Maria Giovanna Salerno

Long-term analysis of clinical outcome and complications in locally advanced cervical cancer patients administered concomitant chemoradiation followed by radical surgery

OBJECTIVE Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases. METHODS Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters. RESULTS Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4. CONCLUSION Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

The expression ratios of estrogen receptor α (ERα) to estrogen receptor β1 (ERβ1) and ERα to ERβ2 identify poor clinical outcome in endometrioid endometrial cancer

The prognostic relevance of estrogen (ER) and progesterone receptor (PR) expression in endometrioid endometrial cancer is still controversially discussed. The present study has focused on the evaluation of the prognostic value of ERα, ERβ1, ERβ2, and PR in this histotype. Specifically, we were interested in evaluating whether the relative level of ER subtype-specific expression (in terms of a ratio ERα/ERβ1 and ERα/ERβ2) would predict clinical outcome better than their absolute levels in patients with endometrioid endometrial cancer. To this end, protein content was assessed by immunohistochemistry in a group of 121 cases and staining was analyzed in relation to clinicopathologic variables, disease-free survival and overall survival. Results obtained have demonstrated that none of the biological markers analyzed possess an independent prognostic role with regard to disease-free survival. Multivariate analysis of overall survival has shown that ERα alone is not an independent prognostic indicator in patients with endometrioid endometrial cancer (hazard ratio [HR]; 0.5; 95% confidence interval [CI], 0.09-3.0; P = .5). On the other hand, an ERα/ERβ1 ratio of 1 or less or an ERα/ERβ2 ratio of 1 or less has proved to be independently associated with a higher risk of death (HR, 6.4 [95% CI, 1.0-40.6; P = .04] and 9.7 [95% CI, 1.1-85.3; P = .04], respectively) along with age, tumor stage, and Ki-67. In conclusion, we report here that the ERα/ERβ1 and ERα/ERβ2 expression ratios are independent prognostic markers of survival in endometrioid endometrial cancer; these findings suggest that phenotyping these interacting markers conjointly may better predict patient survival than each individual marker alone.

Secondary analyses from a randomized clinical trial: age as the key prognostic factor in endometrial carcinoma

OBJECTIVE The purpose of this study was to explore in greater depth the outcomes of the Italian randomized trial investigating the role of pelvic lymphadenectomy in clinical early stage endometrial cancer. In the attempt to identify the patients with poorer prognosis, the impact of age and body mass index were also thoroughly investigated by cancer-specific survival (CSS) analyses. STUDY DESIGN Survival outcomes of trial patients were analyzed in relation to age (≤65 years and >65 years) in the 2 arms (lymphadenectomy and no lymphadenectomy) and in the whole population of the trial. RESULTS Univariate and multivariable analyses of CSS and overall survival (OS) of patients showed that age >65 years is a strong independent poor prognostic factor (5-y OS 92.1% and 78.4% in ≤65 years and >65 years patients, respectively, P < .0001; 5-y CSS 93.8% and 83.5% in ≤65 years and >65 years patients, respectively, P = .003). Among women ≤65 years, node negative patients had 94.4% 5-y OS and 96.3% 5-y CSS vs 74.3% 5-y OS and 74.3% 5-y CSS for node positive patients (P = .009 and P = .002, respectively), while among women >65 y, node negative patients had 75.7% 5-y OS and 83.6% 5-y CSS vs 74.1% 5-y OS and 83.3% 5-y CSS for node positive patients (P = .55 and P = .58, respectively). Univariate and multivariable survival analyses in the whole trial population showed that older age, and higher tumor grade and stage were significantly associated to a worse prognosis. CONCLUSION Older women faced an intrinsic poorer survival whether or not they underwent lymphadenectomy, and, unexpectedly, irrespective of the presence of nodal metastasis. Only in older patients was obesity (body mass index >30) significantly associated with scarce prognosis.

High-dose Chemotherapy with Autologous Peripheral Stem Cell Support in Advanced Ovarian Cancer

Twenty patients with advanced (stage III-IV), previously untreated ovarian carcinoma were treated by: (a) induction chemotherapy (40 mg/m2 cisplatin, days 1-4; 1.5 g/m2 cyclophosphamide, day 4; every 4 weeks for two cycles) followed by (b) intensification chemotherapy (100 mg/m2 cisplatin, day 1; 650 mg/m2 etoposide, day 2; 1.8 g/m2 carboplatin, day 3). Eligibility criteria further included: age less than 55 years, moderately good to poor tumour grade, macroscopic (> 0.5 cm) residual tumour. Autologous peripheral stem cells were recruited after the induction cycles and, to ensure haematological support, autologous bone marrow harvesting was routinely performed in the first 14 cases. Haematological support consisted of autologous peripheral stem cells and autologous bone marrow transplant in 16 and four patients, respectively. All patients are evaluable for toxicity and 19 for pathological response, one being dead of systemic mycosis 35 days after the autologous bone marrow transplant. Severe extra-haematological toxicities were the following: gastrointestinal (100%), neurological (10%), hepatic (10%). Pathological response was detected in 84% of cases (CR 37%, microscopic PR 26%, macroscopic PR 21%). Median follow-up times of 48 and 41 months have been reached respectively from enrolment and second-look. Four-year 62% overall and 57% progression-free survivals have been reached. Ten patients are still alive with NED (six of seven with CR, three of five with microscopic PR, and one of four with macroscopic PR). Autologous peripheral stem cell transplant significantly reduced the duration of aplasia compared with autologous bone marrow transplant, and toxicity was proved to be manageable in those patients undergoing autologous peripheral stem cell transplant. The prolonged disease-free survival in patients showing CR and microscopic PR suggests that further investigation on this new approach is worthwhile.

Perioperative outcomes of total laparoendoscopic single-site hysterectomy versus total robotic hysterectomy in endometrial cancer patients: A multicentre study

OBJECTIVE To compare the peri-operative outcomes between total laparo-endoscopic single-site (LESS) and robotic approaches for the staging and treatment of early stage endometrial cancer patients. METHODS A multicentre retrospective study involving three Italian gynaecological groups and one American centre. The peri-operative outcomes of LESS and robotic approach were compared in similar groups of patients, with regard to surgical outcomes and intra- and post-operative parameters and complications. RESULTS During the study period, 75 patients submitted to a total LESS hysterectomy and 75 patients received a total robotic hysterectomy. The median operative time - 122 versus 175 min (p=0.0001) - and the estimated blood loss - 50 versus 80 mL (p=0.03) - were slightly more favourable in the LESS group. The intra-operative complications were equally distributed (p=0.99); in the robotic group there were 4 (5.3%) post-operative grade IIIb complications versus 1 (1.3%) in the LESS group (p=0.172). CONCLUSIONS The LESS and robotic approaches both appear reasonable and each may have benefits and limitations depending upon the patient population. Further studies are needed to validate these preliminary conclusions.

Very high-dose chemotherapy with autologous peripheral stem cell support in advanced ovarian cancer

20 patients with stage III-IV ovarian cancer were submitted to induction chemotherapy (ICT) (40 mg/m2 cisplatin, days 1-4; 1.5 g/m2 cyclophosphamide, day 4; every 4 weeks for 2 cycles) followed by intensified CT (100 mg/m2 cisplatin, day 1; 650 mg/m2 etoposide, day 2; 1.8 g/m2 carboplatin by 24 h infusion, day 3). Haematological support consisted of autologous peripheral stem cells (APSC) and bone marrow (ABM) transplant (T) in 16 and 4 patients, respectively. All patients were evaluable for toxicity and 19 for pathological response (PR), one patient dying of systemic mycosis after ABMT. Severe (grade 3-4) non-haematological toxic effects were gastrointestinal (100%), neurological (10%) and hepatic (10%). PR was observed in 84% of patients (complete response 37%, partial response with microscopic residual disease 26%, partial response with macroscopic residual disease 21%). Five year overall survival was 60% and progression-free survival was 51% with 9 patients still disease-free (DFS). APSCT significantly reduced the duration of aplasia compared with ABMT, and toxicity was acceptable in those patients undergoing APSCT. The prolonged DFS in patients showing PCR suggests that this new approach may have a therapeutic impact.

Laparoscopic approach for peripartum hysterectomy.

Abnormal placentation is the most common indication for peripartum hysterectomy. To date, the approach described in the literature is laparotomy, which is associated with high morbidity and mortality. A 30-year-old gravida 4 para 3 had a postpartum diagnosis of placenta percreta. She was first treated conservatively. On day 3 after delivery, because of persistent vaginal bleeding, she underwent a laparoscopic hysterectomy. No postoperative complications occurred, and the patient was discharged on postoperative day 3. Laparoscopic peripartum hysterectomy could become the approach of choice in selected patients with abnormal placentation to avoid complications associated with laparotomy.

Robotic Management of Major Vessel Injury During Pelvic Lymphadenectomy

Laparoscopic management of major vessel lesion is a challenging task during pelvic lymphadenectomy, and conversion is frequently necessary. Robotic surgery overcomes the limits of laparoscopy in vascular suturing. We describe a case of a 79-year-old woman with stage IB G3 endometrial adenocarcinoma, where an external iliac vein injury occurred during pelvic lymphadenectomy. This is the first case report that describes robotic management of a major vascular injury during pelvic lymphadenectomy by use of endoscopic bulldog clamps and robotic intracorporeal vascular sutures.

Association between Helicobacter pylori infection and vulvar lichen sclerosus: a clinical comparative study

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Cathecol-O-methyltransferase inhibitors: another possibly useful pharmacological tool for treating Parkinson’s disease in pregnancy?

Experience on the effects of pregnancy on Parkinson’s disease (PD) and vice versa is scarce (Schrag and Schott 2006). In addition, there is controversy in the literature about neurological symptoms control, with various obstetrical outcomes. Nowadays, as women increasingly delay childbearing, and PD being an age-related disease, the prevalence of pregnant women with PD is likely to rise. The report of using a new medication would therefore provide additional information for practicing clinicians looking after pregnant women with PD. Medical schedules described during pregnancy include Levodopa/Carbidopa or Levodopa/Benserazide, also combined with dopamine agonists, Amantadine, Selegeline or dopamine agonist monotherapy (Schrag and Schott 2006). The United States of America Food and Drug Administration lists antiparkinsonian drugs in pregnancy category C. Category C means either: (1) studies on animals have shown potential risk to the foetus, (2) no well-controlled studies in humans have yet been published, (3) studies on humans and animals are unavailable. Regarding Entacapone, small animal reproduction studies have shown a teratogenic effect on the foetus and there are no adequate and well-controlled studies in humans (Hagell et al. 1998). Consequently, even if the real risk to human foetuses is unknown, potential benefits to the mother in terms of disease control may outweigh the potential risks to the foetus (Schrag and Schott 2006; Kranick et al. 2010). No major obstetrical complications have been reported on the use of Levodopa plus Carbidopa or Benserazide during pregnancy, whereas Amantadine has been associated with cardiovascular teratogenicity (Schrag and Schott 2006; Robottom et al. 2008; Kranick et al. 2010). The main published complications potentially linked to PD treatment during pregnancy are first-trimester spotting and spontaneous miscarriage, nausea and vomiting, as exhaustively reviewed by Hagell et al. (1998). This paper reports the case of a pregnant woman affected by early onset PD treated successfully with Levodopa, Carbidopa, and Entacapone, a Cathecol-O-MethylTransferase (COMT) inhibitor. Entacapone is a peripheral inhibitor of COMT, which reduces dyskinesias and motor fluctuations associated with degradation of Levodopa in the peripheral nervous system, contrasting the progressive shortening in the duration of Levodopa action described as ‘wearing off’ (Najib 2001). The main adverse events reported in patients assuming Entacapone are dopaminergic effects related to Levodopa increased bioavailability. These include involuntary movements and nausea that can be easily managed by decreasing the dosage of Levodopa. Main non-dopaminergic side effects are diarrhoea and abdominal pain (Schrag 2005).