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Background: Although the use of multiparametric magnetic resonance imaging (mpMRI) in active surveillance (AS) for prostate cancer is of increasing interest, existing data are derived from small cohorts., Objective: We describe clinical, histological, and radiological outcomes from an established AS programme, where protocol-based biopsies were omitted in favour of MRI-led monitoring., Design, Setting, and Participants: Data on 672 men enrolled in AS between August 2004 and November 2017 (inclusion criteria: Gleason 3 + 3 or 3 + 4 localised prostate cancer, presenting prostate-specific antigen <20 ng/ml, and baseline mpMRI) were collected from the University College London Hospital (UCLH) database., Outcome Measurements and Statistical Analysis: Primary outcomes were event-free survival (EFS; event defined as prostate cancer treatment, transition to watchful waiting, or death) and treatment-free survival (TFS). Secondary outcomes included rates of all-cause or prostate cancer-related mortality, metastasis, and upgrading to Gleason ≥4 + 3. Data on radiological and histological progression were also collected., Results and Limitations: More than 3800 person-years (py) of follow-up were accrued (median: 58 mo; interquartile range 37-82 mo). Approximately 84.7% (95% confidence interval [CI]: 82.0-87.6) and 71.8% (95% CI: 68.2-75.6) of patients remained on AS at 3 and 5 yr, respectively. EFS and TFS were lower in those with MRI-visible (Likert 4-5) disease or secondary Gleason pattern 4 at baseline (log-rank test; p <  0.001). In total, 216 men were treated. There were 24 deaths, none of which was prostate cancer related (6.3/1000 py; 95% CI: 4.1-9.5). Metastases developed in eight men (2.1 events/1000 py; 95% CI: 1.0-4.3), whereas 27 men upgraded to Gleason ≥4 + 3 on follow-up biopsy (7.7 events/1000 py; 95% CI: 5.2-11.3)., Conclusions: The rates of discontinuation, mortality, and metastasis in MRI-led surveillance are comparable with those of standard AS. MRI-visible disease and/or secondary Gleason grade 4 at baseline are associated with a greater likelihood of moving to active treatment at 5 yr. Further research will concentrate on optimising imaging intervals according to baseline risk., Patient Summary: In this report, we looked at the outcomes of magnetic resonance imaging (MRI)-based surveillance for prostate cancer in a UK cohort. We found that this strategy could allow routine biopsies to be avoided. Secondary Gleason pattern 4 and MRI visibility are associated with increased rates of treatment. We conclude that MRI-based surveillance should be considered for the monitoring of small prostate tumours., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Fistula-in-ano is a very common surgical condition, caused by anal cryptoglandular inflammation. Most cases are idiopathic. Other causes such as Crohn's disease, trauma and malignancy are well known. Management of fistula-in-ano is largely surgical, especially if the patient is symptomatic. The goal of surgical therapy is sepsis drainage, delineate anatomy and eradicate the fistula while preserving faecal continence. Establishing the aetiology is also crucial as often a combination of specialist medical therapy is required, for example, in Crohn's disease. We report an extremely unusual case of fistula-in-ano on an elderly man with chronic lymphocytic leukaemia (CLL). Histology from the fistula track demonstrated CLL infiltration. This case, not previously reported on PubMed search, illustrates a good example of joint specialist medical (a haematologist) and surgical effort in successfully treating this symptomatic fistula-in-ano., Competing Interests: Nil.

Background: Patients with rectal cancer who achieve complete clinical response after neoadjuvant chemoradiation have been managed nonoperatively. Thirty percent of these patients may develop a local regrowth, and salvage resection with radical surgery is usually recommended. However, selected patients could be offered additional organ preservation by local excision. We hypothesized that patients with baseline T2 who underwent neoadjuvant therapy (for the specific purpose of achieving a complete clinical response) were more likely to harbor recurrent disease at an earlier stage and amenable to organ preservation strategies (local excision) when compared with T3/T4 (undergoing neoadjuvant chemoradiation for oncologic reasons)., Objective: The purpose of this study was to compare patients with local regrowth requiring salvage resection according to their baseline stage., Design: This was a retrospective review of consecutive patients with nonmetastatic distal rectal cancer undergoing neoadjuvant chemoradiation., Settings: The study included 2 independent tertiary centers with institutional watch-and-wait organ preservation programs., Patients: Consecutive patients with distal rectal cancer (cT2-4N1-2M0) managed by watch and wait and local regrowth from 2 institutions were included., Main Outcomes Measures: Final pathologic features and surgical and oncologic outcomes were compared according to baseline staging., Results: A total of 73 of 257 patients experienced local regrowth. cT2 presented similar to ypT, ypN, R0, and abdominal perineal resection rates (p > 0.05) at the time of salvage when compared with cT3 to cT4. Patients with cT2 at baseline were more likely to undergo an organ preservation procedure for salvage (56.2% vs 26.5%; p = 0.03). Overall and disease-free survival after salvage were similar between groups irrespective of the type of surgery for the regrowth., Limitations: Retrospective study, small sample size, and possible inaccurate baseline staging., Conclusions: Although patients with baseline cT2 rectal cancer had similar pathologic stage at the time of recurrence, these patients were more likely to continue an organ preservation pathway after local regrowth through transanal local excision when compared with cT3 to cT4. Despite differences in the use of radical salvage resection, there were no differences in oncologic outcomes. See Video Abstract at http://links.lww.com/DCR/B254. CIRUGÍA DE RESCATE CON PRESERVACIÓN DE ORGANO PARA PACIENTES CON RECIDIVA LOCAL LUEGO DE WATCH & WAIT: ¿SIGUE SIENDO POSIBLE?: Los pacientes con cáncer rectal que logran una respuesta clínica completa luego de la quimiorradiación neoadyuvante han sido tratados de forma no quirúrgica. El treinta por ciento de estos pacientes pueden desarrollar un nuevo crecimiento local y generalmente se recomienda la resección de rescate con cirugía radical. Sin embargo, en pacientes seleccionados se podría ofrecer la posibilidad de preservación de órgano mediante escisión local. Se formuló la hipótesis de que los pacientes con estadio clinico inicial T2 y sometidos a terapia neoadyuvante (con el propósito específico de lograr una respuesta clínica completa) tenían más probabilidades de presentar una recurrencia local en una etapa más temprana y suceptibles de estrategias de preservación de órgano (escisión local) en comparación con T3 / T4 (sometidos a nCRT por razones oncológicas).Comparar los pacientes con recidiva local que requirieron cirugia de rescate de acuerdo con su estadio inicial.Revisión retrospectiva de pacientes consecutivos con cáncer de recto distal no metastásico sometidos a quimiorradiación neoadyuvante.Dos centros terciarios independientes con programas institucionales de preservación de órgano - Watch & Wait.Pacientes consecutivos con cáncer rectal distal (cT2-4N1-2M0) manejados por Watch & Wait y recidiva local.Las características patológicas finales, los resultados quirúrgicos y oncológicos se compararon de acuerdo con la estadificación inicial.Un total de 73 de 257 pacientes presentaron recidiva local. cT2 presentaron similares ypT, ypN, R0 y tasas de resección abdominoperineal (p>0,05) en el momento del rescate en comparación con cT3-4.Los pacientes con cT2 de base tuvieron más probabilidades de someterse a un procedimiento de preservación de órgano durante el rescate (56,2% frente a 26,5%; p = 0,03). Supervivencia general y DFS después del rescate fueron similares entre los grupos, independientemente del tipo de cirugía para la recidiva.Estudio retrospectivo, tamaño de muestra pequeño, la posible estadificación basal inexacta.Aunque los pacientes con cáncer rectal cT2 de base presentaron estadio patologico similar en el momento de la recidiva, estos pacientes tuvieron más probabilidades de continuar una vía de preservación de órgano luego de una recidiva local a través de la escisión local transanal en comparación con cT3-4. A pesar de las diferencias en el uso de la resección radical de rescate, no hubo diferencias en los resultados oncológicos. Consulte Video Resumen en http://links.lww.com/DCR/B254.

Objective: Preterm premature rupture of membranes (PPROM), associated with prematurity, is an important obstetric complication that may cause neonatal mortality and morbidity. The optimal delivery time is controversial in cases with the expectant approach. The fetal effects of long-term exposure to PPROM are unknown. This study aimed to evaluate the maternal and fetal outcomes of expectantly-managed PPROM cases with different latency periods at 24 0/7 -34 6/7  weeks of gestation. Material and method: The study group consisted of 206 patients at 24 0/7 -34 6/7  weeks of gestation who met the inclusion criteria. Patients were divided into three groups according to their weeks of PPROM diagnosis as 24 0/7 -28 6/7 , 29 0/7 -31 6/7 , and 32 0/7 -34 6/7 . The period from membrane rupture to delivery was defined as the latency period and divided into three subgroups as 3-7 days, 8-13 days and ≥14 days. In addition to the demographic characteristics of the patients, maternal and obstetric complications, primary and secondary neonatal outcomes were compared between the groups. Primary neonatal outcomes were determined in terms of pathological Apgar scores (<5 at minute 1, <7 at minute 5), requiring resuscitation, admission to Neonatal Intensive Care Unit (NICU) and NICU length of stay. Secondary neonatal outcomes were determined in terms of respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, necrotizing enterocolitis, patent ductus arteriosus, periventricular leukomalacia, and neonatal sepsis. In addition, for the prediction of morbidity and mortality, newborns were evaluated by SNAPPE II (Score for Neonatal Acute Physiology with Perinatal extension-II) consisting of the combination of biochemical and physiological parameters, using the parameters including mean blood pressure (mm/Hg), corporal temperature (°C), PO 2 /FiO 2 ratio, lowest serum pH, multiple seizures, urine output (ml/kg/hr), Apgar score, birth weight, and small for gestational age. The higher the score of SNAPPE II, the higher the morbidity and mortality risk of neonates. For the statistical analysis, the Kruskal Wallis and one-way ANOVA tests were utilized for the numerical data. Categorical data were compared using the chi-square test. The receiver operating characteristic (ROC) test was used to determine the threshold value of the data affecting neonatal morbidity. Results: The mean PPROM week was found to be 29.7 ± 3.0 weeks and the mean delivery week was 31.8 ± 2.5 weeks. The mean latency period for all the patients was 15.1 ± 13.8 days. Clinic chorioamnionitis was observed in 17% of the cases. The lowest chorioamnionitis rate (8.6%) was in the 3-7-day latency period group. Total complications were significantly lower in the 29 0/7 -31 6/7  week PPROM group in which the latency period was ≥14 days, compared to those in 3-7 days and 8-13 days ( p  = .001). Total complications were lower in the < 32 weeks PPROM groups in which the latency period was ≥14 days compared to those obtained in 3-7 days and 8-13 days. There was no significant difference between the latency period and total complications after 32 weeks ( p  = .422). The best discriminative cutoff value of SNAPPE-II for neonatal morbidity was 11.0 (sensitivity 82%, specificity 80%). In the present study, the optimal latency period for the best neonatal outcomes was found to be 34.5 days (sensitivity 70% and specificity 84%) between weeks 24 0/7 -28 6/7 , and 11.0 days between weeks 29 0/7 -31 6/7 (sensitivity 68% and specificity 85%). Conclusions: Our findings indicated that a long latency period did not increase neonatal morbidity and there was no increase in neonatal complications after 32 weeks of the gestational period compared to those obtained before 32 weeks.

Background: Subgroup analyses of two large EORTC adjuvant interferon-alpha2b (IFNα-2b) vs observation randomised trials demonstrated that a treatment benefit was observed only in patients with an ulcerated melanoma without palpable nodes (hazard ratio [HR] for recurrence-free survival [RFS] was 0.69). This was confirmed by a meta-analysis of 15 adjuvant IFN trials (HR: 0.79)., Patients and Methods: In the EORTC 18081 trial, sentinel node-negative stage II patients with an ulcerated primary melanoma were 1:1 randomised between pegylated (PEG)-IFNα-2b at 3 μg/kg/week subcutaneously and observation, for 2 years, or until disease recurrence or unacceptable toxicity in spite of dose adjustments to maintain an Eastern Cooperative Oncology Group performance status of 0 or 1. Main end-point was RFS. Secondary end-points included distant metastasis-free survival (DMFS), overall survival, and safety (EudraCT Number: 2009-010273-20)., Results: Between February 2013 and January 2017, only 112 patients were randomised, 56 in each arm. The trial was stopped early for lack of recruitment. At a 3.4-year median follow-up, the estimated HR for the PEG-IFNα-2b group compared with the observation group regarding RFS was 0.66 (95% confidence interval [CI]: 0.32-1.37), and the 3-year RFS rate was 80.0% (95% CI: 65.7-88.8%) and 72.9% (95% CI: 58.3-83.0%), respectively. DMFS was prolonged: HR: 0.39 (95% CI: 0.15-0.97), and the 3-year DMFS rate was 90.6% (95% CI: 78.9-96.0%) vs 76.4% (95% CI: 62.1-85.9%). One patient in the PEG-IFNα-2b group died compared with 4 in the observation group. Fifty-four patients started PEG-IFNα-2b treatment, 16 (29%) completed 2 years of treatment, 2 (4%) stopped due to recurrence, 23 (43%) due to toxicity and 14 (25%) due to other reasons., Conclusions: The EORTC 18081 PEG-IFNα-2b randomised trial, observed a similar HR (0.69) for RFS as the previous EORTC trials (0.69). In countries without access to new drugs, adjuvant (PEG)-IFNα-2b treatment is an option for patients with ulcerated melanomas without palpable nodes., Competing Interests: Conflict of interest statement A.M.M.E. reports receiving personal fees as consultant advisor for Biocad, BioInvent, Bristol Myers Squibb (BMS), CatalYm, Ellipses, Glaxo Smith Kline (GSK), HalioDX, Incyte, IO Biotech, ISA Pharmaceuticals, Nektar, Merck Sharpe & Dohme (MSD), Novartis, Pfizer, Polynoma, Regeneron, Sanofi, Sellas, SkylineDx. P.R. reports receiving personal fees as consultant advisor for Novartis, MSD, BMS, Roche, Pfizer, Blueprint Medicines and Pierre Fabre, outside the submitted work. R.H.-W. reports receiving grants and non-financial support from EORTC, during the conduct of the study. C.R. reports personal fees as consultant advisor for Roche, Pierre Fabre, Merck, Novartis, Amgen, BMS, Novartis, MSD, Sanofi, Biothera, Ultimovacs, outside the submitted work. A.v.A. reports receiving grants from Amgen, Bristol-Myers Squibb, Novartis, MSD-Merck, Merck-Pfizer, Sanofi and 4SC, outside the submitted work. L.B. reports receiving personal fees as consultant advisor for BMS, Novartis, MSD, Swedish Orphan, Bayer and Incyte outside the submitted work. A.M. reports receiving personal fees from Novartis, Pierre Fabre, MSD and SunPharma, outside the submitted work. J.J.G. reports receiving personal fees for advisory role from BMS, Novartis, MSD, Roche, Amgen,Pierre Fabre, Merck, Pfizer and Sanofi, and has also received travel support from BMS, Novartis, MSD, outside the submitted work. D.S. reports receiving grants, personal fees for consulting or advisory role; received honoraria; received travel expenses, accommodations, expenses from MSD, during the conduct of the study; and also received personal fees for consulting or advisory role; honoraria; travel expenses, accommodations, expenses from Roche / Genentech, personal fees, non-financial support and other from Novartis, grants and personal fees from BMS, personal fees and non-financial support from Merck Serono, and Amgen, personal fees from Immunocore, Incyte, 4SC, Pierre Fabre, Mologen, Sanofi / Regeneron, Roche, Sysmex, Agenus, Array BioPharma, AstraZeneca, InFlarX, Philogen, Nektar, Sandoz, non-financial support from Merck, outside the submitted work. M.M., F.G., E.P., E.M., O.B., S.M., M.K. and S.S. report no competing interests. A.A.E.T. reports receiving travel support from Agenus, outside the submitted work., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Joint replacement surgery is a highly effective treatment option for patients with severe osteoarthritis (OA) of the hip and knee when other treatments have failed. Unfortunately, as a result of the COVID-19 pandemic, a temporary suspension of non-urgent elective surgery was implemented. Thousands of patients currently awaiting hip and knee replacements have been affected. Many of these patients will present to their general practitioners for symptom management during this interim period., Objective: The purpose of this article is to summarise current recommendations for the non-operative management of patients with symptomatic OA., Discussion: Non-operative treatment modalities for OA include education, lifestyle modification and exercise, mass reduction, physiotherapy, orthoses, psychology, pharmaceuticals and injections. Multimodal therapy is required for patients with severe symptoms. A number of useful online resources are presented, as access to public allied health services may be limited because of the COVID-19 pandemic.

Background: A watch-and-wait strategy is a nonoperative alternative to sphincter-preserving surgery for patients with locally advanced rectal cancer who achieve a clinical complete response after neoadjuvant therapy. There are limited data about bowel function for patients undergoing this organ-preservation approach., Objective: The purpose of this study was to compare bowel function in patients with rectal cancer managed with a watch-and-wait approach with bowel function in patients who underwent sphincter-preserving surgery (total mesorectal excision)., Design: This was a retrospective case-control study using patient-reported outcomes., Settings: The study was conducted at a comprehensive cancer center., Patients: Twenty-one patients underwent a watch-and-wait approach and were matched 1:1 with 21 patients from a pool of 190 patients who underwent sphincter-preserving surgery, based on age, sex, and tumor distance from the anal verge., Main Outcome Measures: Bowel function was measured using the Memorial Sloan Kettering Cancer Center Bowel Function Instrument., Results: Patients in the watch-and-wait arm had better bowel function on the overall scale (median total score, 76 vs 55; p < 0.001) and on all of the subscales, with the greatest difference on the urgency/soilage subscale (median score, 20 vs 12; p < 0.001)., Limitations: The study was limited by its retrospective design, small sample size, and temporal variability between surgery and time of questionnaire completion., Conclusions: A watch-and-wait strategy correlated with overall better bowel function when compared with sphincter-preserving surgery using a comprehensive validated bowel dysfunction tool. See Video Abstract at http://links.lww.com/DCR/B218. FUNCIÓN EVACUATORIA INFORMADA POR PACIENTES EN CÁNCER RECTAL MANEJADO CON UNA ESTRATEGIA DE OBSERVAR Y ESPERAR DESPUÉS DE LA TERAPIA NEOADYUVANTE: UN ESTUDIO DE CASOS Y CONTROLES: Observar y esperar es una alternativa no operativa a la cirugía de preservación del esfínter para pacientes con cáncer rectal localmente avanzado que logran una respuesta clínica completa después de la terapia neoadyuvante. Hay datos limitados sobre la función evacuatoria en pacientes sometidos a este abordaje para preservación de órganos.Evaluar la función evacuatoria en pacientes con cáncer rectal manejados con observar y esperar comparado a pacientes sometidos a cirugía de preservación de esfínteres (escisión mesorrectal total).Estudio retrospectivo de casos y controles utilizando resultados reportados por pacientes.Centro especializado oncológico.21 pacientes se sometieron a observar y esperar y se compararon con 21 pacientes de un grupo de 190 pacientes que se sometieron a cirugía de preservación de esfínteres controlando por edad, sexo y la distancia del tumor al borde anal.Función evacuatoria utilizando un instrumento de valoración del Centro de Cáncer Memorial Sloan Kettering.Los pacientes de observar y esperar demostraron mejor función evacuatoria en la escala general (puntuación total media, 76 versus 55; p <0,001) y en todas las subescalas, con la mayor diferencia en la subescala de urgencia / ensuciamiento fecal (puntuación media, 20 versus 12; p <0,001).Diseño retrospectivo, numero de muestra pequeño y variabilidad temporal entre la cirugía y el tiempo de finalización del cuestionario.Observar y esperar se correlacionó con mejor función evacuatoria en general en comparación con la cirugía de preservación del esfínter utilizando una herramienta integral validada para la disfunción evacuatoria. Consulte Video Resumen en http://links.lww.com/DCR/B218. (Traducción-Dr. Adrián Ortega).

The practice of colposcopy, a diagnostic procedure to evaluate for vaginal, vulvar, and cervical dysplasia, has evolved to incorporate patient risk factors for high-grade cervical intraepithelial neoplasia (CIN) and cancer. Changes in cervical cancer screening and guidelines, human papillomavirus (HPV) vaccination recommendations, and colposcopy standards from the American Society for Colposcopy and Cervical Pathology (ASCCP) have implications for all primary care clinicians, not only those who perform colposcopies. Primary care clinicians should offer HPV vaccination to all patients between the ages of nine and 26, in addition to cervical cancer screening and follow-up guidance. Primary care clinicians should recognize the degrees of risk of high-grade CIN and cancer conferred by cytology, HPV subtype, and persistence of HPV infection. Clinicians should address modifiable risk factors such as tobacco use, and provide counseling to patients about colposcopy based on their individual risks. Clinicians should conduct shared decision-making about immediate loop electrosurgical excision procedure vs. colposcopy with multiple biopsies and endocervical sampling for patients with the highest risk of cervical cancer, and for patients who are older than 25 years with at least two of the following: HPV-16, HPV-18, and high-grade squamous intraepithelial lesion cytology. Primary care clinicians should be familiar with the 2019 ASCCP guidelines and develop clinic-based systems to ensure appropriate follow-up of abnormal cytology, positive high-risk HPV testing, diagnosed CIN, and cervical cancer. Patients with an abnormal cervical cancer screening history require surveillance, which differs from routine screening for patients with normal prior screening results. Long-term surveillance is recommended for patients with CIN 2 or worse.

Autosomal dominant hypocalcaemia is a rare aetiology of hypocalcaemia, caused by gain-of-function mutations of the calcium-sensing receptor ( CASR ) gene. We present two cases of two asymptomatic women (50-year-old-case 1 and 25-year-old-case 2), referred to our endocrinology department for investigation of hypocalcaemia, hyperphosphatemia and inappropriately low parathormone. Both patients had relatives with the same laboratorial findings. At diagnosis, both patients presented basal ganglia calcifications. Genetic analysis was performed, identifying two novel heterozygous CASR variants: c.2269G>A (p.Glu757Lys) and c.2086C>G (p.Leu696Val), respectively, for case 1 and case 2. Affected individuals started oral calcium and vitamin D analogues, aiming to a low-normal calcium level. They remain under observation and are asymptomatic., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Several studies have shown that abnormal urine levels of cytokeratins 8 and 18 are associated with bladder cancer. However, the clinical benefit of the UBC (urinary bladder cancer) Rapid assay has remained unclear., Patients and Methods: We performed the UBC Rapid assay and voided cytology in 336 patients-297 in surveillance for non-muscle-invasive bladder cancer and 39 with newly diagnosed bladder cancer. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated by contingency. We also controlled for the patients with positive UBC Rapid findings but negative cystoscopy findings to prove the former's ability to provide an anticipatory diagnosis., Results: We diagnosed 27 recurrences (9.8%). Overall, the sensitivity of the UBC Rapid assay was better for the higher risk groups and after adding the cytology findings. The only independent predictor of a positive UBC Rapid assay was the tumor size. Of the 81 patients with positive UBC Rapid findings without positive cystoscopy findings, 8 (10%) had developed a recurrence within the first year. Avoiding cystoscopy for the patients with UBC Rapid negative results could avoid 184 cystoscopies (66%) but would result in missing 7 of 13 high-risk recurrences., Conclusions: The performance of the UBC Rapid assay improved with increasing tumor size. Limiting cystoscopies to patients with UBC Rapid positive results could result in a reduction in surveillance cystoscopies but could result in missing high-risk recurrences. Finally, the UBC Rapid assay was not useful for anticipatory diagnoses., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the recurrence and functional outcomes in a primarily hereditary cohort of patients undergoing partial adrenalectomy for pheochromocytoma., Methods: A retrospective review from a prospectively managed database of patients undergoing partial adrenalectomy from 1995 to 2018 at the National Cancer Institute was performed. Local recurrence was defined as imaging evidence of a recurrent or de novo lesion on the operative side. Steroid dependency was defined as requiring daily steroid replacement at time of last follow-up., Results: One hundred and twenty-four partial adrenalectomies, removing 162 tumors, were performed in 107 patients. Most patients had a known hereditary predisposition to develop bilateral, multifocal, and recurrent pheochromocytoma. Median tumor size was 2 cm (interquartile range (IQR) 1.5-2.8). Median follow-up was 60 months (IQR 13-131). Local recurrence occurred in 17 patients (15.8%) and were managed with active surveillance or surgery. A single patient (1/106, 0.9%) developed metastatic spread of pheochromocytoma approximately 14 years after his first of 2 partial adrenalectomies and remains alive under active surveillance. Median time to recurrence was 71 months (IQR 26-127) with 10 patients (9.3%) requiring daily steroid replacement at time of last follow-up., Conclusion: Partial adrenalectomy offers excellent oncologic and functional outcomes, sparing most patients from lifelong steroid replacement therapy. Recurrences can be easily managed with repeat surgery or active surveillance via functional work-up and imaging. Partial adrenalectomy remains the recommended surgical management for patients pre-disposed to development of bilateral, multifocal and recurrent pheochromocytoma., (Published by Elsevier Inc.)

Purpose: We studied the risk of metastatic prostate cancer development in men with Grade Group 2 disease managed with active surveillance at Memorial Sloan Kettering Cancer Center., Materials and Methods: A total of 219 men with Grade Group 2 prostate cancer had disease managed with active surveillance between 2000 and 2017. Biopsy was performed every 2 to 3 years, or upon changes in magnetic resonance imaging, prostate specific antigen level or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival., Results: Median age at diagnosis was 67 years (IQR 61-72), median prostate specific antigen was 5 ng/ml (IQR 4-7) and most patients (69%) had nonpalpable disease. During followup 64 men received treatment, including radical prostatectomy in 36 (56%), radiotherapy in 20 (31%), hormone therapy in 3 (5%) and focal therapy in 5 (8%). Of the 36 patients who underwent radical prostatectomy 32 (89%) had Grade Group 2 disease on pathology and 4 (11%) had Grade Group 3 disease. Treatment-free survival was 61% (95% CI 52-70) at 5 years and 49% (95% CI 37-60) at 10 years. Three men experienced biochemical recurrence, no men had distant metastasis and no men died of prostate cancer during the followup. Median followup was 3.1 years (IQR 1.9-4.9)., Conclusions: Active surveillance appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer treated at a tertiary cancer center. Definitive conclusions await further followup.

Purpose: We report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance at a tertiary cancer center., Materials and Methods: A total of 2,907 patients were managed with active surveillance between 2000 and 2017, of whom 2,664 had Grade Group 1 disease. Patients were recommended confirmatory biopsy to verify eligibility and were followed semiannually with prostate specific antigen, digital rectal examination and review of symptoms. Magnetic resonance imaging was increasingly used in recent years. Biopsy was repeated every 2 to 3 years or after a sustained prostate specific antigen increase or changes in magnetic resonance imaging/digital rectal examination. The Kaplan-Meier method was used to estimate probabilities of treatment, progression and development of metastasis., Results: Median patient age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer the treatment-free probability at 5, 10 and 15 years was 76% (95% CI 74-78), 64% (95% CI 61-68) and 58% (95% CI 51-64), respectively. At 5, 10 and 15 years there were 1,146, 220 and 25 men at risk for metastasis, respectively. Median followup for those without metastasis was 4.3 years (95% CI 2.3-6.9). Distant metastasis developed in 5 men. Upon case note review only 2 of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2-2.0) at 10 years., Conclusions: Active surveillance is a safe strategy over longer followup for appropriately selected patients with Grade Group 1 disease following a well-defined monitoring plan.

Background: While the surgical correction of moderate aortic stenosis (AS) can be deferred with a watchful waiting according to the present guideline, the clinical outcomes for moderate AS with comorbidity have not extensively been studied. We aimed to explore the factors that would contribute to the outcomes of moderate AS with at least five years of follow-up duration., Methods: Medical records review identified patients with moderate aortic valve (AV) stenosis from January 2008 and December 2012. Echocardiographic data were gathered, and the final 5-year clinical outcomes, defined as the composite of cardiovascular (CV) death, admission for heart failure (HF) aggravation, and AV replacement, were evaluated., Results: Among 148 patients (mean age, 69.3 years; mean AV area, 1.24 cm2), 79 had adverse outcomes (16 CV deaths, 32 AV replacements, and 31 HF cases), during a mean follow-up of 5.6 years. The event group showed worse dyspnea of NYHA III-IV and a higher frequency of diabetes mellitus (DM). They had a higher frequency of moderate or moderate-to-severe functional mitral regurgitation (MR) and smaller AV area. In the multivariate analysis, DM (HR 2.29, 95% CI 1.03-5.10), moderate or moderate-to-severe MR (HR 4.84, 95% CI 1.66-10.07), and NYHA III-IV (HR 3.84, 95% CI 1.72-8.56) independently were associated with adverse outcomes., Conclusions: The symptomatic patients with moderate AS had higher events than expected, and early intervention should be considered in case of concomitant MR and DM.

Background: Plantar heel pain (PHP) is present in a wide range of individuals and creates significant burden to quality of life and participation in physical activity. The high recurrence rates and persistence of PHP suggests current management options may not address all potentially modifiable factors associated with the condition. Reports of intrinsic foot muscle (IFM) atrophy in individuals with PHP, together with biomechanical evidence of their important contribution to optimal foot function, suggests that an intervention focused on IFM training may be beneficial in managing PHP. We will test the feasibility of a prospective, assessor-blinded, parallel-group, randomised clinical trial that compares foot exercise plus education to brief advice in individuals with PHP., Methods: Twenty participants with PHP will be randomly allocated to one of two groups for a 12-week intervention period: (i) foot exercise plus education, or (ii) brief advice. The foot exercise plus education group will attend eight sessions with a physiotherapist and receive detailed education on self-management strategies as well as a progressive exercise program for the IFMs. The brief advice group will attend one session with a physiotherapist and receive brief information about self-management strategies and reassurance. Outcome measures will be obtained at baseline and the primary end-point of 12 weeks. Primary outcomes will be the feasibility of conducting a full-scale randomised clinical trial (RCT), and the credibility and acceptability of the foot exercise plus education intervention. Secondary outcomes will explore treatment effects, which will consist of pain, physical function, physical activity level, pain self-efficacy, perceived treatment effect, magnetic resonance and ultrasound image measurement of IFM morphology, ultrasound imaging measurement of plantar fascia thickness, IFM motor performance, foot posture, foot mobility, ankle dorsiflexion range of motion, toe flexor and plantar flexor strength/endurance., Discussion: To reduce the burden of PHP on individuals and society, there is a need to establish effective treatments that are feasible and accepted by patients and health professionals. This trial will be the first to evaluate the feasibility of conducting a full-scale RCT, as well as the credibility, acceptability, and treatment effects, of education and foot exercise for PHP. The findings of this study will inform the development of a full-scale RCT., Trial Registration: The trial protocol was prospectively registered with the Australia and New Zealand Clinical Trial Registry (ACTRN12619000987167) on 11th July 2019.

Patent foramen ovale (PFO) is the most common anatomical cause of an interatrial shunt. It is usually asymptomatic but may cause paradoxical embolism, manifesting as stroke, myocardial infarction or visceral/peripheral ischaemia. PFO is a risk factor for stroke and may be associated with migraine with aura. New evidence suggests PFO closure reduces the risk of recurrent ischaemic stroke in a highly selected population of stroke survivors: those aged 60 years or younger with a cryptogenic stroke syndrome, a large right-to-left shunt, an atrial septal aneurysm and no evidence of atrial fibrillation. They benefit from percutaneous PFO closure in addition to antiplatelet therapy, rather than antiplatelet therapy alone. Current evidence does not support PFO closure in the treatment of migraine., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We assessed the feasibility, patient acceptability of and compliance of a new surveillance strategy for ovarian cancer surveillance in women with BRCA mutations, based on assessments of serum CA125 and HE4 every 4 months (Risk of Ovarian Cancer Algorithm (ROCA) arm), compared to Standard of Care (SOC) surveillance with CA125 blood tests and pelvic ultrasounds every 6 months., Methods: Women were recruited 6/13/16-9/11/17 from an integrated health care system in California for this non-randomized prospective cohort study. Women were invited to participate in a novel serum biomarker surveillance strategy using ROCA or they could opt to be in the standard of care control arm with ultrasound and CA 125 every 6 months. Outcomes assessed included compliance, self-reported distress using the Impact of Event Scale (IES) and cancer anxiety using the Cancer Worry Scale., Results: There were 159 women in the ROCA arm and 43 in the SOC arm. Overall, compliance was higher in the ROCA arm (83.2%) than in SOC (51.9%), p < 0.0001. Based on the IES, ROCA arm women reported less feelings about intrusion and avoidance at 12 months compared to baseline; the difference approached significance for intrusion (7.6% vs 4.1% severe, p = 0.057) and was statistically significant for avoidance (20.8% vs 9.9% severe, p = 0.034)., Conclusions: This pilot demonstrated that compliance was high with blood tests performed every four months for ovarian cancer surveillance. Moreover, ROCA women had lower stress scores over time than SOC women. Given the lack of clinical utility and poor compliance shown with traditional ultrasound and CA125 tests, further investigation is warranted of longitudinal biomarker surveillance for early detection of ovarian cancer., Competing Interests: Declaration of competing interest Kaiser Permanente provided grant support for authors on this project acknowledged below, all authors declared no other conflict of interest except for Dr. Steven J Skates who declared: Additional grants from US National Cancer Institute, during the conduct of the study; scientific advisory board services for LUNGevity Foundation, and another from SISCAPA Assay Technologies, outside the submitted work; In addition, Massachusetts General Hospital has co-licensed software for early detection of ovarian cancer to Abcodia, with institutional set fraction of payments supporting Dr. Skates' research., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: A proportion of men with grade group (GG) 2 intermediate risk (IR) prostate cancer are downgraded to GG1 or harbor favorable pathology (FP, defined as GG1 or GG2 with <5% Gleason pattern 4) at radical prostatectomy (RP). Prediction of downgrading or FP may help identify potential active surveillance candidates within this group that have outcomes similar to biopsy low-risk (LR) disease., Methods: We performed a comparative cohort study of biopsy LR and IR men who underwent RP at The Johns Hopkins Hospital and Bayview Medical Center between 2005 and 2018. We evaluated pathological outcomes at RP and recurrence-free survival (RFS). Multivariable logistic regression and Cox proportional hazards regression were applied and individual predicted probabilities were calculated., Results: Among 2943 biopsy GG2 IR patients, 223 (7.6%) were downgraded to GG1, while 525 (17.8%) had FP; 730 of 1325 biopsy LR patients (55.1%) were upgraded (GG >1). Concordance statistics for final predictive regression models were 0.76 for downgrading and 0.70 for upgrading. Biopsy GG2 IR patients downgrading to GG1 or harboring FP had similar RFS to biopsy LR patients. A cutoff of >10% predicted probability of downgrading (24.7% of patients; hazard ratio [HR], 1.55; 95% CI, 0.89-2.68) or >20% predicted probability of FP (37.0% of patients; HR, 1.35; 95% CI, 0.81-2.24) led to similar RFS to biopsy LR patients., Conclusion: GG2 IR patients who experience downgrading or harbor FP had similar oncologic outcomes as LR patients. The developed models may serve as tools to inform patients about the risks of pathological downgrading/upgrading and help identify a segment of GG2 IR patients who would consider pursuing active surveillance based on predicted probability cutoffs., (© 2020 American Cancer Society.)

Objective: To evaluate the association between apparent diffusion coefficient (ADC) on initial multiparametric MRI (mpMRI) and biopsy grade reclassification (GR) to grade group (GG) ≥2 prostate cancer (CaP) in men on active surveillance (AS) with GG 1 CaP., Methods: We retrospectively identified 242 AS patients with reported ADC values on their initial mpMRI. ADC value from the index lesion was assessed as an independent predictor of GR using a Cox model. To ease clinical interpretation, we used a log-rank test to establish an ADC cutoff of 1128 × 10 -6 mm 2 /s for Kaplan-Meier analysis., Results: Of the 242 men, 70 underwent GR following initial mpMRI, of which 26 (37%) had GR at the index lesion. There was no significant difference in the median interval between biopsies for men with and without GR (P >.9). Men with GR had significantly lower median ADC than those without GR (P = .01). In multivariable analysis adjusting for age, prostate-specific antigen density, and National Comprehensive Cancer Network risk group, a 100-unit decrease in ADC was associated with a 12% increase in the risk of GR (HR = 1.12, 95% CI: 1.01-1.22, P = .03). Two- and 4-year rates of freedom from GR were significantly lower for men with ADC <1128 × 10 -6 mm 2 /s vs ADC ≥1128 × 10 -6 mm 2 /s (62% and 42% vs 78% and 68%, respectively; P <.001)., Conclusion: For AS patients, lower ADC on initial mpMRI index lesion is associated with increased risk of GR to GG ≥2 CaP and would be a useful component of multivariable risk prediction tools., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Total body photography (TBP) facilitates early melanoma detection, but long-term outcomes have not been well studied. Our objectives were to examine melanoma diagnoses, role of TBP-associated follow-up visits, and survival in patients monitored by TBP. A total of 1955 patients meeting inclusion criteria received TBP from 2004-2013 at a single academic center. We compared the melanoma diagnoses and overall survival of 1253 patients with any follow-up visits (median, three visits; range, 1-18) and 702 patients with no follow-up visits. Use of TBP photographs influenced decision to biopsy 66 of 121 (54.5%) melanomas diagnosed after TBP. Lower invasive melanoma Breslow depth was significantly associated with having one or more follow-up visit (median, 0.83 vs 0.33 mm; P = .002) and photographic review (median, 0.31 vs 0.48 mm; P = 0.02). In multivariable analyses, greater overall survival was significantly associated with having one or more follow-up visit after TBP (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.14-0.91; P < 0.032) and having more than 100 nevi (HR, 0.37; 95% CI, 0.22-0.64; P = 0.004). Worse overall survival was significantly associated with increasing age (HR per year, 1.06; 95% CI, 1.04-1.08; P < 0.001) and male sex (HR, 2.65; 95% CI, 1.48-4.73; P = 0.001). Thus, monitoring by TBP was associated with subsequent melanoma diagnoses of lower stage and depth and greater overall survival., (© 2020 Japanese Dermatological Association.)

Objectives: Biannual ultrasonography, a globally accepted surveillance method, has low sensitivity in detecting early-stage hepatocellular carcinoma (HCC). We aimed to investigate the effectiveness of a surveillance strategy using annual contrast-enhanced MRI to detect HCCs at early-stage., Materials and Methods: We reviewed the data of 294 patients with consistent annual contrast-enhanced MRI and biannual alpha fetoprotein (AFP) surveillance between 2008 and 2017. Patients were stratified for HCC risk as low-intermediate-high risk group using Toronto risk score. HCCs were classified according to Barcelona Clinic Liver Cancer staging system., Results: Thirty-five (11.9%) HCCs were detected with annual surveillance MRI. Of those, 30 (85.8%) were early-stage and 15 (42.9%) were very early-stage. The majority of patients (82.9%) with surveillance detected HCC were high risk at the entry. MRI had sensitivity of 83.3 and 80% with a specificity of 95.4 and 91.4%, for detecting early and very early-stage HCC, respectively. Addition of AFP to MRI displayed similar sensitivity and specificity rates to detect early and very early HCCs. The area under the curve of MRI alone and combination with AFP was not statistically different (Any-HCC: 0.905 vs. 0.924; Early-HCC: 0.853 vs. 0.885; Very early-HCC: 0.838 vs. 0.885, respectively, all P values >0.2)., Conclusion: Annual MRI strategy demonstrated a satisfactory performance in the surveillance of HCC, in terms of detecting most of the lesions in earlier curable stages and indicating high sensitivity with no additional benefit of biannual AFP. New risk stratified screening algorithms may further increase the yield of HCC surveillance among cirrhotic patients.

Objective: To assess the qualitative and quantitative changes on prostate multiparametric magnetic resonance imaging (mpMRI) following partial gland ablation (PGA) with cryotherapy and correlate with histopathology., Methods: We used 3D Slicer to generate prostate models and segment ipsilateral (treated) and contralateral peripheral and transition zones in 10 men who underwent MRI/transrectal ultrasound fusion-guided PGA during 2017-2018. Pre- and post-PGA volumes of prostate segments were compared. Post-PGA mpMRI were categorized according to PI-RADS v2 and treatment response on mpMRI was assessed in a manner similar to the radiology evaluation framework following liver lesion ablation., Results: Median volume of ipsilateral peripheral and transition zones decreased from 10.9 mL and 13.0 mL to 7.2 mL and 10.8 mL (P = .005), respectively. Median volume of contralateral peripheral and transition zones also decreased from 12.1 mL and 12.5 mL to 9.9 mL to 10.4 mL (P = .005), respectively. Five men had clinically significant disease (Grade group ≥2) on post-PGA biopsy (3 within treatment field and 2 outside). Of the men with clinically significant prostate cancer, mpMRI revealed PI-RADS 3 lesions in 2. However, the treatment response framework did not detect residual disease., Conclusion: PGA results in asymmetrical and significant reductions in prostate volume. Our results highlight the need for a separate assessment framework to enable standardization of the interpretation and reporting of post-PGA surveillance mpMRI. Moreover, our findings have significant implications for MRI-targeted surveillance biopsy following PGA with cryotherapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To report biopsy-related and oncologic outcomes in a large prospective active surveillance cohort that was initiated in the premagnetic resonance imaging era and to additionally identify clinical factors associated with disease reclassification in order to inform future studies designed to improve enrollment and follow-up on active surveillance., Methods: Patients were prospectively enrolled at a single institution from 2006 to 2014 and followed until 2016. Men with Gleason 6 or 7 disease were eligible, and those with >6 months follow-up were included in the analysis. Patients were risk stratified based on clinical/pathologic criteria, including based on a combination of baseline and confirmatory biopsy tumor characteristics. Reclassification-free survival, based on tumor volume increase or Gleason score increase, was analyzed using multivariable Cox proportional hazards models., Results: Of 825 enrolled patients, 682 met inclusion criteria. Median follow-up was 40 months (range 6.6-126.8). Disease was reclassified in 249 (36.5%), and 157 (23.0%) underwent treatment. A single positive core with a negative confirmatory biopsy was significantly associated with time to reclassification (median not met vs 43 months, log rank test P <.001). Composite tumor length, defined as the combined tumor length between baseline and confirmatory biopsies, was associated with shorter Gleason upgrade-free survival (hazard ratio 1.24, 95% confidence interval 1.11-1.40, P <.001) in multivariable analysis., Conclusion: Baseline stratification using clinical factors including tumor length may refine risk stratification and offer the foundation on which new systems that incorporate modalities such as magnetic resonance imaging may be based., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: We aimed to determine the interobserver reproducibility of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria for magnetic resonance imaging in patients on active surveillance (AS) for prostate cancer (PCa) at two different academic centres., Methods: The PRECISE criteria score the likelihood of clinically significant change over time. The system is a 1-to-5 scale, where 1 or 2 implies regression of a previously visible lesion, 3 denotes stability and 4 or 5 indicates radiological progression. A retrospective analysis of 80 patients (40 from each centre) on AS with a biopsy-confirmed low- or intermediate-risk PCa (i.e. ≤ Gleason 3 + 4 and prostate-specific antigen ≤ 20 ng/ml) and ≥ 2 prostate MR scans was performed. Two blinded radiologists reported all scans independently and scored the likelihood of radiological change (PRECISE score) from the second scan onwards. Cohen's κ coefficients and percent agreement were computed., Results: Agreement was substantial both at a per-patient and a per-scan level (κ = 0.71 and 0.61; percent agreement = 79% and 81%, respectively) for each PRECISE score. The agreement was superior (κ = 0.83 and 0.67; percent agreement = 90% and 91%, respectively) when the PRECISE scores were grouped according to the absence/presence of radiological progression (PRECISE 1-3 vs 4-5). Higher inter-reader agreement was observed for the scans performed at University College London (UCL) (κ = 0.81 vs 0.55 on a per-patient level and κ = 0.70 vs 0.48 on a per-scan level, respectively). The discrepancies between institutions were less evident for percent agreement (80% vs 78% and 86% vs 75%, respectively)., Conclusions: Expert radiologists achieved substantial reproducibility for the PRECISE scoring system, especially when data were pooled together according to the absence/presence of radiological progression (PRECISE 1-3 vs 4-5)., Key Points: • Inter-reader agreement between two experienced prostate radiologists using the PRECISE criteria was substantial. • The agreement was higher when the PRECISE scores were grouped according to the absence/presence of radiological progression (i.e. PRECISE 1-3 vs PRECISE 4 and 5). • Higher inter-reader agreement was observed for the scans performed at UCL, but the discrepancies between institutions were less evident for percent agreement.

Accurate diagnosis of Pancreatic cysts (PC) is key in the management. The knowledge of indications for surgery, the role of endoscopic ultrasound-guided fine needle aspiration, cyst fluid analysis, imaging, and surveillance of PC are all important in the diagnosis and management of PC. Currently, there are many guidelines for the management of PC. The optimal use of these guidelines with a patient-centered approach helps diagnose early cancer and prevent the spread of cancer., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors related to the manuscript., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

In young children with small angle exotropia, making decisions for the individual patient whether to perform surgery or not, and choosing the optimal time for surgical intervention are quite difficult. We aimed to compare the long-term outcomes of small angle intermittent exotropia of 20 prism diopters (PD) or less after observation versus strabismus surgery. A retrospective study was performed on 164 patients aged 3 to 13 who underwent surgical intervention or observation with or without conservative management for intermittent exotropia of 14 to 20 PD. The minimum follow-up period was 2 years. The average follow-up period was 3.9 ± 2.2 years in the observation group and 4.5 ± 2.3 years in the surgery group. At the final examination, the mean angle of deviation at distance was 11.1 ± 8.9 PD in the observation group and 9.0 ± 7.5 PD in the surgery group, which was not significantly different (P = 0.121). Changes in sensory outcome and fusional control were not significantly different between both groups (P = 0.748 and P = 0.968). Subgroup analysis including patients with poor fusional control also showed similar results. By multivariate analysis, the type of surgery, unilateral recess-resect procedure, was the only predictive factor of good motor outcome in the surgery group. In conclusion, long-term surgical outcomes in small angle exotropia did not appear to be more satisfying than observation in terms of motor and sensory outcomes.

Objectives: To compare the loss of working time due to sick leave by treatment strategy for localised prostate cancer., Design: Nationwide cohort study., Setting: Sweden., Participants: A total of 15 902 working-aged men with localised low or intermediate-risk prostate cancer diagnosed during 2007-2016 from the Prostate Cancer Data Base Sweden, together with 63 464 prostate cancer-free men. Men were followed until 2016., Primary and Secondary Outcome Measures: Using multistate Markov models, we calculated the proportion of men on work, sick leave, disability pension and death, together with the amount of time spent in each state. All-cause and cause-specific estimates were calculated., Results: During the first 5 years after diagnosis, men with active surveillance as their primary treatment strategy spent a mean of 17 days (95% CI 15 to 19) on prostate cancer-specific sick leave, as compared with 46 days (95% CI 44 to 48) after radical prostatectomy and 44 days (95% CI 38 to 50) after radiotherapy. The pattern was similar after adjustment for cancer and sociodemographic characteristics. There were no differences between the treatment strategies in terms of days spent on sick leave due to depression, anxiety or stress. Five years after diagnosis, over 90% of men in all treatment strategies were free from sick leave, disability pension receipt and death from any cause., Conclusions: Men on active surveillance experienced less impact on working life compared with men who received radical prostatectomy or radiotherapy. From a long-term perspective, there were no major differences between treatment strategies. Our findings can inform men diagnosed with localised prostate cancer on how different treatment strategies may affect their working lives., Competing Interests: Competing interests: ML owns Pfizer and AstraZeneca shares., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Various methods categorize tumour response after neoadjuvant therapy, including down-staging and tumour regression grading. Response categories allow comparison of different treatments within clinical trials and predict outcome. A reproducible response categorization could identify subgroups with high or low risk for the most appropriate subsequent treatments, like watch and wait. Lack of standardization and interpretation difficulties currently limit the usability of these approaches. In this review we describe these difficulties for the evaluation of chemoradiation in rectal cancer. An alternative approach of tumour response is based on patterns of residual disease, including fragmentation. We summarise the evidence behind this alternative method of response categorisation, which explains a number of very relevant clinical discrepancies. These issues include differences between downstaging and tumour regression, high local regrowth in advanced tumours during watchful waiting procedures, the importance of resection margins, the limited value of post-treatment biopsies and the relatively poor outcome of patients with a near complete pathological response. Recognition of these patterns of response can allow meaningful development of novel biomarkers in the future., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Striking a balance between cancer treatment and patient-centred care is becoming ever more important in older patients with rectal cancer as the population is ageing. The treatment decision made by the modern multidisciplinary colorectal team will recommend pre-operative chemo-radiotherapy followed by surgery for advance rectal cancer and surgery alone for early rectal cancer, as the "standard of care" is surgery. However, an alternative non-surgical treatment option should be consider for older patients with rectal cancer as the surgical harm can far outweigh the potential benefits. There is published evidence that mortality is higher with increasing age. An alternative treatment option to surgery when patients are not suitable or refusing surgery is to offer them external beam radiotherapy (EBRT) or chemo radiotherapy (EBCRT). A proportion of these patients can achieve a clinical complete response (cCR) which enable adoption of 'watch and wait' strategy to avoid surgery. However, a third of patients who achieved initial cCR can develop local regrowth within the first two years. This require salvage surgery which reduces their chance of organ preservation. Contact X-ray brachytherapy (CXB) or High Dose Rate Endo Brachy Therapy (HDREBT) boost following external beam radiotherapy can improve the initial cCR rate and reduce the risk of local regrowth. Those patients with persistent residual cancer or regrowth after brachytherapy boost following EBCRT or EBRT can have salvage surgery later without compromising their chance of cure. Therefore, patients should be fully aware of their treatment options and have 'a choice' when deciding and consenting their treatment., Competing Interests: Declaration of competing interest ASM- No conflict of interest to declare. JPG - Medical advisor to Ariane Medical Systems., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Aims: To determine the long-term outcomes of ocular adnexal lesions in immunoglobulin G4-related ophthalmic disease (IgG4-ROD)., Methods: This retrospective, non-randomised exploratory study included 82 patients with ocular adnexal lesions. We evaluated the long-term outcomes in 71 patients during the median follow-up period of 30 months, who underwent either watchful waiting (n=20; range 12-90 months) or systemic corticosteroid treatment, delivered according to consensus guidelines (n=51; range 9- 115 months). We also analysed factors that might contribute to recalcitrance to treatment., Results: Of 82 patients, 40 (49%) were male, and the median patient age was 60 years old. Twenty-one (26%) patients with extraocular muscle (EOM) and/or trigeminal nerve branch (CN V) enlargements had a significantly high frequency of multiple ocular adnexal lesions (p<0.0001, Fisher's exact test). In addition, two patients developed EOM and/or CN V enlargements de novo over time. Twenty patients with solitary lacrimal gland enlargements preferred watchful waiting, due to mild symptoms. Of these, 18 (90%) lesions remained dormant throughout a median follow-up of 27 months. Among 51 patients treated with corticosteroids, 31 (61%) experienced relapses after treatment and required systemic low-dose maintenance treatment. A multivariate analysis indicated that EOM and/or CN V enlargements comprised a risk factor for relapse (HR 2.7; 95% CI 1.1 to 6.7)., Conclusions: This exploratory study showed that different types of ocular adnexal lesions in IgG4-ROD displayed distinct proliferative activities. Our results suggested that EOM and/or CN V enlargements might be secondary lesions that confer refractoriness to systemic corticosteroid treatment recommended by consensus guidelines., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: The study aimed to assess if adherence to a total-neoadjuvant-treatment (TNT) protocol followed by observation(watch-and-wait) led to the successful nonoperative-management of low-rectal-cancer., Methods: In this study, patients with primary, resectable-T3-T4, N0-N1 distal-rectal-adenocarcinoma underwent-chemoradiotherapy + consolidation-chemotherapy (TNT). During the-TNT-period, endoscopy, MRI, and FDG-PET/CT were performed. We allocated patients with complete-clinical-tumor-regression, who underwent endoscopy every two months, MRI every-four-months, and PET/CT every-six-months-after-treatment, to the observation-group(OG). All other patients were referred for surgery. The OG was followed-up. The primary endpoint was local tumor-ecurrence after allocation to the OG., Results: Between 2015 and 2018, we enrolled 66-patients. Of 60-patients who were eligible to participate, 39 had complete-clinical-response(cCR) and were allocated to the OG, six underwent local-excision (LE), and 15 underwent total-mesorectal-excision (TME). The median follow-up duration was 22 (9-42) months. The local-recurrence-rate in the OG was 15.3%, and the LE and TME rates were 16.6% and 0%, respectively. All recurrence cases were salvaged through either LE or TME. The-distant-metastasis rate was 5.1%, 16.6%, and 12.5% in the OG, LE, and TME groups, respectively. The endoscopic negative-predictive-value(NPV) was 50%, and the positive-predictive-value(PPV) was 76.9% in the surgery group (LE + TME). MRI; NPV-50%, PPV-76.9%. PET/CT; NPV-100%, PPV-93.3%. Six patients(28.57%) from surgery group achieved complete pathological response (cPR)., Conclusion: Our results indicated a high proportion of selected-rectal-cancers with-cCR after neo-adjuvant-therapy could potentially be managed non-operatively, and major surgery may be avoided., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Active surveillance is a good management option for some men with non-metastatic prostate cancer. In this review, we examine the evidence for several topics related to active surveillance. We examine: (1) which patients should be eligible for active surveillance, (2) what follow-up (monitoring) protocols should be used for men on surveillance, (3) what is the role of prostate magnetic resonance imaging (MRI) for men on surveillance, and (4) what is the prognosis for men who choose surveillance compared to radical treatment. In many instances, the evidence is evolving or lacking. In these situations, we highlight the limitations of the data.

Introduction: The aim was assess the oncological and functional outcome of the watch-and-wait (W&W) approach in older patients with a clinical (near)complete response after neoadjuvant treatment for rectal cancer., Material and Methods: Patients were included in a W&W-approach (2004-2019) when digital rectal examination, endoscopy and MRI showed a (near)clinical complete response. Patients underwent endoscopy and MRI every 3 months during the first year, and 6-monthly thereafter. Patients aged ≥75 and ≥ 2 years of follow-up (FU) were selected. Oncological outcomes were assessed with Kaplan-Meier curves. Functional outcome was assessed with colostomy-free rate, Vaizey incontinence score, low anterior resection syndrome-score and International Prostate Syndrome Score., Results: 43/304 (14%) of patients in a W&W-approach met the inclusion criteria. Median FU was 37 (24-109) months. 5/43(12%) developed a local regrowth. All were treated surgically, with one patient experiencing a pelvic failure. Distant metastases occurred in 3/43 patients and 4 patients died, 3 of whom not related to rectal cancer. The 3-year local regrowth-free rate was 88%, 3-year non-regrowth disease-free survival 91%, overall survival 97% and 3-year colostomy-free rate 93%. Overall, the bowel- and urinary dysfunction scores at 3, 12 and 24 months indicated good continence, no or minor LARS and moderate urinary problems., Conclusion: W&W for older patients with a clinical (near) complete response appears to be a safe alternative to a total mesorectal excision (TME), with a very high pelvic control rate, and few rectal cancer related deaths. Most patients can avoid major surgery and a definitive colostomy, and have a reasonable anorectal and urinary function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen-detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast-conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So-called "recurrences" are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

In the last three to four decades, the increasing caesarean delivery rate has contributed to several fold increment in the incidence of placenta accreta spectrum disorders globally. Placenta accreta spectrum with its subtypes (accreta, increta and percreta) is one of the devastating obstetric complications. As a result, it is the commonest indication for peripartum hysterectomy and common cause of severe maternal morbidity. However, in recent years, there is a growing interest in and practice of expectant management either to minimize emergency hysterectomy related maternal complications or to preserve the fertility potential of a woman with an intact uterus. A large body of observational research findings has demonstrated the success rate of expectant management in many of well selected cases. Similarly, the experience on delayed hysterectomy was encouraging in order to have less hemorrhage. For the best success of placenta accreta spectrum management, multidisciplinary team approach, antenatal diagnosis and managing such cases in a hospital with center of excellence has been strongly recommended. This literature review provides a robust synthesis of up-to-date knowledge and practice on the challenges and successes of placenta accreta spectrum disorders management. The currently practiced management options in the high and middle income countries are also summarized under seven categories. Therefore, the purpose of this review was to shed light on the applicability of the PAS disorder management modalities in our setup., (© 2020 Yifru Berhan, et al.)

Objective: To evaluate the incidence, predictors, and survival for those small renal masses (SRM, solid mass ≤4 cm suspicious for a clinical T1a renal cell carcinoma) that disappear on imaging while undergoing active surveillance (AS)., Subjects/patients and Methods: The Delayed Intervention and Surveillance for SRM registry prospectively enrolled 739 patients with SRMs. Patients having at least 1 image showing no lesion were considered to have a "disappearing" SRM. Logistic regression assessed predictors of having a disappearing SRM and Kaplan-Meier estimates illustrated relative survival., Results: Of 374 patients enrolled in AS, 22 (5.9%) experienced a disappearing SRM. Mean time to tumor disappearance was 2.0 years (SD = 1.9) and 50.0% reappeared on subsequent CT imaging. SRM disappearance, most commonly encountered on ultrasound imaging surveillance, was independently associated with tumors <1 cm on multivariable analysis (OR = 10.6 (95% CI: 1.1-100.3), P = 0.04). Furthermore, patients with disappearing SRMs were healthier than other patients on AS with no compromise in overall survival during follow-up (5-year survival = 100% vs. 73.2%, P = 0.06)., Conclusions: Approximately 5% of SRM on AS will disappear during follow-up on surveillance imaging. Most of these represent artifacts of heterogeneous imaging modalities, including ultrasound, and the SRM will reappear on subsequent imaging. Given the indolent nature of these lesions, disappearance events do not require reflex repeat imaging and patients should continue AS with their original surveillance schedule intact. A smaller percentage of patients undergoing AS for a SRM may have a mass the permanently disappears., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We investigated the utility of multiparametric magnetic resonance imaging (mpMRI) using Prostate Imaging Reporting and Data System, version 2 (PI-RADSv2), scoring in patients with prostate cancer eligible for active surveillance (AS)., Materials and Methods: The medical records of the patients who had undergone mpMRI before radical prostatectomy from 2014 to 2018 were reviewed. All the patients had met the Prostate Cancer Research International AS criteria. PI-RADSv2 scores were assigned to 12 prostate regions. Unfavorable disease was stratified using the American Joint Committee on Cancer (AJCC) prognostic scale as stage IIB (Gleason score [GS], 3+4 and pathologic stage T2) and IIC-III (GS, ≥ 4+3 or pathologic stage T3)., Results: Of 376 eligible patients, 184 (48.9%), 129 (34.3%), and 63 (16.8%) had AJCC stage I, IIB, and IIC-III disease, respectively. The patients with IIC-III disease were older and had a higher prostate-specific antigen density than those with stage I or IIB disease. PI-RADS 5 lesions were more frequent in patients with stage IIC-III than in patients with stage I or IIB disease. Multivariable analysis revealed that ≥ 2 lesions with a PI-RADS 5 score was an independent predictor for unfavorable disease (hazard ratio [HR], 3.612; P < .001 for IIB; HR, 6.562; P < .001 for IIC-III), and PI-RADS score of ≥ 4 was limited for predicting AJCC stage IIB disease (HR, 2.387; P = .01)., Conclusion: mpMRI with PI-RADSv2 showed high negative predictive value for patients with prostate cancer eligible for AS. Multiple PI-RADS 4-5 lesions were associated with unfavorable disease compared with solitary lesions. Multiple PI-RADS 5 lesions were strongly associated with GS ≥ 4+3 or pathologic T3 disease. Targeted biopsy or radical treatment should be considered for these patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To evaluate active surveillance (AS) outcomes including overall survival (OS), freedom from distant metastases (FDM), freedom from therapeutic intervention (FTI), and quality of life (QOL) outcomes in prostate cancer patients using transperineal template-guided mapping biopsy (TTMB) for patient selection., Methods: From April 2005-January 2016, 226 consecutive, prospectively evaluated prostate cancer patients underwent TTMB for either low-grade prostate cancer or persistently elevated prostate-specific antigen (PSA) and/or the presence of ASAP. Evaluated outcomes included OS, FDM, FTI and QOL including urinary, bowel, sexual function and depression. Repeat biopsy was based on PSA kinetics and/or abnormal digital rectal examination., Results: Of the 226 patients, 212 (93.8%) were Gleason 3 + 3 and 14 (6.2%) were Gleason 3 + 4. The median follow-up was 5.0 years (range 0.8-13.0 years). The mean prostate volume was 61.3 cm 3 with a mean of 59.5 TTMB cores/patient. At the time of AS enrollment, an average of 72.9 cores (TRUS + TTMB) had been obtained for each patient. At 8 years, OS, FTI and FDM were 92.5, 96.8 and 100%. Two hundred and twenty-two patients (98.2%) had a PSA doubling time of more than 3 years. No statistical changes in urinary function, bowel function or depression were noted. At 8 years, 73% of the patients maintained erectile function., Conclusion: Within the confines of the follow-up of this study, the use of TTMB for patient selection identifies a cohort of patients unlikely to develop biochemical or clinical progression and maintain a favorable quality of life.

Introduction : Active surveillance of low-risk papillary thyroid microcarcinomas (PTMCs) was initiated in Japan in 1993 and has since been adopted in many countries, especially after its approval by the American Thyroid Association in 2015. Areas covered : We performed a literature review in Medline/PubMed to identify studies that used active surveillance for PTMCs. Moreover, we performed a literature review about the increased incidence of thyroid microcarcinomas in relation to the relative stability of deaths due to thyroid carcinomas. Expert opinion : No patients showed life-threatening metastasis/recurrence or died of thyroid carcinoma during active surveillance or after conversion surgery following PTMC progression. Thus, active surveillance should be the first-line management of PTMCs without high-risk features. In the future, molecular testing of actively growing PTMCs using cytology specimens could be useful to guide the treatment plan.

Purpose of Review: The treatment of small, low-risk papillary thyroid carcinoma has undergone a paradigm shift, with many tumors now initially treated with active surveillance rather than upfront surgery. Further studies on patients enrolled in active surveillance have refined our knowledge of the clinical behavior of papillary thyroid microcarcinomas., Recent Findings: This article summarizes the major conclusions of landmark trials that launched active surveillance as a viable treatment option for selected patients. We discuss patient factors such as age and tumor size, the assessment of candidates for active surveillance, barriers to acceptance of active surveillance, quality of life issues, and economic considerations., Summary: Active Surveillance is a viable first-line treatment option for select papillary microcarcinomas.

Introduction: Conservative active surveillance has been proposed for low-risk papillary thyroid microcarcinoma (PTMC), defined as ≤1.0 cm and lacking clinical aggressive features, but controversy exists with accepting it as not all such PTMCs are uniformly destined for benign prognosis. This study investigated whether BRAF V600E status could further risk stratify PTMC, particularly low-risk PTMC, and can thus help with more accurate case selection for conservative management., Methods: This international multicenter study included 743 patients treated with total thyroidectomy for PTMC (584 women and 159 men), with a median age of 49 years (interquartile range [IQR], 39-59 years) and a median follow-up time of 53 months (IQR, 25-93 months)., Results: On overall analyses of all PTMCs, tumour recurrences were 6.4% (32/502) versus 10.8% (26/241) in BRAF mutation-negative versus BRAF mutation-positive patients (P = 0.041), with a hazard ratio (HR) of 2.44 (95% CI (confidence interval), 1.15-5.20) after multivariate adjustment for confounding clinical factors. On the analyses of low-risk PTMC, recurrences were 1.3% (5/383) versus 4.3% (6/139) in BRAF mutation-negative versus BRAF mutation-positive patients, with an HR of 6.65 (95% CI, 1.80-24.65) after adjustment for confounding clinical factors. BRAF mutation was associated with a significant decline in the Kaplan-Meier recurrence-free survival curve in low-risk PTMC., Conclusions: BRAF V600E differentiates the recurrence risk of PTMC, particularly low-risk PTMC. Given the robust negative predictive value, conservative active surveillance of BRAF mutation-negative low-risk PTMC is reasonable whereas the increased recurrence risk and other well-known adverse effects of BRAF V600E make the feasibility of long-term conservative surveillance uncertain for BRAF mutation-positive PTMC., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: Rectal cancer patients with a clinical complete response after chemoradiotherapy (CRT) may be followed with a 'watch-and-wait' (W&W) approach as an alternative to surgery. MRI plays an important role in the follow-up of these patients, but basic knowledge on what to expect from the morphology of the irradiated tumour bed during follow-up is lacking, which can hamper image interpretation. The objective was to establish the spectrum of non-suspicious findings during long-term (> 2 years) follow-up in patients with a sustained clinical complete response undergoing W&W., Methods: A total of 1509 T2W MRIs of 164 sustained complete responders undergoing W&W were retrospectively evaluated. Morphology of the tumour bed was evaluated (2 independent readers) on the restaging MRI and on the various follow-up MRIs and classified as (a) no fibrosis, (b) minimal fibrosis, (c) full thickness fibrosis, or (d) irregular fibrosis. Any changes occurring during follow-up were documented., Results: A total of 104 patients (63%) showed minimal fibrosis, 38 (23%) full thickness fibrosis, 8 (5%) irregular fibrosis, and 14 (9%) no fibrosis. In 93% of patients, the morphology remained completely stable during follow-up; in 7%, a minor increase/decrease in fibrosis was observed. Interobserver agreement was excellent (κ 0.90)., Conclusions: Typically, the morphology as established at restaging remains completely unchanged. The majority of patients show fibrosis with the predominant pattern being a minimal fibrosis confined to the rectal wall. Complete absence of fibrosis occurs in only 1/10 cases. Once validated in independent cohorts, these findings may serve as a reference for radiologists involved in the clinical follow-up of W&W patients., Key Points: • In rectal cancer patients with a sustained complete response after chemoradiation, the rectal wall morphology as established on restaging MRI typically remains unchanged during long-term MRI follow-up. • The vast majority of complete responders show fibrosis with the predominant pattern being a minimal fibrotic remnant that remains confined to the rectal wall; complete absence of fibrosis occurs in only 10% of the cases. • Once validated in independent cohorts, the findings of this study may serve as a reference for radiologists involved in the clinical follow-up of rectal cancer patients undergoing watch-and-wait.

Aim: Primary orbital mucosa-associated lymphoid tissue (MALT) lymphomas are generally sensitive to radiotherapy (RT), but a "wait and see" strategy has also been used in asymptomatic patients. Recently, orbital MALT lymphoma has been reported to be associated with Chlamydia psittaci infection. This study aimed to assess the current patterns of care in clinical practice for orbital MALT lymphoma in South Korea., Methods: We performed a multicenter, cross-sectional cohort study of patterns of care for orbital MALT lymphoma in South Korea throughout 2016. All patients were pathologically confirmed to have orbital MALT lymphoma., Results: Overall, eight institutions with 90 patients participated. The survey showed that the most frequent upfront treatment for orbital MALT lymphoma was RT (80/90, 90%). Other treatment modalities were given to a limited number of orbital MALT lymphoma patients as follows: watch and wait, 6/90 (7%); antibiotics, 3/90 (3%) and chemotherapy, 1/90 (1%). Generally, RT was administered to the entire involved site such as the entire conjunctiva/eyelid or entire orbit (96%), with a median total dose of 25.2 Gy. Lens shielding was performed for most patients with conjunctival and eyelid tumors (93%)., Conclusions: RT was the conventional treatment modality for orbital MALT lymphoma. Currently, RT is performed for the entire involved subsites at a lower dose than that previously used, and lens shielding was applied to minimize the orbital complication., (© 2019 John Wiley & Sons Australia, Ltd.)

Small pulmonary nodules are most often managed by surveillance imaging with computed tomography (CT) of the chest, but the optimal frequency and duration of surveillance are unknown. The Watch the Spot Trial is a multicenter, pragmatic, comparative-effectiveness trial with cluster randomization by hospital or health system that compares more- versus less-intensive strategies for active surveillance of small pulmonary nodules. The study plans to enroll approximately 35,200 patients with a small pulmonary nodule that is newly detected on chest CT imaging, either incidentally or by screening. Study protocols for more- and less-intensive surveillance were adapted from published guidelines. The primary outcome is the percentage of cancerous nodules that progress beyond American Joint Committee on Cancer seventh edition stage T1a. Secondary outcomes include patient-reported anxiety and emotional distress, nodule-related health care use, radiation exposure, and adherence with the assigned surveillance protocol. Distinctive aspects of the trial include: 1 ) the pragmatic integration of study procedures into existing clinical workflow; 2 ) the use of cluster randomization by hospital or health system; 3 ) the implementation and evaluation of a system-level intervention for protocol-based care; 4 ) the use of highly efficient, technology-enabled methods to identify and (passively) enroll participants; 5 ) reliance on data collected as part of routine clinical care, including data from electronic health records and state cancer registries; 6 ) linkage with state cancer registries for complete ascertainment of the primary study outcome; and 7 ) intensive engagement with a diverse group of patient and nonpatient stakeholders in the design and execution of the study.