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Background: The marginal zone is an anatomically distinct B-cell compartment of lymphoid tissue with an abundant antigenic influx. Among marginal zone-derived lymphomas the WHO classification listed, in addition to extranodal marginal zone B-cell lymphoma of MALT type, two other marginal zone B-cell neoplasms: splenic marginal zone B-cell lymphoma (+/- villous lymphocytes) and nodal marginal zone B-cell lymphoma (+/- monocytoid B cells). These two entities are well characterized histologically, but specific biological markers are lacking. Treatment options are heterogeneous, including a watch-and-wait policy, surgery with or without chemotherapy, purine analogs, and interferon. No prospective studies have been conducted so far., Information Sources: Clinical and pathologic data were reviewed by searches of the published medical literature, including searches in PubMed , important printed publications, and abstracts presented at recent hematology and pathology meetings., State of the Art: Splenic and nodal marginal zone lymphomas are typical low-grade lymphomas with an indolent course. A subset of patients, however, presents with more aggressive disease and have a shorter survival. Clinical and biological prognostic factors identified in reported series are heterogeneous. The role played by hepatitis C virus (HCV) in marginal zone lymphomas is not fully elucidated, but there is demonstration that eradication of HCV infection in splenic lymphoma with villous lymphocytes causes regression of the lymphoma. The optimal treatment has not yet been identified. Retrospective series, however, show that splenectomy is a good option if symptoms from the presence of spleen enlargement or cytopenias need to be treated. The utility of purine analogs and of anti-CD20 immunotherapy needs to be clarified in prospective trials., Perspectives: Clinicians and pathologists should co-operate to define stringent diagnostic criteria for these indolent disorders. The optimal therapeutic approach and the role of new treatments need to be assessed in prospective clinical trials.

Background and Objectives: The purpose of this study was to compare the efficacy and toxicity of two regimens for peripheral blood stem cell (PBSC) mobilization in multiple myeloma (MM) patients., Design and Methods: From 1995 to 2001, 116 patients were enrolled in two high-dose programs including autologous transplantation, adopting two mobilizing regimens: 61 patients were mobilized with high-dose cyclophosphamide (HD-Cy) at 4 g/m2 (group I), and 55 patients with DCEP (dexamethasone, cyclophosphamide, etoposide, and cisplatin) (group II), both followed by granulocyte colony-stimulating factor (G-CSF 5 mg/Kg/day) started 48 hours after chemotherapy., Results: The median number of CD34+ cells harvested was similar in the two groups (5.9 vs 5.82x106 cells/kg). The target of at least 4x106 cells/kg was reached in a higher percentage of patients in the DCEP group (75 vs 59%) (p=0.05). The proportion of poor mobilizers (<2x106 CD34+ cells/kg) was 21% with HD-Cy and 13% with DCEP (P=NS). In group I, 10 patients (16%) required packed red cell transfusions, 5 patients (8%) platelet support, and the majority of patients (87%) had a neutrophil count below 500/mL, whereas none did so in group II (p=0.0009, p=0.01, p=0.0009, respectively). Neutropenia-related fever occurred in 18% of patients in group I versus 0% in group II (p=0.0005). WHO grade >II extra-hematologic toxicities (microhematuria, cystitis, infections) were seen in 8 patients (13%) of group I vs 0 in group II (p=0.007)., Interpretation and Conclusions: DCEP is a better tolerated and more effective regimen than HD-Cy for peripheral stem cell mobilization in MM patients assigned to high-dose therapy programs.

Minimal residual disease (MRD) following sequential administration of CHOP and rituximab was studied in previously untreated patients with follicular lymphoma. At diagnosis, the presence of Bcl-2/IgH-positive cells in the peripheral blood (PB) and/or bone marrow (BM) was demonstrated in all patients (n = 128) by polymerase chain reaction (PCR) analysis. Patients who achieved a clinical response following CHOP but remained PCR-positive were eligible for rituximab (375 mg/m(2) intravenously, weekly for 4 weeks). After CHOP, 57% achieved a complete response (CR), 37% a partial response (PR), and 6% were nonresponders (NR). At this stage, patients proving PCR-negative (n = 41) or failing to achieve a clinical response (n = 8) were excluded from rituximab treatment. Seventy-seven patients received rituximab and entered a scheduled MRD follow-up program. At the first molecular follow-up (+12 weeks), 59% had converted to PCR negativity in the BM and PB, with a further increase documented at the second control (+28 weeks) with 74% PCR negative. At the last molecular follow-up (+44 weeks), 63% of the patients remained PCR negative. At 3 years, the estimated overall survival of all patients is 95% (95% confidence interval [CI], 86-98). For patients achieving PCR-negative status following CHOP and therefore excluded from rituximab treatment, freedom from recurrence (FFR) was 52% (95% CI, 28-71). For patients treated with rituximab, a durable PCR-negative status was associated with a better clinical outcome since FFR was 57% (95% CI, 23-81) compared with 20% (95% CI, 4-46) in patients who never achieved or lost the molecular negativity (P <.001).

Options for relapsed/refractory indolent lymphoma include chemotherapy, immunotherapy and high-dose therapy with autologous support. The best combination of these approaches, however, is not defined. We treated 10 patients with relapsed/refractory follicular (n = 7) or mantle cell lymphoma (n = 3) using chemotherapy, immunotherapy, high-dose therapy and autotransplant in a sequence of four phases, each designed to play a specific role in tumour eradication. After the debulking with VACOP-B (doxorubicin, cyclophosphamide, etoposide, vincristine, prednisone, bleomycin) (phase 1), 9/10 patients responded but none achieved a molecular response. After the immuno-chemotherapy phase, which combined Rituximab with vincristine and cyclophosphamide, seven patients were in complete response (CR) and three in good partial response (PR), and all those with a molecular marker of disease showed a disappearance of the signal from marrow and blood. Phase 3, which coupled high-dose cytarabine with Rituximab, was effective in mobilizing an adequate number of progenitor cells that were polymerase chain reaction negative in all informative cases. Phase 4 consisted of high-dose therapy with autologous support followed by two doses of Rituximab. Autograft was performed in nine patients. The haematopoietic recovery was as expected. This sequence of chemotherapy, immuno-chemotherapy, stem cell mobilization with in vivo purging and autotransplant, organized in four blocks of treatment, was simple to administer and devoid of toxic effects. It permits rapid attainment of clinical and molecular response and enables the harvest of lymphoma-free peripheral blood progenitor cells even in heavily pretreated patients with relapsed or refractory disease.

Background and Objectives: Skeletal involvement is typical of multiple myeloma (MM) and its occurrence increases with the progression of the disease. We performed a study to evaluate the clinical importance of osteocalcin (bone gla-protein, BGP) and bone alkaline phosphatase (b-AP) as indices of osteoblastic activity, and deoxypyridoline (DPD) as a marker of bone resorption., Design and Methods: Fifty-two MM patients, 39 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 normal controls entered the study. Of the 52 MM patients, 10 showed lytic lesions at standard X-rays and 42 did not; 21 were untreated and 31 had been treated with chemotherapy (combined with bisphophonates in 15). Of these last, 12 had progressive disease and 19 were in plateau phase., Results: DPD levels were higher in MM patients than in patients with MGUS or healthy controls (p = 0.0001 and p = 0.0008, respectively). No statistical differences were seen between patients with MGUS and healthy controls. BGP serum levels were significantly lower in MM patients than in MGUS patients (p = 0.001) or healthy controls (p = 0.001). b-AP was significantly higher in MGUS patients than in MM patients (p = 0.04). Biochemical parameters were analyzed in a continuous fashion and after dichotomization into low and high values with respect to normal ones. Abnormal high values of DPD showed statistically significant correlations with presence of osteolysis (p = 0.008), advanced stage (p = 0.03) and abnormal beta2-microglobulin (beta2M) values (p = 0.03), while DPD as a continuous variable correlated significantly only with the presence of osteolysis (p = 0.02). In contrast, neither BGP nor b-AP showed statistical correlations with the presence of lytic lesions, or with other clinical or laboratory parameters. In 15 patients followed with serial controls, modifications of DPD levels reflected bone disease status well. Of the 42 patients without radiologic evidence of skeletal lesions, 15 had abnormal DPD values. Spinal magnetic resonance imaging (MRI) showed initial lytic lesions in 10 of them., Interpretation and Conclusions: Biochemical markers of bone metabolism are useful in evaluating and monitoring skeletal involvement in MM patients. They may help clinicians to identify: 1) from among patients without radiologic evidence of lytic lesions, those who deserve more accurate radiologic examinations (namely MRI); 2) from among asymptomatic patients, and in association with spinal MRI, those patients at higher risk of progression who might benefit from early treatment.

Objectives: Regulation of the vascular system may limit physical performance and contribute to adaptation to high altitude. We evaluated vascular function in 10 Himalayan high-altitude natives and 10 recently acclimatized sea-level natives at an altitude of 5,050 m., Methods: We registered electrocardiogram, blood flow velocity in the common femoral artery, and blood pressure in the radial artery using non-invasive methods under baseline conditions, and during maximal vasodilation after 2 min leg occlusion. Vascular mechanics were characterized by estimating pulse wave velocity and input impedance., Results: Pulse wave velocity and parameters of input impedance did not differ between groups under baseline conditions. In the post-ischemic period, the ratio between maximal hyperemic and baseline blood flow velocity was significantly higher in the high-altitude than in the sea-level natives (5.7 +/- 2.5 versus 3.8 +/- 1.2, P < 0.05). The leg vascular resistance decreased in the post-occlusive period without differences between groups. Characteristic impedance decreased in the post-ischemic period by about one third of the baseline level without differences between groups. The post-ischemic decrease of input impedance modulus was more marked in the high-altitude than in the sea-level natives at low frequencies (28 +/- 12 versus 6.4 +/- 20% at 2 Hz, P < 0.01)., Conclusions: Our results demonstrate a superior ability to increase blood flow velocity as a response to muscular ischemia in high-altitude natives compared to sea-level natives. This phenomenon may be associated with a more effective coupling between blood pressure and blood flow which is probably caused by differences in conduit vessel function.

This study was performed to investigate the influence of breathing control on the autonomic cardiac regulation at high altitude in adapted and non-adapted awake subjects. We recorded electrocardiogram and pulse oximetry in 14 short-term acclimatized lowlanders and 14 Himalayan Sherpas during resting conditions at an altitude of 5,050 m. Spectrum analysis was performed on synchronized 15 min periods of R-R intervals and the oxygen saturation of arterial blood (SaO2). Despite mean SaO2 being similar in lowlanders and Himalayan Sherpas [78.5 (SD 7.0)% compared to 79.4 (SD5.8)%, respectively], fluctuations in SaO2 were significantly increased in lowlanders compared to Sherpas, thus indicating an unstable regulation of respiration control in lowlanders. Regression analysis demonstrated a significant relationship between spectrum power of SaO2 and the relative power of R-R intervals in the frequency band between 0.01 and 0.08 Hz in lowlanders, but not in Sherpas. Our results demonstrate differences in respiratory and autonomic cardiac control between non-adapted lowlanders and Himalayan high-altitude residents and indicate that unstable breathing control during chronic hypobaric hypoxia is significantly correlated with the autonomic cardiocirculatory regulation.

Rituximab is a chimeric monoclonal antibody (MAb) directed against the B-cell CD20 antigen that has been approved for therapy of relapsed and resistant follicular non-Hodgkin's lymphoma (NHL). This study describes the development and validation of a highly sensitive, rapid, accurate, precise enzyme-linked immunosorbent assay (ELISA) to measure Rituximab serum concentrations. This study also describes the application of the ELISA method to a pharmacokinetic study in a homogeneous group of patients with follicular lymphoma who received 4 weekly doses of MAb at the standard dose of 375 mg/m2 as consolidation of chemotherapy. In the patients in this study, the median Rituximab serum concentrations increased during therapy, and showed a slow decline during the posttreatment period. The Rituximab elimination half-life of approximately 20 days accounts for the demonstrated accumulation of MAb in serum samples. Because previous pharmacokinetic studies showed a correlation between Rituximab serum levels and tumor response, the ELISA method used in this study, which allows a precise control of serum concentrations, could be useful for predicting the final response to the MAb and for selecting patients able to benefit from higher dosage or repeated drug administration.

Fludarabine is effective in chronic lymphocytic leukaemia (CLL) and low-grade non-Hodgkin's lymphoma (NHL). A major side-effect of this purine analogue is immunosuppression which may favour opportunistic infections. Additionally, impairment of immunosurveillance might promote Epstein-Barr virus (EBV) reactivation and possibly favour transformation to high-grade malignancy. The aim of this study was to evaluate the immunosuppression-related effects of the fludarabine-based combination Flucyd in advanced low-grade NHL or CLL by serially monitoring T-lymphocyte subsets, opportunistic infections, EBV-reactivation, and histologic transformation. 24 patients with advanced NHL (n = 21) or CLL (n = 3) received fludarabine 25 mg/m2/d + cyclophosphamide 350 mg/m2/d + dexamethasone 20 mg/d in 3 d courses for a maximum of six courses. The overall response rate was 79% (eight CR, 11 PR, five failures); 11 patients relapsed or progressed between 3 and 19 months from response, and eight are in CR or PR at 3-27 months. The CD4+ lymphocyte counts decreased significantly during therapy from a median of 484/microliter pre-treatment (range 142-1865) to a median of 198/microliter (71-367). In 19 responders monitored off therapy every 3 months until relapse/progression, CD4+ counts were persistently low with minimal recovery over time. During treatment, 16 infections occurred in 11/24 patients. No delayed opportunistic infections occurred in responders while off therapy. The circulating EBV DNA load serially measured in 19 patients by a quantitative PCR assay showed an increase in four patients during treatment. A lymph node biopsy performed in two of these was PCR positive for EBV DNA, whereas LMP1 and EBERs were negative. Six NHL patients evolved into high-grade B-cell NHL. In conclusion, fludarabine combined with cyclophosphamide and dexamethasone is an effective therapy for recurrent indolent lymphoma. This combination produces prolonged T-lymphocytopenia and has the potential to reactivate a latent EBV infection. T-cell dysfunction, however, is not associated with higher incidence of clinical opportunistic infections and does not adversely influence clinical outcome.

Background and Objective: In multiple myeloma (MM) patients treated with conventional chemotherapy, the attainment and duration of a plateau phase seems to affect survival more than the degree of response to initial treatment. The aims of this study are: 1) to analyze within a cohort of previously untreated MM patients the incidence and the duration of the plateau phase; 2) to correlate it with the presenting features; 3) to assess its impact on survival., Design and Methods: A series of 146 consecutive MM patients treated with conventional chemotherapy were evaluated for this study. Of 146 patients, 102 responded (13 achieving complete response, 21 partial response, and 68 minimal response), and 44 showed less than minimal response or a progression. A plateau phase was documented in 115 patients (comprising all responders and 13 non responders. The median plateau phase duration was 21.6 months. The majority of patients received intermittent cycles of chemotherapy (melphalan or interferon) during the plateau phase. In multivariate analysis, lytic lesions, response, and time to the best response (TBR) correlated with the attainment of a plateau, while stage, response as a whole, and TBR showed a significant correlation with the duration. In contrast, the type of response did not correlate with either the attainment or the duration of plateau. To analyze the prognostic impact of presenting features, response to therapy and plateau we used a hierarchical model for survival. The analysis showed that the response to therapy and the duration of plateau significantly affect the survival., Interpretation and Conclusions: In multiple myeloma a plateau phase of at least 6 months' duration has a higher impact on survival than the degree of response to conventional chemotherapy so plateau duration could be used as target of therapeutic trials. The best way to maintain the plateau phase remains, however, undefined.

Objective: To assess whether intrauterine insemination (IUI) improves the fertility rates in women with unexplained infertility., Study Design: We recruited 68 women with unexplained infertility and allocated them randomly to treatment with three to five cycles of superovulation plus IUI (36 patients) or superovulation alone (32 patients). Superovulation was obtained with clomiphene citrate, human menopausal gonadotropins and human chorionic gonadotropins., Results: The cycle fecundity rate was 10% in patients who underwent superovulation alone and 19% in those treated with superovulation plus IUI (P < .05)., Conclusion: Our results demonstrate that superovulation plus IUI is more effective than superovulation alone in the treatment of unexplained infertility.

We analyzed the postoperative modifications of dysmenorrhea in 90 patients with septate or subseptate uterus, but no other genital or pelvic disorders, who underwent metroplasty according to Tompkins (n = 28) or hysteroscopic metroplasty (n = 62). The frequency of dysmenorrhea fell from 50% to 32.1% after the Tompkins' procedure and from 54.8% to 17.7% after hysteroscopic metroplasty. The severity of dysmenorrhea evaluated with two scales, one linear and one multidimensional, showed a significant postoperative decrease in both the groups. In view of the limited cost and low risks of hysteroscopic metroplasty, primary dysmenorrhea associated with septate or subseptate uterus may be considered an indication for this intervention.

Objective: To evaluate reproductive prognosis after hysteroscopic metroplasty., Design: The cumulative proportions of women who became pregnant and gave birth, subdivided according to previous obstetric history, were calculated by the product limit method and compared using the log rank test., Setting: Outpatient infertility clinic of Milan University., Patients: One hundred two consecutive patients with complete (n = 23) or partial septate uterus (n = 79) referred because of infertility or repeated abortion., Intervention: Hysteroscopic metroplasty performed by microscissors (n = 80), argon laser (n = 10), or electroresectoscope (n = 12)., Main Outcome Measures: Postoperative cumulative pregnancy and birth rates., Results: At 36 months the cumulative pregnancy and birth rates were 89% and 75%, respectively, in the septate uterus group and 80% and 67% in the subseptate uterus group., Conclusions: Reproductive prognosis after hysteroscopic metroplasty was favorable and not influenced by the malformation subclass.

Objective: To evaluate the diagnostic capability of transvaginal ultrasonography in detecting diffuse adenomyosis., Design: We compared the preoperative transvaginal ultrasound (US) findings and the pathological findings of the surgical specimen in a series of women who underwent hysterectomy for menorrhagia., Patients: Forty-three women (mean [+/- SD] age of 46 +/- 5) with recurrent menorrhagia and enlarged uterus, without evidence of uterine leiomyomas at abdominal US and of endometrial disease at vabra curettage., Setting: Tertiary care center, university medical school., Main Outcome Measures: Sensitivity, specificity, predictive positive and negative values of transvaginal US in the diagnosis of diffuse adenomyosis., Results: The sonographer diagnosed adenomyosis in 22 patients, whereas the pathologist found adenomyosis in 20 women, confirming the US findings in 16 cases and making an ex novo diagnosis in 4. The sensitivity of transvaginal US was 80%, the specificity 74%, the predictive value of a normal test 81%, and that of an abnormal test 73%., Conclusions: Transvaginal US seems to represent a real advance in the preoperative diagnosis of diffuse adenomyosis.

We studied the endometrial structure and ultrastructure in serial biopsies from 16 patients with endometriosis treated with danazol (n = 9) or the combination cyproterone acetate plus ethinyl estradiol (n = 7) for 6 months. Biopsies were performed before and at 3 and 6 months of treatment. The material obtained was studied by light (LM), scanning (SEM) and transmission electron microscopy (TEM). A morphometric analysis was performed evaluating three morphometric and three stereologic indices. The results indicate that danazol had a progestational effect on endometrial glands and stroma, associated with a marked hypotrophy of the mucosa. The cyproterone acetate/ethinyl estradiol combination induced progressive atrophy of the endometrium with an increase in the stromal component and a reduction of glandular tissue.

Until now the indication for hysteroscopic metroplasty has been based on laparoscopic findings and thus depended on the operator's experience. Using ultrasound and magnetic resonance images of double uteri it should be possible to find more objective indications for this operation. When three points are identified on longitudinal scans of the uterine fundus, the two tubal ostia and the mid-point of the fundal perimetrium, hysteroscopic metroplasty is indicated only in uteri in which the third point is at least 5 mm above a straight line drawn between the tubal ostia. This classification criterion includes more cases than laparoscopic criteria in this study; we performed hysteroscopic metroplasty in 23 double uteri and had we followed the laparoscopic criteria the operation would have been performed only in 19.

Forty-two women with symptomatic uterine myomas, candidates for myomectomy or hysterectomy, were randomized to 6 months' treatment with buserelin 1200 micrograms/day intranasally (n = 22) or immediate surgery (n = 20). After buserelin treatment or operation the patients were followed for at least 12 months. Buserelin was well tolerated, the uterine volume fell from 465 +/- 168 to 273 +/- 88 cm3, and hemoglobin values normalized in all anemic patients. Rapid myoma regrowth was observed in all patients in the buserelin group after treatment withdrawal. Pregnancy occurred during follow-up in one of five buserelin-treated myomectomy candidates. Menorrhagia recurred in eight of 15 buserelin-treated hysterectomy candidates, and a hysterectomy was required but no transfusion was needed. Two women entered natural menopause and were considered cured. In the surgery group all operations were uneventful: three women conceived after myomectomy, whereas four of the patients that underwent hysterectomy required transfusions. Thus buserelin treatment appears to be indicated for infertile patients when surgery is contra-indicated or could cause adhesions, and for hysterectomy candidates in perimenopausal age and/or with secondary anemia.

We performed a follow-up hysteroscopy with multiple biopsies at different intervals after surgery in 19 women who underwent hysteroscopic septal incision. Seven days after operation the sectioned areas were very evident and not epithelialized (3 patients). At 14 days, the incised zone was depressed with scattered epithelialization (5 subjects). At 1 month, the sectioned surfaces were still depressed and uniformly covered by thin endometrium (5 cases). After 2 months the uterine cavity was almost normal with minimal tendency to central fundal adhesions (6 women). Thus, spontaneous healing processes after hysteroscopic metroplasty progressed regularly and completely and there is probably no reason to delay attempts at pregnancy for longer than two cycles after surgery.

Laparoscopy was performed on 126 women with undiagnosed chronic pelvic pain. Abnormalities were demonstrated in 62.7% of the cases. Endometriosis was present in 32.5% of the women. Laparoscopy is useful in the differential diagnosis of chronic pelvic pain and is indicated when symptoms persist for over 6 months.

To investigate whether a primary endometrial factor is involved in the pathogenesis of infertility in patients with minimal or mild endometriosis, we compared light, scanning, and transmission electron microscopic studies of preovulatory endometria of 15 endometriotic patients with 12 normal controls. All the women were infertile and normo-ovulating by standard criteria. Six morphometric indexes were considered. The scanning electron microscopic analysis revealed heterogeneity of the endometrial surface epithelium in 77% of the patients with endometriosis and in 16% of the controls. Glandular and stromal mitoses, basal vacuolated cells, and the ciliated:nonciliated cell ratio was significantly reduced in the endometriosis group compared with the controls. Further studies are needed to clarify the role of the observed endometrial anomalies in the pathogenesis of infertility associated with endometriosis.

We analyzed the prevalence of dysmenorrhea, pelvic pain, and dyspareunia in relation to the disease stage in 160 women with endometriosis but no other associated pelvic disease who underwent their first gynecologic surgery (laparoscopy or laparotomy) at the First Obstetric and Gynecology Clinic of the University of Milan between 1985 and 1987. Dysmenorrhea was reported by 78% of the patients, pelvic pain by 39%; and deep dyspareunia by 32%. No relation was found between severity of the pain symptoms and stage of the disease or site of the endometriotic lesions.

Menorrhagia is the most frequent symptom in women with leiomyomata uteri. We induced transient hypoestrogenism with a gonadotropin-releasing hormone agonist, goserelin (Zoladex, I.C.I.), in a depot formulation, to resolve severe anemia in 16 women with uterine myomas. Subcutaneous administration of goserelin 3.6 mg was repeated every 28 days for 6 months. Thirteen patients became amenorrheic in 5 weeks and 3 reported scanty bleeding. Estradiol fell to postmenopausal levels after one month's treatment with hormonal surges on only three occasions. Uterine volume decreased by 49% after 3 months' treatment but subsequent reduction was not achieved. Mean hemoglobin rose from 7.4 g/dl pretreatment to 13.2 g/dl at 3 months (+78.3%) and mean hematocrit from 26.1% to 39.8% (+52.4%) without any further improvement. Serum ferritin increased constantly during the 6 months. Goserelin depot therapy in severely anemic patients with leiomyomas and menorrhagia is practical, safe and may avoid the need for preoperative transfusion.

A total of 62 infertile women with a laparoscopic diagnosis of endometriosis were allocated randomly to two treatment groups, one of which (32 patients) received oral danazol 600 micrograms/day and the other (30 patients) received intranasal buserelin 1200 micrograms/day for 6 months. Suppression of serum levels of estradiol was greater with the gonadotropin-releasing hormone agonist treatment. Pain symptoms improved markedly during treatment in both groups. At the end of treatment a repeat laparoscopy was performed only in the patients who agreed to it (12 in the buserelin group and 13 in the danazol group), and it did not reveal significant differences in the effects of the two treatments on the endometriotic implants. All of the patients were followed up for at least 12 months, during which pregnancy was attempted. At 18 months the cumulative pregnancy rate was 48% in the patients treated with buserelin and 43% in those treated with danazol. Pain recurrence was observed in about half of the patients in each group 1 year after treatment suspension. The side effects were more frequent and more severe in the danazol-treated patients, whereas those given buserelin generally reported only symptoms of hypoestrogenism. The results of this study suggests that buserelin is at least as effective as danazol in the treatment of endometriosis when the outcome is considered in terms of restored fertility, and its side effects are less severe.

Thirty-nine infertile patients with laparoscopic diagnosis of endometriosis were allocated randomly to treatment with gestrinone 2.5 mg twice weekly (20 patients) or danazol 600 mg/day (19 patients) for 6 months. If amenorrhea was not obtained after 1 month of treatment, the gestrinone dose was increased to 2.5 mg three times a week (7 patients) and the danazol dose to 800 mg/day (2 patients). One month after the end of the treatment, a repeat laparoscopy was performed only in the women who agreed (7 of the gestrinone treated group, 9 of the danazol group). All of the patients were followed for at least 12 months after the end of the treatment, during which time they attempted to conceive. There was a marked improvement of pain symptoms during the treatment in the patients of both groups. The repeat laparoscopy did not reveal significant differences between the two groups in the reduction of the disease extent. Eighteen months after treatment suspension, the cumulative pregnancy rate was 33% in the patients treated with gestrinone and 40% in those treated with danazol. Pain symptoms recurred during the follow-up in 57% of the gestrinone and 53% of the danazol group. The side effects were more frequent and severe with the danazol treatment, whereas those caused by gestrinone were mostly weight gain and acne. The results of this study suggest that gestrinone is as effective as danazol in the treatment of infertility associated with endometriosis and is better tolerated.

Seventy-one women underwent follow-up laparoscopy for persistent infertility six to 24 months after conservative treatment of endometriosis. The disease was staged according to the revised American Fertility Society classification of 1985. The serum CA 125 concentration was also measured in each patient to evaluate its efficacy in the diagnosis of endometriosis recurrence. The patients with stages I and II endometriosis had serum CA 125 levels not significantly higher than in the patients with negative findings, whereas those with stages III and IV endometriosis presented significantly higher levels (P less than .005 and P less than .001, respectively) than the disease-free women. The sensitivity of serum CA 125 measurements in the diagnosis of endometriosis recurrence was 14.8%, the specificity was 100%, and the predictive values of normal (less than 35 U/mL) and elevated levels were 27 and 100%, respectively. In some cases, serum CA 125 measurements may be used instead of follow-up laparoscopy, or to indicate when laparoscopy should be performed or postponed.

Chronic pelvic pain (CPP) in adolescent women is a frequent complaint. We assessed the value of laparoscopy in the differential diagnosis of CPP in 47 adolescents 11-19 years old after six months or more of cyclic or acyclic pelvic pain. No pelvic abnormalities were detected in 19 patients (40.4%), endometriosis was detected in 18 (38.3%) (frequently with nonpigmented or "nonclassic" lesions), partially obstructive genital tract malformations were found in 4 (8.4%), and other types of pathology were discovered in 6 (12.8%). Nearly 60% of the patients had a treatable pelvic disease. Laparoscopy is an invaluable tool in the diagnosis of CPP in adolescents and should be performed before starting a psychiatric evaluation or prescribing long-term medical treatment.

GnRH agonists, synthetic peptide analogs of GnRH, desensitize pituitary receptors for the native molecule, thus causing reversible hypogonadotropic hypogonadism. Numerous clinical studies have suggested that these compounds are efficacious in the treatment of endometriosis, but it is not clear whether they are superior to the other drugs used in treatment of this disease. The frequency of recurrence of pain symptoms at the end of treatment is high and the data on recovery of fertility are conflicting. Long-term administration of GnRH agonists is a safe and well tolerated treatment but its role in the management of endometriosis is still not well defined.

Ca 125 levels in serum and peritoneal fluid were measured in 39 patients with endometriosis and 18 patients with normal pelvic anatomy at laparoscopy, and the presence of this antigen in endometriotic tissue and endometrial mucosa was also investigated. Serum CA 125 concentrations were elevated in patients with Stage III or IV endometriosis compared with control subjects (32.9 +/- 11.2 versus 16.4 +/- 8.9 U/ml, means +/- SD; p less than 0.001). CA 125 values were greater than 35 U/ml in 36.8% of women with Stage III or IV endometriosis and in none of the control subjects. No significant differences in CA 125 levels in peritoneal fluid were found between patients with endometriosis and control subjects. The immunohistochemical studies found CA 125 in 10% of the endometriotic lesions and 37.5% of the endometrial samples of patients with endometriosis and in 33.3% of the endometrial samples of control subjects.

Twenty-three patients with laparoscopically diagnosed endometriosis and pelvic pain were allocated randomly to treatment with cyproterone acetate 27 mg plus ethinyl estradiol 0.035 mg/day (11 patients) or danazol 600 mg/day (12 patients). All women received treatment for 6 months, except for one in the cyproterone group who suspended treatment for nonmedical reasons and was excluded from analysis of the results. The clinical condition and pain symptoms were monitored in all patients for 1 year after treatment suspension. The intensity of pelvic pain at diagnosis, during treatment, and at follow-up was evaluated by a multidimensional verbal score and an analogue scale. At the end of treatment, a repeat laparoscopy was performed in those patients who agreed (four in the cyproterone group, five in the danazol group); the results showed a partial regression of endometriotic lesions in both groups, with no significant differences between them. Dysmenorrhea disappeared in all patients during treatment. At 6 months after suspension, dysmenorrhea recurred in 66% of the cyproterone group and 58% of the danazol group, and at 1 year in 89 and 92%, respectively. Intermenstrual pelvic pain improved markedly during treatment in both groups; 6 months after treatment withdrawal it was present in four cyproterone subjects and four danazol group patients, whereas after 1 year, only one woman in the danazol group did not have this symptom. Deep dyspareunia was less affected by treatment, and 6 months later had recurred in all the women.(ABSTRACT TRUNCATED AT 250 WORDS)

A hysteroscopic second look has been performed following sixteen intracavitary myomectomies, twenty-nine metroplasties and thirty-four intra-uterine adhesiolyses. This control has been performed three months after laparotomic operation and after forty-five days of sequential estro-progestogen treatment in cases of transcervical operation. The hysteroscopic second-look proved to be an excellent follow-up method after uterine conservative surgery and it avoids the use of X-rays, allows a detailed morphological evaluation of the uterine cavity and offers the possibility of complementary surgery, when necessary.

Seventy-two teeth from 10 ovarian mature teratomas and 12 unerupted and erupted teeth from subjects aged 8 to 21 years were examined at the scanning electron microscope to evaluate the morphologic and histogenetic differences. The ultrastructure of the teratomatous teeth was similar to that of the corresponding orthotopic tissues. Despite this similarity the morphology of the teratomatous teeth was much less well defined, attesting to the inductive effect of the contiguous tissues that are normally present in the oral cavity.

Serum Ca-125 levels were measured in 154 patients undergoing laparoscopy or laparotomy for infertility and/or pelvic pain. Pelvic endometriosis at various stages was observed in 102 of the patients, and 52 had a visually normal pelvis and served as a control group. We found a significantly higher mean serum Ca-125 concentration in the patients with stages III and IV endometriosis compared with the controls (P less than 0.001) whereas in the patients with stages I and II disease the mean antigen level was comparable to that of the control group. Considering its low sensitivity (14.7%) the usefulness of serum Ca-125 measurements as an initial diagnostic test for endometriosis is scanty. On the contrary, because of its elevated specificity (100%), this test may be useful in indicating early surgical exploration of the pelvis in cases of infertility and/or dysmenorrhea which are associated with high values of Ca-125.

The presence of CA 125 was investigated in endometriotic tissue and endometrial mucosa using two different immunohistochemical methods, indirect immunofluorescence and the avidin-biotin immunoperoxidase technique. Neither of the methods revealed the antigen in the 12 endometriotic fragments studied. The endometrial mucosa both of patients with endometriosis and of the control subjects was positive with indirect immunoperoxidase staining in all cases, whereas with indirect immunofluorescence it was positive in 75 and 67%, respectively. Thus the mechanism(s) responsible for distribution of the antigen in different tissues and its reported high serum levels in advanced endometriosis is still unclear.

Hysteroscopic metroplasty seems the treatment of choice for septate uterus. Little information is available on the possible usefulness of postoperative intrauterine device (IUD) insertion and estrogen administration in preventing fusion of a freshly cut septum and intrauterine adhesion formation. A hysteroscopic incision in a uterine septum was made in 20 women. Postoperatively an IUD was inserted in ten of them and conjugated estrogens administered for 30 days with medroxyprogesterone acetate on days 26-30 (group I); the other ten were given no other therapeutic measures (group II). On follow-up hysterography five women in group I had a normal uterine cavity, and five had a residual fundal notch greater than or equal to 1 cm. In group II four had a normal uterine cavity, and six had a residual fundal notch greater than or equal to 1 cm. No intrauterine adhesions were detected in any of the patients. IUD insertion and hormonal therapy after hysteroscopic metroplasty do not seem to be needed to prevent septal fusion.