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Nephrolithiasis is a classic indication for parathyroidectomy in primary hyperparathyroidism patients; however, the effects of parathyroidectomy on nephrolithiasis recurrence are not well studied. The aim was to determine effect of parathyroidectomy on time to first nephrolithiasis recurrence and recurrence rate per patient-years.A retrospective cohort study of patients diagnosed with primary hyperparathyroidism and at least one episode of nephrolithiasis was performed. The patients were divided into observation, presurgery, and postsurgery groups. Endpoints were time to first recurrence of nephrolithiasis and average recurrence rate per patient-years.The cohort was comprised of 1,252 patients. In addition, 334 (27%) patients underwent parathyroidectomy and 918 (73%) were observed. The surgical and nonsurgical groups differed significantly in age, sex, Charlson, calcium, and primary hyperparathyroidism level. Overall recurrence rate was 31.3%. The 5-, 10-, and 15-year recurrence-free survival rates were 74.4%, 56.3%, 49.5%, respectively (presurgery), 82.4%, 70.9%, 62.8%, respectively (postsurgery; P.0001), and 86.3%, 77.7%, and 70.6%, respectively (observation). The presurgery group had an increased risk of first recurrence compared with the observation group (hazard ratio 1.89; 95% confidence interval, 1.44-2.47). The average recurrence rates among all surgical patients who recurred were 1 event per 4.3 patient-years presurgery versus 1 event per 6.7 patient-years postsurgery (P = .0001).Recurrent nephrolithiasis is a significant problem in patients with primary hyperparathyroidism. Parathyroidectomy prolongs the time to first recurrence and decreases the number of re-recurrences over time but does not eliminate recurrences. Observation may also be a reasonable approach in selected patients.

BACKGROUND: Current guidelines define primary and secondary endocrine resistance according to the periods of adjuvant endocrine therapy (adj-ET); however, the relationship between adj-ET period and endocrine resistance remains unclear. OBJECTIVE: We examined progression-free survival (PFS) after primary ET for recurrent hormone receptor-positive/HER2-negative breast cancer, and evaluated the relationship between endocrine resistance and the periods of adj-ET. METHODS: We assessed PFS among 183 patients who received ET as primary treatment for the first recurrence, according to the period of adj-ET (adj-ET < 1 year, 1–2 years, ≥2 years, and completion). RESULTS: Patients who relapsed during the first year of adj-ET had the significantly shortest PFS. PFS did not significantly differ between patients who relapsed at 1–2 years of adj-ET and patients who relapsed while on adj-ET but after the first 2 years. CONCLUSIONS: Relapse at 1–2 years after adj-ET initiation might be better classified as secondary endocrine resistance rather than primary endocrine resistance.

Background The effect of long‐term surveillance for asymptomatic patients after curative resection of gastric cancer is being debated. We compared the prognosis of Korean patients with recurrent gastric cancer according to the presence or absence of cancer‐related symptoms at the time of recurrence detection. Methods We retrospectively reviewed the medical records of 305 Korean patients who experienced recurrence after curative resection of primary gastric cancer between March 2002 and February 2017 at Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Results The median follow‐up duration was 169.8 months (1–267.2), and the median age at first recurrence was 58.1 years (23.4–81.9). Among 305 patients with recurrence, 97 of 231 (42.0%) patients with early recurrence (≤5 years after curative surgical resection) and 47 of 74 (63.5%) patients with late recurrence (>5 years after curative surgical resection) had cancer‐related symptoms at recurrence (p = 0.001). For survival after recurrence, detection of asymptomatic recurrence was an independent favorable factor (hazard ratio, 0.527; 95% confidence interval, 0.409–0.681; p, Asymptomatic detection of recurrence possibly improved the survival of gastric cancer long‐term survivors after curative surgical resection. The possibility of local control and targeted‐ or immunotherapy for the recurrent disease was related to the favorable survival outcomes. ​

Qian Wei, Ze Li, Honglei Feng, Li Ren Department of Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of ChinaCorrespondence: Li RenDepartment of Laboratory, Tianjin Medical University Cancer Institute and Hospital, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, People’s Republic of ChinaEmail lirentj@163.comBackground: Pancreatic cancer (PC) is one of the worst prognoses amongst all malignant diseases. It is therefore of great significance to identify biomarkers with predictive clinical value for the prognosis and recurrence of PC.Methods: In our study, enzyme-linked immunosorbent assays (ELISA) were used to detect the expression of Exo-EphA2 in the serum of PC patients and controls. Kaplan–Meier curve and Cox regression analyses were used to evaluate the prognostic value of Exo-EphA2 expression in patients with primary and recurrent PC.Results: The level of serum Exo-EphA2 was significantly higher in the PC group when compared to that of the control group. High expression of Exo-EphA2 in PC was associated with shorter overall survival (OS) and proved to be a significant negative prognostic factor in the multivariate analysis (HR = 1.04, 95% CI: 1.00– 1.09, P < 0.001). Additionally, we found that the level of serum Exo-EphA2 in recurrent PC patients (first recurrence < 12 months) was positively correlated with the level of Exo-EphA2 at primary diagnosis. Multivariate analysis showed that a high expression of Exo-EphA2 in recurrent PC was associated with shorter recurrence-free survival (RFS) (HR = 1.41, 95% CI: 1.10– 1.70, P < 0.001).Conclusion: High expression of serum Exo-EphA2 represents a novel biomarker for a poor prognosis in PC patients.Keywords: pancreatic cancer, exosome, EphA2, prognosis

Objective(s) To identify recurrence patterns and outcomes in women with advanced or recurrent epithelial ovarian cancer (EOC) after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods This is an IRB-approved single-institution cohort study of women who underwent CRS+HIPEC for advanced or recurrent EOC followed in a prospective registry from 1/12/2014–3/1/2020. Recurrence locations were defined as pelvic, upper abdominal (UA) and/or extra-peritoneal (EP). Univariate analysis assessed associations between recurrence location, progression-free survival (PFS), and overall survival (OS). Results In total, 92 women with EOC underwent interval (56.5%; n=52) or recurrent CRS+HIPEC (43.5%; n=40). For interval CRS+HIPEC, recurrence locations were pelvic in 50.0% (n=15), UA in 23.3% (n=7) and EP in 56.7% (n=17); 40.0% (n=12) were EP alone. Similarly, for recurrent CRS+HIPEC, recurrence locations were pelvic (22.5%, n=9), UA (5.0%, n=2) and EP (60.0%, n=24); 66.7% (n=20) were EP alone. For both interval and recurrent CRS+HIPEC, median PFS was 10.5 vs. 13.0 months for pelvic and UA vs. EP only recurrences (p=0.02). Similarly, median OS was 29.2 months for pelvic and UA and not reached for EP only (p=0.05). For interval CRS+HIPEC, there was no difference in median PFS (10.6 vs. 11.7 months, p=0.68) and OS (27.1 vs. 24.8 months, p=0.96) for pelvic and UA vs EP alone. However, for recurrent CRS+HIPEC, pelvic and UA sites of recurrence were associated with reduced PFS (10.0 vs. 18.1 months, p=0.03) and OS (33.6 months vs. not reached, p=0.02) vs. EP only. Conclusions In women with advanced or recurrent EOC undergoing CRS+HIPEC, one-half of patients experience their first recurrence outside of the peritoneal cavity. Providers must be aware of the risk of EP failure in patients treated with CRS+HIPEC.

Local recurrence following resection of retroperitoneal liposarcoma (RLPS) is common. Well-differentiated (WD) and dedifferentiated (DD) RLPS are distinct entities with differing outcomes. A few reports suggest that WDLPS can recur as DDLPS and that DDLPS can recur as WDLPS. This study evaluates whether this change in differentiation from the primary tumor to the first local recurrence impacts long-term outcomes. Retrospective review from 22 sarcoma centers identified consecutive patients who underwent resection for a first locally recurrent RLPS from January 2002 to December 2011. Outcomes measured included overall survival, local recurrence, and distant metastasis. A total of 421 RPLS patients were identified. Of the 230 patients with primary DDLPS, 34 (15%) presented WDLPS upon recurrence (DD → WD); and of the 191 patients with primary WDLPS, 54 (28%) presented DDLPS upon recurrence (WD → DD). The 6-year overall survival probabilities (95% CI) for DD → DD, DD → WD, WD → WD, and WD → DD were 40% (32–48%), 73% (58–92%), 76% (68–85%), and 56% (43–73%) (p < 0.001), respectively. The 6-year second local recurrence incidence was 66% (59–73%), 63% (48–82%), 66% (57–76%), and 77% (66–90%), respectively. The 6-year distant metastasis incidence was 13% (9–19%), 3% (0.4–22%), 5% (2–11%), and 4% (1–16%), respectively. On multivariable analysis, DD → WD was associated with improved overall survival when compared with DD → DD (p < 0.001). Moreover, WD → DD was associated with a higher risk of LR (p = 0.025) A change in RLPS differentiation from primary tumor to first local recurrence appears to impact survival. These findings may be useful in counseling patients on their prognosis and subsequent management.

INTRODUCTION: Optimal treatment for recurrent glioblastoma isocitrate dehydrogenase 1 and 2 wild-type (rGBM IDH-WT) is not standardized, resulting in multiple therapeutic approaches. A phase III clinical trial showed that tumor treating fields (TTFields) monotherapy provided comparable survival benefits to physician’s chemotherapy choice in rGBM. However, patients did not equally benefit from TTFields, highlighting the importance of identifying predictive biomarkers of TTFields efficacy. METHODS: A retrospective review of an institutional database with 530 patients with infiltrating gliomas was performed. Patients with IDH-WT rGBM receiving TTFields at first recurrence were included. Tumors were evaluated by next-generation sequencing for mutations in 205 cancer-related genes. Post-progression survival (PPS) was examined using the log-rank test and multivariate Cox-regression analysis. RESULTS: 149 rGBM patients were identified of which 29 (19%) were treated with TTFields. No significant difference in median PPS was observed between rGBM patients who received versus did not receive TTFields (13.9 versus 10.9 months, p = 0.068). However, within the TTFields-treated group (n = 29), PPS was improved in PTEN-mutant (n = 14) versus PTEN-WT (n = 15) rGBM, (22.2 versus 11.6 months, p = 0.017). Within the PTEN-mutant group (n = 70, 47%), patients treated with TTFields (n = 14) had longer median PPS (22.2 versus 9.3 months, p = 0.005). No PPS benefit was observed in PTEN-WT patients receiving TTFields (n = 79, 53%). CONCLUSIONS: TTFields therapy conferred a significant PPS benefit in PTEN-mutant rGBM. Understanding the molecular mechanisms underpinning the differences in response to TTFields therapy could help elucidate the mechanism of action of TTFields and identify the rGBM patients most likely to benefit from this therapeutic option.

Bevacizumab (BEV) is a key anti-angiogenic agent used in the treatment for recurrent glioblastoma multiforme (GBM). The aim of this study was to investigate whether cytoreductive surgery prior to treatment with BEV contributes to prolongation of survival for patients with recurrent GBM. We retrospectively analyzed the treatment outcomes of 124 patients with recurrent GBM who were initially treated with the Stupp protocol between 2006 and 2019. Given that BEV has only been available in Japan since 2013, we grouped the patients into two groups according to the time of first recurrence: the pre-BEV group (N = 51) included patients who had recurrence before BEV approval, and the BEV group (N = 73) included patients with recurrence after BEV approval. The overall survival after first recurrence (OS-R) was analyzed according to the treatment strategy. Among 124 patients, 27 patients (19.4%) received cytoreductive surgery. There were nine cases in the pre-BEV group and 18 cases in the BEV group. Although the mean extent of resection for both groups was almost equal, OS-R was significantly different. The median OS-R was 8.1 m in the pre-BEV group and 16.3 m in the BEV group (P = 0.007). Multivariate analysis revealed that the unavailability of BEV postoperatively (P = 0.03) and decreasing performance status by surgery (P = 0.01) were significant poor prognostic factors for survival after surgery. With the advent of BEV, cytoreductive surgery might provide superior survival benefit at the time of GBM recurrence, especially in cases where surgery can be performed without deteriorating the patient's condition.

Background Extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection. Methods The participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping. Results Extrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively. Conclusion We have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.

espanolObjetivo. Conocer las caracteristicas y factores de riesgo de infeccion por Clostridioides difficile (ICD) en un hospital de convalecencia es clave para mejorar su manejo. Material y metodos. Estudio retrospectivo con 37 pacientes, durante 43 meses. Describimos variables demograficas, datos clinicos, tiempo hasta el diagnostico, el tratamiento y la evolucion. Resultados. Analisis de 46 episodios (37 pacientes, edad media=82,2 anos). 77,8% tenian dependencia absoluta, 41,7% enfermedad renal cronica, 64,9% habian recibido antibioticos en los 3 meses previos, 40,5% recibian antibioticos en el momento del diagnostico. Fue el primer episodio en 78,4%, y la primera recidiva en 21,6%. En el 89,2% se comenzo tratamiento en las primeras 24 horas tras el diagnostico, mayoritariamente metronidazol. El 83,3% se recuperaron. 3 pacientes murieron por ICD. El diagnostico figuraba en el informe de alta en 91,1%. Conclusiones. El tratamiento antibiotico previo, un alto grado de dependencia, y el fracaso renal, fueron los factores de riesgo principales. Hay margen de mejora en el manejo de ICD en nuestro hospital. EnglishObjective. The aim of the study was to know the characteristics and risk factors of Clostridioides difficile infection (CDI) in a long-term hospital is key to improve its management. Material and methods. Retrospective study with 37 patients, along 43 months. We describe demographic variables, clinical data, time to diagnosis, treatment, and evolution. Results. Analysis of 46 episodes (37 patients, mean age=82.2 years). 77.8% were absolutely dependent, 41.7% had chronic kidney disease, 64.9% had received antibiotics in the previous three months, 40.5% received antibiotics at diagnosis. It was the first episode in 78.4%, and first recurrence in 21.6%. Therapy was started in the first 24 hours after diagnosis in 89.2%, mostly metronidazole. 83.3% recovered, 3 patients died from CDI, diagnosis was registered in the discharge report in 91.1%. Conclusions. Previous antibiotic therapy, high grade of dependency and renal failure were the main risk factors. There is room for improvement in CDI management at our hospital.

Objectives: The recurrence rate of benign endometrial polyps after a hysteroscopic polypectomy is low, between 0% and 15%. There are limited follow-up duration data on recurrence factors for benign polyps after hysteroscopic polypectomy, including recurrences with Versapoint® versus resectoscope. This study aims to estimate the rate of symptomatic recurrence following hysteroscopic polypectomy and to analyze the possible risk factors involved with Versapoint® versus resectoscope. Materials and Methods: We designed a retrospective cohort study in a tertiary university hospital in Seville (Spain) which looked at the results of polypectomy with a 9-mm resectoscope on 42 women between 2008 and 2015 compared to 151 women using Versapoint® during 2014. Results: The rate of first recurrence was 24.35%. There was a strong positive correlation between the recurrence and the follow-up duration (odds ratio [OR] = 2.58; 95% confidence interval [CI] = 1.68–5.04; P = 0.000), the polyps causing abnormal uterine bleeding (OR = 2.5; 95% CI: 1.1–3; P = 0.04), and a polyp size >15 mm (OR = 1.63; 95% CI = 1.3–3.1; P = 0.02). There were no statistical differences in polyps' recurrence among the types of hysteroscopic polypectomy (P > 0.05). Conclusion: The main risk factors for recurrence were polyps causing abnormal uterine bleeding, size, and follow-up duration.

Purpose After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. Methods and Materials Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. Results The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5–81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. Conclusions In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

Purpose This study aimed to assess the exposure and knowledge of urology residents in the management of urethral stricture (US) and to determine if they would be able to perform urethroplasty after graduation and whether urethroplasty should be included as a competency in the training program. Patients and Methods An online survey was sent to all residents enrolled in any urology training program in Saudi Arabia. Fifty-eight (approximately 50%) of the 114 residents who were sent the survey provided responses. Results Most of the residents (45 residents, 77.6%) who responded were exposed to fewer than ten cases of US during their last year of training. Fifty-six residents (96.6%) attended five or fewer urethroplasty procedures in their last year of training. Twenty-three (40%) residents did not attend any urethroplasty procedure in the last year. The most common procedures attended by the residents were minimally invasive treatments (89% cystoscopy with dilatation and 79% direct visual internal urethrotomy (DVIU)). Most residents responded that they would manage newly diagnosed 1 cm US with either cystoscopy and dilatation or with DVIU 53 (91%). For the first recurrence of US, 46 (79%) residents responded that they would still prefer dilatation or DVIU. For the second, third, and chronic recurrences of US, 20 (34.5%), 6 (10.3%), and 5 (8.6%) residents, respectively, responded that they would perform dilatation or DVIU. Residents had low expectations for the success rate of urethroplasty; only 32 (55.2%) residents thought it had a high success rate. Conclusion Urethroplasty is a specialized urological procedure, one that residents have variable exposure to. Privilege to perform such a procedure after graduating should be modified to ensure the best outcome for patients.

Question What is the effect of a McKenzie-based self-management exercise and education program on the risk of recurrence of low back pain (LBP) and on the impact of LBP? Design Randomised controlled trial with concealed allocation, blinded assessors and intention-to-treat analysis. Participants 262 adults recently recovered from an episode of LBP. Intervention The experimental group received a McKenzie-based self-management exercise and education program delivered over two individual sessions of 30 to 45 minutes with a physiotherapist, approximately 2 weeks apart. The control group received a single advice session over the phone. Outcome measures The primary outcome was time to first recurrence of an episode of activity-limiting LBP. Secondary outcomes included time to recurrence of any LBP, time to a recurrence causing care seeking and a composite measure of pain and function (‘impact of LBP’). Participants were followed-up monthly for ≥ 12 months. Results The estimated effect of the experimental intervention on the risk of recurrence of an episode of: activity-limiting LBP was HR 1.11 (95% CI 0.80 to 1.54), any LBP was HR 0.95 (95% CI 0.72 to 1.26), and LBP for which care was sought was HR 0.69 (95% CI 0.46 to 1.04). The quarterly estimates of the experimental intervention’s effect on impact of LBP and their 95% CIs were all within 4 points above or below 0 (no effect) on this scale from 8 to 50. Conclusion This study’s best estimate is that a McKenzie-based self-management exercise and education program does not produce a worthwhile reduction in the risk of an activity-limiting episode of LBP; however, modestly reduced or moderately increased risk cannot be ruled out. It may markedly reduce the risk of an episode of LBP resulting in care seeking, but does not have any worthwhile effect on the impact of LBP over 12 months. Trial registration ACTRN12616000926437.

The inevitable recurrence of glioblastoma (GBM) results in patients often undergoing multiple resections with questionable benefit to overall survival (OS). To systematically review and analyze prior studies examining the potential added benefit of repeat resection (RR) in recurrent GBM. We performed a PRISMA-compliant systematic review of literature published between 1969 to 2019 involving patients undergoing RR at GBM recurrence. The search yielded 3994 non-duplicate citations. Final abstraction included 43 articles, with 2 level II and 41 level III studies. The earliest paper we included was published in 1987 [1], and 35 identified papers (81.4%) were published within the last 10 years. The survival data of 9236 patients (55% male) were analyzed, with a median age of 56; 3726 patients underwent RR. In 31 studies with a comparable single-surgery-only cohort, 20 articles reported a statistically significant increase in OS with RR, 7 reported nonsignificant trends toward increased OS with RR, and 4 reported no significant increase in OS with RR. Twenty-two articles with multivariate analyses of Karnofsky performance scores and 17 articles with extent-of-resection reported these as significant prognostic factors of OS. In 26 studies, median OS among all patients was 17.85 months inclusive of median OS following RR totaling 9.6 months. Notably, in 10 studies with data on subsequent progressions (2+ recurrences), 6 studies reported significant increases in OS with subsequent repeat resection (sRR) compared to those not undergoing sRR. Recurrent GBM presents a treatment challenge. There appears to be an OS benefit for RR upon first recurrence as well as sRR. Such findings warrant further investigation of the potential benefits of continued surgical intervention after subsequent progressions of GBM.

Background Overall survival of breast cancer patients has been calculated many times but there is no precise research available regarding the survival time of breast cancer patients after recurrence. We investigated the effects factors on mortality due to breast cancer. Methods All Factors were analyzed using statistical tools and techniques to find out rate of mortality after recurrence. Descriptive statistics, cox proportional hazard models were used to find statistical significant variables. In the present study recurrence is considered as an important event which may play a role in study of breast cancer progression. In this study, we evaluated breast cancer risk factors in relation to mortality due to this disease among 1028 women with breast cancer in Lahore, Pakistan. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and mortality due to breast cancer were estimated in subtype-specific Cox regression models. Results Survival of breast cancer patients depends upon many factors. A total of 581 alive and 447 deaths due to breast cancer occurred during a median follow-up period of 1977 days. Median survival time after recurrence was 3 years. Significant factors were included post- menopausal women who diagnosed and had recurrence at the age < 45 of molecular subtype estrogen receptor positive, progesterone receptor negative, Her2.neu positive with tumor size ≥ 3 & involved lymph nodes >5. Radiotherapy has increased life span of patients even after recurrence. Conclusion Younger women had higher risk of mortality after recurrence even gone through chemotherapy while lower grade tumor had good prognosis. Radiotherapy played a major role in increasing life time of breast cancer women after recurrence. Our findings are consistent with those from previously published data.

Meningiomas are the most common intracranial extra-axial tumor. While the literature is abundant on the therapeutic management of meningioma recurrence after the initial surgery, the natural history of repeated recurrences is poorly described, as well as and their respective management. A partly retrospective, partly prospective review was conducted in a Norwegian cohort of 1469 consecutive cases of meningioma surgically treated, totaling 11 414 patient-years of follow-up. 114 recurrences (7.7%) were treated surgically with a risk a surgical retreatment of 1% per patient-year of follow-up. 36 patients were operated on 3 times or more. The time-to-retreatment (TTR) decreased significantly and steadily between surgeries, from 4.3 ± 4 years after the first surgery to 2.4 ± 2.9 years after the third surgery. The primary driver for recurrence was the WHO grade (OR 7.13 [4.40;11.55], p

Summary: Objective: We aimed to evaluate oncological outcomes after repeat metastasectomies in patients having undergone previous resections for colorectal cancer metastases. Methods: We examined 248 patients who underwent metastasectomies for lung and/or liver metastases at our center during a 7-year period, from January 2005 to December 2011. Recurrence-free survival 1 (RFS1) after the metastasectomy for the initial recurrence, recurrence-free survival 2 (RFS2) after the second, and recurrence-free survival 3 (RFS3) after the third repeated resections for recurrence were assessed. The overall survival (OS) rate after the first metastasectomy for the first recurrence (OS) was also assessed. Results: Sites of recurrence of the first metastasectomy were the liver, lung, and liver and lung in 115, 117, and 16 cases, respectively, and 133 patients had a second recurrence (133/248, 53.6%). Twenty-seven patients had a third recurrence (27/52, 51.9%), of whom 14 underwent a third metastasectomy. The 5-year and 10-year OS rates were 74.8% and 57.9%, respectively. The 1-year RFS1, RFS2, and RFS3 rates were 76%, 75%, and 39%, respectively. The hazard ratios for RFS were 1.142 and 2.590 for the first and second repeat surgeries, when compared to the first metastasectomy. The third metastasectomy showed significantly lower RFS than did the second metastasectomy. Conclusion: A second metastasectomy should be considered the optimal treatment for a second recurrence. However, careful considerations should be made before performing a third metastasectomy. Keywords: Colorectal cancer, Metastasectomy, Oncologic outcome, Repeated resection

In this study, we evaluated the topographic pattern of retinal edema in eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) using a widefield retinal thickness map of optical coherence tomography and its association with ME recurrence. In 87 eyes with ME secondary to BRVO who were treated with anti-vascular endothelial growth factor (VEGF) injections and followed up for ≥ 1 years, 12 × 9 mm macular volume scans of swept-source optical coherence tomography (DRI-OCT Triton; Topcon Inc, Japan) were performed and retinal thickness maps were automatically generated at baseline and follow-up visits. Topographic patterns of retinal edema on the maps at baseline and 1 month after the first anti-vascular endothelial growth factor (VEGF) treatment were classified as extramacular (outside the ETDRS grid), macular (within the grid), and combined pattern and correlated with ME recurrences. Seventy-five of 87 (86.2%) eyes with BRVO ME showed combined edema at baseline. There were 4 topographic patterns of edema at 1 month following anti-VEGF injection as follows: no residual edema, extramacular only, macular only, and combined edema. In contrast to the baseline pattern, the pattern of retinal edema 1 month following anti-VEGF therapy showed significant association with 6-month recurrence, number of ME recurrences during a 1-year period, and time to first recurrence. (all P

Predicting survival time has many Effective implications in life quality management for the remainder of the patient's life. Also, survival data are highly variable and make accurate predictions difficult or impossible. Random Survival Forest by repeated tree construction on Bootstrap samples and averaging on the results of these trees reduce the prediction error and cause further generalization of these results. In this retrospective study, the records of 141 patients with epithelial ovarian cancer who were referred to the oncology and radiotherapy ward of Imam Hossein Hospital in Tehran from 2007 to 2018 were used. Random Survival Forest was fitted to the data to investigate the key factors affecting the first recurrence of epithelial ovarian cancer. The mean age of the patients in our study was 52 (23-82) years and the median time to the first recurrence in these was 17 (0.5-127) months, respectively. According to RSF results, using variable importance criterion (VIMP) metastatic tumor with relative importance 2.665 and also using minimal (MD) by depth 2.349, tumor stage with relative importance 1.993 and depth 2.678, and maximum platelet count with relative importance 2.132 and depth 2.683 were the most important variables affecting in the first recurrence of Epithelial Ovarian Cancer. One of the disadvantages of classical methods is the inappropriate fitting of many variables and the need for specific assumptions. More advanced methods such as RSF without the need for any specific assumptions with less prediction error can well explain event variations when exposed to high-dimensional data.

Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation.

Background Improvements in surgery, imaging, adjuvant treatment, and management of metastatic disease have led to modification of previous approaches regarding the risk of recurrence and prognosis in colorectal cancer. The aims of this study were to map patterns, risk factors, and the possibility of curative treatment of recurrent colorectal cancer in a multimodal setting. Methods This was a cohort study based on the COLOFOL trial population of patients who underwent radical resection of stage II or III colorectal cancer. The medical files of all patients with recurrence within 5 years after resection of the primary tumour were scrutinized. Follow-up time was 5 years after the first recurrence. Primary endpoints were cumulative incidence, site, timing, and risk factors for recurrence, and rate of potentially curative treatment. A secondary endpoint was survival. Results Of 2442 patients, 471 developed recurrences. The 5-year cumulative incidence was 21.4 (95 per cent c.i. 19.5 to 23.3) per cent. The median time to detection was 1.1 years after surgery and 87.3 per cent were detected within 3 years. Some 98.2 per cent of patients who had potentially curative treatment were assessed by a multidisciplinary tumour board. A total of 47.8 per cent of the recurrences were potentially curatively treated. The 5-year overall survival rate after detection was 32.0 (95 per cent c.i. 27.9 to 36.3) per cent for all patients with recurrence, 58.6 (51.9 to 64.7) per cent in the potentially curatively treated group and 7.7 (4.8 to 11.5) per cent in the palliatively treated group. Conclusion Time to recurrence was similar to previous results, whereas the 21.4 per cent risk of recurrence was somewhat lower. The high proportion of patients who received potentially curative treatment, linked to a 5-year overall survival rate of 58.6 per cent, indicates that it is possible to achieve good results in recurrent colorectal cancer following multidisciplinary assessment., The 5-year cumulative recurrence rate after radical surgery for stage II–III colorectal cancer was 21.4 per cent. A total of 47.8 per cent of recurrences could be treated potentially curatively, which was associated with a 5-year overall survival rate of 58.6 per cent. Treatment of recurrences confined to the liver was most likely to be potentially curative (75.7 per cent). A high proportion of recurrences confined to the lungs and peritoneum were also treated with curative intent.

The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.

Despite curative resection, hepatocellular carcinoma (HCC) has a high probability of recurrence. We validated the potential role of liver resection (LR) for recurrent HCC. Patients with intrahepatic recurrence with up to three lesions were included. We compared survival times of patients undergoing their first LR to those of patients undergoing repeated LR. Then, survival times of the patients who had undergone LR and transcatheter chemoembolization (TACE) for recurrent HCC after propensity score matching were compared. After a median follow-up period of 3.1 years (range, 0.2–16.3), median overall survival times were 6.5 years (95% CI 6.0–7.0), 5.7 years (5.2–6.2), and 5.1 years (4.9–7.3) for the first LR (n = 1234), second LR (n = 273), and third LR (n = 90) groups, respectively. Severe complications frequently occurred in the first LR group (p = 0.059). Operative times were significantly longer for the third LR group (p = 0.012). After the first recurrence, median survival times after one-to-one pair matching were 5.7 years (95% CI 4.5–6.5) and 3.1 years (2.1–3.8) for the second LR group (n = 146) and TACE group (n = 146), respectively (p

PURPOSE: Recurrent head and neck squamous cell carcinoma (HNSCC) after chemoradiation is a challenging clinical problem. Salvage surgery (SS) is often extensive and mutilating. Oncological outcomes of SS are relatively well known, but little is published about the course of disease after the first recurrence, especially in patients without salvage possibilities. The aim of this study was to analyze the course of disease in patients with recurrent HNSCC after chemoradiation.METHODS: We retrospectively analyzed and descriptively reported the disease course in 198 patients with recurrent HNSCC after chemoradiation in the time period after the first recurrence. We scored any type of event, salvage treatment, systemic treatment and overall survival (OS).RESULTS: Of the 198 patients with recurrent HNSCC, salvage surgery was attempted in 104 (53%). SS was more frequently given in patients with recurrent laryngeal cancer, isolated regional failure (p CONCLUSIONS: Main factors influencing the course of disease in recurrent HNSCC are the possibilities for SS and HPV-status. Therefore, SS should always be considered and discussed. In patients without possibilities for SS, overall survival is 3-6 months.

The purpose of this study was to determine outcomes in recurrent pediatric ependymoma. We performed a systematic review of PubMed, Embase, Web of Science and the Cochrane Library for studies reporting on survival outcomes for pediatric patients with recurrent ependymoma. We then performed a meta-analysis of all eligible results. Survival outcomes were identified across location of recurrence, therapy at recurrence, and age at recurrence. Eleven studies met final inclusion criteria. Pooled median progression free survival (PFS) from date of first recurrence was 6.7 months (95% confidence interval [95% CI] 4.7–8.8). Pooled median overall survival (OS) from date of first recurrence was 11.2 months (95% CI 6.4–16.0). Participants with supratentorial recurrences demonstrated a shorter OS of 8.3 months (95% CI 3.2–13.3) compared to 20.1 months (95% CI 8.4–31.7) for those with infratentorial recurrence. Patients who underwent surgery at recurrence had a median OS of 24.2 months (95% CI 14.2–34.1) compared to 29.2 months (95% CI 17.4–41.1) in those who received radiation compared to 19.3 months (95% CI 10.3–28.3) in those who received chemotherapy. Patients younger than age 3 years at time of recurrence demonstrated a median OS of 31.0 months (95% CI − 25.3–87.3) compared to 17.5 months (95% CI 9.9–25.2) for those that recurred beyond 3 years of age. Our findings illustrate that children with recurrent ependymoma suffer from poor outcomes; however, these outcomes range widely depending on patient, tumor, and treatment characteristics. New therapies and treatment strategies are needed to improve outcomes in this group.

The objectives of this study were to describe the patterns and duration of primary and recurrent treatment in patients with ovarian cancer (OC) harboring germline BRCA1 and BRCA2 (BRCA) mutations. A retrospective review of BRCA mutation carriers with advanced, high-grade OC diagnosed between 2004 and 2014 with at least 3 years of follow-up (or until death) was undertaken. Descriptive statistics were calculated and a Swimmer's Plot used to depict disease course. Forty BRCA mutation carriers (26 BRCA1, 14 BRCA2) were identified. Mean age was 54 (range 32–77). All had cytoreductive surgery and received platinum chemotherapy. Median platinum-free interval was 11.9 months (IQR 3.6–21.9). Among 28 patients who recurred, median number of treatment lines was 4 (IQR 3–6), with a median of 2 (IQR 2–3) platinum lines. On average, patients who recurred spent 32% (IQR 20–43%) of their time after diagnosis receiving cytotoxic chemotherapy and 54% (IQR 42–67%) of the time on some cancer-directed therapy, including maintenance. Median overall survival was 79.1 months from diagnosis and 25.4 months after first recurrence. In conclusion, beyond first-line therapy, there was treatment and outcome heterogeneity for BRCA-mutated OC. After OC diagnosis, patients spent close to half their life on treatment., Highlights • There was considerable heterogeneity of treatments and outcomes for BRCA-mutated ovarian carcinoma. • While 15% of women had first remissions exceeding 5 years, 10% were platinum resistant. • Women spent nearly half their life after ovarian cancer diagnosis on some form of cancer-directed therapy.

OBJECTIVES: To assess outcomes after secondary surgical resection in patients with recurrent uterine leiomyosarcoma (uLMS). METHODS: We retrospectively identified all patients who had no evidence of disease after initial surgery for uLMS, who underwent surgery for a first recurrence at our institution between 1/1991-10/2013. We excluded patients who received any therapy for recurrence prior to secondary resection, and patients who underwent surgery soon after morcellation [of presumed benign fibroids] showed widespread disease. Overall survival (OS) was determined from time of first recurrence to death or last follow-up. RESULTS: We identified 62 patients: 29 with abdominal/pelvic recurrence only, 30 with lung recurrence only, 3 with both. Median time to first recurrence was 18 months (95% CI: 13.3-23.3): 15.8 months (95% CI: 13.0-18.6) abdominal/pelvic recurrence; 24.1 months (95% CI: 14.5-33.7) lung-only recurrence (p=0.03). Median OS was 37.7 months (95% CI: 25.9-49.6) abdominal/pelvic recurrence; 78.1 months (95% CI: 44.8-11.4) lung recurrence (p = 0.02). Complete gross resection (CGR) was achieved in 58 cases (93%), with gross residual ≤1cm in 2 (3.5%) and >1cm in 2 (3.5%). Median OS based on residual disease was 54.1 months (95% CI: 24.9-83.3), 38.7 months (95% CI: NE), 1.7 months (95% CI: NE), respectively (P

BACKGROUND/AIM Regional lymph node recurrence (RLNR) is the most common pattern of recurrence within 2 years from the diagnosis of patients with non-metastatic malignant cutaneous melanoma. However, isolated RLNR without distant metastasis has been rarely studied. PATIENTS AND METHODS Forty patients with isolated RLNR as a first recurrence were analyzed retrospectively. The clinical outcomes and prognostic impact of clinicopathologic parameters were analyzed. Immunostaining for FOXP3, VEGF, pAKT, and pS6 was also performed. RESULTS The median disease-free interval from first diagnosis to isolated RLNR and post-recurrence recurrence-free survival (pRFS) were 12 months and 7.2 months, respectively. Distant failure was the most common pattern of failure after isolated RLNR (67.5%). The number of initially harvested lymph nodes (LN) >7 and LN ratio >22.2% at the time of recurrence were prognosticators for pRFS in multivariate analysis. None of the tested biomarkers were significantly related to prognosis. The 5-year post-recurrence overall survival rate was 84.9%. CONCLUSION Most patients with isolated RLNR will experience a second failure within months, especially distantly. The number of initially harvested LNs and LN ratio at the time of recurrence could predict pRFS.

Atypical meningioma (AM) tends to be tumor with high rates of recurrence and mortality. In this retrospective study, 131 recurrent AM patients underwent AM surgery in Beijing Tiantan Hospital between January 2008 and December 2015. Of the 131 cases collected, 61 were male (46.6%), and 70 (53.4%) were female. 53 (40.5%) patients chose observation instead of therapy, 53 (40.5%) received repeat surgery and 25 patients (19.0%) received gamma knife surgery (GKS). The median overall survival (OS) was 34.6 months and actuarial OS of patients at 1, 3 and 5 years were 88.6%, 48.8%, 36.0%, respectively. In the treatment group including 78 patients with surgery and GKS group, a tumor progression happened to 35 patients (44.9%). The median duration of progression-free survival (PFS) was 34.5 months and the median OS was 61.7 months. Second PFS at 1, 3 and 5 years were 84.1%, 46.5% and 24.0%, respectively; the corresponding OS was 98.5%, 75.1%, 57.9%, respectively. Multivariate analysis revealed treatment strategy was the only independent factor (P 0.001). In the treatment group, non-peritumoral edema (P = 0.002), preoperative KPS (per 10 scores increase) (P 0.001) and GKS (P = 0.042) was related to better OS. Short interval (24 months) from symptoms onset to intervention was related to better PFS (P = 0.004) in univariate analysis. This retrospective study presents the largest cohort of recurrent AM patients, surgical treatment is recommended in patients with tumor recurrence, and GKS is considered a promising therapeutic option of recurrence atypical meningioma.

The study sought to assess the impact of age on recurrent ventricular tachyarrhythmias, appropriate ICD therapies and all-cause mortality at 5 years in consecutive ICD recipients. Age ≥ 75 years was associated with higher rates of first recurrent ventricular tachyarrhythmias, appropriate ICD therapies and all-cause mortality at 5 years. Elderly ICD recipients aged ≥ 75 years are at increased risk of recurrent ventricular tachyarrhythmias, appropriate ICD therapies and all-cause mortality at 5 years. Data regarding the prognostic impact of age in implantable cardioverter defibrillator (ICD) recipients is limited. The study sought to assess the impact of age on recurrences of ventricular tachyarrhythmias in ICD recipients. This “secondary prevention” study is based on a large retrospective registry including consecutive ICD recipients with documented ventricular tachyarrhythmias from 2002 to 2016. Patients

The malignant transformation of conventional giant cell tumor of bone (GCTOB) is rare and usually occurs with irradiation. Here we report two neglected cases of conventional GCTOB with spontaneous malignant transformation at 11 and 16 years after initial diagnosis. In the former case, the patient refused to receive any treatment following the incisional biopsy, and in the latter, the first recurrence that occurred 5 years after initial treatment, was neglected. Although rare, the occurrence of sarcomatous changes in these cases indicates that secondary malignant transformation may be part of the natural course of this tumor. In addition, in both cases, immunohistochemistry showed diffuse and strong p53 expression in the malignant tumor but not in the primary lesion. It suggests that p53 overexpression may play a key role in the malignant transformation of GCTOB and that investigating for p53 expression in recurred lesions may help in predicting cases of giant cell tumor, prone to malignant transformation.

Cutaneous squamous cell carcinoma (cSCC) is the leading cause of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). We provide the management and prognosis of cSCC in RDEB patients at a Spanish reference center. We retrospectively included patients with RDEB attended in La Paz University Hospital from November 1988 to October 2018. Fourteen patients developed at least one cSCC. Tumors were predominantly well differentiated. Nearly half of the tumors have recurred. Median time to first recurrence was 23.4 months (95% CI: 17.2–29.5). Five patients have developed distant metastases. Median overall survival (mOS) was 136.5 months since the diagnosis of the first cSCC (95% CI: 30.6–242.3). When distant metastases occurred, mOS was 6.78 months (95% CI: 1.94–11.61). cSCC is a life-threatening complication of RDEB patients. Although tumors are usually well differentiated, they tend to relapse. This is the first Spanish report of cSCC arising in RDEB patients.

Purpose: Following primary systemic treatment (PST), the optimal strategies for regional nodal irradiation (RNI) are currently under active investigation, especially in patients with pretreatment cN1 and posttreatment ypN0-1. The Neo-Bioscore staging system has showed promising prospect in assessing prognosis after PST. In this analysis, we evaluate the role of Neo-Bioscore staging system in guiding RNI following PST in patients with cN1 and ypN0-1. Methods and Materials: Continuous women with cN1 pretreatment and who received PST with ypN0 or ypN1 posttreatment between 2009 and 2014 were retrospectively reviewed. According to the report by Mittendorf et al, the Neo-Bioscore staging system is on the basis of pretreatment clinical stage, posttreatment pathologic stage, estrogen receptor (ER) status, HER2 status and grade stage, and assigned and summed points for each factor as shown in. A pathologic complete response (pCR) was defined as no invasive disease in the breast or regional lymph nodes after surgery. The curves for survival were generated using the Kaplan-Meier method and compared using the Log-rank test. Point Assignments for the Neo-Bioscore Staging SystemsFactorsPointsClinical stage I0IIA0IIB1IIIA1IIIB2IIIC2Pathologic stage 00I0IIA1IIB1IIIA1IIIB1IIIC2Tumor Biomarker ER negative1HER2 negative1Grade 31 Results: One hundred and sixty-three patients were enrolled in this study, of them 18 patients received breast conserving surgery. Of the 163 patients, 119 (73%) received RNI. At surgery, 36 patients (22.1%) achieved pCR, while 89 patients (54.6%) achieved ypN0. The median follow-up was 59.4 months (rang: 16-106). In the whole cohort, RNI was associated with non-significant improved outcomes, with a 5-year locoregional recurrence free survival (LRRFS) rate of 98.6% vs. 95.7% (P=0.393), a regional recurrence free survival (RRFS) rate of 98% vs. 97.7% (P=0.865), a 5-year distant metastasis free survival (DMFS) rate of 91.6% vs. 83.4% (P=0.052), a 5-year any first recurrence free survival (RFS) rate of 90.9% vs. 87.4% (P=0.43), and a 5-year overall survival (OS) rate of 98% vs. 91.9% (P=0.097) in the RNI and non-RNI group, respectively. In the subgroup of patients with Neo-Bioscore score of 1 to 3, RNI significantly increased the 5-year DMFS rate of 97% vs. 76.9% (P=0.002), 5-year RFS rate of 95.5% vs. 76.9% (P=0.007) and 5-year OS rate of 100% vs. 89.2% (P=0.005). However, no significant difference in outcomes was found between RNI and non-RNI group in patients with Neo-Bioscore score of 4 to 6. Among patients who not achieved pCR and those with ypN1, RNI significantly increased DMFS (both P Conclusions: Not all patients with cN1 and ypN0-1 could significantly benefit from RNI following PST, those with low Neo-Bioscore score were likely to benefit more. Citation Format: Cao L, Chen J-Y. The role of neo-bioscore staging system in guiding the optimal strategies for regional nodes irradiation following primary systemic treatment in breast cancer patients with cN1 and ypN0-1 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-08.

Clostridioides difficile infection possesses a significant economical burden, specifically in the inpatient and rural settings. Fecal Microbiota Transplant has been used for treatment of recurrent Clostridioides difficile but its utility is limited by current guidelines and resources. We conducted a retrospective chart review to evaluate the financial benefit of using Fecal Microbiota Transplant after first recurrence of Clostridioides difficile infection. We found that while its use was restricted, on average Fecal Microbiota Transplant can save $11,603.49 per patient. In conclusion, our study shows that using Fecal Microbiota Transplant could prove to be economically beneficial in treating recurrent CDI in rural hospitals.

Glioblastoma (GBM) is among the most aggressive of brain tumors and confers a dismal prognosis despite advances in surgical technique, radiation delivery methods, chemotherapy, and tumor-treating fields. While immunotherapy (IT) has improved the care of several adult cancers with previously dismal prognoses, monotherapy with IT in GBM has shown minimal response in first recurrence. Recent discoveries in lymphatics and evaluation of blood brain barrier offer insight to improve the use of ITs and determine the best combinations of therapies, including radiation. We highlight important features of the tumor immune microenvironment in GBM and potential for combining radiation and immunotherapy to improve prognosis in this devastating disease.

Complicated Crohn's disease (CD) will require surgical treatment during patients' lifetime, with a considerable recurrence rate requiring additional surgery. The present study is a retrospective analysis of a prospectively maintained database in an IBD Tertiary Centre that included all the consecutive, unselected patients undergoing surgery for CD between 1993 and 2019. Patients treated with small bowel resections, colonic resections, conventional and non-conventional strictureplasties were considered. The aim was to evaluate morbidity and long-term recurrence of repeated surgery. Among the population included, the following procedures were performed: 713 (58.2%) primary surgery (group S1), 325 (26.5%) first recurrence (group S2), and 186 (15.3%) multiple recurrences (group S3). Patients undergoing repeat surgery were older (p < 0.0001) and had a longer disease duration (p < 0.0001), extended disease (p = 0.0001), shorter time frame to first surgery (p < 0.0001), nutritional impairment (p < 0.0001), and a history of aggressive medical therapy (p = 0.04). Patients undergoing surgery for recurrences required higher complexity level surgery, with more conservative approaches (p = 0.0004) and a higher ostomy number (p = 0.06). Recurrent patients had higher short bowel syndrome rate (p < 0.0001), higher minor (p = 0.04) but not major (p = 0.2) postoperative complications rate. The 10-year surgical recurrence rate was 18% for group S1, 27% for S2, and 48% for S3, with significant differences at the log-rank test. Repeated surgery for complicated CD was associated with an increased rate of minor, but not major complications, requiring high-risk surgery, with a major ostomy rate and short bowel syndrome, and is associated with an increased long-term surgical recurrence, even on strictureplasty sites.

Purpose Local recurrence after treatment of ductal carcinoma in situ (DCIS) with breast-conserving surgery (BCS) is more common than after mastectomy, but it is unclear if patterns of invasive recurrence vary by initial surgical therapy. Among patients with invasive recurrence after treatment for DCIS, we compared patterns of first recurrence between those originally treated with BCS vs. mastectomy. Methods From 2000 to 2016, women with an invasive recurrence occurring ≥ 6 months after initial treatment for DCIS were retrospectively identified. Clinicopathologic features and adjuvant treatment of the initial DCIS, as well as characteristics of first invasive recurrences, were compared between patients who had undergone BCS vs. mastectomy. Results 452 patients with an invasive recurrence after surgery for DCIS were identified: 367 patients (81%) had initially undergone BCS and 85 patients (19%) mastectomy. Patients originally treated with mastectomy were younger and were more likely to have had high grade, necrosis, and multifocal or multicentric DCIS (p p p = 0.12). Conclusions Among women who experienced a first invasive recurrence after treatment for DCIS, those who had originally undergone mastectomy more commonly presented with advanced disease compared to those treated with BCS, likely related to the absence of the breast and the higher risk profile of their initial DCIS.

To describe the clinical features, management, and outcomes of choroidal neovascularization (CNV) in children less than 18 years of age. This was a retrospective, case control study of 111 eyes of 96 patients. CNV was clinically diagnosed in all patients. Eyes were classified as those that were observed (Controls; Group 1) or those that had treatment (Cases; Group 2). CNV was categorized as regressed, persistent, or recurrent in order to evaluate the anatomical outcomes. Of 96 patients, 68(71%) were male. Mean presenting age was 11.4 ± 3.4 years (median = 11 years, range = 1–17 years). CNV was bilateral in 15(16%) patients. Of 111 eyes, 38 eyes had treatment (Cases) and 73 eyes did not (Natural history group or Controls). Subfoveal CNV was seen in majority of cases (59%). Most common etiology was post-inflammatory (38%), followed by trauma (16%). Eyes were classified as those that were observed (controls; Group 1) or those that had treatment (cases; Group 2). In group 1, spontaneous regression of CNV was seen in 26(36%) eyes and there was no recurrence in this group. In group 2 following treatment, 25(66%) of 38 eyes achieved complete regression at mean 4.9 months and was persistent in 5 eyes. CNV recurrence was seen in 10 eyes with the mean time to first recurrence being 9 months. At presentation, mean best-corrected visual acuity (BCVA) of eyes with subfoveal CNV was logMAR 0.99 that improved to logMAR 0.63 with treatment. Mean follow-up was 17 months. CNV results in significant visual decline in children; most commonly of post-inflammatory etiology. Treatment achieves high regression rates, albeit with limited visual improvement.

Repeat surgical resection (redo) for pulmonary metastases is a questionable, albeit intriguing topic. We performed an extensive review of the literature, to specifically analyze results of redo pulmonary metastasectomies. We reviewed a total of 3,523 papers. Among these, 2,019 were excluded for redundancy and 1,105 because they were not completely retrievable. Out of 399 eligible papers, 183 had missing information or missing abstract, while 96 lacked data on survival. A total of 120 papers dated from 1991 onwards were finally included. Data regarding mortality, major morbidity, prognostic factors and long-term survivals of the first redo pulmonary metastasectomies were retrieved and analyzed. Homogeneity of data was affected by the lack of guidelines for redo pulmonary metastasectomy and the risks of bias when comparing different studies has to be considered. According to the histology sub-types, redo metastasectomies papers were grouped as: colorectal (n=42), sarcomas (n=36), others (n=20) and all histologies (n=22); the total number of patients was 3,015. Data about chemotherapy were reported in half of the papers, whereas targeted or immunotherapy in 9. None of these associated therapies, except chemotherapy in two records, did significantly modify outcomes. Disease-free interval before the redo procedure was the prevailing prognostic factor and nearly all papers showed a significant correlation between patients' comorbidities and prognosis. No perioperative mortality was reported, while perioperative major morbidity was overall quite low. Where available, overall survival after the first redo metastasectomy ranged from 10 to 72 months, with a 5-years survival of approximately 50%. The site of first recurrence after the redo procedure was mainly lung. Despite the data retrievable from literature are heterogeneous and confounding, we can state that redo lung metastasectomy is worthwhile when the lesions are resectable and the perioperative risk is low. At present, there are no "non-surgical" therapeutic options to replace redo pulmonary metastasectomies.

Objective: Rapid technological advances in the last century and the large amount of information have made it difficult to analyze a large number of independent variables. In such circumstances, the existence of interactions of different degrees in the model is expected, in this case, the Cox model cannot be useful and the nonparametric method of random survival forest can be a useful alternative. This study compares the prediction error of random survival forest with Cox and Weibull models in predicting the time to the first recurrence in patients with epithelial ovarian cancer. Method: In this retrospective study, the records of patients with epithelial ovarian cancer who referred to Imam Hossein Hospital in Tehran from 2007 to 2018 were used. To investigate the factors affecting the first recurrence of these patients, RSF was fitted to the data. Finally, prediction error of Cox, Weibull and RSF were compared using C-Index and Brier score. Results: Brier score was calculated 0.16 for RSF, and 0.24 for Cox, also C-Index was calculated 0.34 for RSF and 0.42 for Cox. Brier score was calculated 0.092 for Cox and 0.089 for Weibull, so the prediction error of RSF was lower than both Cox and Weibull models. Conclusion: Random survival forest with a suitable fit on many variables and without the need for a special default with a prediction error less than the Weibull and Cox methods can predict the response variable when confronted with high-dimensional data.

International audience; Objective: To examine which characteristics predict the time to a first mood recurrence at three years in Bipolar Disorder type I (BD-I) and type II (BD-II). Methods: Individuals with BD were followed up to 3 years. Turbull's extension of the Kaplan-Meier analysis for interval-censored data was used to estimate the cumulative probability of recurrence over time. Separate models were performed according to BD subtype to determine which baseline factors were predictive of recurrences and were adjusted for age, gender and educational level. Results: We included 630 individuals with BD-I and 505 with BD-II. The first recurrence of any polarity occurred earlier in BD-II (p = 0.03). The first depressive recurrence occurred earlier in BD-II (p < 0.0001), whereas the first (hypo)manic recurrence occurred earlier in BD-I (p = 0.0003). In BD-I, the clinical variables that were associated to the time to a first mood recurrence were depressive symptoms, lifetime rapid cycling, global activation and the number of psychotropic medications at baseline. In BD-II, the time to a first recurrence was associated with a younger age at onset of BD and a higher number of lifetime mood episodes. The Areas Under the Curve for both models were moderate. Conclusion: Predictors of recurrences showed few specificities to BD-I or BD-II. The ability to predict recurrences in BD based on socio-demographic and clinical variables remained too moderate for a transfer in daily practice. This study highlights the need for further studies that would include other types of predictors, such as molecular, cognitive or neuro-imaging ones, to achieve an accurate level of prediction of recurrences in BD.

Background: Radiation therapy (RT) is prescribed using an empiric one-size-fits-all paradigm. We hypothesize that the Genomic Adjusted Radiation Dose (GARD), a quantification of personalized RT dose effect, will reveal interpatient heterogeneity associated with opportunities to improve outcomes compared to physical RT dose alone. To test this hypothesis, we performed a pan-cancer, pooled analysis of all available cohorts with information available to calculate GARD. Methods: Using 9 previously-published datasets, we defined two clinical endpoints: (i) time to first recurrence and (ii) overall survival, comprising 1,257 (972 +RT, 285 -RT) and 636 patients (414 +RT, 222 -RT), respectively. We used Cox regression stratified by disease site to test association between GARD and outcome with separate models using RT dose and sham-GARD for comparison. Interaction tests between GARD and treatment (+/- RT) were performed using the Wald statistic. Results: Pooled analysis reveals GARD is a continuous predictor of recurrence (HR = 0.984, CI [0.982,0.996], p=0.004) and survival (HR = 0.975, CI [0.958, 0.993], p=0.005). Interaction term was significant for OS (p =0.026) and for recurrence for patients who achieve GARD>19.2 (p=0.04). Physical RT dose and sham-GARD were not significantly associated with either outcome. Conclusions: Biologic effect, as quantified by GARD, is significantly associated with recurrence and survival: it is predictive of RT benefit; and physical RT dose is not. We propose integration of genomics into radiation dosing decisions, using a GARD-based framework, as the new paradigm for personalizing RT treatment. Funding: There was no funding for this work Declaration of Interest: JGS, SAE and JFTR hold IP on RSI, GARD and RxRSI, in addition to equity in Cvergenx, a company which seeks to commercialize these methods. All other authors have nothing to declare.

Introduction Mucosal melanomas (MM) of the female genital tract are rare a. We aimed to study the prognostic factors of vulvar and vaginal locations of MM. Material and method A multicenter, retrospective cohort study conducted between 01/01/2000 and 01/06/2019. Result Of the 33 patients included 25 (75.8 %) had vulvar (VuM) and eight (24.2 %) vaginal melanomas (VaM). VaMs were deeper: median Breslow index: 17.5 mm [3.5−22] versus 4.3 mm [0.35−18] (p = 0.013). Average follow-up was 24.0 ± 59.8 months. Twenty-six patients (78.8 %) experienced recurrence. Disease-free survival was 52.9 % at 1 year (64.7 % for VuM and 14.3 % for VaM) and 8.4 % at 3 years (11 % for VuM and 0% for VaM) (p = 0.002). Median time to the first recurrence was 9.01 months [CI95 %: 2.07–56.71]. VaM recurred earlier than VuM (3.12 months [CI95 %: 2.07–12.49] versus 17.72 [CI95 %: 3.58–56.71], p = 0.011). VaM had a higher risk of recurrence (HR = 5.64 [CI95 %: 2.01–15.82], p = 0.001) in multivariate analysis. Overall survival was 88.5 % at 1 year (100 % for VuM and 50 % for VaM), and 59.4 % at 3 years (69.3 % for VuM and 25 % for VaM). Women with VaM died earlier: median specific death occurrence of 8.76 months [CI95 %: 6.54–24.72] versus 39.61 [CI95 %: 21.89–209.21], p = 0.013 (HR = 5.08 [CI95 %: 1.39–18.60], p = 0.014). A lesion size ≥3 cm was associated with an increased risk of mortality (HR = 8.45 [CI95 %: 1.60–44.52], p = 0.012). In multivariate analysis, vaginal location remained an independent and predictive variable of a higher risk of specific death (HR = 8.56 [CI95 %: 1.95–37.64], p = 0.005). Conclusion A vaginal location of MM is associated with a poorer prognosis than a vulvar location.

OBJECTIVES We aimed to describe accurately the timing and site-specific recurrence pattern for surgical resected lung adenocarcinoma and develop genetic-pathological risk prediction models to guide individual postoperative surveillance strategies. METHODS We retrospectively analysed radiological, pathological and sequencing data concerning 9 common oncogenic driver mutations from 1531 patients with resected lung adenocarcinoma between 2008 and 2015. The first recurrence site and time-to-recurrence were recorded. Independent risk factors were identified by multivariable regression analysis and consequently incorporated into prediction models. RESULTS With a median follow-up of 53.2 months, postoperative recurrences were noted in 483 (31.5%) patients. Bone and brain recurrence tended to occur early (median 11.7 and 17.0 months, respectively) while thorax recurrence occurred later (median 22.2 months), which was validated across different tumour stages. EGFR mutation was an independent predictor for brain and bone recurrence and KRAS mutation for early recurrence. Both internal and external validation of the nomograms for brain and bone recurrence prediction showed optimal discrimination (concordance index: internal, 0.75 and 0.81, respectively; external, 0.77 and 0.84, respectively) and calibration. Recurrence occurred relatively evenly during the follow-up period in low-risk groups but mainly occurred within 2 years in high-risk groups. CONCLUSIONS Unique biological differences exist among lung adenocarcinoma leading to distinct patterns of recurrence. These user-friendly genetic-pathological nomograms may help physicians to better stratify patients and make individual postoperative follow-up plans.

Background: Idiopathic Nephrotic Syndrome (INS), which is caused by a defect in the glomerular filtration barrier, is the most common chronic glomerular disease in children. Objectives: The present study aimed to assess the clinical features of INS and some recurrence-related factors in children. Methods: This population-based, cross-sectional study was conducted on 302 children with INS referring to the Pediatric Nephrology Clinic of Imam Reza Hospital of Kermanshah city, Iran, during 1998-2018. Results: The mean age (SD) at the time of diagnosis and the follow-up duration were 4.87 (2.89) years and 49.83 (37.52) months, respectively. The numbers of boys and girls were 185 (61.9%) and 114 (38.1%), respectively. The mean number (SD) of recurrences, annual recurrence rate during the follow-up, and the time to the first recurrence after responding to treatment were 1.71 (1.91), 0.48 (0.77), and 10.15 (10.63) months, respectively. The most common type of INS was steroid-dependent/frequent relapse, with a frequency of 151 (50.5%). Furthermore, 33 (11.0%) and 266 (89.0%) patients were resistant and respondent to treatment, respectively. There was a statistically significant relationship between age at the time of diagnosis and the type of INS (P = 0.007). Conclusions: This study revealed a statistically significant association between higher age and steroid resistance. However, in steroid responders, there was no relationship between gender, age at the time of diagnosis, and the time to the first recurrence, and the recurrence rate.

The lymphatic system is known to be the primary pathway of metastasis for colorectal cancer. However, beyond regional lymph node metastases, little is known about the pathway of lymphatic metastases and the differences in the recurrence site risk. The aim of this study was to clarify the relationship between lymph node metastasis and the first recurrence site in colorectal cancer.Patients with colorectal cancer who underwent curative resection in our institution between January 2003 and December 2016 were included in this analysis. The relationship between the first recurrence site and clinicopathological factors was analyzed by the Cox regression model and competing risk regression model.In total, 1,249 patients with colorectal cancer were included in this analysis. We found that the stages of lymph node metastases (N0 vs N1: P = .008, N0 vs N2a: P.001, N0 vs N2b: P.001) were significantly associated with lung metastasis in the multivariate analysis. Furthermore, in the competing risk analysis, the stages of lymph node metastases were significantly correlated with lung metastasis (N0 vs N1: P = .002, N0 vs N2a: P.001, N0 vs N2b: P.001) but were not correlated with other recurrence sites.The severity of lymph node involvement had a strong correlation with lung metastases in patients with colorectal cancer.

BACKGROUND Pembrolizumab is a potent humanized immunoglobulin G4 monoclonal antibody with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 2 (PD-L2). Survivin is a 16.5 kDa intracellular protein that belongs to the inhibitor of apoptosis protein (IAP) family. It acts in concert with the mitotic spindle apparatus to regulate cell division and localizes to the spindle microtubule organizing center (MTOC) during the G2/M phase of cell cycle progression. Survivin has also been shown to modulate the function of a number of terminal effector cell death proteases (caspases) leading to an inhibition of apoptosis. METHODS This is a Phase II study of two arms in patients with recurrent glioblastoma. Arm A is patients with first recurrence of glioblastoma who have failed prior chemotherapy and radiation but have not received any immunotherapy. Arm B is an exploratory arm of 10 patients who have failed prior anti-PD1 therapy. The ongoing study is a phase II clinical study with a 10 patient, toxicity run-in. All patients will receive the study drug combination consisting of SurVaxM and pembrolizumab with no randomization, stratification or dose escalation. RESULTS So far ten patients have been enrolled on the study as safety run in. Primary endpoint is Progression free survival at 6 months. Safety and tolerability of Pembrolizumab and SurVaxM, Response rates of Pembrolizumab and SurVaxM determined using RANO criteria are secondary endpoints. Additional secondary endpoints include Overall survival and Progression Free survival Exploratory endpoints include Cellular and humoral immune responses during concurrent administration of Pembrolizumab and SurVaxM. CONCLUSION This is an ongoing clinical trial.