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.

Gastrointestinal stromal tumors mimicking gynecological masses on ultrasound: a report of two cases.

Gastrointestinal stromal tumors (GISTs) are among the most common mesenchymal tumors of the gastrointestinal tract. Diagnosis of GIST on ultrasound examination can be difficult because of their similarity in appearance to gynecological neoplasms. We present two cases of GIST originating from the small bowel and the stomach, which were preoperatively misdiagnosed as a uterine leiomyoma and an ovarian tumor, respectively. The ultrasonographic differential diagnosis of these pelvic masses is discussed.

[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.

A dominant ovarian follicle induces unilateral changes in the origin of the blood supply to the tubal corner of the uterus.

BACKGROUND: The blood supply to the tubal corner of the uterus may originate from the uterine and ovarian arteries. The border of supply from the arteries has been found to move in young women; the change seemed dependent on ovarian steroid production. The present work investigated whether the border of supply could differ between the two sides of the uterus in the same woman having one dominant follicle (>10 mm). METHODS: Vagina was flushed with saline of room temperature in 15 women with a dominant follicle >10 mm. The temperature was measured in the mid-uterine lumen and in the tubal corner of the uterus at 2, 5 and 7 min after starting cooling. The investigation was repeated 30 min later measuring the temperature in the other tubal corner. RESULTS: The temperature decrease was, as found in previous investigations, more pronounced in the uterine cavity than in the tubal corners. However, a difference was found between the two tubal corners. At all measurement times the decrease was significantly smaller in the tubal corner corresponding to the dominant follicle than in the contralateral side. CONCLUSIONS: In our model, 'cold' is transferred from the vaginal venous blood to the uterine artery and the cooling defines the supply area of the uterine artery. Therefore, the results indicate that the area of supply from the ovarian artery in the tubal corner ipsilateral to the dominant follicle is greater than that in the contralateral side. It is possible to speculate that this difference is related to the hormonal production of the dominant follicle.

[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.

[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.

[Polycystic mesothelioma of the peritoneum. Description of 4 cases]. / Mesotelioma multicistico del peritoneo. Descrizione di quattro casi.

Cystic mesothelioma is a rare tumor of the peritoneal cavity arising from mesothelial cells. About 130 cases have been reported in the literature. The tumor is more frequent (85%) in adult women and rarely occurs in children. It is benign but recurrences are often described. The differential diagnosis with adenomatoid tumors, lymphangiomas, cystic malignant mesotheliomas and metastatic serous cystic tumors of the ovary is supported by immunohistochemistry. We describe four cases of cystic mesothelioma of the peritoneum; two of the cases occurred in pregnant women, one in a 45-year-old man and one in a 5-year-old boy. Asbestos exposure was not documented. The mesothelial origin of the neoplasms was supported by immunohistochemical analysis. Furthermore, tests for simian virus 40 (SV40 T antigen), to determine whether this virus was also present in the lesions, were negative.

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.

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.

[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.

Alexithymia, immunity and cervical intraepithelial neoplasia: replication.

BACKGROUND: In a previous study [Psychother Psychosom 1994;61:199-204] we investigated the relationship between alexithymia, carcinogenesis and immunity in a group of women who were unconscious sufferers from precancerous lesions of the cervix (CIN). The results of this study showed a high level of association between alexithymia and CIN and, an even more interesting fact, between alexithymia and reduced levels of immunity. METHODS: The aim of the present study is to check the results of the previous one by testing a larger group (43 women affected by cervical dysplasia and 67 healthy women) and by the use of a self-administered test for detection of alexithymia, the well-validated Twenty-Item Toronto Alexithymia Scale (TAS-20). RESULTS: The results confirm that women suffering from CIN have higher average TAS-20 ratings (55) than normal women (47.32) and that the level of alexithymia detected in the group of women suffering from dysplasia (42.5%) is higher than that of normal women (12.85%). Moreover, the present study confirms that alexithymic women have lower rates of a number of lymphocyte subsets than non-alexithymic women. CONCLUSIONS: This study fully confirms the results of our previous work and those of a number of other studies: (1) personality might be one of the factors jointly responsible for the outbreak of cancer; (2) the immune system appears to play an important part as a mediator between personality and cancer.

Exocervical pregnancy.

A case of cervical pregnancy with implantation of the fertilized ovum on the exocervix is described. This pregnancy was mistaken for an endometriotic lesion and treated by simple surgical excision. Discussion is centered on etiology, predisposing factors and management.

Solitary intracranial metastases from primary endometrioid ovarian cancer.

A rare case of involvement of the Central Nervous System characterized by brain and subsequent cerebellar metastases without abdomino-pelvic spread is reported. The patient was treated by craniotomy plus external radiation to the brain. Subsequently, Carboplatin-based chemotherapy was started when paraaortic lymph-nodes involvement has been detected. Follow-up is uneventful after clinical complete remission.

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.

[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.

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.

[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.

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.

[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.