Targeted next-generation sequencing identified novel mutations associated with hereditary anemias in Brazil.

Hereditary anemias are a group of heterogeneous disorders including hemolytic anemias and hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA). Causative mutations occur in a wide range of genes leading to deficiencies in red cell production, structure, or function. The genetic screening of the main genes is important for timely diagnosis, since routine laboratory tests fail in a percentage of the cases, appropriate treatment decisions, and genetic counseling purposes. A conventional gene-by-gene sequencing approach is expensive and highly time-consuming, due to the genetic complexity of these diseases. To overcome this problem, we customized a targeted sequencing panel covering 35 genes previously associated to red cell disorders. We analyzed 36 patients, and potentially pathogenic variants were identified in 26 cases (72%). Twenty variants were novel. Remarkably, mutations in the SPTB gene (ß-spectrin) were found in 34.6% of the patients with hereditary spherocytosis (HS), suggesting that SPTB is a major HS gene in the Southeast of Brazil. We also identified two cases with dominant HS presenting null mutations in trans with α-LELY in SPTA1 gene. This is the first comprehensive genetic analysis for hereditary anemias in the Brazilian population, contributing to a better understanding of the genetic basis and phenotypic consequences of these rare conditions in our population.

Phase II study of bleomycin, vindesine, mitomycin C and cisplatin (BEMP) in recurrent or disseminated squamous cell carcinoma of the uterine cervix.

OBJECTIVE: We carried out a phase II trial with BEMP [bleomycin, vindesine (Eldisine(R)), mitomycin C and cisplatin] in patients with recurrent and/or metastatic squamous cell carcinoma of the uterine cervix with the specific aim to assess whether BEMP was of particular interest when certain disease sites were involved. PATIENTS AND METHODS: Eligible patients received four cycles of E 3 mg/m(2), day 1 + 8; P 50 mg/m(2), day 1; B 15 mg/day (continuous infusion), day 2-4 and M 8 mg/m(2), day 5 (on alternate cycles), every 3 weeks during an induction phase. Thereafter, those without progression continued with MEP every 4 weeks in a maintenance phase. MEP consisted of E 3 mg/m(2), day 1 + 8, M 6 mg/m(2) (on alternate cycles) and P 50 mg/m(2), both on day 1. All drugs were given i.v. Both response evaluation and toxicity grading were assessed according to World Health Organization criteria. RESULTS: Of the 161 eligible patients, 143 were assessable for survival, 148 for toxicity and 131 for response. Overall response rate was 45% [complete (CR) 14.5%, partial response (PR) 30.5%]. Most responsive disease sites were lung, lymph nodes and skin metastases (>60% response, CR rate >25%). Median duration of response was 7.6 months. Survival was significantly better in patients with only distant metastases: 12.9 months versus 8.6 months in those with other disease sites involved (P = 0.002). In a multivariate analysis, patients with a good performance status yielded a better prognosis (P = 0.0017), as did the patients with only metastatic disease compared with those who had pelvic disease also or solely (P = 0.045). There were two toxic deaths and 21% of patients stopped treatment because of excessive toxicity. CONCLUSIONS: Patients with a good performance status and only distant metastases seem optimal candidates to receive the BEMP regimen. This benefit should be balanced against the expected serious toxic effects.

Evaluation of ventilators used during transport of ICU patients -- a bench study.

OBJECTIVES: To evaluate portable ventilators. DESIGN AND SETTINGS: Bench study. MATERIALS AND METHODS: Five portable ventilators used for transporting ICU patients [Osiris 1, (ventilator a), Osiris 2, (ventilator b), Oxylog 1000, (ventilator c), Oxylog 2000, (ventilator d), AXR1a, (ventilator e)] and three ICU ventilators which can be used for this purpose [Horus, (ventilator f), T-Bird, (ventilator g), and SV 300, (ventilator h)] were compared using a test lung regarding: 1) their capability to maintain set tidal volumes (V(T)) of 300 ml, 500 ml, and 800 ml under a normal condition A [resistance (R) 5 cmH(2)O/l/s and compliance (C) 100 ml/cmH(2)0] and two abnormal conditions B (R 20-C 30) and C (R 50-C 100); 2) trapped volume (expired V(T)relative to inspired V(T)at 0.7 s, 1 s, and 1.4 s), an estimate of the expiratory resistance of both circuit and valve; and 3) the triggering system assessed from the measurements of Delta t, Delta P for two inspiratory efforts at a PEEP of 0 cmH(2)0 and 5 cmH(2)0 in ventilators b, d, f, g, and h. Flow and airway pressure were measured with an independent physiologic recording system. RESULTS: 1) V(T). For ventilators a-h, the mean+/-SD changes of a set V(T)of 300 ml were -2.6+/-0.2%, -9.7+/-0.2%, 0+/-0%, -6.1+/-0.2%, 1.0+/-0.3%, -2.1+/-1.7%, 0.3+/-0%, and -1.3+/-0.1% ( P<0.001), respectively, during condition B relative to A. Similar results were obtained for a V(T)of 500 ml and 800 ml and during condition C relative to A; 2) Trapped volume. For ventilators a-h, trapped volume averaged 1+/-1%, 20+/-0%, 30+/-0.4%, 20+/-1%, 1+/-0%, 19+/-0%, 15+/-0%, and 14+/-0% at 0.7 s ( P <0.001) and 0.6+/-0%, 5+/-0%, 0.5+/-0%, 0+/-0%%, 0+/-0%, 0.6+/-0%, 0+/-0%, and 0+/-0% at 1.4 s ( P=NS); and 3) the triggering system of Oxylog 2000 was poor whereas it was of good quality for Horus, T-Bird, SV 300, and Osiris 2. CONCLUSIONS: The small portable ventilators presently investigated varied between each other and were less accurate than ICU ventilators.

Transvaginal color Doppler ultrasound for de novo ovarian carcinoma. How a good chance can be missed.

Early de novo ovarian cancer is one of the most challenging entities in gynecologic oncology as early diagnosis is extremely difficult. We describe the case of a 77-year woman who had incidental diagnosis of normally shaped ovaries with low resistance blood flow. Despite the suspicious finding and despite the documentation of elevated serum CA 125 levels she did not undergo surgery. Twelve months later she was found with an enlarged ovary. Laparotomy documented a stage IIIB ovarian carcinoma. Lack of communication among subspecialists and incomplete acceptance of new diagnostic aids contributed to this disappointing case.

Randomized phase III trial of bleomycin, vindesine, mitomycin-C, and cisplatin (BEMP) versus cisplatin (P) in disseminated squamous-cell carcinoma of the uterine cervix: an EORTC Gynecological Cancer Cooperative Group study.

PURPOSE: Three previous mitomycin-cisplatin-based chemotherapy trials conducted within the EORTC Gynecological Cancer Cooperative Group (GCCG) in patients with disseminated squamous-cell carcinoma of the uterine cervix (SCCUC) suggested that with such regimens a higher overall response rate and a higher complete response rate could be obtained compared to what might have been expected from cisplatin alone. In that respect the combination of bleomycin, vindesine (Eldesine), mitomycin C and cisplatin (BEMP) was the most promising. In the present study BEMP has been compared with the best single agent, cisplatin (P) in the expectation that improved response rates might translate into a better survival. PATIENTS AND METHODS: Eligible patients were those with SCCUC and disseminated measurable disease outside previously irradiated areas, aged < or = 75 years, with a WHO performance status < or = 2 and adequate bone marrow, renal, hepatic and pulmonary function, who gave consent according to regulations followed in individual institutions. Patients were randomized to BEMP: E 3 mg/m2 day 1, P 50 mg/m2 day 1, B 15 mg (24-hour infusion) day 2-4 and M 8 mg/m2 (at alternate cycles), or P 50 mg/m2. The first four cycles were given every 3 weeks (induction phase). Subsequent cycles were given every four weeks (maintenance phase), during which B was deleted from BEMP (MEP). Patients failing on P could be treated with BEM. Of the 287 patients entered, 235 were eligible and 201 evaluable for response. RESULTS: BEMP induced a significantly higher response rate than P (42% vs. 25%, P = 0.006). There was no difference in complete response rate (11% vs. 7%). BEMP was significantly more toxic than P (+/- BEM), both with respect to hematologic and nonhematologic toxicities. After a median follow-up of 6.1 years, survival curves were not significantly different. Median progression-free survival and overall survival were 5.3 and 10.1 months with BEMP and 4.5 and 9.3 months with P (+/- BEM), respectively. In a multivariate analysis of prognostic factors for survival, a lower age (P = 0.003), a lower performance status (P = 0.0001) and a short (<1 year) interval since diagnosis (P = 0.0152) were all associated with an increased risk of dying. For progression-free survival, lower age, prior radiotherapy, locoregional involvement and no prior surgery were associated with a high risk. Treatment with BEMP or P had no significant impact on survival, but for progression-free survival there was a trend in favor of BEMP (P = 0.0893). Adjusting for prognostic factors did not change the effect of treatment. CONCLUSIONS: Combination chemotherapy with BEMP produces more toxicity and more responses compared with cisplatin alone in patients with disseminated SCCUC, but this does not translate into a better survival. Therefore, in the palliative setting single-agent cisplatin should remain the standard therapy for these patients.

Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer.

OBJECTIVE: To investigate tumor response rate and treatment toxicity of a modified combination chemotherapy consisting of bleomycin (B), methotrexate (M), and CCNU (C) for patients with locally advanced, squamous-cell carcinoma of the vulva (not amenable to resection by standard radical vulvectomy) or recurrent disease (after incomplete resection). Tumor resectability was reassessed in patients who had responded to chemotherapy. METHODS: The regimen consisted of bleomycin 5 mg intramuscular (im) days 1-5, CCNU 40 mg per os (po) days 5-7, and methotrexate 15 mg po days 1 and 4 during the first week. During weeks 2-6 the patient was administered bleomycin 5 mg im days 1 and 4, and methotrexate 15 mg po on day 1 of the week. This 6-week cycle was repeated at 49-day intervals. RESULTS: Twenty-five eligible patients with a median age of 66 years (range, 39-82 years) were entered in this phase II trial. Twelve patients had primary locally advanced disease, 13 patients had a locoregional recurrence, and all received up to three BMC cycles. Two complete and twelve partial responses were observed (response rate, 56%; 95% confidence limits, 35-76%). The BMC regimen was associated with major hematological side effects and mild signs of bleomycin-related pulmonary toxicity. At a median follow-up of 8 months, 3 patients were alive, 18 had died due to malignant disease, 2 had died due to toxicity, and 2 had died due to intercurrent disease and unknown cause. The median progression-free survival was 4.8 months and the median survival was 7.8 months. The 1-year survival was 32% (95% confidence limits, 13-51%). CONCLUSION: The present data confirm the therapeutic activity of the BMC regimen in locoregionally advanced or recurrent squamous-cell carcinoma of the vulva. Following neoadjuvant chemotherapy, the overall response rate was 56%. BMC is an outpatient treatment that may play a role in the palliative therapy of advanced or recurrent vulva cancer.

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.

Ultrasound, physical examination, and CA 125 measurement for the detection of recurrence after conservative surgery for early borderline ovarian tumors.

BACKGROUND: Borderline ovarian tumors often affect women of childbearing age and the prognosis is outstanding. Given the young age of several patients and the good prognosis, fertility-sparing surgery is considered adequate for stage I tumors. However, women treated conservatively have a relatively small but well-defined risk of recurrence and no study has specifically addressed the optimal follow-up technique. METHODS: From 1981 to 1997, 164 women underwent fertility-sparing surgery for stage I borderline ovarian tumor and were followed prospectively. After surgery all women underwent physical examination and ultrasound examination every 3 months for 2 years after first diagnosis and every 6 months thereafter. Measurement of serum CA 125 levels was planned every 6 months in patients with a serous tumor. RESULTS: With a median follow-up of 71, months 28 women treated with fertility-sparing surgery (28/164 = 17%) had either recurrence of borderline tumor (23) or recurrence with carcinoma. Complete details of follow-up procedures are available for 24 women and they represent the study population. An abnormal adnexal mass was detected in 18 of 19 women with recurrent borderline tumor. One patient had diagnosis due to persistent free fluid. All five women with invasive carcinoma had diagnosis of a complex adnexal mass. Gynecologic examination was suspicious (palpable mass) in 7 cases and obviously abnormal (large mass or nodules) in another 7. CA 125 serum levels were elevated in 8 cases. CONCLUSION: Transvaginal ultrasound is currently the most effective diagnostic technique for the follow-up of young patients treated conservatively for early borderline ovarian tumor.

Survival and reproductive function after treatment of malignant germ cell ovarian tumors.

PURPOSE: Germ cell ovarian tumors are curable. The possible sequelae of chemotherapy on long-term survivors are still unknown, but these patients may expect normal lives. The aim of this study was to evaluate the outcome and reproductive function in a population of women treated since 1982. MATERIALS AND METHODS: Between 1982 and 1996, 169 women with malignant germ cell ovarian tumors were seen (70 dysgerminomas, 28 endodermal sinus tumors, 24 mixed tumors, and 47 immature teratomas). Seventy-one had advanced or recurrent disease. Fertility-sparing surgery was performed in 138 (81%) women, 81 of whom received postoperative chemotherapy. RESULTS: With a median follow-up of 67 months, the survival rate was 94% for dysgerminoma, 89% for endodermal sinus tumors, 100% for mixed types, and 98% for immature teratoma. For women who were treated conservatively, the survival rate was 98%, 90%, 100%, and 100%, respectively. Two women had adnexal recurrences, and both received salvage treatment. After treatment, all but one postpubertal woman had recovery of menses within 9 months. During follow-up, 12 untreated and 20 treated patients had 55 conceptions. We recorded 40 pregnancies at term, six terminations, and nine miscarriages. Four malformations were observed: one in 14 conceptions of patients who had not received chemotherapy and three in 41 conceptions of treated patients. CONCLUSION: Irrespective of subtype and stage, conservative surgery should become the standard approach to treating most patients with malignant ovarian germ cell tumors. Fertility seems to be only marginally affected by treatments. Miscarriages are in the expected range for the general population. The malformation rate is slightly higher than in the general population, but no significant difference was seen between patients who did and did not receive chemotherapy.

Differential distribution of sequence variations in HPV-16 E6.

OBJECTIVE: The E6 regions of the oncogenic human papillomaviruses (HPVs) are important in carcinogenesis and immune recognition. We examined the E6 DNA sequence from HPV-16-associated cervical cancers to determine the frequency and degree of variation from the consensus sequence in selected populations. METHODS: Samples positive for HPV-16 were analyzed using polymerase chain reaction followed by automated DNA sequencing: 62 from U.S. women, 20 each from Italian and Indian women, and 21 from Thai women. RESULTS: Of 151 codons, 18 contained 24 base substitutions, reflecting the overall conserved nature of this region. The HPV-16 E6 region from U. S. women showed considerably more sequence variation than that from European and Asian women. Five patterns common to U.S. and European and Asian samples accounted for 78% of all tumor-associated viruses. The E6 regions known to be involved in p53 binding and degradation are involved with a surprising degree of sequence variation, whereas the carboxy end of the molecule is highly conserved. CONCLUSIONS: The area of greatest sequence variation includes a proposed human leukocyte antigen interaction site. A novel large deletion in one sample results in loss of all functional regions of E6. These findings were analyzed for possible significance with regard to immune selection and functional importance of the carboxy end of the E6 protein.

Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis.

OBJECTIVE: Endometriosis is extremely common in developed countries. Obesity is a major health concern and may cause hyperestrogenism. Hormonal replacement, particularly unopposed estrogens after hysterectomy, is becoming popular. Because endometriosis is ectopic endometrium, hyperestrogenism (either endogenous or exogenous) may cause hyperplasia or transformation into cancer. This study was conducted to describe the main clinical and pathologic features of malignancies in endometriosis and define the treatment and outcome and to compare patients who had cancer arising in endometriosis with patients who had endometriosis but no cancer. METHODS: Patients who had tumors from endometriosis diagnosed from 1986 to 1997 were analyzed retrospectively. Each patient was matched with two control patients (endometriosis without cancer) treated during the same study interval. Clinical and epidemiologic variables were compared to identify risk factors for the development of cancer. RESULT: We identified 31 patients with cancer developing from endometriosis. Fifteen women were obese, 9 had a history of endometriosis, and 9 were taking unopposed estrogen. Endometrioid adenocarcinoma was the most common histologic type (16 patients). When the patients with cancer were compared with controls, no significantly higher risk for the development of cancer was found with prolonged use of unopposed estrogens or with higher body mass index, but a trend was observed. When obesity and use of unopposed estrogens were considered together, the difference was statistically significant (P = 0.05). CONCLUSION: Hyperestrogenism, either endogenous or exogenous, is a significant risk factor for the development of cancer from endometriosis. The prevalences of endometriosis, obesity, and use of hormonal replacement therapy in women in developed countries are increasing, and this trend justifies the assumption that cancer developing in endometriosis might become more common in the future.

Chemotherapy with paclitaxel, ifosfamide, and cisplatin for the treatment of squamous cell cervical cancer: the experience of Monza.

The medical treatment of squamous cell cervical carcinoma is receiving increasing attention. Cisplatin and ifosfamide are known effective drugs. Paclitaxel has been tested with interesting results in cervical cancer. We evaluated the toxic effects and the antitumor activity of a multiagent regimen that included paclitaxel, ifosfamide, and cisplatin (TIP) in two different settings: bulky and locally advanced cervical cancer and recurrent-persistent disease. Treatment consisted of paclitaxel 175 mg/m2 given over 3 hours on day 1, cisplatin 50 mg/m2 (75 mg/m2 in 24 patients), ifosfamide 5 g/m2 and mesna 5 g/m2 given on day 2, and mesna 3 g/m2 given on day 3. In the neoadjuvant setting, the course was repeated every 3 weeks for three courses. Unless there was progression of disease or reason to avoid surgery, all patients were scheduled for radical hysterectomy and pelvic lymphadenectomy. Thirty-eight patients with locally advanced cervical cancer were studied: 11 women achieved a clinical complete response, 21 had a partial response, five had stable disease, and one had disease progression. Among the 34 patients who underwent surgery, six had a pathologically documented complete response, seven had an optimal partial response (only microscopic residual disease), 19 had a suboptimal partial response, and two stable diseases. Grade 3-4 neutropenia was recorded in 71% of patients, grade 3-4 thrombocytopenia in 10.5%, and grade 2 peripheral neuropathy in 2.6%. With a median follow-up period of 22 months for the patients who remain alive, 28 women are alive without recurrence and five are alive with persistent/recurrent disease. Five patients have died of disease. In the salvage setting, 45 women with persistent-recurrent disease after primary treatment were treated; 31 of these women had received prior radiation. In the salvage setting we observed 15 clinical complete responses, 15 partial responses, nine stable diseases, and six disease progressions. The objective response rate was 66.6%. Ten complete responders underwent subsequent surgery and seven had pathologic complete response (two in radiated areas). The response rate was 52% in radiated areas and 75% in nonradiated areas. The median survival time is 6 months for the nonresponders, 9+ month for the partial responders, and 13+ months for the complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3-4 myelotoxicity. One woman had life-threatening toxicity. This regimen yields a high response rate with acceptable toxicity and should be prospectively compared with other regimens. The high rate of pathologic complete and optimal responses might impact positively on survival, but only a longer follow-up period will allow objective assessment of this impact. The specific roles of paclitaxel and ifosfamide in this regimen remain to be fully understood.

Unusual recurrence of cervical adenosquamous carcinoma after conservative surgery.

The use of less radical procedures for the treatment of early cervical cancers is gaining interest among physicians and young patients. Some authors have described surgical procedures aimed at reducing the surgical aggressiveness but the safety of such procedures remains debated. After a polypectomy, a young patient had a diagnosis of stage Ia(2) cervical adenosquamous carcinoma in 1995. As she wished to preserve her fertility, she underwent a cone biopsy and pelvic lymphadenectomy, without evidence of tumor spread. In 1998, at the 13th week of gestation, she had a diagnosis of a pelvic mass. The mass was a recurrence of carcinoma involving the myometrium, just underneath the peritoneum. She underwent a radical hysterectomy with bilateral oophorectomy. An ovarian metastasis was also detected at pathological exam. She received chemotherapy postoperatively and remains alive without evidence of disease. The recurrence of cervical cancer is traditionally regarded as an issue concerning the cervix, the parametria, or the lymph nodes. When the uterus is preserved we must also consider the possibility of a recurrence involving the corpus. With wider acceptance of limited therapeutic approaches we must be prepared for the detection of previously unknown patterns of recurrence and the follow-up modalities must be consequently adapted.

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.

Paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy for recurrent or persistent squamous-cell cervical cancer.

PURPOSE: The results of salvage chemotherapy for recurrent or persistent squamous-cell cervical cancer are unsatisfactory. Cisplatin and Ifosfamide are effective compounds in cervical cancer. Paclitaxel has recently been tested with promising results. The aim of this study was to assess the efficacy of a combination of paclitaxel, ifosfamide and cisplatin (TIP) for persistent/recurrent squamous-cell cervical carcinoma in a phase II trial. PATIENTS AND METHODS: Forty-five women were treated with the TIP regimen. Thirty-one had received prior irradiation. Paclitaxel was given at a dose of 175 mg/m2, ifosfamide at a dose of 5 g/m2, and cisplatin at a dose of 75 mg/m2 (50 mg/m2 in irradiated patients) at three-week intervals. RESULTS: We observed 15 clinical complete responses, 15 partial responses, 9 stable diseases and 6 progressions. The objective response rate was 67% (95% confidence interval: 51%-81%). Ten complete responders underwent subsequent surgery and seven had pathology-defined complete responses (two in irradiated areas). The response rate was 52% in irradiated and 75% in non-irradiated areas. The median survival for non-responders is 6 months, 9+ month for partial responders and 13+ for complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3-4. One woman had life-threatening toxic effects. CONCLUSIONS: This combination is highly effective for salvage treatment in non-irradiated patients. For irradiated women the response rate is higher than that observed with other regimens but further investigation is warranted. The toxicity is relevant but adequate hydration and prolonged infusion of ifosfamide make it acceptable.

Laparoscopic excision of ovarian dermoid cysts with controlled intraoperative spillage. Safety and effectiveness.

OBJECTIVE: To compare the operative and postoperative course in patients undergoing laparoscopy for dermoid cyst to that observed in subjects with other types of ovarian masses and of patients undergoing laparotomy for teratomas. STUDY DESIGN: Retrospective analysis. From 1994 to 1996, 49 women underwent laparoscopic cystectomy for dermoid cysts. The operative and postoperative course was compared to that of 190 patients undergoing operative laparoscopy for other adnexal masses and to that of 43 patients undergoing laparotomy for dermoid cysts from 1992 to 1996. The cysts were aspirated to reduce spillage and removed via a laparoscopic bag inserted in a 10-mm trocar. Culdotomy was never used. The abdominal cavity was abundantly flushed during the procedure and before closure. RESULTS: Dermoid cystectomy was successfully performed laparoscopically in 47 of 49 cases. Spillage occurred in 43 cases (88%), and postoperative fever occurred in 3 (6.1%). No case of peritonitis was recorded. Significant differences between laparoscopy and laparotomy were observed in the rate of bilaterality (4% vs. 25%), spillage (88% vs. 9%) and mean hospital stay (37 vs. 83 hours). When laparoscopic excision of dermoid cysts and other masses was compared, we did not observe any significant difference in operative time or complication rates, apart from transient fever. CONCLUSION: Laparoscopy is safe and effective for dermoid cysts and allows shorter hospitalization than laparotomy. As observed for other benign cysts, laparoscopy should become the technique of choice for the removal of most, if not all, ovarian dermoid cysts.

Uterine rupture after hysteroscopic metroplasty and labor induction. A case report.

BACKGROUND: Hysteroscopic metroplasty has become the method of choice for the treatment of uterine septa. Uterine perforation has been reported in about 1% of surgical hysteroscopic procedures. Ultrasound allows the detection of uterine lesions. CASE: A woman who conceived after complicated hysteroscopic metroplasty underwent emergency cesarean section because of uterine rupture during labor induced with prostaglandins (PGE2). An ultrasound scan performed two years later revealed a uterine lesion that corresponded to the myometrial tear reported at cesarean section. CONCLUSION: Complicated hysteroscopic metroplasty may promote acute uterine rupture during pregnancy and labor. Ultrasound is a useful tool for the detection of uterine lesions. If adequately considered, it might have allowed more rational management of labor in this case. PGE2 should never be used for induction of labor after complicated metroplasty.

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.

Foscarnet-induced crystalline glomerulonephritis with nephrotic syndrome and acute renal failure after kidney transplantation.

Foscarnet nephrotoxicity has been reported to be associated with acute tubulointerstitial nephritis. Crystals in glomerular capillary lumens have also been observed in patients with acquired immunodeficiency syndrome who were treated with foscarnet for cytomegalovirus disease. We describe a kidney transplant recipient who developed a nephrotic syndrome with microscopic hematuria and nonoliguric acute renal failure within 15 days after starting foscarnet therapy for cytomegalovirus infection. A kidney biopsy specimen showed the presence of crystals in all glomeruli and in proximal tubules. Fourier transform infrared microscopy analysis demonstrated that crystals were made from several forms of foscarnet salts: mixed calcium and sodium salts, and unchanged trisodium foscarnet salts. Renal function and proteinuria spontaneously improved, and a second transplant biopsy performed 8 months after the first one revealed fibrotic organization of half of the glomeruli and of interstitial tissue, and crystal vanishing. We were thus able to provide proof of the possible precipitation of foscarnet in a transplanted kidney.