LACC Trial: Final Analysis on Overall Survival Comparing Open Versus Minimally Invasive Radical Hysterectomy for Early-Stage Cervical Cancer.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.The aim of this study was to compare overall survival between open and minimally invasive radical hysterectomy with participants followed for 4.5 years. The primary objective was to evaluate whether minimally invasive surgery was noninferior in disease-free survival (DFS) to abdominal radical hysterectomy. Secondary outcomes included overall survival. Sample size was based on DFS of 90% at 4.5 years and 7.2% noninferiority margin for minimally invasive surgery. A total of 631 patients were enrolled: 319 assigned to minimally invasive and 312 to open surgery. Of these, 289 (90.6%) patients underwent minimally invasive surgery and 274 (87.8%) patients open surgery. At 4.5 years, DFS was 85.0% in the minimally invasive group and 96% in the open group (difference of -11.1; 95% CI, -15.8 to -6.3; P = .95 for noninferiority). Minimally invasive surgery was associated with lower rate of DFS compared with open surgery (hazard ratio [HR], 3.91 [95% CI, 2.02 to 7.58]; P < .001). Rate of overall survival at 4.5 years was 90.6% versus 96.2% for the minimally invasive and open surgery groups, respectively (HR for death of any cause = 2.71 [95% CI, 1.32 to 5.59]; P = .007). Given higher recurrence rate and worse overall survival with minimally invasive surgery, an open approach should be standard of care.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

OBJECTIVE: The etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding. We re-analyzed lymph nodes by pathologic ultrastaging in node-negative patients who recurred in the LACC (Laparoscopic Approach to Cervical Cancer) trial. METHODS: Included patients were drawn from the LACC trial database, had negative lymph nodes on routine pathologic evaluation, and recurred to the abdomen and/or pelvis. Patients without recurrence or without available lymph node tissue were excluded. Paraffin tissue blocks and slides from all lymph nodes removed by lymphadenectomy were re-analyzed per standard ultrastaging protocol aimed at the detection of micrometastases (>0.2 mm and ≤2 mm) and isolated tumor cells (clusters up to 0.2 mm or <200 cells). RESULTS: The study included 20 patients with median age of 42 (range 30-68) years. Most patients were randomized to minimally invasive surgery (90%), had squamous cell carcinoma (65%), FIGO 2009 stage 1B1 (95%), grade 2 (60%) disease, had no adjuvant treatment (75%), and had a single site of recurrence (55%), most commonly at the vaginal cuff (45%). Only one patient had pelvic sidewall recurrence in the absence of other disease sites. The median number of lymph nodes analyzed per patient was 18.5 (range 4-32) for a total of 412 lymph nodes. A total of 621 series and 1242 slides were reviewed centrally by the ultrastaging protocol. No metastatic disease of any size was found in any lymph node. CONCLUSIONS: There were no lymph node low-volume metastases among patients with initially negative lymph nodes who recurred in the LACC trial. Therefore, it is unlikely that manipulation of lymph nodes containing clinically undetected metastases is the underlying cause of the higher local recurrence risk in the minimally invasive arm of the LACC trial.

Isolation and Identification of Staphylococcus Species Obtained from Healthy Companion Animals and Humans.

The close contact between people and their pets has generated the exchange of skin microbiota, accompanied by bacteria that present resistance to antibiotics. Staphylococcus spp., opportunistic pathogens present in the skin and mucosa of mammals, have had their importance recognized in human and veterinary medicine. The objectives of this study were to identify Staphylococcus spp. present in isolates from the nostrils of healthy humans, dogs and cats as well as to determine their phenotype of resistance to methicillin. Strain identification was performed by MALDI-TOF mass spectrometry and antimicrobial susceptibility was determined using a disk diffusion assay for 12 antibiotics. Sixty humans (veterinary and technicians), sixty dogs and sixty cats were sampled; of them, 61.6%, 56.6% and 46.6%, respectively, carried Staphylococcus spp. in their nostrils, and only two people carried two different species of Staphylococcus in the only anatomical site sampled. A methicillin-resistant phenotype was present in 48.7% of the humans, 26.5% of the dogs and 57.1% of the cats, and sampled. These results demonstrate the presence of Staphylococcus spp. strains resistant to methicillin in personnel who work in contact with animals, as well as in dogs and cats that entered the same hospital or veterinary clinic, which alerts us to the potential transfer of these strains to or between people, dogs and/or cats.

Oncological outcomes of laparoscopic radical hysterectomy versus radical abdominal hysterectomy in patients with early-stage cervical cancer: a multicenter analysis.

INTRODUCTION: Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. METHODS: We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. RESULTS: A total of 1379 patients were included in the final analysis, with 681 (49.4%) operated by laparoscopy and 698 (50.6%) by laparotomy. There were no differences regarding the surgical approach in the rates of positive vaginal margins, deep stromal invasion, and lymphovascular space invasion. Median follow-up was 52.1 months (range, 0.8-201.2) in the laparoscopic group and 52.6 months (range, 0.4-166.6) in the laparotomy group. Women who underwent laparoscopic radical hysterectomy had a lower rate of disease-free survival compared with the laparotomy group (4-year rate, 88.7% vs 93.0%; HR for recurrence or death from cervical cancer 1.64; 95% CI 1.09-2.46; P=0.02). In sensitivity analyzes, after adjustment for adjuvant treatment, radical hysterectomy by laparoscopy compared with laparotomy was associated with increased hazards of recurrence or death from cervical cancer (HR 1.7; 95% CI 1.13 to 2.57; P=0.01) and death for any cause (HR 2.14; 95% CI 1.05-4.37; P=0.03). CONCLUSION: In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy.

Quality of life in patients with cervical cancer after open versus minimally invasive radical hysterectomy (LACC): a secondary outcome of a multicentre, randomised, open-label, phase 3, non-inferiority trial.

BACKGROUND: In the phase 3 LACC trial and a subsequent population-level review, minimally invasive radical hysterectomy was shown to be associated with worse disease-free survival and higher recurrence rates than was open radical hysterectomy in patients with early stage cervical cancer. Here, we report the results of a secondary endpoint, quality of life, of the LACC trial. METHODS: The LACC trial was a randomised, open-label, phase 3, non-inferiority trial done in 33 centres worldwide. Eligible participants were women aged 18 years or older with International Federation of Gynaecology and Obstetrics (FIGO) stage IA1 with lymphovascular space invasion, IA2, or IB1 adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma of the cervix, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who were scheduled to have a type 2 or 3 radical hysterectomy. Participants were randomly assigned (1:1) to receive open or minimally invasive radical hysterectomy. Randomisation was done centrally using a computerised minimisation program, stratified by centre, disease stage according to FIGO guidelines, and age. Neither participants nor investigators were masked to treatment allocation. The primary endpoint of the LACC trial was disease-free survival at 4·5 years, and quality of life was a secondary endpoint. Eligible patients completed validated quality-of-life and symptom assessments (12-item Short Form Health Survey [SF-12], Functional Assessment of Cancer Therapy-Cervical [FACT-Cx], EuroQoL-5D [EQ-5D], and MD Anderson Symptom Inventory [MDASI]) before surgery and at 1 and 6 weeks and 3 and 6 months after surgery (FACT-Cx was also completed at additional timepoints up to 54 months after surgery). Differences in quality of life over time between treatment groups were assessed in the modified intention-to-treat population, which included all patients who had surgery and completed at least one baseline (pretreatment) and one follow-up (at any timepoint after surgery) questionnaire, using generalised estimating equations. The LACC trial is registered with ClinicalTrials.gov, NCT00614211. FINDINGS: Between Jan 31, 2008, and June 22, 2017, 631 patients were enrolled; 312 assigned to the open surgery group and 319 assigned to the minimally invasive surgery group. 496 (79%) of 631 patients had surgery completed at least one baseline and one follow-up quality-of-life survey and were included in the modified intention-to-treat analysis (244 [78%] of 312 patients in the open surgery group and 252 [79%] of 319 participants in the minimally invasive surgery group). Median follow-up was 3·0 years (IQR 1·7-4·5). At baseline, no differences in the mean FACT-Cx total score were identified between the open surgery (129·3 [SD 18·8]) and minimally invasive surgery groups (129·8 [19·8]). No differences in mean FACT-Cx total scores were identified between the groups 6 weeks after surgery (128·7 [SD 19·9] in the open surgery group vs 130·0 [19·8] in the minimally invasive surgery group) or 3 months after surgery (132·0 [21·7] vs 133·0 [22·1]). INTERPRETATION: Since recurrence rates are higher and disease-free survival is lower for minimally invasive radical hysterectomy than for open surgery, and postoperative quality of life is similar between the treatment groups, gynaecological oncologists should recommend open radical hysterectomy for patients with early stage cervical cancer. FUNDING: MD Anderson Cancer Center and Medtronic.

Incidence of adverse events in minimally invasive vs open radical hysterectomy in early cervical cancer: results of a randomized controlled trial.

BACKGROUND: Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. OBJECTIVE: The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. STUDY DESIGN: The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. RESULTS: Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). CONCLUSION: For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

Minimally Invasive versus Abdominal Radical Hysterectomy for Cervical Cancer.

BACKGROUND: There are limited data from retrospective studies regarding whether survival outcomes after laparoscopic or robot-assisted radical hysterectomy (minimally invasive surgery) are equivalent to those after open abdominal radical hysterectomy (open surgery) among women with early-stage cervical cancer. METHODS: In this trial involving patients with stage IA1 (lymphovascular invasion), IA2, or IB1 cervical cancer and a histologic subtype of squamous-cell carcinoma, adenocarcinoma, or adenosquamous carcinoma, we randomly assigned patients to undergo minimally invasive surgery or open surgery. The primary outcome was the rate of disease-free survival at 4.5 years, with noninferiority claimed if the lower boundary of the two-sided 95% confidence interval of the between-group difference (minimally invasive surgery minus open surgery) was greater than -7.2 percentage points (i.e., closer to zero). RESULTS: A total of 319 patients were assigned to minimally invasive surgery and 312 to open surgery. Of the patients who were assigned to and underwent minimally invasive surgery, 84.4% underwent laparoscopy and 15.6% robot-assisted surgery. Overall, the mean age of the patients was 46.0 years. Most patients (91.9%) had stage IB1 disease. The two groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, rates of parametrial and lymph-node involvement, tumor size, tumor grade, and the rate of use of adjuvant therapy. The rate of disease-free survival at 4.5 years was 86.0% with minimally invasive surgery and 96.5% with open surgery, a difference of -10.6 percentage points (95% confidence interval [CI], -16.4 to -4.7). Minimally invasive surgery was associated with a lower rate of disease-free survival than open surgery (3-year rate, 91.2% vs. 97.1%; hazard ratio for disease recurrence or death from cervical cancer, 3.74; 95% CI, 1.63 to 8.58), a difference that remained after adjustment for age, body-mass index, stage of disease, lymphovascular invasion, and lymph-node involvement; minimally invasive surgery was also associated with a lower rate of overall survival (3-year rate, 93.8% vs. 99.0%; hazard ratio for death from any cause, 6.00; 95% CI, 1.77 to 20.30). CONCLUSIONS: In this trial, minimally invasive radical hysterectomy was associated with lower rates of disease-free survival and overall survival than open abdominal radical hysterectomy among women with early-stage cervical cancer. (Funded by the University of Texas M.D. Anderson Cancer Center and Medtronic; LACC ClinicalTrials.gov number, NCT00614211 .).

Terapéutica quirúrgico-ortodóntica en adultos con dientes supernumerarios múltiples. Presentación de caso / Surgical-orthodontic therapy on adults with multiple supernumerary teeth

Se presentó a la consulta estomatológica, una paciente femenina de 39 años de edad, sin antecedentes médicos de interés, por presentar pérdida espontánea de un diente temporal. A través del examen físico intrabucal, se pudo corroborar la ausencia clínica del diente número 13, y en su lugar, la presencia de mucosa, que evidenciaba una exfoliación reciente de un diente, con notable disminución del espacio entre el incisivo lateral y la primera bicúspide superior izquierda. El examen radiográfico periapical mostró la presencia de una imagen radiopaca, ubicada entre el incisivo lateral y la primera bicúspide de la hemiarcada superior izquierda, la cual sugiere la presencia de múltiples órganos dentarios. Dada la afectación funcional, estética y psicológica de la paciente, y la existencia de discrepancia negativa moderada hueso-diente, se decidió realizar la exéresis quirúrgica de los dientes supernumerarios y en una segunda etapa, la corrección ortodóncica. El tratamiento quirúrgico se realizó sin complicaciones, pues la paciente mostró una evolución postquirúrgica positiva. Luego de la recuperación total del área intervenida, comenzaron los movimientos ortodóncicos, que finalmente permitieron obtener un resultado estético y funcional óptimo.

A 39 years old female patient, with no medical records, comes to dentistry consulting because of a temporal tooth loss. During the intraoral physical examination the absence of the 13 tooth was corroborated, and the recently exfoliation of a teeth with a considerable diminish of space between the left upper lateral incisor and the left first upper bicuspid were corroborated. The x-rays showed radiopacity, located between the lateral incisor and the first upper bicuspid of the left hemi-arcade, suggesting several dental organs. Due to functional, aesthetic and psychological influencies on the patient, and the presence of a moderated negative bone-teeth discrepancy, it was decided to practice surgical extraction of supernumerary teeth and the orthodontic correction. Surgical treatment was practiced without complications, and the patient showed a good postsurgical evolution. After a total recovery of the affected area, orthodontic movement began. It allowed an optimum aesthetic and functional outcome.

Radical parametrectomy after 'cut-through' hysterectomy in low-risk early-stage cervical cancer: Time to consider this procedure obsolete.

OBJECTIVE: The goal of this study is to identify predictive factors in patients with a diagnosis of early-stage cervical cancer after simple hysterectomy in order to avoid a radical parametrectomy. METHODS: A retrospective review was performed of all patients who underwent radical parametrectomy and bilateral pelvic lymphadenectomy at MD Anderson Cancer Center and at the Instituto de Cancerologia Las Americas in Medellin, Colombia from December 1999 to September 2017. We sought to determine the outcomes in patients diagnosed with low-risk factors (squamous, adenocarcinoma or adenosquamous lesions<2cm in size, and invading<10mm) undergoing radical parametrectomy and pelvic lymphadenectomy. RESULTS: A total of 30 patients were included in the study. The median age was 40.4years (range; 26-60) and median body mass index (BMI) was 26.4kg/m2 (range; 17.7-40.0). A total 22 patients had tumors<1cm and 8 had tumors between 1 and 2cm. A total of 6 (33%) of 18 patients had evidence of lymph-vascular invasion (LVSI). No radical parametrectomy specimen had residual tumor, involvement of the parametrium, vaginal margin positivity, or lymph node metastasis. None of the patients received adjuvant therapy. After a median follow-up of 99months (range; 6-160) only one patient recurred. CONCLUSION: Radical parametrectomy may be avoided in patients with low-risk early-stage cervical cancer detected after a simple hysterectomy. Rates of residual disease (parametrial or vaginal) and the need for adjuvant treatments or recurrences are very low.

Presentación de una paciente con granuloma periférico de células gigantes / Presentation of a Patient with Peripheral Giant Cell Granuloma

Se presentó una paciente femenina de 37 años de edad, sin antecedentes generales de interés, con hábito de onicofagia desde la niñez, que presentaba aumento de volumen localizado en la papila interdentaria entre incisivo lateral y canino maxilar derecho, de aproximadamente dos años de evolución, que le ocasionaba molestias y sangramiento durante el cepillado dentogingival. La lesión se presentó con aspecto de una pieza dentaria, de coloración rosa a rojo, superficie lisa, base sésil, no doloroso a la palpación, rebasaba el borde incisal, sin interferir con la oclusión y sobrepasaba el ancho vestíbulo lingual de los dientes contiguos en aproximadamente dos milímetros. Radiográficamente se observó reabsorción superficial de la cresta del tabique interdentario entre ambos dientes y espaciamiento del trabeculado óseo. Se realizó la escisión quirúrgica y posterior examen anatomopatológico, el cual confirmó la presencia de granuloma periférico gigante celular completamente resecado, lo cual corroboró el diagnóstico presuntivo. Se apreció una satisfactoria evolución postquirúrgica.

A female patient of 37 years old with no history of general interest, nail biting habit from childhood, which had increased volume within the interdental papilla between lateral incisor and maxillary right canine about two years of evolution was presented, which caused discomfort and bleeding during dentogingival brushing. The lesion appeared with appearance of a tooth, pink color to red, smooth, sessile base, not painful on palpation, exceeded the incisal margin, without interfering with the occlusion and surpassing the broad lingual hall of the contiguous teeth in approximately two millimeters. The radiographic exam evidenced superficial reabsorption of the crest of the interdental partition between both teeth and bone-like spacing of the trabeculate. The lesion was eliminated by surgical excision. The histologic test confirmed the presence of peripheral giant cell granuloma completely eliminated. A satisfactory post-surgical evolution was observed.

Periodontopatías y algunos factores de riesgo en población adulta de la Policlínica César Fornet Fruto / Periodontal Pathology and Some Risk Factors in Adult Patients of César Fornet Fruto Polyclinic

Introducción: las periodontopatías son alteraciones patológicas que se producen en los tejidos periodontales, su origen puede ser cualquiera. La enfermedad periodontal se considera la segunda causa de pérdida dentaria. En Cuba más del 70% de la población adulta ha padecido gingivitis o periodontitis, o ambas. Objetivos: caracterizar el comportamiento de la enfermedad periodontal en la población de 20 a 59 años de edad de los consultorios atendidos por el Departamento Docente de la Policlínica César Fornet Fruto del municipio Banes. Método: se realizó un estudio descriptivo de corte transversal. Se empleó el índice periodontal revisado (IP-R) de la OMS para medir la presencia y gravedad de la enfermedad periodontal. Se describió el comportamiento de algunos factores de riesgo relacionados con la aparición de la enfermedad periodontal. Se calculó el índice de análisis de higiene bucal de Love. Resultados: la presencia de periodontopatías fue del 64,70%. En cuanto a la gravedad de la enfermedad periodontal predominaron la inflamación gingival que rodeaba completamente el diente (grado II) con 35,06% y la presencia de bolsa periodontal (grado VI) con 32,46%. La higiene bucal deficiente alcanzó el 41,17%. El 23,52% de los individuos estudiados estuvo expuesto al tabaquismo. Conclusiones: se observó una elevada presencia de periodontopatías. La inflamación gingival que rodea completamente los dientes fue la condición que predominó. La higiene bucal deficiente constituyó el factor de riesgo que más alto porcentaje obtuvo.

Introduction: periodotal diseases are alterations that affect the periodontal tissue. Periodontal disease is considered the second cause of dental loss. In Cuba over 70% of the adult population has suffered from periodontal disease. Objective: to characterize periodontal disease in patients aged between 20 and 59 who were assisted at César Fornet Polyclinic of Banes, from January 2009 and December 2010. Methods: a descriptive cross-sectional study was done. The Revised Periodontal Rate of the World Health Organization (WHO) was used to know the prevalence and severity of periodontal disease. The behavior of some risk factors of the periodontal disease was described. The Test Rate of the Oral Hygiene (IAH) was calculated. Results: prevalence of periodontal pathology was of 64.70%. The gingival inflammation that totally surrounds teeth attained 35.06% and the presence of periodontal pocket obtained 32.46%. Poor oral hygiene reached 41.17% and 23.52% of the studied patients were exposed to smoking. Conclusions: high presence of periodontal disease was obtained. The gingival inflammation that totally surrounds teeth was the prevailed condition. Poor oral hygiene was the highest risk factor.

Presentación de un paciente geriátrico con retención de tercer molar mandibular / Presentation of a Geriatric Patient with Third Molar Retention

Se presentó un paciente masculino de 80 años de edad con retención del tercer molar inferior, que acudió a cuerpo de guardia con cuadro inflamatorio subagudo y dolor de moderada intensidad. El examen radiográfico evidenció la presencia del tercer molar inferior retenido en posición horizontal, el cual presentaba en su corona área radiolúcida compatible con caries dental. El paciente fue tratado con antibiótico, analgésico y antiinflamatorio y una vez rebasada la fase aguda fue intervenido quirúrgicamente con excelente evolución.

A 80-year-old male patient with retention of third lower molar that was admitted at Emergency Service with inflammatory sub-acute status and pain of moderated intensity is presented. The radiographic exam evidenced the presence of the third molar retained at horizontal position, which presented in its crown, a dark area compatible with dental cavity. The patient was treated with antibiotic, analgesic and anti-inflammatory and when acute phase was over, the third molar was extracted. The surgery was completed without complications with an excellent evolution.