A. Lissoni

A prospective study of the role of ultrasound in the management of adnexal masses in pregnancy

Objective To assess the clinical relevance of adnexal masses in pregnancy and the usefulness of ultrasound in their management.

A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study

BACKGROUNDnThe efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control.nnnPATIENTS AND METHODSnIn all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with < or = 3 mm stromal invasion (PR1)] or suboptimal response.nnnRESULTSnPatient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III-IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3-4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP.nnnCONCLUSIONnTP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.

Neoadjuvant chemotherapy with cisplatin, ifosfamide and paclitaxel for locally advanced squamous-cell cervical cancer

BACKGROUNDnNeoadjuvant chemotherapy is increasingly being used for the treatment of bulky and locally-advanced cervical cancer. Cisplatin and ifosfamide are known to be effective in cervical cancer, while paclitaxel is one of the promising new drugs for the treatment of this neoplasm.nnnOBJECTIVEnTo assess the toxic effects and antitumor activity of a multidrug neoadjuvant regimen consisting of cisplatin, ifosfamide, and paclitaxel in bulky and locally advanced cervical cancer.nnnPATIENTS AND METHODSnThirty-eight patients with pathology-confirmed squamous-cell cervical cancer (27 IB2-IIA, two IIB, eight IIIB, one IVA) were prospectively enrolled in the study. Their treatment consisted of paclitaxel 175 mg/m2 given over three hours on day 1, cisplatin 50 mg/m2 (75 mg/m2 in 10 patients), ifosfamide 5 g/m2 in a 24-hour continuous infusion and mesna 5 g/m2 in a 24-hour continuous infusion on day 2, and mesna 3 g/m2 in a 24-hour continuous infusion on day 3. The course was repeated every three weeks for three courses and all of the patients, except those with disease progression or who were inoperable, were scheduled for radical hysterectomy and pelvic lymphadenectomy.nnnRESULTSnAll patients are evaluable for response. Eleven achieved clinical complete responses, 21 had partial responses, five had stable disease and one had progression of disease. Of 34 patients who underwent surgery, six (16%) had pathology-documented complete responses, seven (18%) had partial responses with only microscopic residual disease in the cervix, 19 had sub-optimal partial responses, and two had stable disease, for an overall response rate of 84% (95% confidence intervals (CI): 68.7%-94%). Grade 3-4 neutropenia was recorded for 27 (71%) patients, grade 3-4 thrombocytopenia for four (10.5%), and grade 2 peripheral neuropathy for two (2.5%). At a median follow-up of 16 months (range 7-22), 29 (76%) women are alive without recurrence, seven are alive with persistent/recurrent disease and two have died of their disease.nnnCONCLUSIONSnAccording to pathology examination, this regimen yields a 34% complete and optimal partial response rate with acceptable toxicity, and it should be prospectively compared to other regimens.

Cisplatin-, epirubicin- and paclitaxel-containing chemotherapy in uterine adenocarcinoma

PURPOSEnTo evaluate the toxic effects and antitumour activity of a multidrug regimen with cisplatin, epirubicin and paclitaxel (CEP) as initial therapy in patients with uterine adenocarcinoma.nnnPATIENTS AND METHODSnForty-nine patients with histologically-confirmed diagnoses of locally advanced, recurrent or metastatic cervical or endometrial adenocarcinoma entered the study. Treatment consisted of epirubicin (E) given at 70 mg/m2 followed by paclitaxel (P) (175 mg/m2 over three hours) and cisplatin (C) (50 mg/m2), repeated every three weeks. Eligibility criteria also included age < or = 75 years, no previous chemotherapy, no previous radiotherapy to the tumour parameters, bidimensionally-measurable lesions, no previous or ongoing cardiac disease, and renal and liver function within normal limits. Complete blood cell counts were repeated weekly, and tumor response was assessed every three cycles. A maximum of eight courses was administered in responding patients.nnnRESULTSnFrom January 1996 to January 1997, 30 patients with endometrial adenocarcinoma and 19 with cervical adenocarcinoma entered the study, for a total of 213 cycles of treatment. In patients with endometrial carcinoma the overall clinical and pathological response rates were 73% (95% CI, range 54%-88%) and 35% (95% CI, range 16%-57%) respectively; in patients with locally advanced cervical carcinoma the overall clinical and pathological response rates were 64% and 62%. WHO grade 3-4 neutropenia occurred in 61% of the patients, with one possible toxic death. Retreatment had to be delayed for at least one week because of persisting neutropenia in 34% of the patients. Mild peripheral neuropathy and stomatitis were observed in 46% and 23% of the patients. One patient presented acute congestive heart failure after the third cycle of treatment.nnnCONCLUSIONnThe high antitumour activity and the good tolerability of CEP suggest that this regimen should be prospectively compared to standard combinations as initial treatment of advanced endometrial carcinoma.

Paclitaxel, ifosfamide and cisplatin (TIP) chemotherapy for recurrent or persistent squamous-cell cervical cancer

PURPOSEnThe results of salvage chemotherapy for recurrent or persistent squamous-cell cervical cancer are unsatisfactory. Cisplatin and Ifosfamide are effective compounds in cervical cancer. Paclitaxel has recently been tested with promising results. The aim of this study was to assess the efficacy of a combination of paclitaxel, ifosfamide and cisplatin (TIP) for persistent/recurrent squamous-cell cervical carcinoma in a phase II trial.nnnPATIENTS AND METHODSnForty-five women were treated with the TIP regimen. Thirty-one had received prior irradiation. Paclitaxel was given at a dose of 175 mg/m2, ifosfamide at a dose of 5 g/m2, and cisplatin at a dose of 75 mg/m2 (50 mg/m2 in irradiated patients) at three-week intervals.nnnRESULTSnWe observed 15 clinical complete responses, 15 partial responses, 9 stable diseases and 6 progressions. The objective response rate was 67% (95% confidence interval: 51%-81%). Ten complete responders underwent subsequent surgery and seven had pathology-defined complete responses (two in irradiated areas). The response rate was 52% in irradiated and 75% in non-irradiated areas. The median survival for non-responders is 6 months, 9+ month for partial responders and 13+ for complete responders. The most relevant side effect was myelotoxicity, with 91% of patients experiencing grade 3-4. One woman had life-threatening toxic effects.nnnCONCLUSIONSnThis combination is highly effective for salvage treatment in non-irradiated patients. For irradiated women the response rate is higher than that observed with other regimens but further investigation is warranted. The toxicity is relevant but adequate hydration and prolonged infusion of ifosfamide make it acceptable.

From Conventional Radiotracer Tc-99 m with Blue Dye to Indocyanine Green Fluorescence: A Comparison of Methods Towards Optimization of Sentinel Lymph Node Mapping in Early Stage Cervical Cancer for a Laparoscopic Approach

AbstractBackgroundnThe credibility of sentinel lymph node (SLN) mapping is becoming increasingly more established in cervical cancer. We aimed to assess the sensitivity of SLN biopsy in terms of detection rate and bilateral mapping in women with cervical cancer by comparing technetium-99 radiocolloid (Tc-99m) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG).MethodsData of patients with cervical cancer stage 1A2 to 1B1 from 5 European institutions were retrospectively reviewed. All centers used a laparoscopic approach with the same intracervical dye injection. Detection rate and bilateral mapping of ICG were compared, respectively, with results obtained by standard Tc-99m with BD.ResultsOverall, 76 (53 %) of 144 of women underwent preoperative SLN mapping with radiotracer and intraoperative BD, whereas 68 of (47 %) 144 patients underwent mapping using intraoperative ICG. The detection rate of SLN mapping was 96 % and 100 % for Tc-99m with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99m with BD; this difference was statistically significant (p < 0.0001).ConclusionsThe fluorescence SLN mapping with ICG achieved a significantly higher detection rate and bilateral mapping compared to standard radiocolloid and BD technique in women with early stage cervical cancer. Nodal staging with an intracervical injection of ICG is accurate, safe, and reproducible in patients with cervical cancer. Before replacing lymphadenectomy completely, the additional value of fluorescence SLN mapping on both perioperative morbidity and survival should be explored and confirmed by ongoing controlled trials.

Surgical resection of solitary brain metastasis from ovarian carcinoma: An analysis of 22 cases

OBJECTIVEnCentral nervous system (CNS) involvement is considered an uncommon complication in patients with ovarian carcinoma. The aim of this study was to evaluate prognostic factors for survival following surgical resection of brain metastases in patients with ovarian carcinoma.nnnMETHODSnA retrospective chart review was conducted on 22 patients who had been submitted to neurosurgical resection of a solitary brain metastasis from ovarian carcinoma.nnnRESULTSnEighteen lesions were cerebral, 4 were cerebellar. CNS was the only site of disease in 9 patients, 9 patients had CNS and abdominopelvic disease, and 4 also had concomitant extraperitoneal dissemination. Following surgery, 17 received whole-brain radiotherapy and 5 received systemic chemotherapy. Median survival from diagnosis of cerebral metastasis for the entire series was 16 months (range, 4-41 months). Extracranial disease at the time of CNS metastasis and time interval between diagnosis of ovarian cancer and CNS involvement manifestation were the only factors significantly affecting survival.nnnCONCLUSIONSnNeurosurgical resection of brain metastasis from ovarian carcinoma is indicated in solitary lesions in the absence of systemic disease. The role of chemotherapy and stereotactic radiosurgery should be investigated.

Modified radical hysterectomy versus extrafascial hysterectomy in the treatment of stage I endometrial cancer: results from the ILIADE randomized study

BackgroundFive percent to 20% of stage I endometrial cancer patients undergoing total abdominal hysterectomy and bilateral salpingo-oophorectomy develop vaginal and pelvic recurrences. Adjuvant radiotherapy can improve locoregional control but not survival. This randomized trial aimed to determine whether a modified radical (Piver–Rutledge class II) hysterectomy can improve survival and locoregional control compared to the standard extrafascial (Piver–Rutledge class I) hysterectomy.MethodsEligible patients (nxa0=xa0520) with stage I endometrial cancer were randomized to class I or class II hysterectomy. Primary endpoint was overall survival.ResultsThe median length of parametria and vagina removed were 15 and 5 vs. 20xa0mm and 15xa0mm for class I and class II hysterectomy, respectively (Pxa0>xa00.001). Operating time and blood loss were statistically significantly higher for class II hysterectomy. At a median follow-up of 70xa0months, 51 patients had died. Five-year disease-free and overall survival were similar between arms (87.7 and 88.9% in the class I arm and 89.7 and 92.2% in the class II arm, respectively). The unadjusted hazard ratios for recurrence was 0.91 (95% confidence interval, 0.55–1.51, Pxa0=xa00.72), and the hazard ratio for death was 0.77 (95% confidence interval, 0.44–1.33, Pxa0=xa00.35).ConclusionsClass II hysterectomy did not improve locoregional control and survival compared to class I hysterectomy, but when an adequate vaginal cuff transection is not feasible with class I hysterectomy, a modified radical hysterectomy allows to obtain an optimal vaginal and pelvic control of disease with a minimal increase in surgical morbidity.

Changes in the management and outcome of central nervous system involvement from ovarian cancer since 1994

To identify differences in the management and outcome of patients with central nervous system metastases from epithelial ovarian cancer.

Potential role of BCL2 in the recurrence of uterine smooth muscle tumors of uncertain malignant potential

Uterine smooth muscle tumors are the most common female genital tract neoplasms. While leiomyosarcoma has been studied at length, smooth muscle tumors of uncertain malignant potential (STUMPs) still have ambiguous and unresolved issues, with a risk of relapse and evolution largely undefined. We performed an array comparative genomic hybridization analysis on a primitive STUMP and its local recurrence, histologically diagnosed as undifferentiated sarcoma. To the best of our knowledge, our report is the first genomic study on primitive STUMPs and the different relapsed tumors. The results showed few copy number alterations shared between both samples and the high heterogeneity in the STUMP was apparently lost in the sarcoma. Surprisingly the STUMP presented an amplification of the BCL2 gene, not observed in the relapsed tumor. Additionally, fluorescence in situ hybridization and immunohistochemical staining were performed to confirm BCL2 amplification and expression in these samples and in two other cases of primitive STUMPs and their corresponding relapsed tumors. The presence of BCL2 in multiple copies and expression in the two primitive STUMPs and two relapsed tumors was confirmed. The marked amplification of the BCL2 gene present in the primitive STUMP and the multiple copies also observed in other cases, suggest its potential role as a marker of STUMP malignant potential and recurrence.