Post-traumatic amenorrhea: the role of diagnostic and operative hysteroscopy in the prevention, diagnosis, differential diagnosis and treatment.

AIM: The aim of the study was to evaluate the clinical usefulness of the selective removal of residual intrauterine trophoblastic tissue by using a hysteroscopic procedure, especially in the prevention of the Intra-Uterine Adhesion's Syndrome. METHODS: Seventy-six patients had an Asherman's Syndrome: 5 cases after laparotomic myomectomy, 1 after caesarean section, 2 after hysteroscopic myomectomy, 10 after VIP, 1 with a severe vaginal endometriosis, 1 after conisation, 4 after a post-partum hemorrhage due to coagulopathy or uterine atony, 20 cases after D&C because of PPH due to placental retention, 26 after repetitive D&Cs because of AUB due to post abortion chorial residues' retention, 6 cases after D&C for post menopausal AUB. Thirty-six patients presented AUB due to chorioplacental residues retention: 14 cases after a vaginal delivery or a caesarean section, 4 after VIP, 18 cases after repetitive D&Cs for incomplete or internal spontaneous abortion. Complete physical examination, transvaginal ultrasonography and operative hysteroscopy was offered as first treatment to all patients. Surgical treatment of IUA depends on the type (I-IV) and is based on the section of synechiae, liberation of the uterine cavity and tubal recesses, recovery of the residual endometrium to restore the physiology of the reproductive tract. Our technique to remove the chorioplacental residues is based on: correct use of loops and electric currents, enucleation by cold loops of the base of the placental implant, and to single out the level of miometrial infiltration. RESULTS: After treatment we have noticed: two hysterectomies (for persistent AUB after myomectomy and for severe bleeding after dehiscence of a C. section), restoration of regular menstruations in 94.6% of patients (6 women in menopause), disappearance of pelvic pain and dysmenorrhea in all cases (100%), 8 pregnancies of the 9 women who were wanting child after hysteroscopic synechiolysis (88.9%). CONCLUSION: According to the present study, the best way to prevent IUA is to make D&C for abortion, avoiding waiting longer than 24 hours, perform a D&C and then a diagnostic hysteroscopy after PPH in symptomatic women, reserve D&Cs only for a PPH, or an incomplete abortion, limit to only one D&C, always make a diagnostic hysteroscopy after D&C and uterine plugging for PPH.

[Sensitivity, specificity, predictive positive and negative value of the main clinical signs and symptoms of hydatiform mole]. / Sensibilità, specificità, valore predittivo positivo e negativo dei principali segni clinici e sintomi della mola idatidea.

AIM: Especially in the first weeks of pregnancy, complete and partial hydatiform moles are not easily detected by sonography, symptoms and clinical signs. Due to the rarity of moles, it is possible that they may be confused with abortive pregnancies until the pathological examination. The aim of this study is to identify the sensitivity, specificity, predictive positive and negative value of the main symptoms and clinical signs of molar pregnancies. METHODS: Thirteen molar pregnancies have been detected after pathological examination from January 2003 to July 2005 in Perugia. Their main clinical signs and symptoms are compared with those recorded in 288 abortive pregnancies, 56 ectopic pregnancies and 27 Hyperemesis gravidarum, observed in the same period. RESULTS: Vaginal bleeding and pelvic pain are the most sensitive symptoms and have the highest predictive negative values. The size of the uterus greater for date is the most specific sign. Pelvic pain with hyperemesis, and uterus size greater for date have the highest predictive positive values, but the lowest sensitivity. CONCLUSIONS: A mole should be excluded in patients with hyperemesis and pelvic pain, and in patients with uterus size greater for date. In the first case, a hyperemesis gravidarum may be diagnosed and, in the second one, a twin pregnancy may be confirmed with a sonographic scan.

Phase II trial of edatrexate in patients with advanced hepatocellular carcinoma.

BACKGROUND: The methotrexate analogue edatrexate (10-ethyl-10-deaza-aminopterin, or 10-EDAM) has demonstrated greater activity than methotrexate has against murine tumors and human tumor xenografts. Phase II trials of edatrexate have already demonstrated its activity against breast, lung, and head and neck carcinomas. A phase II trial of edatrexate was conducted in patients with advanced hepatocellular carcinoma. PATIENTS AND METHODS: Seventeen patients with previously untreated unresectable hepatocellular carcinoma were enrolled on the study. Edatrexate, 80 mg/m2 weekly for 5 weeks, was administered intravenously. The treatment course was repeated every 6 weeks. Tumor response was evaluated by computerized tomographic scan after 2 courses. RESULTS: No complete or partial responses were observed in this trial. Two minor responses, each lasting less than 12 weeks, were observed. Twelve patients had elevated serum alpha-fetoprotein (AFP) levels at entry into the study; 4 of the 12 patients experienced a > or = 25% decrease in the level of this tumor marker; 3 of the 4 had a > 50% reduction in AFP level. Grade 3 and 4 toxic effects were granulocytopenia, thrombocytopenia, anemia, oral mucositis, skin reactions, fatigue, anorexia, and diarrhea. CONCLUSIONS: Edatrexate administered at this dose and schedule appears to have little therapeutic efficacy against advanced hepatocellular carcinoma.

High-dose N,N',N"-triethylenethiophosphoramide (thiotepa) with autologous bone marrow transplantation: phase I studies.

N,N',N''-triethylenethiophosphoramide (thiotepa) is a polyfunctional alkylating agent similar in structure to nitrogen mustard. Thiotepa (synthesized by American Cyanamid Company, Wayne, NJ) underwent clinical trials in the 1960s that showed that it was active against a wide variety of tumors. At a standard dose level (10 to 30 mg/m2), the dose-limiting toxicity is myelosuppression; other toxicities are infrequent. Therefore, high-dose phase I evaluation was encouraged by these observations. Approximately 217 patients have been treated with single-agent high-dose thiotepa administered intravenously daily over 2 hours for 3 days followed by hematopoietic stem cell rescue to prevent prolonged myelotoxicity. The total doses administered ranged from 135 to 1,575 mg/m2. As anticipated, myelotoxicity was substantial, with 180 mg/m2 being the highest dose not requiring stem cell rescue to ensure hematopoietic recovery. Extramedullary toxicities consisted of stomatitis, dermatitis, hepatoxicity, and central nervous system (CNS) toxicity. CNS toxicity was dose-limiting; other toxicities were problematic, ie, dose-dependent but not truly dose-limiting. The maximal tolerated dose of thiotepa is 900 to 1,125 mg/m2, with the lower dose being the maximal dose for evaluation in combination chemotherapy. In high-dose phase I evaluation, the overall response rate was approximately 50% with responses seen in a wide variety of solid tumors, lymphomas, and pediatric tumors. High-dose thiotepa appears to be an alkylating agent with broad-spectrum antitumor efficacy, which should add to the cytoreductive regimens for both solid and hematopoietic tumors.

High-dose thiotepa with autologous bone marrow transplantation for metastatic malignant melanoma: results of phase I and II studies of the North American Bone Marrow Transplantation Group.

We evaluated thiotepa in escalating dose in a broad phase I and II study using cryopreserved autologous bone marrow transplantation to assure hematopoietic recovery. Thiotepa was administered intravenously (IV) over two hours daily for three consecutive days followed in three to four days by marrow transplantation. The daily dose ranged from 60 to 525 mg/m2 (total dose, 180 to 1,575 mg/m2). A total of 71 patients with malignant melanoma were treated. Forty-three patients (61%) had received prior cytotoxic therapy and 28 were untreated. Sixty-two patients (87%) had melanoma disseminated to at least one visceral site, nine patients had skin and/or lymphatic metastases only. As of January 1, 1988 one patient was too early to be evaluated, 15 patients were inevaluable for tumor response, four patients had a complete response (CR), and 25 patients had a partial response (PR) to treatment. The response rates (95% confidence interval) for the 55 evaluable patients and for all 71 treated patients were 53% (40% to 65%) and 41% (30% to 53%), respectively. The median duration of response was 3 months, with a range of 1 to 31 + months. Three patients were alive and well without evidence of tumor more than 1 year after treatment. Analysis of patient subsets indicated that neither total dose, previous cytotoxic therapy, or sites of metastases influenced response rate. In this study, high-dose thiotepa has demonstrated a high response rate in patients with metastatic malignant melanoma with both PRs and CRs noted. Although most of the responses were not durable, 10% of the responses lasted more than 1 year. Future studies will evaluate additional methods for increasing the response rate and improving the duration of response.

Use of the BCR probe to demonstrate extramedullary recurrence of CGL with a T cell lymphoid phenotype following bone marrow transplantation.

A case of Philadelphia chromosome (Ph1) positive chronic granulocytic leukemia (CGL) is described in which the patient underwent successful treatment with supralethal chemoradiotherapy and allogeneic bone marrow transplantation (BMT) after transformation to blast crisis. Supraclavicular adenopathy developed 5 months after BMT and biopsy revealed a hematopoietic lymphoid neoplasm with an early T cell phenotype. A concurrent bone marrow was microscopically and cytogenetically normal. A metaphase chromosome preparation could not be obtained from nodal tissue. Lymph node DNA, however, was easily extracted and a rearrangement of BCR identical to that in the bone marrow prior to BMT was demonstrated indicating recurrent CGL rather than a de novo lymphoproliferative process. Appropriate therapy for lymphoid blast crisis resulted in a marked regression of measurable disease. The BCR probe may prove to be a useful tool for the diagnosis of CGL when standard cytogenetic techniques cannot be applied.

Recent progress in the treatment of seminoma.

Effective treatment for seminoma of the testicle has improved markedly since the initial reports utilizing orthovoltage radiotherapy. Contributing to this progress have been the use of chemotherapy in advanced disease and the development of a staging system to predict outcome for patients treated with radiation therapy alone. Those groups of patients manifesting poor survival with radiation have benefited from cisplatin-based chemotherapy. At the present time, 80-100% of patients with limited disease and 60-80% of patients with more advanced disease will become long-term survivors. Areas requiring further investigation include the significance of elevated HCG, extragonadal primaries, residual radiographic abnormalities following chemotherapy, and the treatment of relapse after chemotherapy.

[Hypohidrotic ectodermal dysplasia]. / Displasia ectodermica ipoidrotica.

The authors report a case of Hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome). Diagnosed at the age of 2 months.

High-dose chemoradiotherapy with syngeneic bone marrow transplantation for multiple myeloma: a case report and literature review.

We had the opportunity to treat a patient with progressive heavily pretreated multiple myeloma with high-dose chemoradiotherapy with hematopoietic rescue by syngeneic bone marrow transplantation. The patient was a 53-year-old male who had previously received melphalan, prednisone, 1,3-bis (2-chloroethyl)-l-nitrosourea (BCNU), vincristine, and standard radiation therapy. At the time of bone marrow transplantation, he had increasing bone pain, increasing M-protein (IgG kappa), and a bone marrow diagnostic of myeloma. The transplant regimen consisted of cyclophosphamide, 60 mg/kg intravenously for 2 days, and total body irradiation--1,200 rads given as 200-rad fractions, twice daily for three days. The transplant course was complicated by confusion, herpes simplex mucositis, fever, and two episodes of idiopathic diffuse interstitial pneumonia. Over the next 2 years the patient did well and was in immunologic and bone marrow complete remission. Unfortunately, 3 years after treatment, the myeloma relapsed with detectable M-protein. Three and one-half years after transplant, clinical relapse occurred with bone pain and lytic lesions necessitating additional radiation and chemotherapy. Salvage therapy has produced clinical improvement and the patient is alive almost 4 years from transplant and almost 7 years from diagnosis. Although intense chemoradiotherapy did not cure this patient, substantial control of a refractory tumor was observed. This case, together with other cases of intense therapy for myeloma which are reviewed in this paper, support the concept of high-dose therapy and should foster further investigation of high-dose therapy.

Phase II treatment of central nervous system gliomas with high-dose etoposide and autologous bone marrow transplantation.

A total of 16 patients with progressive CNS gliomas who had previously received maximal radiation therapy and chemotherapy were treated on a phase II study using high-dose etoposide with autologous bone marrow transplantation to assure hematopoietic recovery. Three patients (19%) responded with both improved neurological status and decreased mass on computerized tomographic scan. Median survival for all treated patients was 4 months with the three responders living 9, 10, and 54+ months.

Disseminated Merkel cell tumor. Treatment with systemic chemotherapy.

Four patients with disseminated Merkel cell tumors were treated with cyclophosphamide (C), doxorubicin (A), and vincristine (V). Two partial responses (PR) were noted and in one case disease remained stable. One of the patients who achieved a PR achieved a second PR when treated with VP-16 (E) and cis-platin (P) after progressive disease developed. Systemic chemotherapy appears capable of inducing objective responses in some patients with disseminated Merkel cell tumors.

Pure red cell aplasia associated with administration of sustained-release procainamide.

Pure red cell aplasia developed in a patient with small-cell lung cancer who was also taking sustained-release procainamide. Shortly after discontinuation of the procainamide preparation, a reticulocytosis and increasing hemoglobin level were observed.

Favorable prognosis of brain metastases in small cell lung cancer.

Brain metastases are found at diagnosis in 10% of patients with small cell lung cancer. To clarify the effect of central nervous system metastases on prognosis, the records of 429 patients with small cell lung cancer were reviewed. Forty-three patients (10%) presented with brain metastases. In 18 patients the brain was the only site of metastatic disease, whereas the remaining 25 patients had at least one additional metastatic site. Forty-one of forty-three patients were treated with combination chemotherapy and cranial radiotherapy. Systemic response rates were similar for both groups. Twenty-seven patients underwent repeat central nervous system staging: 19 (70%) had a complete response, 4 (15%) a partial response, and 4 (15%) no response. Median survival of patients with only one site of metastatic disease was 11 months; patients with additional sites lived 5 months (p = 0.153). Survival in patients with only one site is similar to that in patients with limited disease (11 compared with 13 months; p = 0.074).

Combination chemotherapy for patients with advanced carcinoma of the cervix: trial of mitomycin-C, vincristine, bleomycin, and cisplatin.

Sixteen patients with metastatic or recurrent carcinoma of the cervix were treated with combination chemotherapy consisting of mitomycin-C, vincristine, bleomycin, and cisplatin. Seven of 14 (50%) evaluable patients responded. In 2 patients all measurable disease resolved. Median duration of response was 4.5 months. Toxicity was severe and consisted of myelosuppression, pulmonary fibrosis, nausea, vomiting, stomatitis, asthenia, and fever. Two treatment-related deaths occurred. This combination chemotherapy regimen appears to have a response rate similar to other cisplatin containing regimens. Response durations were short and toxicity was severe.

Combination intraventricular chemotherapy for meningeal neoplasia.

Twenty two patients with meningeal neoplasia were treated with biweekly combination intraventricular chemotherapy using methotrexate, cytosine arabinoside, and thiotepa. Patients with the following malignancies were included: breast cancer, ten patients; lung cancer, seven; non-Hodgkin's lymphoma, two; malignant melanoma, one; transitional cell carcinoma of the bladder, one; and malignant glioma, one. Eight of 22 patients (36%) had a Karnofsky performance status of less than 50%. Eleven of 22 patients received radiotherapy to symptomatic areas, and seven received systemic chemotherapy in addition to combination intraventricular therapy. Patients were evaluated for both toxicity and response to therapy. Myelosuppression was the major toxic condition and occurred in 17 of 22 patients (77%). Ten patients (45%) had a nadir WBC count of less than 1000/microL or a platelet count of less than 25,000/microL. No patient achieved a complete response (CR), although nine patients (41%) had partial responses (PRs) lasting 4 to 24 + weeks. Median survival for the entire group was 10 weeks (range, 6 to 24+ weeks). In this small group of patients, simultaneous triple-drug intraventricular chemotherapy caused unacceptable myelosuppression without increasing the response rate, response duration, or survival when compared with single-agent methotrexate and radiotherapy.

Serum neuron-specific enolase in metastatic Merkel cell tumors.

Three patients with widely disseminated Merkel cell tumors of the skin are presented. In all three cases, neuron-specific enolase (NSE) was demonstrated in neoplastic tissue by immunohistochemical staining, and serum NSE levels were also elevated in all three patients. Serum NSE may prove to be a useful tumor marker in this and other malignancies of neuroendocrine origin.