients with severe disease however showed very high viral loads which for HHV-6 may be indicative of viral integration. In conclusion, this study suggests that CMV and HHV-7 alone are probably not implicated in the oncogenesis of CC whilst HHV-6 alone or together with CMV may contribute to the development of CC.

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

Controversial issues in the management of early epithelial ovarian cancer: conservative surgery and role of adjuvant therapy.

The feasibility of conservative surgery and the role of postoperative adjuvant therapy are still controversial issues in the management of early ovarian cancer. Data on 99 patients below the age of 40 with stage I ovarian cancer are reported and conservative surgery was performed in 56 (56%) patients (36 stage Ia, 1 stage Ib, and 19 stage Ic). Relapse occurred in 3 stage Ia (grades 1, 2, and 3) patients, but only 1 occurrence was in the residual ovary and the patient was rescued by surgery. The other 2 patients who relapsed in distant sites died as a result of their tumors. Seventeen patients who desired to become pregnant did so for a total of 25 conceptions. These data support the possibility of some extension of the traditional conservative approach. Only two randomized studies so far have tested cisplatin as an adjuvant treatment of early disease. A Norwegian trial compared cisplatin to 32P in stage I-III ovarian cancer without residual tumor after primary surgery and found no difference in survival. An Italian study compared cisplatin to observation in stage Ia and Ib grade 2 and 3 tumors and cisplatin to 32P in stage Ic patients. While disease-free survival was statically longer in cisplatin-treated patients of both groups, no difference in survival could be detected. These results supported the design of a currently ongoing multicenter trial testing platinum-based therapy soon after surgery or at time of relapse.

Early-stage epithelial ovarian cancer: an overview.

The clinical treatment of malignant epithelial ovarian cancer limited to the gonad(s) involves many problems that have given rise to analyses in recent literature and to different approaches: i. intensive anatomo-radio-surgical staging, evaluation and clinical incidence of prognostic risk factors; ii. re-staging of patients after inadequate and incomplete surgery; iii. indications, role and topicality of second-look surgery; iv. conservative surgery in patients of a fertile age wishing to have children and retain activity of the gonads; v. laparoscopic surgery for treatment, staging, re-staging and surveillance; vi. the lymph node issue; vii. adjuvant therapy: indications, options, type of drugs, doses and length; viii. quality and frequency of surveillance; ix. malignant epithelial ovarian cancer limited to the gonads in pregnancy. The clinical handling of these tumours entails many complex problems causing emotional involvement since it is most frequent at a fertile age.

Absence of deletions but frequent loss of expression of p16INK4 in human ovarian tumours.

The cyclin-dependent kinase inhibitor p16 gene (P16, MTS1, CDKN2) has been shown to be altered by deletion or point mutation in some human tumours and cancer cell lines, suggesting that it works as a tumour suppressor. We analysed p16 gene mutation and p16 protein expression in 42 primary ovarian carcinomas and in five human ovarian cancer cell lines. Polymerase chain reaction (PCR) amplifications of exons 1 and 2 of the gene showed no deletion or gross rearrangement in the p16 gene. The lack of deletion was further demonstrated by Southern blot analysis. Looking for point mutations, we used single-strand confirmation polymorphism (SSCP) analysis and, in half of the tumours, we sequenced both strands of exons 1 and 2. No mutations were detected. In 11 out of 42 patients (26%), however, we detected no protein expression by Western blot analysis, suggesting that decreased expression of p16 rather than deletion of the gene can occur in a significant percentage of human ovarian cancers. In the same experiment CDK4 protein was found homogeneously expressed in all the tumour specimens and in the five cell lines. The lack of expression of p16 was not due to hypermethylation of the gene assessed by digestion of genomic DNAs with a methylation sensitive enzyme, suggesting that other mechanisms, not yet identified, are involved in the decreased expression of the p16 gene in human ovarian tumours.

Conservative surgery for stage I ovarian carcinoma in women of childbearing age.

OBJECTIVE: To assess the results of a policy of tailored conservative surgical management for young women with stage I ovarian carcinomas. DESIGN: Retrospective study. PARTICIPANTS: Ninety-nine women aged 40 years or younger who underwent either primary surgery in our department or were referred after primary surgery performed elsewhere. METHODS: Of the 99 women in our study, 56 underwent fertility-sparing surgery and 43 more radical surgery. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Conservative treatment was conducted in 84% of nulliparous and in 33% of parous women; 62% of grade 1 tumours, 48% of grade 2, and 50% of grade 3 were treated conservatively. With a median follow up of seven years, we observed five recurrences (9%) of carcinoma in women treated conservatively and five (12%) in those treated more radically. Two women (one in each treatment arm) were saved after recurrence. Two recurrences after conservative surgery involved the residual ovary (3.6%). Two women developed borderline tumour in the contralateral ovary and both were treated by surgery. CONCLUSION: After adequate staging and accurate information is given to the patient, conservative treatment may be safe in some women with early ovarian cancer. The risk of recurrence in the contralateral ovary is low. Conservative surgery may be also considered in some Stage I grade 3 tumours and in some women with stage JC tumours.

Conservative treatment followed by chemotherapy with doxorubicin and ifosfamide for cervical sarcoma botryoides in young females.

Sarcoma botryoides of the cervix is an extremely rare tumour and seems to be associated with a better prognosis than its vaginal counterpart. Recent studies have suggested that it is possible to limit surgery to local excision in stage I cases. We report three cases of young subjects treated successfully with polypectomy or diathermy loop excision followed by adjuvant chemotherapy. One patient had a local recurrence which was treated with further local excision. All subjects remain alive without evidence of recurrence and with normal menstrual function 36, 38 and 38 months following initial diagnosis. A conservative surgical approach to early cervical sarcoma botryoides is possible. The efficacy of adjuvant chemotherapy and the regimen of choice still need to be investigated.