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.

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.

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.

HIV infection and invasive cervical carcinoma in an Italian population: the need for closer screening programmes in seropositive patients.

OBJECTIVE: To evaluate in an Italian population the prevalence, characteristics at first diagnosis and outcome of HIV-seropositive individuals with cervical carcinoma referred to a tertiary-care institution. DESIGN: A retrospective evaluation of all patients referred for invasive cervical carcinoma from 1991 to 1994. SETTING: The departments of obstetrics and gynaecology, and radiotherapy at San Gerardo Hospital, University of Milan, Italy. PATIENTS: A total of 340 women were treated over a 3-year period (186 aged < 50 years). Six patients were found to be HIV-seropositive. INTERVENTIONS: Seropositive patients were treated according to current institutional protocols, irrespective of HIV status. Four underwent radiotherapy and two radical hysterectomy as primary treatment. RESULTS: Although five HIV-seropositive patients were known to be infected 13-81 months before diagnosis of cervical cancer, none had received a PAP smear in the last year and only one in the last 2 years. HIV patients were younger than general population (P = 0.02), with a significant history of intravenous drug use (P = 0.000001) and with more advanced disease (P = 0.04). Two HIV-positive patients also received polychemotherapy (one adjuvant and one salvage treatment) and both completed the planned treatment. Within 24 months two patients had died of cancer and one of AIDS; one is alive with AIDS and cancer and two are free of disease. CONCLUSIONS: This study confirms that in a southern European population, HIV-seropositive women present to tertiary-care institutions with more advanced disease and have a poorer prognosis than the general population. Strict screening programs for cervical dysplasia and cancer are warranted for HIV-seropositive patients.

Phenotypic and functional characteristics of tumour-derived microvascular endothelial cells.

We recently developed a method for the isolation and purification of tumour-derived endothelium. In this study the phenotypic and functional properties of human tumour-derived microvascular endothelial cells (TdMEC) were examined. Endothelium obtained from human adrenal gland specimens (HAMEC) was used as a reference microvascular endothelial cell population. TdMEC formed a confluent monolayer with the typical morphological appearance of endothelium and were positive for endothelial markers such as Ulex-1 lectin, CD31 antigen, von Willebrand Factor and VE-cadherin. The addition of acidic Fibroblast Growth Factor (aFGF), basic FGF (bFGF) or Vascular Endothelial Growth Factor (VEGF) substantially improved proliferation of TdMEC; and kidney carcinoma derived endothelial cells were more responsive to FGFs, whereas glioblastoma derived endothelial cells greatly responded to VEGF TdMEC expressed high levels of the VEGF receptors, KDR/flk-1 and Flt-1, as shown by northern blot analysis. TdMEC expressed the adhesion molecules ICAM-1, VCAM-1 and E-selectin that could be further increased by exposing TdMEC culture to interleukin-1. All the TdMEC expressed interleukin-8 mRNA. These findings show that TdMEC in vitro maintain several of the features described for microvasculature. Thus, TdMEC represent a useful tool to study markers for tumor vasculature.

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.

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.

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.

Ureteral endometriosis diagnosed at ureteroscopy.

BACKGROUND: Intrinsic ureteral endometriosis is rare. Early detection and treatment is extremely important to preserve renal function. CASE: A 37-year-old woman with right flank pain was diagnosed with a polypoid lesion at excretory urogram. The polyp was removed under ureteroscopy and was found to be endometriosis. Subsequent exploratory laparotomy and ureterolysis failed to document other foci of endometriosis. Resection of the ureter was not needed. She received medroxyprogesterone for 6 months, and a ureteral stent was left in place for 3 months postoperatively. Excretory urogram showed no obstruction 6 months postoperatively. CONCLUSION: This appears to be the first reported case of ureteral endometriosis documented initially at ureteroscopy. Prompt treatment may relieve symptoms and preserve renal function. Resection of the ureter may be avoided in some patients.

Prevention of postoperative urinary stress incontinence after surgery for genitourinary prolapse.

OBJECTIVE: To compare cystopexy alone versus cystopexy with posterior pubourethral ligaments plication for the occurrence of postoperative stress incontinence after prolapse surgery, and to compare the two surgical series in terms of complications and urodynamic effects. METHODS: One hundred two continent patients randomly underwent cystopexy alone (N = 52) or cystopexy with posterior pubourethral ligaments plication (N = 50). All had a urethrocystocele grade 2 or greater and a negative stress test with the prolapse repositioned. A full urodynamic investigation was repeated 6 months after surgery. RESULTS: Twelve (23%) and 14 (28%) patients (P = .73) required intermittent self-catheterization for 11.1 +/- 5.1 and 16.5 +/- 11.1 days, respectively (cystopexy alone versus cystopexy with posterior pubourethral ligaments plication, P = .002). Long-lasting difficulties in voiding were present in zero and five (10%) patients (P = .02). One subject receiving posterior pubourethral ligaments plication underwent urethral dilation for complete urinary retention. At 1 year follow-up, four patients (8%) in each series developed postoperative stress incontinence (P = .62). Symptomatic detrusor instability complicated the postoperative course in one patient (2%) of each group. CONCLUSION: Cystopexy alone implied lower morbidity in terms of resumption of spontaneous voiding and long-lasting difficulties in voiding. The procedure could be recommended as an effective and safe treatment for continent patients with severe urethrocystocele. Additional plication of the posterior pubourethral ligaments did not seem superior to cystopexy alone in preventing the postoperative occurrence of stress incontinence.

Three-year results after neoadjuvant chemotherapy, radical surgery, and radiotherapy in locally advanced cervical carcinoma.

OBJECTIVE: To evaluate the complications and results of neoadjuvant treatment before surgery and radiotherapy in locally advanced cervical carcinoma. METHODS: Between March 1988 and June 1989, 24 consecutive patients with locally advanced cervical carcinoma received chemotherapy consisting of six weekly courses of cisplatin (50 mg/m2), vincristine (1 mg/m2), and bleomycin (30 mg), followed by radical hysterectomy and radiotherapy. Lymph node metastases were detected by means of lymphangiography and confirmed by fine-needle aspiration in 21 patients. RESULTS: Twenty-one women (87.5%) completed the planned sequence of treatment and 16 (66.7%) achieved objective responses. Three patients did not complete chemotherapy (one refusal, one myocardial infarction, one severe allergic reaction) and were treated further by radiotherapy. Nineteen subjects (79%) underwent subsequent radical surgery and radiotherapy without serious complications. After a minimal follow-up of 3 years, 16 patients had died of disease. Distant recurrences developed in only three of eight women in whom the nodes were negative originally, possibly reflecting systemic effectiveness of the chemotherapy. CONCLUSION: This sequence of treatment, although feasible, does not seem to improve long-term survival compared to standard treatment.

Pre-operative cervical preparation before first trimester missed abortion: a randomized controlled comparison between single or double intracervical administration of PGE2 gel.

The aim of this study was to evaluate whether a single intracervical application of prostaglandin E2 (PGE2) gel is as effective as a repeated administration with respect to the % of curettage for a missed abortion and to incidence of side effects. 32 consecutive patients with ultrasonographic diagnosis of missed abortion from 6th-13th week of gestation were randomly allocated to either single (group A) or repeated, 2 h apart (group B), intracervical application of PGE2 gel. No differences were observed in cervical dilatation before the administration of the gel between the two groups. In group B, evaluation of cervical dilatation 2 h after the first administration of PGE2 gel and before the second one did not show significant changes as compared to baseline values. The degree of cervical dilatation before surgery was significantly improved as compared to the initial dilatation in both groups; no significant difference was observed between the two study groups. A single administration of PGE2 gel followed by surgery 5 h later has the same effectiveness on cervical dilatation but fewer side effects than repeated administration of the drug 2 h apart.

Ultrasound-guided aspiration of endometriomas: possible applications and limitations.

OBJECTIVES: To evaluate the role of needle aspiration in the management of endometriomas. DESIGN: Retrospective evaluation of the activity of the section of interventional ultrasound in a single tertiary care institution. SETTING: Department of Obstetrics and Gynecology, Ospedale S. Gerardo, Monza, University of Milan, Italy. PATIENTS: Two hundred nine premenopausal patients underwent aspiration for diagnostic purpose (n = 166), for relief of symptoms (n = 25), or with therapeutic intent (n = 18). RESULTS: Adequate material was obtained by all punctures. Early complications (self-limiting vagal symptoms or pain) occurred in eight cases. Short-term complications consisted of acute abdominal pain in three cases and infection in one. Three women required surgical treatment of the complication. At first examination after aspiration, persistence of the cyst was observed in all but four cases, including all cases who had undergone therapeutic aspiration. Nine patients reported relief of symptoms but six other patients referred onset or worsening of pelvic discomfort after aspiration. CONCLUSIONS: Ultrasound-guided aspiration of endometriomas is feasible. The transvaginal route reduces early complication but implies a risk of infection of 1.3%. However, drainage alone is ineffective as a therapeutic procedure and the applications of aspiration of endometriomas appear limited to some cases with diagnostic intent.

Long-term results of sequential postoperative treatment with vincristine, bleomycin, mitomycin c, cis-platin and radiotherapy after surgery for high-risk patients with cervical carcinoma stage IB-IIA.

Adjuvant treatment of patients with risk factors after surgery for cervical carcinoma remains unsatisfactory. A combination of radiotherapy and chemotherapy might improve the control of microscopic metastases. In this prospective study, 28 patients with risk factors after surgery for cervical carcinoma underwent a sequential treatment consisting of two courses of chemotherapy with vincristine, bleomycin, mitomycin c and cis-platin (VBMP), followed by radiotherapy with 54 Gy to the pelvis and the aortic nodes. Risk factors mainly consisted of nodes metastases (25 patients), but patients with parametrial invasion or histologic evidence of neoplastic vascular permeation outside the tumor were also included in the study. The treatment was well tolerated and all patients received the planned dose of chemotherapy and radiotherapy; in the follow-up one patient died of ileal necrosis and one died of pulmonary embolism after being medically treated for subocclusion. With a minimal follow-up of 70 months, 15 patients are alive and free of disease, two have died of complications (one with local recurrence), one has died of intercurrent disease and 10 have died of disease (six distant, four local). The site of recurrence was outside the field of irradiation in six cases (lungs in two cases, liver and para-aortic nodes in one and distant nodes in three). This treatment is feasible but control of distant metastases in high-risk patients after surgical treatment remains unsatisfactory.

Bleomycin, ifosfamide and cis-platin chemotherapy in recurrent and persistent cervical cancer, a prospective study.

Thirty patients with histologically proven recurrent or persistent squamous cell cervical carcinoma were treated with chemotherapy, consisting of a combination of bleomycin, ifosfamide and cis-platin (BIP). All patients were evaluable for response. An objective response was seen in nine of the 30 patients (30%): complete in two (6.7%) and partial in the other seven (23.3%). A total of 39 tumor sites was treated: five responses were observed in 26 irradiated areas (19%), whereas seven responses were observed in 13 nonirradiated areas (53.8%). Side-effects were mainly nausea, vomiting, alopecia, myelosupression, fever and impaired renal function. Encephalopathy was recorded in four patients (severe in one). No patient died from the toxic effects of chemotherapy. The results indicate that BIP is an active combination in recurrent and advanced cervical carcinoma, with acceptable toxicity; however, this combination failed to prove any superiority over other single or multi-drug treatments proposed in the last decade.

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.

Treatment of fallopian tube carcinoma with cyclophosphamide, adriamycin, and cisplatin.

Primary carcinoma of the fallopian tube is uncommon; optimal primary treatment is still not well defined, and little information is available about the efficacy of cisplatin-based combination chemotherapy. Thirty-eight patients with fallopian tube carcinoma were treated with cyclophosphamide (500 mg/m2), Adriamycin (50 mg/m2), and cisplatin (50 mg/m2) (CAP). Thirty-two patients received the combination chemotherapy as first-line treatment after cytoreductive surgery, whereas six subjects were treated for recurrent disease. The patients received a median of six cycles of therapy (range, four to nine). At the initiation of chemotherapy, 24 patients had measurable lesions. In this group of patients, 15 had a clinical complete response (CR), four had a partial response (PR), three had stable disease (SD), and two had progressive disease (PD) after chemotherapy. The overall clinical response rate (CR + PR) was 80%. Ten of the 14 CR patients who were submitted to second-look operation (SLO) were found free of disease, in pathologic complete response (pCR). Three pCR patients relapsed, and two of them died despite second-line treatment. Nine patients achieving PR, SD, and PD after first-line chemotherapy were further treated (five with chemotherapy, two with radiotherapy, two with progesteron), but none responded to second-line treatment and all died (median survival, 9 months). Fourteen patients without gross residual disease after cytoreductive surgery had no measurable lesions and were not evaluable for response. Seven of them had negative SLO and remain disease free. Three patients (two stage III and one stage II) who refused SLO relapsed 14, 16, and 26 months after completion of chemotherapy. The median survival for the entire group was 38 months, and the 5-year survival rate was 35%. The toxicity of the regimen was moderate. The CAP regimen appears to be active in primary fallopian tube carcinoma and yields response rates comparable to those reported for epithelial ovarian cancer.

Complete remission of brain metastases from ovarian carcinoma with carboplatin.

Central nervous system involvement by epithelial ovarian carcinoma is rare. We report the case of a 49 year old woman with stage IV serous carcinoma of the ovary who developed multiple cerebral and cerebellar metastases 7 months after achieving complete response to platin-based chemotherapy. Eight courses of carboplatin (400 mg/m2) were administered and after the second cycle complete remission of the brain deposits occured. The treatment afforded rapid subjective and objective relief and was associated with a good quality of life. Abdominal recurrent disease was diagnosed 22 months after treatment for brain involvement. Paltin-based chemotherapy was reinstated, but the patient died from progressive adbominal disease without any sign of cerebral involvement and any neurological symptomatology. Carboplatin should be considered for the treatment of ovarian carcinoma metastatic to the brain.

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.

Argentaffin pulmonary tumorlets.

The left lung, surgically removed from a patient, was found to be bronchiectasic and polycystic. Using light microscopy it was possible to locate multiple tumorlets originating from the Kulchitsky cells of the bronchial and bronchiolar mucosae. With the traditional histochemical staining, argyrophilia and argentaffinity were demonstrated. The latter, not previously reported in the literature, suggests the presence of different monoamines in the neurosecretory cytoplasmic granules of the tumorlet cells.