Conservative surgical approaches for small volume FIGO stage IB1 cervical cancer. Updated survival and obstetric outcomes of an expanded cohort.

OBJECTIVE: Standard surgical treatment of FIGO stage 1B1 cervical cancer is open radical surgery. However, there is increasing evidence that for small tumours a more conservative approach can minimise fertility consequences without impacting on long term oncologic outcomes. The objective of our study is to present survival and obstetric outcomes following extended follow-up for patients who underwent conservative management of small-volume stage 1B1 disease. METHODS: All patients with FIGO stage 1B1 cancer and estimated tumour volume of <500 mm3 in a loop biopsy specimen treated in Northern Gynaecological Oncology Centre between December 2000 and December 2021, were included in the study. Clinico-pathological and demographic data were collated alongside detailed follow-up and obstetric outcomes in conjunction with primary care and death register. RESULTS: 117 patients underwent conservative surgery for small volume stage 1B1 disease. 58 (49.5%) underwent fertility sparing conservative management with LLETZ while 59 (50.5%) underwent simple hysterectomy. Overall, 95% (111/117) of the patients underwent bilateral pelvic lymphadenectomy and 1 positive node was identified. There was no death related to cervical cancer and 1 recurrence identified during a median follow up of 8.5 years (1-20). 17 pregnancies have been recorded in patients underwent LLETZ and 17 live babies were born. No second trimester miscarriages were noted and there was one preterm delivery (36 weeks). CONCLUSION: Non-radical surgery with negative pelvic lymphadenectomy for smallvolume stage 1B1 cervical cancer ensures excellent survival without compromising obstetric outcomes. Should these results be verified by the ongoing prospective studies, radical surgery for these patients may be avoided.

Protective Role of Conization Before Radical Hysterectomy in Early-Stage Cervical Cancer: A Propensity-Score Matching Study.

PURPOSE: The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma. METHODS: This multicenter, retrospective observational cohort study included patients with FIGO 2009 stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case-control matching was used to adjust the baseline characteristics. RESULTS: A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (p = 0.542 and p = 0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (p < 0.001) and had a better 5-year disease-free survival (DFS) than patients who did not receive conization (89.8% vs. 80.0%, respectively; p = 0.010). No difference in 5-year overall survival (OS) (97.1% vs. 91.4%, respectively; p = 0.114) or recurrence pattern (p = 0.115) was reported between the two groups. Factors independently related to higher risk of recurrence were pathologic tumor diameter >20 mm and no conization before radical hysterectomy (p = 0.011 and p = 0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (p = 0.020). CONCLUSIONS: Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.

Post-operative pancreatic fistula following splenectomy with or without distal pancreatectomy at cytoreductive surgery in advanced ovarian cancer.

OBJECTIVE: Splenectomy with or without distal pancreatectomy may be necessary at time of cytoreductive surgery to achieve complete cytoreduction in advanced ovarian cancer. However, these procedures have been associated with peri-operative morbidity. The aims of this study were to determine the incidence of distal pancreatectomy among patients undergoing splenectomy during cytoreductive surgery for advanced ovarian cancer and to determine the incidence, management, treatment, and prognosis of patients with post-operative pancreatic fistula. METHODS: Retrospective cohort study of all consecutive patients with FIGO stage IIIC-IVB ovarian, fallopian tube, or primary peritoneal cancer who underwent splenectomy with or without distal pancreatectomy, during primary, interval, or secondary cytoreductive surgery between January 2007 and December 2017. All histologic subtypes were included; patients with borderline ovarian tumor and those undergoing emergency surgery were excluded from analysis. Univariate analyses for survival were generated by Kaplan-Meier survival curves and log-rank (Mantel-Cox) tests for statistical significance. Patients who underwent surgery for recurrence were excluded from survival analysis. Inter-group statistics were performed using Student's t-test for continuous variables, and chi-square test and Fisher's exact test for categorical variables. RESULTS: A total of 156/804 (19.4%) women underwent splenectomy, and of these 22 (14.1%) patients had distal pancreatectomy. Of patients who underwent splenectomy only, 2/134 (1.5%) developed grade B post-operative pancreatic fistula and 6/22 (27.3%) patients who underwent distal pancreatectomy developed grade B and C post-operative pancreatic fistula. Five (83.3%) of six of these patients were symptomatic. Distal pancreatectomy patients had a higher risk of developing post-operative pancreatic fistula when compared with patients who underwent splenectomy only (63.7% vs 9.7%, p=0.0001). Median length of hospital stay was longer in patients with post-operative pancreatic fistula: 16.5 (range 7-38) days compared with 10 (range 7-15) days (p=0.019). There was no progression-free survival (p=0.42) and disease-specific survival (p=0.33) difference between patients undergoing splenectomy with or without distal pancreatectomy. CONCLUSION: Clinically relevant post-operative pancreatic fistula is a relatively frequent complication (27.3%) following distal pancreatectomy and it is a possible complication after splenectomy only (1.5%).

Expression of vascular endothelial factor-A, gelatinases (MMP-2, MMP-9) and TIMP-1 in uterine leiomyomas.

BACKGROUND: Leiomyomas growth involves cellular hypertrophy, modulation of mitotic activity and upregulation of extracellular matrix (ECM). Vascular factors and matrix metalloproteinases (MMPs) play a coordinated role during neoplasia and tissue remodeling. The present study investigates the role of angiogenic factor vascular endothelial growth factor (VEGF)-A with the activity of main gelatinases, MMP-2/MMP-9 and their tissue inhibitor TIMP-1 in patients with leiomyomas. METHODS: Peripheral blood of 46 women with uterine leiomyomas was obtained prior hysterectomy to assess VEGF-A, MMP-2, -9, TIMP-1 levels by enzyme-linked immunosorbent assay compared to 39 healthy controls. Protein expression levels of VEGF-A, MMP-2 and MMP-9 were evaluated by western immunoblotting and immunohistochemistry in leiomyomas tissue specimens after hysterectomy. Furthermore, the activity of gelatinases in leiomyoma tissue extracts and control myometrium was evaluated by semi-quantitative zymography. RESULTS: Circulating levels of VEGF-A, MMP-2 and TIMP-1 were significantly elevated in leiomyoma patients compared to controls (p<0.001, p=0.004, p=0.003, respectively). A positive correlation was found between VEGF-A and MMP-2 (p=0.021) as well as MMP-9 (p=0.001) peripheral levels in the patient's group. Furthermore, increased VEGF-A protein levels were detected in leiomyoma tissue compared to control myometrium, followed by increased localization of both VEGF-A and MMP-2 in the ECM embedding bundles of smooth muscle cells of leiomyomas. The activity of MMP-2 was significantly higher in leiomyomas than normal myometrium in all investigated tissues. CONCLUSIONS: This study demonstrates a possible coordinated role of VEGF-A and MMP-2 during uterine leiomyomas growth and angiogenesis with potential prognostic significance.

A comparison of ICG-NIR with blue dye and technetium for the detection of sentinel lymph nodes in vulvar cancer.

INTRODUCTION: The sentinel lymph node (SLN) procedure for vulva cancer is a safe alternative to a radical inguino-femoral lymphadenectomy (IFLN) for small unifocal tumours. SLN evaluation through biopsy and ultra-staging has helped gynaecological oncology surgeons improve operative morbidity with no cost to oncologic safety. Established techniques for groin SLN detection and excision in vulvar cancer use 99mTc-nanocolloid radiotracer and blue dye (BD) for identification of the SLN. Indocyanine green (ICG)-near infrared (ICG-NIR) techniques for SLN mapping have proven utility in other gynaecological cancer sites and is gaining interest as a technique for SLN mapping in vulvar cancer METHODS: Fifty consecutive patients with unifocal vulvar squamous cell cancers of <40 mm lateral diameter and with depth of invasion > 1 mm underwent SLN mapping and excision using a combination of 99mTc-nanocolloid, BD and ICG. SLN detection results were recorded on a per-patient and per-groin basis. The success rates SLN for detection by individual tracer substance or combinations of tracer were determined by presence of one or more tracer, detectable in the SLN specimen. RESULTS: 92% of patients had a successful SLN procedure. The per-groin detection rate was 84%. All successfully mapped SLN were identified with the combination of ICG-NIR and 99mTc-nanocolloid compared to 69% with BD 99mTc-nanocolloid. Success rates for the SLN procedure were not dependent on prior excision of the primary lesion or operator experience. CONCLUSIONS: Incorporation of ICG-NIR into standard SLN mapping protocols may allow for the abandonment of routine use of BD and its poor side effect profile.

Risk of ovarian recurrence after ovarian conservation in early-stage cervical cancer treated with radical surgery: A propensity match analysis.

INTRODUCTION: The primary aim of the present study was to assess the incidence of ovarian metastasis/recurrence and the survival of patients undergoing radical hysterectomy with ovarian conservation (CONSERV) versus oophorectomy (OOPHOR). Secondary aim was to assess the incidence and the characteristics of menopausal symptoms in both groups. MATERIALS AND METHODS: Retrospective, multi-center, observational cohort study including patients <50 years with clinical FIGO 2009 stage IA1-IB1/IIA1 cervical carcinoma, treated by primary surgical treatment between 02/2007 and 07/2019. One-to-one case-control matching was used to adjust the baseline prognostic characteristics in survival analysis. RESULTS: 419 patients were included. 264 in the OOPHOR (63.0%) and 155 (37.0%) in the CONSERV group. Ovarian transposition was performed in 28/155 (18.1%) patients. 1/264 (0.4%) patient had ovarian metastasis from endocervical adenocarcinoma. After propensity-matching, 310 patients were included in the survival analysis (155 per group). 5-year disease-free survival of patients undergoing CONSERV versus OOPHOR was 90.6% versus 82.2%, respectively (p = 0.028); 5-year overall survival was 94.3% versus 90.8%, respectively (p = 0.157). Two patients (1.3%) developed recurrence on the conserved ovary. CONSERV represented an independent protective factor of recurrence (HR:0.361, 95%CI 0.169-0.769; p = 0.008). 28 (20.6%) in the CONSERV group versus 116 (60.4%) in the OOPHOR group complained of menopausal symptoms during follow up (p < 0.001). HRT was prescribed to 12.0% of patients (median HRT time was 20 months). CONCLUSION: CONSERV was associated with reduced risk of recurrence and menopausal symptoms in early-stage cervical cancer. As the risk of ovarian metastasis and ovarian recurrence is relatively low, CONSERV in pre-menopausal women has to be considered.

MicroRNAs: Novel diagnostic and prognostic biomarkers in atherosclerosis.

MicroRNAs (miRNAs) are an emerging class of highly conserved, non-coding small RNAs that regulate gene expression on the post-transcriptional level by inhibiting the translation of protein from mRNA or by promoting the degradation of mRNA. The involvement of miRNAs in the regulation of lipid metabolism, inflammatory response, cell cycle progression and proliferation, oxidative stress, platelet activation, endothelial function, angiogenesis and plaque formation and rapture indicates important roles in the initiation and progression of atherosclerosis. In the light of this evidence we will review the role of miRNAs in atherosclerosis.

Association of sarcoidosis with endothelial function, arterial wall properties, and biomarkers of inflammation.

BACKGROUND: Sarcoidosis is an inflammatory disease, which may affect vascular function. The study was designed to assess the impact of sarcoidosis on endothelial function and arterial stiffness. METHODS: Eighty-seven sarcoidosis patients and eighty-seven matched healthy subjects (Cl) were included in the study. Sarcoidosis patients were divided into two groups. Group 1 included patients never treated and group 2 included patients receiving cortisone treatment. Endothelial function was evaluated by flow-mediated dilatation (FMD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness and augmentation index (AI75) as a measure of arterial wave reflections. Serum levels of soluble intercellular adhesion molecule-1 and tumor necrosis factor-α (TNF-α), were measured. RESULTS: In the totality of the population, sarcoidosis patients had significantly lower FMD (P < 0.01) and significantly higher AI75 (P < 0.05). There was also a significant difference, between group 1, and Cl in FMD and AI75, but there was no difference between group 2 and Cl in FMD and AI75. AI75 values were significantly correlated with serum levels of intercellular adhesion molecule-1 (ICAM-1) (r = 0.370, P < 0.01) and TNF-α (r = 0.219, P = 0.049). CONCLUSIONS: In the present study, we have shown that sarcoidosis patients have impaired endothelial function and increased arterial stiffness. Sarcoidosis patients on cortisone treatment had no differences compared to controls on the vascular parameters. Moreover, there was a significant correlation between inflammatory process and vascular function impairment. These findings indicate that sarcoidosis patients have impaired vascular function and increased inflammatory status, which may improve with cortisone treatment.