Tertiary cytoreductive surgery in recurrent epithelial ovarian cancer: A multicentre MITO retrospective study.

OBJECTIVES: To evaluate the impact of tertiary cytoreductive surgery (TCS) on survival in recurrent epithelial ovarian cancer (EOC), and to determine predictors of complete cytoreduction. METHODS: A multi-institutional retrospective study was conducted within the MITO Group on a 5-year observation period. RESULTS: A total of 103 EOC patients with a ≥6month treatment-free interval (TFI) undergoing TCS were included. Complete cytoreduction was achieved in 71 patients (68.9%), with severe post-operative complications in 9.7%, and no cases of mortality within 60days from surgery. Multivariate analysis identified the complete tertiary cytoreduction as the most potent predictor of survival followed by FIGO stage I-II at initial diagnosis, exclusive retroperitoneal recurrence, and TCS performed ≥3years after primary diagnosis. Patients with complete tertiary cytoreduction had a significantly longer overall survival (median OS: 43months, 95% CI 31-58) compared to those with residual tumor (median OS: 33months, 95% CI 28-46; p<0.001). After multivariate adjustment the presence of a single lesion and good (ECOG 0) performance status were the only significant predictors of complete surgical cytoreduction. CONCLUSIONS: This is the only large multicentre study published so far on TCS in EOC with ≥6month TFI. The achievement of postoperative no residual disease is confirmed as the primary objective also in a TCS setting, with significant survival benefit and acceptable morbidity. Accurate patient selection is of utmost importance to have the best chance of complete cytoreduction.

Long-term follow-up is crucial after treatment for granulosa cell tumours of the ovary.

OBJECTIVE: The aim of this study is to evaluate the long-term outcome of granulosa cell tumour (GCT) of the ovary in a large series of patients treated in MITO centres (Multicentre Italian Trials in Ovarian Cancer) and to define prognostic parameters for relapse and survival. METHODS: A retrospective multi-institutional review of patients with GCTs of the ovary treated or referred to MITO centres was conducted. Surgical outcome, intraoperative and pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival and recurrence. RESULTS: A total of 97 patients with primary GCT of the ovary were identified. The median follow-up period was 88 months (range 6-498). Of these, 33 patients had at least one episode of disease recurrence, with a median time to recurrence of 53 months (range 9-332). Also, 47% of recurrences occurred after 5 years from initial diagnosis. At multivariate analysis, age and stage were independent poor prognostic indicators for survival; surgical treatment outside MITO centres and incomplete surgical staging retained significant predictive value for recurrence in both univariate and multivariate analyses. CONCLUSIONS: This study confirms the generally favourable prognosis of GCTs of the ovary, with 5-year overall survival approaching 97%. Nevertheless, prognosis after 20 years was significantly poorer, with 20-year survival rate of 66.8% and a global mortality of 30-35. These findings support the need for lifelong follow-up even in early-stage GCT.

[Sonoembryological criteria in the evaluation of gestational age]. / Utilizzo di criteri sonoembriologici nella valutazione dell'età gestazionale.

AIM: The progressive appearance of specific embryological structures has been successfully used to define the ultrasonographic gestational age (GA). In our study we have revised this technique by comparing our results with the ones from Warren et al. obtained in 1989. Aim of the study is to evaluate the accuracy of this technique when applied working with new instrumentations and average skilled sonographers. METHODS: Sixty-five pregnant women with correct GA ranging between 4 and 12 weeks have been observed between April 2003 and March 2004. We exposed them to an ultrasound examination looking for these structures in terms of presence/absence: gestational sac, yolk sac, embryo pole with cardiac activity, thromboencephalic cavity, falx cerebri and physiologic midgut herniation. We used transvaginal sonography (TVS) until 11 weeks of GA, from 11 weeks + 1 day we switched to transabdominal sonography (TAS). We have compared our results with the ones published by Warren et al. RESULTS: Gestational sac's visualization has been possible between 4 weeks+3 days/5 weeks of GA. Yolk sac has been visualized between 5 weeks+4 days/6 weeks of GA, embryo with cardiac activity has been observed between 5 weeks+6 days/6 weeks+2 days of GA, romboencephalic cavity has been visualized between 7 weeks and 7 weeks+5 days, falx cerebri has been detected between 9 weeks+1 day/10 weeks+3 days. Visualization of physiologic midgut herniation has been possible between 8 weeks+3 days/8 weeks+6 days; it disappeared between 10 weeks+3 days/11 weeks +1 day. CONCLUSIONS: Although the technological improvement in the US equipment in the last 15 years and the combination of TVS with TAS, there has been no advanced visualization of those single embryological structures. Indeed there has been a reduction of the time range during which those structures have been visualized. This improvement might have important practical implications in the ultrasonographic assessment of GA.

[Uncommon etiology of acute abdomen in pediatric age: the torsion of spleen]. / Una causa non comune di addome acuto in età pediatrica: la torsione splenica.

The torsion of spleen on its vascular shank represents an uncommon problem, responsible of acute and chronic pain. The mobile spleen is fixed only through hilus vessels the gastrosplenic ligament. The incidence is unknow, greater in the male with an M:F ratio 6.1 in the first ten years of life, even if an episode of intrauterine torsion has been reported. The diagnosis can be performed with ultrasonography, angiography, scintigraphy and CT scan. There are reported two cases: male of 2.5 years female of 14 years who presented with recurrent pain to the left side, vomit diarrhoea and fever. Objectively a palpable mass was present. Ultrasonography and angio-CT scan of abdomen revealed splenomegaly, ptosis of the spleen and malrotation with signs of obstruction of the vessels. The treatment in both cases was splenectomy. The spleen appeared rotated on its shank and increased of volume, deprived of anatomical structures of fixation. The histological report confirmed the haemorrhagic infarction. The excessive mobility of the spleen, from insufficiency or absence of the ligamentous attachments is case of abdominal pain or acute abdomen, that can complicate with the infarction of the spleen. Angio-CT scan, in the cases here reported, has shown to greater sensibility in comparison to the ultrasonography. The Authors believe that the video-laparoscopic splenopexy, when the diagnosis is made of "wandering spleen" with painful repeated episodes, can be finalized, to the preservation of organ.

Value of quantitative analysis of mitral regurgitation jet eccentricity by color flow Doppler for identification of flail leaflet.

Early surgical intervention improves the outcome of patients with mitral regurgitation (MR) secondary to flail leaflet. Current criteria for the diagnosis of flail leaflet require a detailed definition of mitral valve anatomy, which is often challenging by transthoracic echocardiography (TTE) and, occasionally, even by transesophageal echocardiography (TEE). We studied 57 patients (mean age 63 +/- 15 years) with anatomically confirmed flail mitral leaflet and a control group of 57 patients (mean age 68 +/-14 years) with at least moderate MR but no flail leaflet. In patients with flail mitral leaflet, the mean angle formed by the axis of the MR jet and the plane of the mitral annulus was 33 +/- 11 degrees and 29 +/- 16 degrees when measured with TTE and TEE, respectively. In controls the mean angle was 66 +/- 16 degrees and 66 +/- 17 degrees by TTE and TEE, respectively (p <0.0001). Based on receiver- operating characteristic analysis, the optimal cutoff jet angle value for diagnosing flail mitral leaflet was 45 degrees with TTE (sensitivity 88%, specificity 88%), and 47 degrees by TEE (sensitivity 88%, specificity 88%). MR jet angles < or =45 degrees were also correctly identified by visual assessment of TTE images in >90% of cases, with good interobserver agreement (k = 0.76). Thus, quantitative analysis of MR jet eccentricity by color flow Doppler is highly sensitive and specific for diagnosing flail mitral leaflet.

Gonadotrophin releasing hormone (GnRH) receptor and steroid receptors in human uterine leiomyoma, myometrium and endometrium.

The present study evaluated the presence of GnRH-R in leiomyomas, in associated, non-involved uterine tissues (myometrium and endometrium) and the possible relationships between GnRH-R and the receptors for estrogen and progesterone in the same tissues. GnRH-R was found in all uterine tissues and both GnRH and the GnRH analog, goserelin, displaced its binding consistent with a single type of high affinity receptor (Kd approximate to 10(-8) M). GnRH-R were found more frequently in myometrium (81% of samples) than in endometrium (58%) or leiomyoma (42%). However, the mean receptor content was lowest in myometrium (139+/-19 fmol/mg protein) with both leiomyomas (288+/-77 fmol/mg protein) and endometrium (372+/-96 fmol/mg protein) having significantly higher values. Endometrial GnRH binding varied from 596+/-42 in uteri that were GnRH-R positive in the endothelium alone to 231+/-49 when GnRH-R was present also in the other tissues. Endometrium negative for the GnRH-R had significantly higher levels of estrogen receptor than all the other uterine samples (266+/-25 vs 61+/-7.5 fmol/mg protein, respectively). Endometrial GnRH-R seem to be dependent on its presence and/or level in other uterine tissues. Further, when GnRH-R is absent in the endometrium this tissue expresses greatly increased levels of steroid receptors.

Cervical mucus secretory IgA in adenomatous polyp, intraepithelial neoplasia and squamous cell carcinoma of the cervix.

Cervical mucus secretory IgA concentration ([sIgAc]) was significantly higher in 36 CIN (cervical intraepithelial neoplasia) patients than in 360, age, reproductive status and smoking habit-matched controls. Also, CIN ranked first compared with adenomatous polyp (29 cases), primary or secondary invasive esocervical carcinoma (IEC) (21), ectropion/erosion (49) and specific (27) or aspecific (80) cervicitis. CIN carried the highest proportion of cases with [sIgAc] detectable (86%) or beyond the cut-off value (33%) (IEC: 14% and 0%, respectively). [sIgAc] was inversely related to CIN grade and higher, though nonsignificantly, in patients with HPV-positive CIN biopsy specimens. Histologic and immunologic factors can account for the differences in [sIgAc] observed within the spectrum of neoplastic lesions of the cervix.

Preoperative evaluation of ferritinemia in primary epithelial ovarian cancer.

AIMS AND BACKGROUND: High ferritin serum levels have been reported in patients suffering from various malignancies. The aim of this study was to evaluate the role of ferritinemia in the preoperative diagnosis of ovarian carcinoma. METHODS: Between March 1993 and September 1996, 60 patients suffering from ovarian carcinoma were surgically treated at our Department. Their ferritin serum levels were measured preoperatively by a solid-phase, two-site chemiluminescent immunometric assay and compared with those of a group of 60 healthy, age-matched, non pregnant controls. RESULTS: The mean serum concentration of ferritin was 54.7 +/- 7.8 ng/ml (range, 14-135) in healthy controls and 112.3 +/- 21.2 ng/ml (range, 9-947) in patients with ovarian carcinoma. The difference was statistically significant (P = 0.005, X2 test = 7.951). Serum ferritin was elevated preoperatively (cutoff > or = 120 ng/ml) in 18/60 patients with malignancy (sensitivity 30%), whereas the CA 125 levels were above the cutoff in 53/60 patients (sensitivity 88.3%). Only 2/60 women of the control group had ferritin titers > 120 ng/ml (specificity 96.7%). The ferritin levels increased with advancing disease stage; no significant correlation was found between ferritin concentration and neoplastic histology and grading. The mean serum iron levels were also measured preoperatively in patients with ovarian carcinoma and healthy controls. They were 57.2 +/- 3.8 and 66.3 +/- 2.61 micrograms/dl, respectively, and the difference was not significant (P = 0.655, X2 test = 0.200). CONCLUSIONS: The present study underlines that although ferritin shows an elevated specificity, its low sensitivity does not suggest any true usefulness as a tumor marker in epithelial ovarian cancer.

Simplified ondansetron regimens for antiemetic prophylaxis in cisplatin-based chemotherapy of ovarian cancer.

In past years prevention of emesis and nausea induced by antiblastics has been based on extremely heterogeneous protocols with little efficacy. However, by the use of selective antagonists of serotonin S3 receptors there has been a remarkable improvement in the control of side effects. Among these antagonists ondansetron has been till now the most studied. The dosage protocols with which it has usually been employed establish an i.v. administration of the drug of 1 mg/h for 24 hours or the repetition of ondansetron 0.15 mg/kg x 2 every 2-4 hours after the end of chemotherapy. In our study, carried out from September 1991 till September 1992, 21 patients affected by ovarian carcinoma and treated by cisplatin chemotherapy protocols were evaluated (for a total of 63 cycles). Ten patients were under first line adjuvant chemotherapy treatment, whereas 11 patients were in relapse and had already undergone previous antiblastic treatments with serious side effects. In 18 out of 21 patients cyclophosphamide which has a strong emetic factor was associated with cisplatin. According to the total quantity of cisplatin contained in each cycle (in all < or =/> 100 mg) we used ondansetron in two different dosages simplified and shortened in time. They have been illustrated with particular details in the text. The control of nausea and vomiting during the first 24 hours was similar to the controls obtained in other studies in which ondansetron was administered according to the "traditional schemes".(ABSTRACT TRUNCATED AT 250 WORDS)

Leuprolide acetate as a salvage-therapy in relapsed epithelial ovarian cancer.

A large number of studies have been conducted in patients affected by epithelial ovarian cancer to assess the potential utility of a variety of different regimens in patients who have relapsed after primary surgery and adjuvant chemotherapy. In this open prospective study, 32 patients with ovarian cancer of epithelial histology who had relapsed after platinum-based line chemotherapy and had exhausted all standard treatments, received Leuprolide acetate depot 3.75 mg, intramuscularly once a month until tumor progression. Four patients (12.5%) had clinical and/or radiological partial response; remission was then maintained for a mean duration of 8.7 months (range 6-11 months) before new progression occurred. Five patients (15.6%) remained stable for a mean time of 5.2 months (range 4-6 months) and 23 patients (71.9%) continued to progress following therapy and have since died by tumor with a median survival of 3.6 months after initiation of the protocol. Treatment is well-tolerated and no toxicity has been noted. These data stress the significant activity of Leuprolide acetate as a salvage therapy in patients with relapsed advanced epithelial ovarian cancer after previous platinum-based chemotherapies.

Serum progesterone, estradiol-17beta and testosterone at the time of relapse in patients with epithelial ovarian cancer.

Raised levels of steroid hormones may be detected in women with ovarian cancer at the time of diagnosis. The goal of this study was to investigate the levels of progesterone, testosterone and estradiol-17beta in patients with relapsed epithelial ovarian cancer. We studied 52 patients with a histologic diagnosis of ovarian cancer; 46 of 52 patients were affected by epithelial tumors, two patients had sexcord-stromal tumors, one patient had a germ cell tumor and three patients had a metastatic cancer from the bowel. Of 34 patients with disease relapse, none had elevated serum testosterone levels (>1 ng/ml), one patient (2.9%) had an elevated serum progesterone level (>1.24 ng/ml) and two patients (5.9%) had elevated estradiol-17beta levels (>28 pg/ml). The relationship between the three hormone levels at the time of initial treatment and at relapse was tested using the Students's t-test. At the time of initial treatment venous concentrations of progesterone, estradiol-17beta and testosterone were higher and statistically different (p<0.05) from samples obtained at the time of relapse in the same patients. No significant differences were found between patients studied at the time of relapse and the control group. Measurement of progesterone, estradiol-17beta and testosterone is not helpful in detecting disease relapse in patients with epithelial ovarian cancer.

[The estimation of LHRH receptors in the tissue of human leiomyoma, myometrium and endometrium]. / Valutazione dei recettori per LHRH nel tessuto di leiomioma, miometrio ed endometrio umano.

Uterine leiomyoma is the most common female benign pelvic tumor, affecting 20-25% of women during their reproductive years. There is strong clinical evidence that these tumors are estrogen-dependent for their growth, as also supported by their clear regression after the menopause. Although large clinical trials have not yet been reported, according to the estrogen dependency of uterine fibroids, LHRH agonists have been shown to be effective in the treatment of these conditions because they produce a condition of temporary hypoestrogenism secondary to the specific hypogonadotrophinism. This study was designed to evaluate if specific binding sites for LHRH are present in human uterine leiomyomata, myometrium and endometrial tissue. These tissues were taken from the fresh operative specimens of 14 patients who had undergone total hysterectomy for uterine leiomyomata. The results of this study demonstrate the presence of a LHRH specific binding site in uterine leiomyomata in 26% of cases; this specific binding site is also present both in myometrium and in endometrial tissue in 71% of cases. Moreover our study shows, for the first time, the high specificity of binding between LHRH agonist (goserelin) and natural LHRH receptor. In accordance with our results, a direct effect of LHRH agonists on fibroid tissue can be stressed.

[Abdominal pregnancy. An ever present challenge]. / La gravidanza addominale. Una sfida sempre attuale.

A case of abdominal pregnancy resulting from the rupture of the atresic horn of a bicornuate uterus and asymptomatic till the 23rd week of amenorrhea is reported. The peculiarities of this case lie in the advanced gestational age and in the association between two pathologies undoubtedly unusual as cornual and abdominal pregnancy. Discussion is focused on the limits of classical obstetrical semeiology, the possibilities of the instrumental examinations, the criteria that should guide decision-making and on the correct surgical management of this uncommon even if potentially life-threatening clinical pathology.

[Peroperative diagnosis of pure retroperitoneal neurinoma misdiagnosed as uterine leiomyoma]. / Diagnosi intraoperatoria di neurinoma puro a sviluppo retroperitoneale pelvico confuso con leiomioma uterino.

A case of pure neurinoma of the retroperitoneal space developing in the pelvis is described. This tumor (phi max, 15 cm) responsible for intense compressive symptomatology involving the pelvic organs, was at first mistaken for a uterine fibroid. The ultimate diagnosis both of neurinoma as well as every other neoplasm originating in the retroperitoneum can sometimes be very hard to obtain. Those tumors can indeed be misdiagnosed for other more common conditions both clinically and instrumentally and the rarity of this particular localization adds further trouble to the matter.

[Kerion of the vulva. Report of a case and review of the literature]. / Kerion a localizzazione vulvare. Descrizione di un caso e revisione della letteratura.

We report a case of a 43 year old woman who developed an extensive vulvar kerion caused by Trichophyton menthagrophytes that was initially mistaken for a bacterial infection. The peculiarity of this case lies in the fact that the kerion is rarely located in the vulva and it has not yet been described in the literature. On the contrary, cases have been found in the scalp, beard, eye-brow, etc. We discuss the etiopathogenetic aspects, criteria for differential diagnosis and therapy management of this rare clinical picture.

[Uncomplicated pregnancy in patients with unrecognized primary biliary cirrhosis]. / Gravidanza non complicata in paziente con cirrosi biliare primitiva misconosciuta.

A 32 yr-old woman suffering from an unsuspected primary biliary cirrhosis (PBC), completed an uneventual pregnancy. She only experienced diffuse pruritus and subicterus, which misled to an antepartum diagnosis of intrahepatic cholestasis of pregnancy. The most remarkable points of the reported case are: (a) the younger age of onset of PBC; (b) the paucisymptomatic course of PBC; (c) the rarity of PBC-associated pregnancy (only 15 previous instances in 12 patients, from a review of the literature); (d) the uncomplicated course of pregnancy for both the mother and the fetus, which is the exception rather than the rule, in such a condition. The present observation calls our attention to the possible existence of an underlying latent liver cirrhosis in pregnant women with pruritus, jaundice and mild alterations of liver function indexes. This association, which is expected to increase in frequency in the near future, may have important implications in the management of pregnancy.

[Blood groups of the ABO system and survival rate in gynecologic tumors]. / Gruppi sanguigni del sistema ABO e sopravvivenza nei tumori ginecologici.

A retrospective analysis of 968 women affected by gynecological tumors was conducted to assess the existence of a difference in survival between patients with different blood groups. Data are presented on 237 cases of endometrial cancer, 92 cases of ovarian cancer and 639 cases of invasive cervix cancer, detailing their ABO blood antigenic phenotypes, the stage of neoplasia and the treatment received. With regard to endometrial cancer, a sensibly better 5-year and 10-year survival is associated with blood group 0 if compared with blood group A. This finding is more evident when 5-year survival is considered among patients affected by ovarian cancer. With regard to cervical cancer, analysis showed that a little better than 5-year survival is associated with 0 blood phenotype; on the contrary, when a 10-year or longer survival is considered, a better survival is associated with A blood phenotype. The present study confirms evidence of an association between the A blood group and gynecological tumors. Endometrial and ovarian cancer occur more frequently in women with blood type A than in those with the other blood types, moreover, in the same tumors blood group A is associated with a poor prognosis. The possible reason for these findings are discussed with detailed regard to the possible biological importance that, at present, is conferred to the ABO group system in the complex activities of the immune system.

[Meckel's diverticulum in childhood. The authors' own experience]. / Diverticolo di Meckel in età pediatrica. Esperienza personale.

Meckel's diverticulum occurs in approximately 2 percent of the population and may present at any age. Although Meckel's diverticulum may produce an intestinal obstruction or perforation, simulating an appendicitis, hemorrhage is its most important clinical presentation. From 1989 to 1994, Meckel's diverticulum was discovered in ten children at laparotomy. Three cases were asymptomatic, representing an incidental finding at laparotomy. Of the seven symptomatic patients, four presented with bowel obstruction (intussusception), three had rectal bleeding one of whom had diverticulitis. Contrast studies--in gastrointestinal hemorrhage--were not helpful in establishing the diagnosis; colonoscopy and gastroscopy ruled out other causes of bleeding. Five of seven symptomatic patients had an intestinal resection while two a diverticulectomy after assessment that the ulcer did not require resection. No postoperative morbidity and mortality is reported in either groups. A Meckel's diverticulum found incidentally at laparotomy should be always resected as the risk of complication is high and that of resection low.

[Esophageal atresia and tracheoesophageal fistula: personal contribution]. / Atresia esofagea e fistola tracheoesofagea: contributo personale.

From January 1988 to December 1999, 21 new born babies, 13 boys and 8 girls, with esophageal atresia (EA) and tracheosophageal fistula (TEF) were treated at Division of Pediatric Surgery in Foggia (Italy). At birth their weight ranged from 1.600 to 3.000 g, the gestional age ranged from 36 to 41 weeks. Five (23%) of them were premature, seven (58%) SGA, seventeen (80%) associated congenital anomalies. Complete surgical correction was performed in all patients. In three AE cases with wide-gap an azygos vein flap was used to strengthen the anastomosis under excessive tension. The pathogenetic factors involved in these complications such as leak, stricture (stenosis), recurrent TEF and gastro-esophageal reflux are (are taken into account) and analysed. No baby died owing to anastomatic complication. Survival rate was 100% in Montreal I and 83% in Montreal II. A new born baby died but his death was due to major associated conenital anomalies and not to surgical complications. The Authors believe that the azygos vein flap is a useful technique in the treatment of esophageal atresia wide-gap.

[Intestinal invagination in childhood: our experience]. / Invaginazione intestinale in età pediatrica: esperienza personale.

The Authors report their experience in the treatment of twenty-one patients with intussusception operated in the Paediatric Surgery Division ASL FG/3 between January 1988 and December 1994. Eighty-nine percent of the patients were between 2 and 12 months of age, with a peak between 2 and 6 months (60%). Ultrasound allowed to identify the pathological picture in forty-two percent of the cases and diagnosis was confirmed by barium enema. In 8 patients a pathology more or less responsible of the intussusception or associated with it was detected. The time between the onset of symptoms and admission as well as the relation between intestinal resection and duration of symptomatology were analyzed. The resection rate was maximal (55%) in those patients presenting symptoms beyond 25 hours. Intestinal resection was performed in 9 patients (47%): 6 ileo-colic; 1 ileo-colic resection extended to the splenic flexure; and 2 ileo-ileal ones. In this series no postoperative complications or recurrences or deaths were registered. Long term results proved that ileo-colic resection, even in few-months old infants, is well tolerated.