Predictors of recurrence following laparoscopic radical hysterectomy for early-stage cervical cancer: A multi-institutional study.

OBJECTIVE: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). METHODS: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. RESULTS: 428 patients were included in the analysis. With a median follow-up of 56 months (1-162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01-1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34-20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11-0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01-1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58-24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12-0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13-0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39-17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. CONCLUSIONS: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study.

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.

Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.

117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).

Mitral valve repair for the treatment of degenerative mitral valve disease with or without prosthetic ring annuloplasty: long-term outcomes.

AIM: Aim of the study was to evaluate late outcomes of mitral valve repair with and without the use of prosthetic ring annuloplasty and standardized techniques for the treatment of degenerative mitral regurgitation (MR). METHODS: Three hundred and five patients (mean age 62 ± 12 years) underwent mitral valve repair between January 1992 and February 2010 for degenerative MR. In the last five years, all repair techniques were performed routinely using prosthetic ring annuloplasty, with or without quadrangular or triangular resection of posterior leaflet and/or edge-to-edge technique. Mean follow-up (99% complete) was 78 ± 46 (2-220) months. RESULTS: Operative mortality was 0.9% (3/305), 15-year actuarial survival 82% ± 4%. At 15 years freedom from cardiac death was 89% ± 3.7%, from reoperation 84% ± 5.8%, from endocarditis 100%. Independent predictors of all-causes mortality were advanced age at operation (P=0.0006) and mitral valve repair without reductive prosthetic annuloplasty (P=0.0019). Death for cardiac causes was significantly higher when reductive annuloplasty was performed without the use of prosthetic ring (P<0.01). Late progression to moderate or severe MR was observed in 23/299 patients (7.7%). Independent predictors of progression to moderate or severe MR was annuloplasty without the use of prosthetic ring (P=0.0053) and postoperative residual mild MR (P=0.0014). Reoperation was required in 13/299 patients (4.4%). At 10 years freedom from moderate or severe MR was 86% ± 6% and 92% ± 4% in patients with postoperative absent or trivial residual MR, respectively, as compared to 38% ± 15% in those with postoperative residual mild MR (P<0.0001), freedom from reoperation 94% ± 4% and 90% ± 14% vs. 56% ± 16% (P<0.0001). CONCLUSION: Prosthetic annuloplasty in association with standardized techniques confers over 10 years survival advantage and better durability.

Trace metals, peroxidase activity, PAHs contents and ecophysiological changes in Quercus ilex leaves in the urban area of Caserta (Italy).

Trace metals and polycyclic aromatic hydrocarbons, severely affecting human, animal and plants health, highly contribute to the air pollution in urban areas mainly due to car traffic. In this study the air biomonitoring of the city of Caserta (South Italy) has been performed by using Quercus ilex L., a widespread ornamental plant in parks, gardens and avenues. The plant leaves from different sites within the urban area were collected and used to determine the concentrations of V, Cd, Cr, Pb, Ni, Cu, and PAHs as well as the free amino acid content and peroxidase enzyme activity as indices of the leaf physiological conditions. All the tested trace metals showed concentrations higher than the control site. Lead was positively correlated to Cd and Cr and showed, also, a positive trend with Ni and Cu that, in their turn, were highly correlated between them. Positive and significant correlations were evidenced between total PAHs and carcinogenic PAHs and negative correlations between those and all trace metals assayed except V. Cu and Cd contents evidence negative correlations with peroxidase activity, and the free amino acid contents. The PAHs, in particular Carc-PAHs, were negatively correlated to the tested heavy metals. POD was positively correlated only with V and negatively correlated with Cu and Cd.

Multidetector computed tomographic coronary angiography as an alternative to conventional coronary angiography in non-coronary surgical patients.

AIM: Aim of our study was to evaluate multidetector 64-slice spiral computed tomography (MSCT) as an alternative to traditional coronary angiography (CA) to detect concomitant coronary artery disease (CAD) in patients initially admitted for non-coronary surgical procedures. METHODS: We have analyzed data of 380 consecutive patients operated from 2006 to 2008 initially admitted for aortic (N.=170) or mitral (N.=67) valve disease, ascending aorta aneurysm ± aortic valve disease (N.=99), and other (combined valve diseases, tumors; N.=44). These patients were submitted either to MSCT (Group CT, N.=112) or to CA (Group A, N.=268). Inclusion criteria to perform MSCT were no previous myocardial infarction or documented CAD, normal left ventricular function, sinus rhythm, less than 2-3 premature ventricular or atrial contractions /min. RESULTS: In Group CT, CAD was definitively excluded in 95 patients (85%) and was detected in 17; 8 of those 17 patients were subsequently submitted to CA and coronary artery bypass surgery for significant CAD. As compared to those in Group A, patients in Group CT were younger (64±15 vs. 70±10 years, P<0.0001), had less hypertension (P=0.0001), chest pain (P<0.05), peripheral vascular disease (P<0.05). NYHA class, incidence of diabetes, smoking habit, family history of CAD were similar. The incidence of operative mortality, postoperative myocardial infarction was not significantly different in both Group CT (0%) and A (0.4%) (P=NS). CONCLUSION: In selected cardiac surgical patients less invasive 64-slice MSCT can be with some limits an alternative to CA to rule out CAD, as confirmed by the absence of postoperative ischemic complications.

Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in locally advanced stage IB2-IIB cervical cancer patients after neoadjuvant chemotherapy.

OBJECTIVE: To evaluate the feasibility and morbidity of total laparoscopic class C2 radical hysterectomy (TLRH) with pelvic lymphadenectomy in patients with locally advanced cervical cancer stage IB2 to IIB after neoadjuvant chemotherapy (NACT). METHODS: A prospective study was conducted from October 2004 to September 2009. Cervical cancer patients, stage IB2-IIB with complete clinical response after 3 courses of NACT with paclitaxel 175 mg/m(2), ifosfamide 5 g/m(2) and cisplatin 75 mg/m(2) (TIP) underwent TLRH. RESULTS: Forty patients were included, with a median age of 46 years (range, 25-65), BMI of 24 kg/m(2) (range, 15-49). FIGO staging was IB2 in 23, IIA > 4 cm in 6 and IIB in 11 patients. Four patients required conversion to laparotomy. Pathological evaluation showed 9 complete response (pCR), 9 partial response (pPR1) with microscopic tumour, and 15 partial response (pPR2) with macroscopic tumour. Three patients had no response. The median operative time was 305 min (range, 215-430); the median estimated blood loss was 250 ml (range, 100-400), with four postoperative blood transfusion; the median number of removed pelvic lymph nodes was 25 (range, 11-64). The median length of hospital stay was 6 days (range, 3-12). The median follow-up time was 37 months (range, 10-69), with three patients having a recurrence. One patient died of disease (DOD) after 12 months. CONCLUSIONS: TLRH can be safely performed in patients with stage IB2-IIB carcinoma of cervix after NACT, with advantages of minimal blood loss and morbidity.

[Teniasis in a child with finding of Taenia saginata proglottids in the school environment: a case report]. / Un caso pediatrico di teniasi con reperimento di proglottidi di Taenia saginata in ambiente scolastico.

We describe a case of teniasis in a child, associated to the finding of Taenia proglottids in a classroom of a primary school in the area of Cuneo (Local Health Unit Cn-1, Piedmont Region, Italy). Several proglottids had been repeatedly found by cleaners on the bookbox of several schooldesks in the same classroom. Laboratory investigation was able to identify Taenia saginata proglottids and cooperation of the local Public Health Unit with the school management allowed to identify and treat the affected child. Laboratory investigation was crucial to exclude a Taenia solium infection, which should have had important public health implications. In fact, infection among humans can follow the ingestion of Taenia solium eggs and in this case larval forms in several tissues can occur (cysticercosis). Moreover the disease can be particularly severe when cysticerci invade the brain, causing seizures and hydrocephalia.

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.

BACKGROUND: The 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. PATIENTS AND METHODS: In 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. RESULTS: Patient 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. CONCLUSION: TP 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.

Total laparoscopic radical hysterectomy and pelvic lymphadenectomy in patients with Ib1 stage cervical cancer: analysis of surgical and oncological outcome.

AIM: To evaluate safety, feasibility and oncological outcome of total laparoscopic radical hysterectomy (TLRH) in patients with early invasive cervical cancer. METHODS: Data of patients with Ib1 cervical cancer who underwent TLRH were prospectively collected. Inclusion criteria were: good general condition, tumor size <3 cm, and no evidence of lymph node metastases in imaging study (MRI and/or CT and/or PET). Radical hysterectomy was performed with a PlasmaKinetic tissue management system. Adjuvant therapy was administered according to surgical risk factors. RESULTS: Between September 2001 and October 2007 107 patients underwent laparoscopic radical hysterectomy and pelvic lymphadenectomy. Conversion to laparotomy was necessary in 6 patients. Median number of resected pelvic lymph nodes was 26. Median blood loss was 200 ml and median duration of surgery was 305 min. Minor intraoperative complications were registered in two patients, while five patients needed a second surgery for postoperative complications. Thirteen patients had microscopic nodal metastasis. A total of 24 patients received adjuvant therapy. After a median follow-up of 30 months 11 patients had a recurrence; survival rate is 95%. CONCLUSION: Total laparoscopic radical hysterectomy, in experienced hands, has to be considerate an adequate and feasible surgical technique. Considering historical data the oncological outcome can be considered comparable to patients treated with laparotomy, as the relapse rate in our population was 11% and the overall survival good.

Randomised study of systematic lymphadenectomy in patients with epithelial ovarian cancer macroscopically confined to the pelvis.

No randomised trials have addressed the value of systematic aortic and pelvic lymphadenectomy (SL) in ovarian cancer macroscopically confined to the pelvis. This study was conducted to investigate the role of SL compared with lymph nodes sampling (CONTROL) in the management of early stage ovarian cancer. A total of 268 eligible patients with macroscopically intrapelvic ovarian carcinoma were randomised to SL (N=138) or CONTROL (N=130). The primary objective was to compare the proportion of patients with retroperitoneal nodal involvement between the two groups. Median operating time was longer and more patients required blood transfusions in the SL arm than the CONTROL arm (240 vs 150 min, P<0.001, and 36 vs 22%, P=0.012, respectively). More patients in the SL group had positive nodes at histologic examination than patients on CONTROL (9 vs 22%, P=0.007). Postoperative chemotherapy was delivered in 66% and 51% of patients with negative nodes on CONTROL and SL, respectively (P=0.03). At a median follow-up of 87.8 months, the adjusted risks for progression (hazard ratio [HR]=0.72, 95%CI=0.46-1.21, P=0.16) and death (HR=0.85, 95%CI=0.49-1.47, P=0.56) were lower, but not statistically significant, in the SL than the CONTROL arm. Five-year progression-free survival was 71.3 and 78.3% (difference=7.0%, 95% CI=-3.4-14.3%) and 5-year overall survival was 81.3 and 84.2% (difference=2.9%, 95% CI=-7.0-9.2%) respectively for CONTROL and SL. SL detects a higher proportion of patients with metastatic lymph nodes. This trial may have lacked power to exclude clinically important effects of SL on progression free and overall survival.

Unusual cardiac tumour with perivascular myoid differentiation: a case report.

A previously healthy 70 year old woman was admitted for fatigue and dyspnoea on exertion and cough. A two dimensional echocardiography revealed a mass in the right atrium, which obstructed filling and infiltrated the cardiac chamber wall. Postsurgical histological examination revealed an unusual tumour with prevalent myoid glomangiopericytoma-type and haemangiopericytoma-like patterns. Mitosis and necrosis were absent. A computed tomography scan excluded the presence of metastasis to distant organs or, conversely, metastatic involvement of the heart. Therefore, a diagnosis of tumour with perivascular myoid differentiation was made. This new entity, recently described in soft tissues, can easily recur. Its recognition helps to differentiate from metastasis and other primitive cardiac tumours sharing some morphological features but a different clinical behaviour, with consequent improvement to the management of patient care.

Advanced operative office hysteroscopy without anaesthesia: analysis of 501 cases treated with a 5 Fr. bipolar electrode.

BACKGROUND: The aim of this study was to evaluate treatment efficacy and patient acceptability of a new bipolar probe used during office hysteroscopic treatment of benign intrauterine pathologies. METHODS: In this observational clinical study, 501 women were treated for benign intrauterine pathologies using an office hysteroscopic procedure, without analgesia or anaesthesia. A Versapoint 5 Fr. bipolar electrical generator was used to treat endometrial polyps ranging between 0.5 and 4.5 cm, as well as submucosal and partially intramural myomas between 0.6 and 2.0 cm. Treatment efficacy and patient compliance were evaluated. RESULTS: At follow-up, the uterine cavity was normal in all patients without any recurrence or persistence of the pathology. One focal adenocarcinoma was discovered at histology in an endometrial polyp of a menopausal patient. Patient acceptance was satisfactory; 47.6-79.3% of the patients underwent the procedure without discomfort. CONCLUSIONS: The combination of a new generation small diameter hysteroscope and a new bipolar 5 Fr. electrode enables the gynaecologist to treat intrauterine pathologies in an office setting without anaesthesia. Experimentation of a special set-up of the electrical generator reduced patient discomfort during the operative part of the hysteroscopic procedure.

Endometrial biopsies using small-diameter hysteroscopes and 5F instruments: how can we obtain enough material for a correct histologic diagnosis?

STUDY OBJECTIVE: To evaluate the quantity of biopsy tissue obtained by hysteroscopic grasp technique compared with classic punch technique. DESIGN: Observational study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: One thousand two hundred seventy-six women. INTERVENTION: Targeted biopsies performed in an office setting using two biopsy forceps, classic spoon and crocodile, and two methods, classic punch and grasp technique. MEASUREMENTS AND MAIN RESULTS: With either biopsy forceps, the mean increase in amount of tissue obtained by grasp technique compared with punch technique was statistically significant (p <0.005). With grasp technique, the mean amount of tissue obtained was even larger with crocodile than with spoon forceps. CONCLUSION: Targeted biopsy, when performed with the appropriate instrument and applying correct technique, can provide the pathologist with a large amount of tissue (mean 5.7 mm2) that is invariably adequate for histologic examination.

Multiple myeloma and mycosis fungoides in the same patient: clinical, immunologic, and molecular studies.

The coexistence of multiple myeloma (MM) and mycosis fungoides (MF), and hence of both B- and T-cell neoplastic clones, is a rare event. We describe a case of plaque-stage MF associated with IgG lambda MM. The clinical onset of MF preceded that of MM, supporting the hypothesis that MF predisposed to the development of the B-cell proliferative disorder. The skin tumor cells were found to originate from CD4(+) T-lymphocytes, characterized by a V beta 8 receptor and no proviral human T-lymphotropic virus (HTLV)-I monoclonal integration. They also displayed a polarized Th1-type cytokine profile containing mRNAs for interleukin (IL)-2, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-beta, but not for IL-4, IL-5, or IL-10. The CD8(+)/CD57(+) suppressor-cytotoxic subpopulation was significantly increased in the peripheral blood and was associated with MM progression. Expression of p16INK4A, a gene from the INK family that inhibits cyclin-dependent kinases and regulates the cell cycle, was lacking in MF cells and bone marrow (BM) plasma cells. The p16INK4A gene was silenced by hypermethylation, suggesting that it plays a role in the early phase of the pathogenesis of both diseases. Thus, a lymphoid precursor cell presumably contains aberrations that induce the development of both clonal diseases in a multistep process.

Early diagnosis of acute mesenteric ischemia after cardiopulmonary bypass.

BACKGROUND: The aim of this study is to identify significant risk factors and eventual clinical markers associated with acute mesenteric ischemia (AMI) after cardiopulmonary bypass. METHODS: The study was retrospectively performed on a group of 19 patients (group A) undergoing cardiac surgery between January 1991 and December 1999, who developed AMI within 30 days of their hospitalization. A control group of 48 patients (group B) was compared in order to define preoperative and operative risk factors for AMI. RESULTS: At the abdominal operation, a non-occlusive mesenteric ischemia was found in every case. In-hospital mortality was 84.2% (16/19). Compared to the control, there was a significant difference in aortic cross-clamp time (p<0.001) and use of inotropic drugs (p<0.01). Postoperatively, the studied group (group A) had a significantly higher mean value of the enzymatic serum levels at any time. CONCLUSIONS: A high index of suspicion for mesenteric ischemia after cardiopulmonary bypass should be considered in patients with conditions of hypoperfusion. The early laboratory signs of AMI might be searched during the first postoperative hours.

Familial and environmental risk factors in Parkinson's disease: a case-control study in north-east Italy.

BACKGROUND AND OBJECTIVE: The aetiology of Parkinson's disease remains unknown, although both genetic susceptibility and environmental factors are considered putative contributors to its origin. We performed a case-control study to investigate the association of familial and environmental risk factors with Parkinson's disease (PD). METHODS: We studied 136 patients with neurologist confirmed PD and 272 age- and sex-matched controls, affected by neurological diseases not related to PD. The risk of developing idiopathic PD associated with the following familial and environmental factors: positive family history of PD, positive family history of essential tremor (ET), age of mother at subject's birth, rural birth, rural living, well water use, farming as an occupation, exposure to pesticides, head tremor, exposure to general anaesthesia and to ionizing radiations, food restriction, concentration camp imprisonment and smoking has been assessed by using univariate and multivariate statistical techniques. RESULTS: In the conditional multiple logistic regression analysis, positive family history of PD (OR 41.7, 95% CI 12.2-142.5, P < 0.0001), positive family history of ET (OR 10.8, 95% CI 2.6-43.7, P < 0.0001), age of mother at subject's birth (OR 2.6, 95% CI 1.4-3.7, P=0.0013), exposure to general anaesthesia (OR 2.2, 95% CI 1.3-3.8, P=0.0024), farming as an occupation (OR 7.7, 95% CI 1.4-44.1, P=0.0212) and well water use (OR 2.0, 95% CI 1.1-3.6, P=0.0308) exhibited a significant positive association with PD, whereas smoking showed a trend toward an inverse relationship with PD (OR 0.7, 95% CI 0.4-1.1, P < 0.06). CONCLUSIONS: We conclude that both familial and environmental factors may contribute to PD aetiology.