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Introduction Papillary thyroid carcinoma is the most frequent endocrine neoplasia and its incidence has tripled over the past 35 years. Although papillary thyroid carcinoma carries a good prognosis, 10%−30% of patients still develop recurrence and metastasis. Some clinical and genetic features are associated with worse prognosis. The most frequent mutation is the BRAF p.V600E, which has been associated with many clinical features of poor prognosis. However, many studies have produced controversial results without any association between BRAF mutation and clinicopathological features of poor prognosis. Objective Since the prognostic value of BRAF mutations remains controversial, this study aims to investigate the importance of this mutation in therapeutic decisions for papillary thyroid carcinoma. Methods Therefore, we evaluated whether the presence of BRAF mutation is associated with features of poor prognosis in 85 patients with papillary thyroid carcinoma older than 45 years treated at A.C. Camargo Cancer Center, from 1980 to 2007. BRAF mutation was evaluated by pyrosequencing. Statistical analysis was performed using SPSS. Results The mean age of patients was 54 years (range: 45 − 77 years), 73 were women (85.8%) and 12 were men (14.2%). Among them, 39 cases (45.9%) presented extrathyroidal extension and 11 cases had recurrent disease. BRAF mutation was detected in 57 (67%) patients. No significant association was observed between BRAF mutation and gender (p = 0.743), age (p = 0.236), N-stage (p = 0.423), vascular and perineural infiltration (p = 0.085 or multifocality (p = 1.0). Although not statistically significant, the majority of patients with recurrent disease were BRAF positive (9 out of 11) (p = 0.325). Patients affected by BRAF mutation are associated with tumors larger than 1 cm (p = 0.034) and with extrathyroidal extension (p = 0.033). Conclusion Although BRAF testing is widely available, there are no consistent data to support improvement in outcomes from incorporating it into therapeutic decision for thyroid cancer.

Background & Aims: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival.Methods: We included 736 patients (77% female, mean age 42 +/- 1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis.Results: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT

INTRODUCTION Pneumatosis intestinalis (PI) is air collections within the wall of the intestine that can be associated with life threatening conditions. Recurrent episodes of PI have been reported; however, little is known about risks for recurrent disease. This study aims to identify predictors of recurrent PI and evaluate long-term outcomes in patients with recurrent PI. METHODS This retrospective case-control study evaluated patients, ages 6 months to 18 years, with imaging evidence of PI over a 30-month period. Images were analyzed by consensus to confirm PI. Recurrent PI was defined as new findings of PI after resolution by imaging and/or at least 1-month interval between episodes of PI. Univariate and multivariable analyses were performed using logistic regression, with significance set to P

Purpose We performed a systematic review and a meta-analysis to investigate the successful ablation rate after radioiodine (RAI) administration in patients with differentiated thyroid cancer (DTC) at intermediate-high risk of recurrence. Methods A comprehensive literature search of the PubMed, Scopus, and Web of Science databases was conducted according to the PRISMA statement. Results The final analysis included 9 studies accounting for 3103 patients at intermediate-high risk of recurrence. In these patients, the successful ablation rates ranged from 51 to 94% with a 71% pooled successful ablation and were higher in intermediate (72%) than in high (52%)-risk patients. Despite the rigorous inclusion standards, a significant heterogeneity among the evaluated studies was observed. Higher administered RAI activities are associated with a lower successful ablation rate in the whole population and in the subgroup of high-risk patients. Furthermore, pooled recurrence rate in intermediate-risk patients achieving successful ablation was only 2% during the subsequent 6.4-year follow-up while the pooled recurrence rate was 14% in patients who did not achieve a successful ablation. Conclusion In a large sample of 3103 patients at intermediate-high risk of persistent/recurrent disease, 71% of patients achieved a successful ablation. In these intermediate-risk patients, the probability of subsequent recurrence is low and most recurrence occurred in those with already abnormal findings at the first control.

Radiology has an important role in the diagnosis, staging and treatment of lung cancer and can offer minimally invasive therapies for poor surgical candidates. Radiology is also important in the follow up of patients after treatment, the assessment of treatment complications and detection of recurrent disease. Understanding the normal post-operative and post-radiation appearances, and recognizing early and late complications is useful for all clinicians involved in the care of patients with cancer.

Background/aim In selected patients, pelvic exenteration (PE) is curative, but morbidity and mortality are feared. Unfortunately, prerequisites for indicating PE are not generally defined. The aim of the study was to identify prognostic factors for survival after PE in advanced pelvic gynecological malignancies for finding possible prerequisites for the indication of PE. Patients and methods Between 2002 and 2016, 49 patients underwent pelvic exenteration for advanced pelvic malignancies apart from ovarian cancer. Progression-free survival (PFS) and overall survival (OS) were calculated based on the Kaplan-Meier method. Factors significantly affecting 5-year overall survival were identified using multivariate regression analysis. Survival distributions between the best and the worst group were compared by the log rank test. Results Forty-nine patients with recurrent or primary pelvic gynecological malignancy (20 recurrent disease, 29 primary disease) were included. Seventeen patients had oligometastatic disease at surgical intervention. Resection margin, age, primary versus secondary exenteration and metastatic disease were independent prognostic factors in multivariate regression analysis. A significant difference was observed in 5-year overall survival regarding the best group (57.14%) and the worst group (10%) (p=0.009). Cervical cancer was the only identified risk factor for increased morbidity. Conclusion Pelvic exenteration is a valuable therapeutic option with most long-term survivors in the group of patients below 63 years, as primary treatment, with clear microscopic margins and no distant metastases. These four factors may serve as valuable prerequisites for the indication of pelvic exenteration as survival and morbidity in this group of patients compares favorably to alternative therapeutic options.

Introduction: The objective of our study was to identify the clinicopathologic factors that are associated with increased risk of recurrence in borderline ovarian tumors (BOTs). Materials and Metho...

Magnetic resonance imaging (MRI) is increasingly used in the management of prostate cancer (PCa). Quantitative MRI (qMRI) parameters, derived from multi-parametric MRI, provide indirect measures of tumour characteristics such as cellularity, angiogenesis and hypoxia. Using Artificial Intelligence (AI), relevant information and patterns can be efficiently identified in these complex data to develop quantitative imaging biomarkers (QIBs) of tumour function and biology. Such QIBs have already demonstrated potential in the diagnosis and staging of PCa. In this review, we explore the role of these QIBs in monitoring treatment response during and after PCa radiotherapy (RT). Recurrence of PCa after RT is not uncommon, and early detection prior to development of metastases provides an opportunity for salvage treatments with curative intent. However, the current method of monitoring treatment response using prostate-specific antigen levels lacks specificity. QIBs, derived from qMRI and developed using AI techniques, can be used to monitor biological changes post-RT providing the potential for accurate and early diagnosis of recurrent disease.

Collagenofibrotic glomerulopathy (CG) is a rare disease characterized by the deposition of collagen type 3 fibrils in the glomeruli. Patients may have proteinuria, hematuria, and/or renal dysfunction. CG is considered a progressive disease with variable rates of progression. The definitive diagnosis is made by electron microscopy with the presence of characteristic subendothelial and mesangial curved, comma-like, banded collagen type 3 fibers of 40-65 nm periodicity. We are reporting the first case of CG in a kidney transplant recipient with kidney disease of unknown cause.

Background Invasive papillary carcinoma (IPC) of the breast is thought to carry a more favorable prognosis than invasive ductal carcinoma (IDC). The aim of this study is to investigate the clinicopathological characteristics between IPC and IDC and their prognosis using a large nationwide data set. Methods Female patients diagnosed with malignant IPC and IDC between 2005 and 2014 were analyzed. Patients with incomplete survival data, stage 0/IV, unknown stage, or recurrent disease were excluded. Five-year overall survival was compared between IPC and IDC. Results Among 308,426 patients, 1147 had IPC and 307,279 had IDC. IPC presented more in older postmenopausal women, black Americans, and people who had government insurance. IPC had larger tumor size, lower-grade, and earlier-stage disease, less node-positive disease, higher hormone positivity, and lower human epidermal growth factor receptor 2 amplification. Adjuvant radiation and chemotherapy rates were lower in IPC than those in IDC. IPC had a similar 5-year overall survival as compared with IDC overall (86.8% versus 88.7%) (P = 0.06). Age, pathologic stage, and radiation treatment were shown to be independent prognostic factors of IPC. Conclusions IPC has a similar prognosis as IDC, suggesting that these patients should follow the same treatment protocols.

Introduction Patients with NSCLC may be treated with curative intent, yet they remain at high risk of both disease recurrence and second primary lung cancer (SPLC) and increased risk of early death. Guidelines provide recommendations for follow-up, but there is little consensus, and review of available evidence is necessary. The use of a systematic follow-up strategy for the detection of disease recurrence or SPLC after curative-intent treatment of NSCLC may increase the proportion of patients available for retreatment and increase the survival of patients with surveillance detection. Methods We performed a systematic review and meta-analysis of prospective studies on follow-up of NSCLC after curative-intent treatment to answer the following three questions: What is the effect of follow-up on detection of recurrence or SPLC? What is the effect of surveillance detection on curative-intent retreatment? What is the survival impact? Results Recurrence or SPLC was observed in 17.8% to 71% of patients. Scheduled imaging-detected recurrence in 60% to 100% of cases, yet neither computed tomography–based (OR = 2.31, 95% confidence interval [CI]: 0.27–19.49, p = 0.44) nor positron emission tomography-computed tomography–based follow-up (OR = 1.431, 95% CI: 0.92–2.22, p = 0.12) was statistically superior to standard follow-up strategies. Detection of disease recurrence/SPLC significantly increased the odds of curative-intent retreatment (OR = 4.31; 95% CI: 2.10–8.84, p Conclusions The early detection of disease recurrence/SPLC may increase the likelihood of curative-intent retreatment and prolong survival. There is a clear need for prospective randomized controlled studies of follow-up to confirm effectiveness of available follow-up modalities.

Background: High-risk non-muscle invasive bladder cancer (NMIBC) is thought to be associated with a higher risk of recurrence and progression. A recent study revealed that a high De Ritis ratio was a risk factor in some solid malignancies. This study examined the importance of the De Ritis ratio as a prognostic marker in high-risk NMIBC. Materials and Methods: A total of 138 patients who were initially diagnosed with high-risk NMIBC between January 2012 to December 2016 were enrolled in this study. The criteria for the high-risk classification followed the EAU guidelines. The recurrence-free and progression-free survival of the higher and lower De Ritis ratio groups were compared. The cut-off value of the De Ritis ratio was set at 1.35, based on a receiver operator curve analysis. Results: The median observation period was 50.3 months. Among these patients, 32 (23.1%) patients developed recurrent disease and 15 (10.9%) patients showed progression. A multivariate analysis revealed that non-BCG treatment was an independent risk factor for recurrence, and a higher De Ritis ratio was an independent risk factor for cancer progression. Conclusions: The De Ritis ratio might be a risk factor for progression in high-risk NMIBC.

The number of patients diagnosed with endometrial cancer surpasses that of any other gynaecological cancer. This disease is usually detected early after disease onset and with current therapy 80 percent of patients with early-stage disease reach a five-year survival milestone. However, patients with advanced or recurrent disease have a grim outcome and the five-year survival rate for these patients is only about 16 percent. In several cancer types there is accumulating evidence that immune cells play a crucial role in the initiation, progression and outcome of disease. In order to provide novel and effective immunotherapeutic treatments for advanced disease endometrial cancer, an understanding of the relevance of immune cells needs to be addressed. This review briefly discusses current knowledge in the area of immune cells and how they may alter the course of endometrial cancer, as well as the implications of these cells for novel therapy and outcome.

Background Surgical treatment of sacrococcygeal pilonidal sinus disease (SPSD) consists of radical excision of the entire tract and treatment of the resultant raw area. Here, the authors have reviewed the results of the rotation flap for closure of the SPSD. Aim This study aims to evaluate the outcomes following SPSD excision and rotation flap closure. Materials and Methods All patients were treated for SPSD with excision and closure using a rotation flap from January 2010 to September 2018. Cases having a follow-up of at least 6 months post surgery were evaluated. Result A total of 52 patients were included in the study; 42 cases were of primary disease while 10 were of recurrent disease. The patients’ follow-up records on the 3rd day, 10th day, 1 month, and 6 months were evaluated.None of the patients showed any signs of recurrence on follow-ups. One patient developed a hematoma on the third day post surgery which was treated conservatively. One patient developed a seroma in the perianal region on the fifth postoperative day which required aspiration. Both these patients healed well subsequently. Conclusion Rotation flap is a (simple and reliable) treatment option for closure of postexcision SPSD defect. It not only takes the tension away from suture line, but also pushes the gluteal fat from the sides into the midline, obliterating the deep crevice of the natal cleft which is believed to be one of the important factors in the causation of SPSD, thus minimizing recurrence.

BackgroundChordomas stem from notochordal vestiges and rank as low-grade bone malignancies although fraught with high risk of recurrence. This study assesses the clinical outcomes of twelve chordoma cases treated in our clinic, in an effort to shed light on the often under-represented pool of results deriving from non-referral centers.MethodsWe reviewed the clinicopathological traits of all chordoma patients registered in our center since 1991. Major endpoints were overall survival (OS) and progression-free survival (PFS) estimated using the Kaplan–Meier and Nelson–Aalen methods.ResultsTwelve patients, aged on average 47.9 years, were treated for primary or recurrent disease. Seven had chordomas originating in the cranium, 5 in the spine, including a bifocal tumor, and the mean time lapse between the beginning of symptoms and diagnosis was 15.4 months, marked by dull ache. Subtotal resection was achieved in 5 cases, incomplete in 5, while in 2, only biopsy was accomplished. Conformal radiotherapy was administered to 5 and stereotactic radiosurgery to 2 in the setting of recurrence. Protons were used once and targeted agents induced no clinical response in 3 patients. Median OS and PFS were 36 and 12 months, respectively, with the best outlook linked to maximal resection, spinal location, and good preoperative functional status. In all, 6 patients died of chordoma, 4 are alive, and 1 was lost. Relapse was the rule for most cases, except 2, and pulmonary metastases were ascertained in 1.ConclusionsOur cases were typical of chordomas, implying that inadequate surgical margins and successive recurrence are negative determinants of prognosis and that interinstitutional cooperation counterbalances shortages in non-referral institutes.

(1) Background: Several techniques for the treatment of pilonidal sinus disease (PSD) are in vogue, though none have emerged as the gold standard. Laying open (deroofing) and curettage under local anesthesia is one of the most straightforward procedures to treat PSD. In this study, the long-term follow-up in a large series was analyzed. (2) Methods: The laying open approach was performed for all types of consecutive PSD patients—simple, complicated, and abscess. The primary outcome parameter of the study was the healing rate. The secondary outcome parameters were operating time, hospital stay, time to resumption of normal work, and healing time. (3) Results: 111 (M/F–92/19, mean age-22.9 ± 5.7 years) consecutive patients were operated on and followed for 38 months (6–111 months). Of these, 24 had pilonidal abscesses, 87 had chronic pilonidal disease, while 22 had recurrent disease. Operating time and hospital stay were 24 ± 7 min and 66 ± 23 min, respectively. On average, patients could resume normal work in 3.6 ± 2.9 days and the healing time was 43.8 ± 7.4 days. Three patients were lost to follow-up. Complete resolution of the disease occurred in 104/108 (96.3%) patients, while 4 (3.7%) had a recurrence. One recurrence was due to a missed tract, while three recurrences presented after complete healing had occurred. Two patients with recurrence were operated on again with the same procedure, and both healed completely. Thus, the overall success rate of this procedure was 98.1% (106/108) with a recurrence rate after first surgery of 3.7% over a median follow-up of 38 months. (4) Conclusions: Pilonidal disease managed by laying open (deroofing) with curettage under local anesthesia is associated with a high cure rate. This procedure is effective in treating all kinds of pilonidal disease (simple, complicated, and abscess).

Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. Questions/purpose This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. Methods This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. Results Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3–85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group. Conclusion Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.

PURPOSE OF REVIEW Although a standard of care in the treatment of organ-confined prostate cancer, use of radiation for treatment in the high-risk, metastatic and salvage settings is evolving rapidly. RECENT FINDINGS Recent clinical trials have explored the role of increased treatment for high-risk disease with the addition of adjuvant chemotherapy and expanded the role of radiation in settings previously reserved for systemic therapy. Addition of adjuvant chemotherapy for high-risk prostate cancer is controversial and recent evidence is discussed that continues to refine the patient population for further evaluation. Evidence recently published demonstrates that for patients with low burden metastatic disease and those with oligometastatic disease may have a survival benefit with radiation treatment to all sites of known disease. Finally, reirradiation after prior radiotherapy-based treatment offers a potential salvage option for patients with locally recurrent prostate cancer. SUMMARY As treatment paradigms evolve for prostate cancer, recent evidence continues to demonstrate benefit for the use of local therapy, both in patients with organ-confined disease and, more increasingly, in those with limited metastatic or locally recurrent disease. Further work is needed to identify subgroups of patients who may benefit from available treatment escalation approaches.

INTRODUCTION In primary Crohn's disease (CD), laparoscopic ileocolic resection has been shown to be both feasible and safe, and is associated with improved outcomes in terms of postoperative morbidity and length of hospital stay. However, it is unclear whether the laparoscopic approach can be routinely proposed as a safe procedure for patients with complex enterovisceral fistulas.The aim of this study is to assess the feasibility and safety of laparoscopic surgery for complex enterovisceral fistulas, and compare it with CD patients who underwent primary laparoscopic ileocolic resection. PATIENTS AND METHODS All patients who underwent laparoscopic primary ileocolic resection (LICR) for complex enterovisceral fistulas between July 2006 and July 2017 were included. They were compared with all consecutive patients who underwent LICR for nonfistulizing CD in the same period of time. Patients with previous bowel resections or recurrent disease were excluded. RESULTS Nineteen patients with 20 enterovisceral fistulas (group I) were compared with 61 patients who underwent LICR for nonfistulizing disease (group II). There were no differences between the groups in age, sex, preoperative body mass index, nutritional status, and American Society of Anesthesiology score. There was no conversion to open surgery in both groups.There were no significant differences between groups in terms of operative time [120 (range: 65 to 232) vs. 117 (range: 62 to 217) min, P=0.7], hospital stay [6 (5 to 8) vs. 7 (5 to 65) days, P=0.56], overall morbidity 26.3% versus 16.4% (P=0.33), major morbidity (Clavien-Dindo >3) 15.7% versus 10% (P=0.66) and reoperation rates 5.3% versus 4.9% (P=0.9). There was no mortality in both groups. CONCLUSIONS Our experience shows that the laparoscopic approach for complex enterovisceral fistulas in selected CD patients is both feasible and safe in the hands of experienced inflammatory bowel disease surgeons with extensive expertise in laparoscopic surgery. Larger study cohorts are needed to confirm these findings.

Peritoneal carcinomatosis (PC) commonly represent drug resistance to intravenous (IV) chemotherapy in advanced or recurrent disease of solid tumors. For improving the prognosis of PC, intraperitoneal (IP) chemotherapy has been introduced in the clinical setting, and phase III trials proved the superiority of IP chemotherapy to IV chemotherapy, in particular, in advanced ovarian cancer. However, increased toxicities by IP chemotherapy lead to reduced cycles of chemotherapy, which does not guarantee its effectiveness. Moreover, hyperthermic IP chemotherapy after cytoreductive surgery also showed improved survival compared to IV chemotherapy in advanced ovarian cancer. Nevertheless, limited distribution and diffusion of drugs, and grade 3 or 4 renal and hepatic toxicity of 20% preclude the expansion of its application. On the other hand, pressurized intraperitoneal aerosol chemotherapy (PIPAC) is known to show the effect by delivering drugs to the parietal and visceral peritoneum in the form of aerosol under the abdominal pressure of 12 mmHg induced by laparoscopic system. Although low dose equivalent to about 1% dose of resistant drugs for IV chemotherapy and normothermia are used in PIPAC, it may improve tumor response and quality of life by repetitive application of PIPAC due to the increased distribution and penetration depth of drugs. However, the heterogeneous distribution of drugs is still the major limitation of PIPAC because the nozzle is placed at the possible outlying position to the tumor-bearing tissues during laparoscopic surgery. Therefore, we developed a novel prototype for PIPAC, rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) system because rotation of the nozzle and change of spray direction can contribute to homogenous distribution of drugs, and compared the distribution of drugs between PIPAC and RIPAC in a porcine model mimicking human body. As a result, RIPAC was more effective than PIPAC in terms of the distribution of drugs into the visceral and parietal peritoneum.

Despite advances in diagnostics and therapy of non-small cell lung cancer (NSCLC), the problem of prognosis and prevention of tumor progression is still highly important. Even if NSCLC is diagnosed in the early stages, almost a quarter of patients develop relapse; most of them die from recurrent disease. A large number of different markers have been proposed to predict the risk of NSCLC progression; however, none of them are used in clinical practice. It is obvious that this situation is related to the economic and methodological complexity of the proposed markers and/or their insufficient efficiency due to a lack of effective study models and tumor heterogeneity. Another reason may be that potential markers are developed for NSCLC progression in general, which is represented by at least four pathogenetically-distinct processes: synchronous lymph node metastasis, local, regional, and distant recurrence. In this review, we summarize data from published literature on clinicopathological, genetic, and molecular factors associated with different types of NSCLC progression and emphasize challenges and approaches to developing prognostic factors. In conclusion, we highlight the importance of further studies to reveal molecular mechanisms of NSCLC progression and the need for differential analysis of markers of local, regional, and distant recurrences for disease prognosis.

Background Borderline ovarian tumors (BOTs) are an intermediate form of neoplasia, between benign and malignant. The aim of this retrospective analysis is to evaluate the clinicopathological characteristic profile of BOTs and to determine the predictors of recurrence in BOTs. Methods A retrospective review of all patients diagnosed, treated, and followed up for BOTs between 2010 and 2017 at Amrita Institute of Medical Sciences, Kerala, India, was conducted. Clinicopathological details and details of management, outcome, and survival were retrieved, and data were analyzed descriptively and for survival. Results A total of 103 patients were identified. During the median follow-up of 46.0 months, 15 (14.6%) patients developed recurrent disease, 6 (5.82%) had recurrence with progression to invasive carcinoma, and 9 had recurrent disease with borderline or benign histology. Mucinous tumors were found to have more recurrences than serous BOT (17.8 vs. 12.3%). Disease-related deaths (5/103 [4.9%]) were observed only in patients with progression to invasive carcinoma. Univariate analysis indicated that staging surgery was the most important prognostic factor that affected the disease-free survival ([DFS] 103 vs. 97 vs. 71 months, respectively, for complete staging vs. fertility-preserving staging vs. conservative surgery; p < 0.05). Conclusions Conservative surgery was associated with a higher risk of recurrence. Fertility-preserving staging surgery is an acceptable option in younger patients. The overall survival is not affected by the mode of surgery.

Background: The RegistEM study is a non-interventional cohort study that will provide prospective data from >1,800 advanced breast cancer (ABC) patients (pts), either after recurrence or as first diagnosis in 38 Spanish sites. Primary objective is the distribution of BC subtypes. A new nomenclature has been proposed for those cases with immunohistochemistry (IHC) 1+ or 2+ and negative in situ hybridization (ISH), HER2-low BC. In clinical practice these tumors are reported as HER2 negative. This subpopulation has been identified as an interesting group from a clinical perspective. Methods: In this analysis (cut-off date 01/April/2020; database is ongoing) we describe the characteristics of 229 pts with hormone receptor (HR)+/HER2-low BC documented in a metastatic lesion after early disease recurrence and who received adjuvant endocrine therapy (ET). Three subgroups of pts have been considered for this analysis based on HER2 results: HER2 IHC 0, HER2-low, and HER2 ISH- (without IHC). Biological samples collection is part of study procedures. Results: The distribution of HER2 IHC 0, HER2-low, and HER2 ISH- subgroups was 52.4%, 42.8% and 4.8%, respectively. The median time to advance disease was 98.6, 88.8 and 106.9 mo in each group. Almost all pts were female and Caucasian (99%), and at ABC diagnosis, 75.5% were postmenopausal. Median age was 59 years (range 33-88). Fourteen (6.1%) pts had HER2+ (IHC 3+ or ISH amplified) BC subtype during their disease. Family history of BC and/or ovarian cancer was reported in 31.4% pts, an hereditary-risk genetic test was performed in 11.4% (n=26) pts in total and BRCA2 gene mutation (n=6) was the only one reported. The most frequent metastases are included in Table 1. Visceral disease was present in 63.3% pts and 76% pts had ≤2 locations. The most frequent 1st-line therapies were ET/biological therapy (BT) (46.7%) and ET (28.8%), and were equal distributed in the 3 subgroups. The most common ET/BT regimens were aromatase inhibitor (AI)/cyclin-dependent kinase 4/6 inhibitor (CDKi) (49.1%/48.9%/42.9% in each subgroup) and fulvestrant (FUL)/CDKi (35.8%/27.7%/28.6%); AIs (50%/64%/66.7%) and FUL (31.6%/20%/0%) were also the most common drugs for monotherapy ET. A 2nd-line therapy was reported in ~53% pts in HER2 IHC 0 and HER2-low, and in 36% pts in HER2 ISH-. The median time to progression (TTP) to 1st-line therapy was 11.4 mo (1.2-37.0), being similar in pts with HER2 IHC 0 and HER2-low (~11 mo), and higher in pts with HER2 ISH- (16 mo). The most frequent 2nd-line therapies were ET/BT (~34% in HER2 IHC 0 and HER2-low, and 25% in HER2 ISH-) [FUL/CDKi (36.4%/47.1%/100%), AI/CDKi (36.4%/23.5%/0%)], chemotherapy as monotherapy (17 pts out of 63 in HER2 IHC 0, 17 pts out of 53 in HER2-low and 1 pt (capecitabine) out of 4 in HER2 FISH-) (capecitabine 29.4%/52.9% in HER2 IHC 0 and HER2-low). Median duration of 2nd-line therapy was ~5 mo in HER2 IHC 0 and ~8 mo in HER2-low and HER2 ISH-; disease progression was reported in 52.4%/62.3%/50% pts, respectively. Conclusions: In this population of HR+ tumors, the proportion of HER2 IHC 0 and HER2-low groups was similar. Time to advance relapse and the distribution of distant metastases were similar among the groups. The most common first- and second-line therapy was the ET/BT combination, with AI/CDKi and FUL/CDKi, respectively. Table 1Location of metastatic lesionsIHC 0HER2-lowISH- non IHCN=120 N (%)N=98 N (%)N=11 N (%)Bone74 (61.7)55 (56.1)6 (54.5)Liver36 (30.0)37 (37.8)3 (27.3)Lung27 (22.5)21 (21.4)5 (45.5)Lymph Node27 (22.5)21 (21.4)2 (18.2)Soft Tissue6 (5.0)11 (11.2)0CNS3 (2.5)4 (4.1)0Other43 (35.8)31 (31.6)5 (45.5) Citation Format: Isabel Álvarez, Angel Guerrero, Sara López-Tarruella, Purificación Martínez, Marta Mori, Catalina Falo, Silvia Antolín, César A Rodríguez, Mireia Margeli, Isabel Garau, Ariadna Tibau, Diana Moreno, Josefina Cruz, María José Echarri, Antonio Antón, Álvaro Rodríguez-Lescure, María José Escudero, Susana Bezares, Federico Rojo, Carlos Jara. Characteristics of HR+/HER2- patients with recurrent disease by HER2 expression from a prospective registry of unresectable locally advanced or metastatic breast cancer: GEICAM/2014-03 (RegistEM) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-24.

C. difficile infection (CDI) is a worldwide healthcare problem with ~30% of cases failing primary therapy, placing a burden on healthcare systems and increasing patient morbidity. We have little understanding of why these therapies fail. Here, we use a clinically validated in vitro gut model to assess the contribution of biofilms towards recurrent disease and to investigate biofilm microbiota-C. difficile interactions. Initial experiments show that C. difficile cells became associated with the colonic biofilm microbiota and are not depleted by vancomycin or faecal microbiota transplant therapies. We observe that transferring biofilm encased C. difficile cells into a C. difficile naïve but CDI susceptible model induces CDI. Members of the biofilm community can impact C. difficile biofilm formation by acting either antagonistically or synergistically. We highlight the importance of biofilms as a reservoir for C. difficile, which can be a cause for recurrent infections.

Endoscopic ear surgery is increasingly accepted as a primary modality for cholesteatoma surgery. A major advantage is the enhanced visualization of the middle ear in traditionally poorly accessible locations by the microscope. We discuss novel techniques for selective mastoid obliteration when a canal wall down mastoidectomy is necessary. Postoperatively, indications for non-echo planar diffusion-weighted imaging MRI versus second-look surgery are discussed. Finally, outcome data for endoscopic versus microscopic ear surgery are reviewed, which show equivalent outcomes regarding residual and recurrent disease, similar rates of complications, decreased pain, and shorter healing time.

The NCCN Guidelines for Prostate Cancer address staging and risk assessment after a prostate cancer diagnosis and include management options for localized, regional, and metastatic disease. Recommendations for disease monitoring and treatment of recurrent disease are also included. The NCCN Prostate Cancer Panel meets annually to reevaluate and update their recommendations based on new clinical data and input from within NCCN Member Institutions and from external entities. This article summarizes the panel’s discussions for the 2021 update of the guidelines with regard to systemic therapy for metastatic castration-resistant prostate cancer.

Not 1 year has passed since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Since its emergence, great uncertainty has surrounded the potential for COVID-19 to establish as a seasonally recurrent disease. Many infectious diseases, including endemic human coronaviruses, vary across the year. They show a wide range of seasonal waveforms, timing (phase), and amplitudes, which differ depending on the geographical region. Drivers of such patterns are predominantly studied from an epidemiological perspective with a focus on weather and behavior, but complementary insights emerge from physiological studies of seasonality in animals, including humans. Thus, we take a multidisciplinary approach to integrate knowledge from usually distinct fields. First, we review epidemiological evidence of environmental and behavioral drivers of infectious disease seasonality. Subsequently, we take a chronobiological perspective and discuss within-host changes that may affect susceptibility, morbidity, and mortality from infectious diseases. Based on photoperiodic, circannual, and comparative human data, we not only identify promising future avenues but also highlight the need for further studies in animal models. Our preliminary assessment is that host immune seasonality warrants evaluation alongside weather and human behavior as factors that may contribute to COVID-19 seasonality, and that the relative importance of these drivers requires further investigation. A major challenge to predicting seasonality of infectious diseases are rapid, human-induced changes in the hitherto predictable seasonality of our planet, whose influence we review in a final outlook section. We conclude that a proactive multidisciplinary approach is warranted to predict, mitigate, and prevent seasonal infectious diseases in our complex, changing human-earth system.

Nasopharyngeal carcinoma (NPC) results from the aberrant and uncontrolled growth of the nasopharyngeal epithelium. It is highly associated with the Epstein-Barr virus, especially in regions where it is endemic. In the last decade, significant advances in genetic sequencing techniques have allowed the discovery of many new abnormal molecular processes that undoubtedly contribute to the establishment, growth and spread of this deadly disease. In this review, we consider NPC as EBV induced. We summarise the recent discoveries and how they add to our understanding of the pathophysiology of NPC in the context of genomics first in primary and then in recurrent disease. Overall, we find key early events lead to p16 inactivation and cyclin D1 expression, allowing latent viral infection. Host and viral factors work together to affect a variety of molecular pathways, the most fundamental being activation of NF-κB. Nonetheless, much still yearns to be discovered, especially in recurrent NPC.

Minimally invasive surgery (MIS) in pediatric oncology remains controversial. Our unit aims to surgically stratify patients for MIS and here we present our data. Oncology patients who had undergone surgery were identified from prospectively collected databases and retrospectively analyzed. Between 04/2004 and 12/2019, 905 procedures in 757 patients were identified. Patients were excluded if their intervention was superficial leaving 585 procedures in 451 patients. In Group 1 (G1) (2004–2011), there were 250 procedures in 175 patients: 26 (10.4%) MIS and 167 (67%) open. In Group 2 (G2) (2012–2019,) there were 335 procedures in 276 patients: 113 (33.7%) MIS and 185 (55.2%) open. The remainder were percutaneous biopsies. The 139 MIS cases included 23 neural crest tumors; 18 ovarian; 19 renal; 14 rhabdomyosarcoma; 23 thoracic; 20 other abdominal tumors; and 22 cryopreservation. Mean age at surgery was 78 months. In the MIS group, 3 patients had recurrent disease of whom 1 died. In the open group 38 patients had recurrent disease; there were 36 deaths of whom 22 died following recurrent disease. MIS cases have gone from 3.7/year in G1 to 16.1/year in G2 representing an increase of 435%. This is the biggest single series of pediatric oncology resections by MIS. It shows an almost exponential increase in the number of MIS resections per year whilst maintaining excellent outcomes. Is it time to make MIS in pediatric oncology inclusive and not exclusive?

BACKGROUND Sinusoidal obstructive syndrome (SOS) is a disease that damages hepatic sinusoidal endothelial cells, resulting in progressive occlusion and fibrosis of the lobular central vein and the occurrence of intrahepatic sinusoidal portal hypertension. However, SOS after liver transplantation (LT) is uncommon and potentially fatal. Here, we report a rare case of second-time recurrence of SOS after liver retransplantation (rLT). CASE SUMMARY A 22-year-old woman received a living donor LT due to SOS. Four years later, she developed abdominal distention and ascites with no apparent cause. She was diagnosed with recurrence of SOS and underwent rLT. But 2 mo post rLT, the patient suffered from aggravated jaundice and ascites again. She was diagnosed with second-time recurrence of SOS post-rLT according to computed tomography and liver pathology. After treatment with warfarin anticoagulation and immunosuppressant conversion, she gradually recovered with improvement of liver function and liver pathology. During the 17-mo follow-up period, she was in good condition with normal liver function and no ascites. CONCLUSION SOS can be a recurrent disease after LT, and autoimmune antibody and genetic sequencing should be screened before LT. For susceptible patients, anticoagulant drugs should be used for an extended period, and tacrolimus or other pathogenic agents should be avoided. Early diagnosis and treatment can improve the prognosis of patients and avoid graft failure or death.

Radiation therapy (RT) continues to play a central role as an effective therapeutic modality for a variety of tumors and vascular malformations in the central nervous system. Although the planning and delivery techniques of RT have evolved substantially during the past few decades, the structures surrounding the target lesion are inevitably exposed to radiation. A wide variety of radiation-induced changes may be observed at posttreatment imaging, which may be confusing when interpreting images. Histopathologically, radiation can have deleterious effects on the vascular endothelial cells as well as on neuroglial cells and their precursors. In addition, radiation induces oxidative stress and inflammation, leading to a cycle of further cellular toxic effects and tissue damage. On the basis of the time of expression, radiation-induced injury can be divided into three phases: acute, early delayed, and late delayed. Acute and early delayed injuries are usually transient and reversible, whereas late delayed injuries are generally irreversible. The authors provide a comprehensive review of the timeline and expected imaging appearances after RT, including the characteristic imaging features after RT with concomitant chemotherapy. Specific topics discussed are imaging features that help distinguish expected posttreatment changes from recurrent disease, followed by a discussion on the role of advanced imaging techniques. Knowledge of the RT plan, the amount of normal structures included, the location of the target lesion, and the amount of time elapsed since RT is highly important at follow-up imaging, and the reporting radiologist should be able to recognize the characteristic imaging features after RT and differentiate these findings from tumor recurrence. ©RSNA, 2020.

Background Alopecia areata (AA) is considered an autoimmune disorder caused by altered T-cell-mediated immunity. MicroRNAs (miR) are important translational regulators of genes in various tissues and biological processes involved in autoimmune responses and have been identified in autoimmune diseases such as rheumatoid arthritis and type I diabetes mellitus. However, little is known about their role in pathogenesis of AA. Objective To assess serum levels of miR-155 and miR-146a in patients with AA and to correlate them with different clinical variables. Patients and methods MiR-155 and miR-146a serum levels were identified by real-time PCR in 50 patients with AA and 50 healthy age-matched and sex-matched patients as controls. Disease severity in the patients was assessed by Severity of Alopecia Tool score. Results There was a statistically significant increase in serum miR-155 and miR-146a levels in patients with AA than in controls. A significant increase in serum levels of miR-155 was found in patients with active disease and recurrent lesions of AA, whereas significant increase in serum level of miR-146a was found in patients with recurrent disease only. Significant positive correlations were found between serum miR-155 and miR-146a levels and disease severity. Conclusion Serum levels of miR-155 and miR-146a seem to have an essential role in the etiopathogenesis of AA and could be markers for severity and early detection of recurrent AA. In addition, serum miR-155 could be a marker of activity in AA, whereas serum miR-146a could be a marker of multiplicity. Further understanding of the function and regulation of miR-155 and miR-146a could be of great value for the introduction of new therapeutic approaches for AA.

Objective To examine the association between lymph node status and recurrence patterns in completely resected gastric adenocarcinoma. Methods We retrospectively assessed 1,694 patients who underwent curative gastrectomy from January 2010 to August 2014. Patients stratified according to lymph node status and recurrence patterns among different subgroups were compared. Results Of all, 517 (30.5%) patients developed recurrent disease, and complete data of recurrence could be obtained in 493 (95.4%) patients. For pN0 patients, the patterns of recurrence were different according to pT stage: locoregional recurrence was most common in patients with pT1-2 disease (57.1%), distant recurrence was most common in patients with pT3 disease (57.1%), and peritoneal recurrence was most common in patients with pT4a disease (66.7%). For pN+ patients, distant metastasis was most common pattern irrespective of pT stage. The site-specific trend of recurrence showed that locoregional recurrence increased within 5 years in patients with pN0-2 disease but plateaued 3 years after surgery in patients with pN3 disease. Time to recurrence was significantly longer for the pN0 patients compared with the pN+ patients (median: 25 vs. 16 months, P=0.001). Moreover, post-recurrence survival was significantly better for the pN0 patients than for the pN+ patients (median: 12 vs. 6 months, P

OBJECTIVE: To assess the prognostic value of the ChOLE classification in predicting the severity of acquired cholesteatoma. METHOD: A retrospective chart review of patients undergoing primary cholesteatoma surgery in our tertiary referral center. The primary outcome measures were analyzed in three groups of follow up (FU): residual cholesteatoma in group A, FU > 52 weeks after last-look surgery or MRI-DWI; recurrent cholesteatoma in group B, FU > 52 weeks after last outpatient visit; and adverse events (AE) in group C, FU > 12 weeks after surgery. Cholesteatomata were staged according to the ChOLE classification. Kaplan-Meier curves were used to determine the prognostic value of the classification in predicting cholesteatoma severity, while correcting for FU. RESULTS: No significant differences were observed between the various stages of the ChOLE classification and residual or recurrent cholesteatoma rate, nor the occurrence of AE. Cholesteatoma extension to the sinus tympani or widespread in the mastoid, as well as absence of the stapes superstructure were predictive of residual disease. Sclerotic mastoids had a lower risk of residual disease than mastoids with good or poor pneumatization and ventilation. Poorly ventilated and poorly pneumatized mastoids were associated with increased risk of recurrence. Widespread cholesteatoma in the mastoid as well as presence of preoperative extracranial complications were correlated with an increased risk of AE. CONCLUSION: The ChOLE classification does not predict residual nor recurrent disease, nor the occurrence of AE, in our study population. Risk factors for severe cholesteatoma were identified, potentially useful for the development of future classifications.