Photodynamic therapy with M-ALA as non surgical treatment option in patients with primary extramammary Paget's disease.

INTRODUCTION: Extramammary Paget disease (EMPD) is a rare neoplasm of the skin that presents with erythematous or leukoplacic plaques causing pruritus and pain. Standard treatment is surgical but local failures and recurrences are frequent, leading to multiple mutilating surgeries. Aim of the study is to evaluate the effectiveness of photodynamic therapy (PDT) to obtain a clinical response and symptom control with a non surgical approach in these patients. MATERIALS AND METHODS: After disease extension evaluation and symptoms assessment women with EMPD were prospectively treated with aminolevulinic-acid methyl-esther (M-ALA) PDT. Clinical and symptoms response were evaluated after 3 cycles and after any further PDT. RESULTS: Thirty-two patients with vulvar EMPD underwent M-ALA PDT. In sixteen (50%) patients the lesion extended to the perineal and/or perianal area. After three courses of treatment, three patients (9.4%) had a complete resolution of the symptoms; 25 patients (78.1%) a partial resolution and a stable disease was recorded in four patients (12.5%). None of the patients had progression of disease. Both size of the lesion and EMPD associated symptoms decreased significantly after three courses of treatment. Eighteen patients (56.2%) recurred and 16 (88.9%) were treated with further PDT. Among the 26 patients who underwent a further PDT, 16 patients (61.5%) achieved at least a partial response. CONCLUSION: M-ALA PDT even if not curative is a reliable strategy to control EMPD and its associated symptoms even in an outpatient setting. M-ALA PDT is able to control large and multiple lesions regardless of the area involved, preserving cosmetic and/or functional anatomy.

Diagnostic accuracy of sentinel node in endometrial cancer by using hysteroscopic injection of radiolabeled tracer.

OBJECTIVE: Retrospective and perspective series have shown the feasibility of sentinel lymph-node (SLN) identification of pelvic nodes in endometrial cancer using a cervical injection of tracers. We designed a perspective study to assess the detection rate and diagnostic accuracy of the SLN procedure by means of hysteroscopic injection of a radiolabeled tracer in endometrial cancer patients. METHODS: Patients with endometrial cancer underwent hysteroscopic technetium injection. SLN assessment was performed intraoperatively. A systematic pelvic and paraaortic dissection was carried out thereafter. SLNs were examined by standard and immunochemistry methods. The primary endpoint was estimation of sensitivity and negative predictive value (NPV) of sentinel-node biopsy. RESULTS: From 2005 to 2010, 80 consecutive patients entered the study. No severe complications occurred during or after the injection or during surgical SLN biopsy. At least one SLN was detected in 76 of the 80 eligible patients. Fifty nine patients were evaluable according to the study protocol. Ten of these patients (17%) had node metastases. Thirty-three patients (56%) had SLN in the para-aortic area. NPV was 98% (95% CI 89.4-100) and sensitivity 90% (55.5-99.8). CONCLUSIONS: SLN detection for endometrial cancer patients has a high sensitivity and NPV when injection is carried out by hysteroscopy. The occurrence of a 56% of sentinel node in paraaortic area may suggest a better sensitivity in this area using hysteroscopic injection compared to cervical injection.

Third-line chemotherapy with tyrosine kinase inhibitor (imatinib mesylate) in recurrent ovarian granulosa cell tumor: case report.

Granulosa cell tumors (GCT) of the ovary represent less than 5% of malignant ovarian tumors. Primary treatment of GCT is surgery. GCT present indolent growth and also tend to relapse many years after diagnosis. Radiotherapy, chemotherapy and hormonal therapy are of little benefit. We report a case of a 60-year-old woman with a heavily pretreated recurrent, c-kit positive, GCT of the ovary who underwent an experimental therapy with imatinib, a tyrosine kinase inhibitor. Imatinib (400 mg/day during the first 2 months; 800 mg/day after) was given, without notable side-effects. Monthly positron emission tomography-computed tomography scan evaluations were performed revealing a marked reduction of disease after 6 months of treatment. To our knowledge this is the first case of highly recurrent and unresponsive GCT of the ovary responding to imatinib. Further studies evaluating this drug in recurrent and/or aggressive GCT are warranted.

Class III NSRH: oncological outcome in 170 cervical cancer patients.

OBJECTIVE: To analyze local recurrence rate (LRR), morbidities and oncologic outcome of class III nerve-sparing radical hysterectomy. PATIENTS AND METHODS: 170 consecutive class III NSRH cases were performed. Nineteen patients were addressed directly to surgery whilst neoadjuvant chemotherapy was administered in 151 patients. The majority of patients had SCC (75%). The median follow-up was 31 months. RESULTS: The mean age was 50 [27-78] years. Mean post-operative hospital stay was 7 [3-16] days. 2 intraoperative complications occurred. Operating time and blood loss was similar to the state-of-the-art of conventional radical hysterectomy. Overall G3-4 complication rate was 8.2 % (14/170). Early G3-4 complication rate was 3.5% (6/170). Late G3-4 complication rate was: 4.7%. (8/170). Positive pelvic nodes were noted in 31 patients (18.2%). Vagina and parametrial involvement were present in 38 (22%) and 27 (15.8%) patients, respectively. LRR was 10% (17/170). The sites of relapse were: 12 pelvic, 5 vaginal. There were 9 patients DOD. The 2-year and 5-year DFS rates were 89% and 81%, respectively. Univariate and multivariate analysis identified vagina involvement and postoperative treatment as significant prognostic factors. CONCLUSIONS: The oncologic results of NSRH were similar to the state-of-the-art of conventional radical hysterectomy. Two years DFS in relation to FIGO stage of disease was 92.3, 89.2 and 86.1 % respectively for IB1, IB2, IIB comparable to literature data. The early and late complications rate related to autonomic injury was significantly lower. The nerve-sparing technique should be considered in all cervical cancer patients addressed to surgery.

Nerve-sparing radical vaginectomy: two case reports and description of the surgical technique.

BACKGROUND: Radical vaginectomy (RV) is related to significant bladder dysfunctions. We describe 2 cases of RV with nerve-sparing technique (NSRV). CASE REPORTS: A 58-year-old woman with a diagnosis of locally advanced cervical cancer underwent neoadjuvant chemotherapy with local and nodal progression of disease. The patient underwent NS radical hysterectomy plus NSRV, with prompt recovery of bladder function. A 14-year-old adolescent girl with a diagnosis of recurrent embryonal-botryoidal rhabdomyosarcoma was referred to us. She underwent 6 courses of chemotherapy with persistent disease. She then underwent NSRV. Two months after the surgical procedure, she was able to void the bladder. CONCLUSIONS: These are the first 2 cases of NSRV reported in literature. This new surgical technique is feasible, with prompt recovery of bladder function.

Quality of life and sexual, bladder, and intestinal dysfunctions after class III nerve-sparing and class II radical hysterectomies: a questionnaire-based study.

BACKGROUND: To compare quality of life and bladder, intestinal, and sexual dysfunctions in 2 groups of patients undergoing different types of radical hysterectomies (RHs). METHODS: Patients with cervical cancer who underwent RH have been enrolled in a questionnaire-based study. Quality of life (QoL) and bladder, intestinal, and sexual dysfunctions were evaluated with the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx). Patients were grouped according to the type of RH: group 1, class II RH and group 2, class III nerve-sparing RH (NSRH). RESULTS: Of 157 women included in the study, 127 filled out the questionnaire. Overall, QoL score assessed with the FACT questionnaire did not differ significantly between the 2 groups. The FACT subscales assessing physical, functional, emotional, and social well-being did not differ significantly between the 2 groups, whereas the FACT-Cx subscales assessing disease-related symptoms in group 2 patients showed a significantly worse score (72 vs 66; P = 0.03). Evaluating singularly the 15 items of the Cx subscales assessing disease-related symptoms, we did not find any significant difference between the 2 groups, but only Cx1 ("I am bothered by discharge or bleeding from my vagina") was significantly worse in group 2 patients. At univariate analysis, we found that NSRH and adjuvant radiotherapy (RT) impact negatively on the FACT-Cx subscales regarding pelvic visceral function. However, at multivariate analysis, only adjuvant RT impact negatively. CONCLUSIONS: Patients submitted to class III NSRH did not present worse QoL and pelvic visceral dysfunctions when compared with class II RH. The RT seems to be a factor impacting negatively on bladder and sexual function.

Surgical treatment of ovarian dermoid cysts: a comparison between laparoscopic and vaginal removal.

BACKGROUND: In the last years transvaginal ultrasonographic diagnosis of ovarian dermoid cyst together with laparoscopic approach have greatly improved the treatment of this benign lesion. Vaginal approach with laparoscopic assistance has been proposed as an alternative to total laparoscopic removal. METHODS: A retrospective comparison between total laparoscopic (56 patients) and direct vaginal removal (30 patients) of ovarian dermoids. RESULTS: There were few, but significant, advantages of vaginal removal, especially regarding operating time, intraperitoneal spillage of dermoid tissue and post-operative outcome. CONCLUSION: Vaginal approach to the removal of dermoid cysts can be considered a safe alternative procedure to laparoscopy.

In vivo detection of choline in ovarian tumors using 3D magnetic resonance spectroscopy.

OBJECTIVES: To assess the clinical feasibility of 3-dimensional (3D) proton magnetic resonance spectroscopy (MRS) of ovarian masses at 1.5 T. MATERIALS AND METHODS: We prospectively evaluated 16 patients with 23 ovarian masses using contrast-enhanced magnetic resonance imaging and 3D chemical shift imaging MRS (time of reception/time of echo = 700/135 ms, number of excitations = 6, interpolated voxel = 5 × 5 × 5 mm(3), water and fat suppression). Spectral editing consisted of water reference, filtering, zero-filling, Fourier transformation, frequency shift, automatic baseline and phase correction, and curve fitting. The volume of interest was placed to encompass both solid and cystic tumor components as well as apparently healthy pelvic tissues. The presence of a choline peak at 3.14 to 3.34 ppm was considered as a marker of malignancy. All patients underwent surgery and histopathological evaluation. RESULTS: Of 23 masses, 19 were malignant and the remaining 4 benign lesions were a fibrothecoma, an endometriosis, a cyst, and a cystadenofibroma. A choline peak was detected in 17/19 malignant tumors (sensitivity 89%), absent in 2 G1 tumors. It was visible in 16 solid components of 19 malignant tumors (in one of them, a choline peak was detected only in the cystic component, in 6 in both solid and cystic components). The choline peak was absent in 20/21 apparently healthy pelvic tissues, with a very low choline peak being detected in one intraperitoneal fluid collection with malignant cells at cytologic analysis; 3/4 benign tumors showed a choline peak (overall specificity 21/25 = 84%). A significant difference between the mean choline peak integral detected within the solid component and that within the cystic component was observed (P = 0.002). No correlation between the choline peak integral and the tumor size was found (r = 0.120, P = 0.615). CONCLUSIONS: 3D MRS of ovarian masses is clinically feasible at 1.5 T. This opens new research strategies for early diagnosis of ovarian cancer.

Analysis of two polymorphisms in the promoter region of matrix metalloproteinase 1 and 3 genes in women with endometriosis.

BACKGROUND: Matrix metalloproteinases are a family of proteolytic enzymes that can degrade extracellular matrix components and have been implicated in connective tissue remodeling associated with cancer invasion and metastasis. These proteins are also involved in the invasive events underlying endometriotic lesion formation and aggressive behavior. Given the established genetic background of endometriosis, the aim of this study was to examine the potential impact of two polymorphisms in the gene promoter region of two of these enzymes, matrix metalloproteinases 1 and 3, on predisposition and severity of the disease. METHODS: Genomic DNA was obtained from 56 Italian Caucasian women with a surgical diagnosis of endometriosis and a control group of 71 age-matched Caucasian healthy female blood donors. In control women, endometriosis was ruled out by evaluation of the medical history, gynecologic examinations, and ultrasound scanning. Two polymorphisms have been specifically investigated: 1. a single insertion polymorphism (2G) in the matrix metalloproteinase-1 promoter region known to elevate transcriptional level of matrix metalloproteinase-1; and 2. a single insertion/deletion polymorphism (5A/6A) located in the promoter of the matrix metalloproteinase-3 gene with functional significance in the regulation of its expression. Genotypes were determined by PCR amplification and sequence analysis. RESULTS: Allele and genotype frequencies of both polymorphisms did not significantly differ between endometriosis and control groups. Moreover, no significant difference for both polymorphisms was observed in relation to the clinical stage and recurrence status of the disease. CONCLUSIONS: This is the first study that has evaluated the possibility that gene variants of matrix metalloproteinases might be involved in the susceptibility to endometriosis. However, these results suggest that matrix metalloproteinases 1 and 3 promoter polymorphism do not constitute an important factor for the genetic predisposition to endometriosis and its invasive behavior in the Italian population.

Gemcitabine combined with oxaliplatin (GEMOX) as second-line chemotherapy in patients with advanced ovarian cancer refractory or resistant to platinum and taxane.

OBJECTIVES: The aim of this multicenter feasibility study was to determine the toxicity profile and antitumor activity of the gemcitabine plus oxaliplatin combination as second-line treatment in platinum plus paclitaxel resistant/refractory advanced ovarian cancer. METHODS: Twenty patients received a 30-60-min infusion of gemcitabine a week for 2 weeks, followed by 120-180 min infusion of oxaliplatin every 3 weeks. The doses used were 1,000 and 130 mg/m(2), respectively. Seventeen cases (85% of the total) were platinum resistant and 3 (15%) were platinum refractory. RESULTS: Grade 3/4 thrombocytopenia occurred in 14/20 of cases (70%); there were no symptomatic cases. 2 patients required platelet transfusion and 8 patients received hydrocortisone. The dose- limiting toxicity was thrombocytopenia. Combined grade 3/4 neutropenia was observed in 8/20 (40%) of cases (no sepsis was registered). Five patients were treated with recombinant erythropoietin because of grade 3 anemia and 4 cases received G-CSF prophylactically from the first cycle. The overall response rate of the combination in terms of antitumor activity was 26% (95% CI = 9-51%). CONCLUSION: A combination of gemcitabine and oxaliplatin using this schedule gave rise to a moderate/severe toxicity profile and would be feasible only if growth factors were used and/or gemcitabine were administered at lower doses. The antitumor activity of the combination was insufficient reward for the resultant toxicity profile. However, equivalent to that of other drugs used in platinum refractory and resistant patients.