Disease Recurrence In Patients Research Articles

HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer.

HER2 overexpression has been investigated as a potential biomarker and therapeutic target in biliary tract cancer (BTC), but a prognostic role of such alteration has not been demonstrated yet. We retrospectively evaluated HER2 protein expression by immunohistochemistry (IHC) in 100 patients with radically resected BTC. HER2 gene amplification was assessed by fluorescence in situ hybridization (FISH) in 2+ and 3+ cases at IHC. High HER2 protein expression was defined as either IHC 3+ or 2+ associated with FISH positivity. The primary objective of the study was to evaluate the prognostic role of HER2 overexpression in terms of disease-free survival (DFS) and overall survival (OS). Secondary endpoints were the prevalence of HER2 overexpression and the possible correlation with other clinicopathological features. HER2 overexpression was identified in 11 patients and was not related to other clinicopathological factors. DFS was significantly shorter in HER2-positive compared with HER2-negative patients (10.6 vs. 20.9 months, log-rank p = .017). HER2 confirmed its prognostic value for DFS at multivariate analysis (hazard ratio 2.512; 95% confidence interval, 1.232-5.125; p = .011) together with nodal stage (p < .001), resection margin (p = .027), and tumor site (p = .030). There was no difference in OS between HER2-positive and -negative patients (p = .068). HER2 overexpression represents an independent prognostic factor for disease recurrence in patients with BTC treated with potentially curative surgery. HER2 overexpression may play an independent role in promoting an aggressive behavior in resectable biliary tract cancer. This evidence could be helpful in improving prognostic stratification after resection and, primarily, should endorse the rationale to investigate HER2 as a therapeutic target in biliary tract cancer.

Safety of Percutaneous Cholecystostomy Early Removal: A Retrospective Cohort Study.

There are no strong recommendations regarding the management of percutaneous cholecystostomy (PC). The aim of this study was to assess the safety of early PC removal in terms of complications and recurrent disease. Retrospective observational study of consecutive patients who underwent PC for acute cholecystitis from January 2012 to December 2017. We first evaluated PC-related complications and recurrent disease in patients whose drainage was removed as inpatients (IPR) or as outpatients (OPR). Patients were then divided into 2 groups according to the timing of PC removal: G1 with the PC removed within the first 7 days after its collocation and G2 with the PC removed after 7 days. We included 151 patients. Patients in the OPR group had their catheters removed after 52 days (26 to 67 d) while the IPR group after 8 days (6 to 11 d); P<0.001. No difference was seen regarding complications, recurrent disease rate, or readmissions.G1 was comprised of 56 patients (37.1%), whereas G2 had 95 (62.9%). When G1 was compared with G2, no differences were seen in terms of complications. However, G1 presented a shorter duration of antibiotic treatment with 11 days (8 to 14 d) versus 15 days (12 to 23 d) in G2; P<0.001, but had a higher rate of recurrent disease 32.1% versus 14.7% in G2; P=0.014 and a higher rate of readmission 30.3% versus 13.6% in G2; P=0.019. Removal of the PC during the index admission was not associated with a higher risk of complications. However, the PC removal before 7 days could be related to an increase in recurrent disease and readmissions.

MON-448 Detection of Thyroid Cancer Recurrence in Patients with Positive Thyroglobulin Antibody Receiving Immunoglobulin Therapy

Introduction: Differentiated thyroid cancers such as papillary and follicular thyroid cancer make up more than 90% of all thyroid cancers. The presence of thyroglobulin autoantibodies makes interpretation of the thyroglobulin level unreliable, as it could be falsely low or falsely high. Studies have shown that rising thyroglobulin antibody levels, could be used to monitor for disease recurrence in patients with negative thyroglobulin and imaging studies. However, there are challenges in detecting recurrence in patients with normal thyroglobulin level and thyroid imaging studies, who are on lifelong immunoglobulin therapy and who have increasing thyroglobulin antibody levels.Clinical case: A 63 yr old female was found to have an incidental left thyroid nodule at age 48yrs from a carotid ultrasound. She underwent US guided FNA of the thyroid nodule and was found to have papillary thyroid cancer. She had total thyroidectomy a month later, with removal of a 1.4cm primary, with no evidence of extrathyroidal extension, clear margins and no evidence of lymphovascular invasion – Stage T1bN0M0. There was left level 6 neck dissection with no carcinoma identified in the 2 lymph nodes removed. She received 105.3 mCi radioactive iodine (RAI) and whole body thyroid scan done 7 days later revealed, increased uptake involving the thyroid bed likely residual thyroid tissue. Activity was noted inferolateral to the right thyroid bed which most likely represents a lymph node. There was no evidence of distant metastasis.She was commenced on levothyroxine post operatively. Her other past medical history is significant for idiopathic urticaria and angioedema, immune deficiency disorder with low IgG and IgM and asthma. She was commenced on monthly IV immunoglobulins 5yrs post RAI therapy, due to recurrent sinusitis, rhinitis and chronic diarrhea. She was later transitioned to weekly SQ immune globulin – Hizentra which she is on till date.Over the past 15 years, serial neck ultrasounds post radioiodine ablation have been negative for recurrence. Her TSH ranged 14.91 to 0.04 (ref 0.27-4.2 uiu/ml) and thyroglobulin (Tg) titer remains <0.1 (ref <0.1). Her thyroglobulin antibody titers have trended up from <0.2 (ref <2.0) 5yrs post RAI therapy to 49 (ref <4 iu/ml)) on her most recent test this year. She is currently undergoing further work up to rule out recurrence of her cancer. In our review of the literature we found one report that showed use of Liquid Chromatography–Mass Spectrometry (LC-MS) was able to differentiate thyroid cancer recurrence in an individual with positive antithyroglobulin antibody receiving immunoglobulin therapy.Conclusion: In patients with negative Tg levels, but elevated thyroglobulin antibody while receiving immune globulin therapy, thyroglobulin antibody levels may not be a reliable indicator of thyroid cancer recurrence. Measurement of Tg levels using a LC-MS may provide some clarity.

Impact of Surveillance After Lobectomy for Lung Cancer on Disease Detection and Survival

IntroductionExisting guidelines for surveillance after non–small-cell lung cancer (NSCLC) treatment are inconsistent and have relatively sparse supporting literature. This study characterizes detection rates of metachronous and recurrent disease during surveillance with computed tomography scans after definitive treatment of early stage NSCLC. Materials and MethodsThe incidence of metachronous and recurrent disease in patients who previously underwent complete resection via lobectomy for stage IA NSCLC at a single center from 1996 to 2010 were evaluated. A subgroup analysis was used to compare survival of patients whose initial surveillance scan was 6 ± 3 months (early) versus 12 ± 3 months (late) after lobectomy. ResultsOf 294 eligible patients, 49 (17%) developed recurrent disease (14 local only, 35 distant), and 45 (15%) developed new NSCLC. Recurrent disease was found at a mean of 22 ± 19 months, and new primaries were found at a mean of 52 ± 31 months after lobectomy (P < .01). Five-year survival after diagnosis of recurrent disease was significantly lower than after diagnosis of second primaries (2.3% vs. 57.5%; P < .001). In the subgroup analysis of 187 patients, both disease detection on the initial scan (2% [2/94] vs. 4% [4/93]; P = .44) and 5-year survival (early, 80.8% vs. late, 86.7%; P = .61) were not significantly different between the early (n = 94) and the late (n = 93) groups. ConclusionSurveillance after lobectomy for stage IA NSCLC is useful for identifying both new primary as well as recurrent disease, but waiting to start surveillance until 12 ± 3 months after surgery is unlikely to miss clinically important findings.

Statins may reduce disease recurrence in patients with ulcerated primary melanoma

Statins may restrict the cellular functions required for melanoma growth and metastasis. To determine whether long-term statin use commenced before diagnosis of a primary melanoma is associated with reduced risk of melanoma recurrence. We prospectively followed a cohort of patients newly diagnosed between 2010 and 2014 with localized tumour-stage T1b to T4b melanoma in Queensland, Australia. We used Cox regression analyses to examine associations between long-term statin use and melanoma recurrence for the entire cohort, and then separately by sex and by presence of ulceration, due to evidence of effect modification. Among 700 patients diagnosed with stage T1b to T4b primary melanoma (mean age 62 years, 59% male, 28% with ulcerated tumours), 94 patients (13%) developed melanoma recurrence within 2 years. Long-term statin users (n = 204, 29%) had a significantly lower risk of disease recurrence than nonusers [adjusted hazard ratio (HRadj ) 0·55, 95% confidence Interval (CI) 0·32-0·97] regardless of statin subtype or potency. Compared with nonusers of statins, risk of recurrence was significantly decreased in male statin users (HRadj 0·39, 95% CI 0·19-0·79) but not in female statin users (HRadj 0·82, 95% CI 0·29-2·27) and in statin users with ulcerated (HRadj 0·17, 95% CI 0·05-0·52) but not nonulcerated (HRadj 0·91, 95% CI 0·46-1·81) primary melanoma. Statins commenced before melanoma diagnosis may reduce the risk of melanoma recurrence, especially in men and in those with ulcerated tumours. Clinical trial evaluation of the potential role of statins in improving the prognosis of high-risk melanoma is warranted.

Niraparib for the Treatment of Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

To review the efficacy and safety of niraparib for the treatment of recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (OC, FTC, and PPC). A literature search via MEDLINE through PubMed from August 2013 to January 2020 was performed using the key terms niraparib, PARP inhibitors, ovarian cancer, fallopian tube cancer, and primary peritoneal cancer. Completed and ongoing trials were identified through a review of the website trial registry https://www.clinicaltrials.gov. In a phase III, double-blind clinical trial, progression-free survival improved in patients treated with niraparib compared with placebo as maintenance treatment for patients with platinum-sensitive, recurrent OC: 21 versus 5.5 months in the germline breast cancer susceptibility gene (gBRCA) cohort (hazard ratio [HR] = 0.27; 95% CI = 0.17 to 0.41; P < 0.001) and 9.3 versus 3.9 months in the overall nongermline breast cancer susceptibility gene (non-gBRCA) cohort (HR = 0.45; 95% CI = 0.34 to 0.61; P < 0.001). Adverse events included thrombocytopenia and anemia. Poly (ADP-ribose) polymerase (PARP) inhibitors have gained a place in the therapeutic management of OC, FTC, and PPC because of their ability to suppress growth of homologous recombination deficiency-positive tumors, including those with BRCA1/2 mutations. Niraparib inhibits the DNA repair mechanism vital to the survival of cancer cells, poly-ADP ribose polymerase. PARP inhibitors can be used as a single agent for maintenance therapy for platinum-sensitive recurrent disease in patients with partial or complete response following 2 or more rounds of platinum-based therapy.

Altered Monocyte and Langerhans Cell Innate Immunity in Patients With Recurrent Respiratory Papillomatosis (RRP).

The micromilieu within respiratory papillomas supports persistent human papillomavirus (HPV) infection and disease recurrence in patients with recurrent respiratory papillomatosis (RRP). These patients show polarized (TH2-/Treg) adaptive immunity in papillomas and blood, enriched immature Langerhans cell (iLC) numbers, and overexpression of cyclooxygenase-2/prostaglandin E2 (PGE2) in the upper airway. Blood monocyte-derived, and tissue-derived iLCs from RRP patients and controls were now studied to more fully understand innate immune dysregulation in RRP. Patients' monocytes generated fewer iLCs than controls, due to a reduced fraction of classical monocytes that generated most but not all the iLCs. Prostaglandin E2, which was elevated in RRP plasma, reduced monocyte-iLC differentiation from controls to the levels of RRP patients, but had no effect on subsequent iLC maturation. Cytokine/chemokine responses by iLCs from papillomas, foreskin, and abdominal skin differed significantly. Freshly derived tissue iLCs expressed low CCL-1 and high CCL-20 mRNAs and were unresponsive to IL-36γ stimulation. Papilloma iLCs uniquely expressed IL-36γ at baseline and expressed CCL1 when cultured overnight outside their immunosuppressive microenvironment without additional stimulation. We conclude that monocyte/iLC innate immunity is impaired in RRP, in part due to increased PGE2 exposure in vivo. The immunosuppressive papilloma microenvironment likely alters iLC responses, and vice versa, supporting TH2-like/Treg HPV-specific adaptive immunity in RRP.

Overall tumor genomic instability: an important predictor of recurrence-free survival in patients with localized clear cell renal cell carcinoma

ABSTRACTMeasurement of a tumor’s overall genomic instability has gathered recent interest over the identification of specific genomic imbalances, as it may provide a more robust measure of tumor aggressiveness. Here we demonstrate the association of tumor genomic instability in the prediction of disease recurrence in patients with clinically localized clear cell renal cell carcinoma (ccRCC). Genomic copy number analysis was performed using SNP-based microarrays on tumors from 103 ccRCC patients. The number of copy number alterations (CNAs) for each tumor was calculated, and a genomic imbalance threshold (GIT) associated with high stage and high-grade disease was determined. Cox proportional hazards regression analyzes were performed to assess the effect of GIT on recurrence-free survival adjusting for known confounders. In the cohort, copy number losses in chromosome arms 3p, 14q, 6q, 9p, and 1p and gains of 5q and 7p/q were common. CNA burden significantly increased with increasing stage (p < .001) and grade (p < .001). The median CNA burden associated with patients presenting with advanced stage (IV) and high-grade (III/IV) tumors was ≥9, defining the GIT. On regression analysis, GIT was a superior predictor of recurrence (Hazard Ratio 4.44 [CI 1.36–14.48], p = .01) independent of stage, with similar results adjusting for grade. These findings were confirmed using an alternative measure of genomic instability, weighted Genomic Integrity Index. Our data support a key role for genomic instability in ccRCC progression. More importantly, we have identified a GIT (≥ 9 CNAs) that is a superior and independent predictor of disease recurrence in high-risk ccRCC patients.

Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer

ObjectivesTo establish and evaluate a first generation patient-derived xenograft (PDX) model in nude mice using tumors resected from pancreatic cancer (PC) patients for the identification of key factors that influence xenograft success and prediction of patient prognosis. MethodsPrimary tumor samples harvested from PC patients who underwent curative resection between May 2016 and April 2018 at our hospital were xenografted into nude mice. Tumor size was evaluated for 2 months. Patients’ baseline characteristics and follow-up data were analyzed. ResultsTumor xenograft models were generated from 67 patients; 30 (44.8%) were successful and 37 (55.2%) failed. Xenograft models could recapitulate the pathology and genetic information of the primary tumors. Univariate analysis identified tumor engraftment, post-operation CA19-9, tumor size, lymph node status, and lymphovascular invasion as significant predictors (P=0.000, 0.023, 0.004, 0.035 and 0.005, respectively) of disease-free survival (DFS). Multivariate Cox regression analysis confirmed tumor engraftment, tumor size and lymphovascular invasion function as independent risk factors for DFS (P=0.000, 0.039 and 0.025, respectively). The hazard ratio of tumor engraftment for DFS was 0.239 (95% confidence interval, 0.109 to 0.524). Kaplan–Meier analysis of DFS indicated an unfavorable outcome in the engraftment group compared to that in the failed engraftment group (6.2 vs. 12.2 months, log rank P=0.000). ConclusionThe pathology and genetic information of primary PC tumors are recapitulated in the PDX tumor model in nude mice. Furthermore, engraftment success is an effective predictor of disease recurrence in patients after surgery.

Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma

BackgroundNeuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence.MethodsA total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children’s Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence.ResultsOf the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL.ConclusionsHigh plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.

Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer.

PURPOSEPlasma circulating tumor human papillomavirus DNA (ctHPVDNA) is a sensitive and specific biomarker of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). We investigated whether longitudinal monitoring of ctHPVDNA during post-treatment surveillance could accurately detect clinical disease recurrence.METHODS AND MATERIALSA prospective biomarker clinical trial was conducted among patients with nonmetastatic HPV-associated (p16-positive) OPSCC. All patients were treated with curative-intent chemoradiotherapy (CRT). Patients underwent a 3-month post-CRT positron emission tomography/computed tomography scan and were thereafter clinically evaluated every 2-4 months (years 1-2), then every 6 months (years 3-5). Chest imaging was performed every 6 months. Blood specimens were collected every 6-9 months for analysis of plasma ctHPVDNA using a multianalyte digital polymerase chain reaction assay. The primary endpoint was to estimate the negative predictive value (NPV) and positive predictive value (PPV) of ctHPVDNA surveillance.RESULTSOne hundred fifteen patients were enrolled, and 1,006 blood samples were analyzed. After a median follow-up time of 23 months (range, 6.1-54.7 months), 15 patients (13%) developed disease recurrence. Eighty-seven patients had undetectable ctHPVDNA at all post-treatment time points, and none developed recurrence (NPV, 100%; 95% CI, 96% to 100%). Twenty-eight patients developed a positive ctHPVDNA during post-treatment surveillance, 15 of whom were diagnosed with biopsy-proven recurrence. Sixteen patients had 2 consecutively positive ctHPVDNA blood tests, 15 of whom developed biopsy-proven recurrence. Two consecutively positive ctHPVDNA blood tests had a PPV of 94% (95% CI, 70% to 99%). Median lead time between ctHPVDNA positivity and biopsy-proven recurrence was 3.9 months (range, 0.37-12.9 months).CONCLUSIONDetection of ctHPVDNA in two consecutive plasma samples during post-treatment surveillance has high PPV and NPV for identifying disease recurrence in patients with HPV-associated oropharyngeal cancer and may facilitate earlier initiation of salvage therapy.

Prognostic Significance of Serum Complement Component 3 in Chronic Rhinosinusitis with Nasal Polyps

Objective: The aim of this study was to assess the relationship between serum complement component 3 (C3) levels and disease recurrences in patients with chronic rhinosinusitis with nasal polyps (NPs). Methods: Ninety-seven patients with NPs and 30 controls were recruited. Clinical features were collected. Serum concentrations of C3 and C4 were measured before and after endoscopic sinus surgery. Results: Compared to the controls, increased C3 levels were found in patients with NPs. Patients with polyp recurrences had higher pre- and postoperative serum C3 levels than patients without polyp recurrences. Serum C3 levels dropped after surgery. After polyp regrowth, the mean C3 level in the recurrent group elevated again to the degree similar to that before surgery. When patients were stratified by tissue eosinophilia, no significant difference was seen in pre-/postoperative, absolute change after surgery, and post-recurrent C3 levels between patients without and with eosinophilic NPs in the group with disease recurrences. Conclusion: Serum C3 may be involved in the pathogenesis of NPs. Higher serum C3 levels may pinpoint patients at high risk of recurrence as an independent factor. Furthermore, the change in C3 levels after surgery may have the potential to serve as a predictor for polyp progression. Adding serum C3 measurement to the routine walk-up in the clinical management of NPs is worth further investigation and may help physicians make a more rational diagnostic and/or therapeutic decision regarding this disease.

Microscopic Positive Tumor Margin Increases Risk for Disease Persistence but Not Recurrence in Patients with Stage T1-T2 Differentiated Thyroid Cancer.

Introduction Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients' charts from 1995–2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. Results 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. Conclusions Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.

FOLLICULAR THYROID CARCINOMA - CLINICAL AND DIAGNOSTIC FINDINGS IN A 20-YEAR FOLLOW UP STUDY.

Follicular thyroid carcinomas (FTC) represent 6-10 % of all thyroid carcinomas; the evolution of FTC is quite controversial, partly due to frequent changes of the histopathological definition (minimally invasive-MIFTC or widely invasive carcinoma-WIFTC) and treatment strategies adjustments. This research aims to examine the diagnostic procedure, therapeutic attitude and survival rates of patients with FTC, over a period of 16 years in the same institution, with a follow-up of at least 4 years, by analyzing correlations between histology subtype, treatments and the rate of recurrent disease. We have studied 5891 patients with thyroid carcinomas who have undergone surgical or oncological treatment within the institution, between 1st January 2000 - 31st December 2015; among them we found 133 patients (2.25%) with "pure" follicular thyroid carcinoma: 114 (86%) women and 19 (14%) men, with a female-male ratio of 6:1. The age of the patients ranged from 10 to 76 years, with an average of 47.8 years. Statistical analysis was done comparing differences among groups of MIFTC and WIFTC. There was an unexpected high percentage of WIFTC and also an increased number of biochemically persistent and/or recurrent disease in patients with MIFTC. A stronger correlation was observed with the tumour dimensions, rather than with the histopathological subtype. This research observed that overall survival was associated with tumour size rather than histopathological subtype and there is an important need to perform further studies to assess the effectiveness of treatment strategies.

Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells.

ObjectiveEarly detection and treatment are particularly important to epithelial ovarian cancer (EOC). Studies have shown that circular RNA (circRNA) dysregulation is associated with the proliferation and metastasis of ovarian cancer cells. This study focused on the role of serum exosomal circular forkhead box protein P1 (circFoxp1) on survival outcome and cisplatin (DDP) resistance in patients with EOC.MethodsQuantitative polymerase chain reaction, 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8, luciferase reporter assay, RNA immunoprecipitation, tumor xenograft in nude mice, and bioinformatic analysis were performed.ResultsCirculating exosomal circFoxp1 was significantly increased in patients with EOC, especially in DDP-resistant EOC patients. circFoxp1 expression was positively associated with International Federation of Gynecology and Obstetrics stage, primary tumor size, lymphatic metastasis, distant metastasis, residual tumor diameter, and clinical response. Exosomal circFoxp1 also was an independent factor predicting survival and disease recurrence in patients with EOC. Overexpression of circFoxp1 could promote cell proliferation and confer DDP resistance, while knockdown of circFoxp1 could inhibit cell proliferation and enhance DDP sensitivity in vitro and in vivo. In addition, miR-22 and miR-150-3p mimic treatment attenuated circFoxp1-meadiated DDP resistance, while miR-22 and miR-150-3p inhibitor treatment enhanced DDP resistance that mitigated by circFoxp1 knockdown. Furthermore, circFoxp1 positively regulated the expression of CCAAT enhancer binding protein gamma (CEBPG) and formin like 3 (FMNL3) through miR-22 and miR-150-3p.ConclusionscircFoxp1 is an oncogene in EOC cells and can confer DDP resistance to EOC cells. Circulating exosomal circFoxp1 can be used as a biomarker and potential therapeutic target for EOC.

Stage-specific prognostic value of carcinoembryonic antigen and cancer antigen 19-9 serum levels on survival and recurrence in pancreatic adenocarcinoma

Background: Few studies reported on carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) as markers for overall survival (OS) and disease free survival (DFS). This study aimed to determine the stage-specific prognostic value of CEA and CA19-9 serum levels at diagnosis on OS and DFS in patients with pancreatic ductal adenocarcinoma (PDAC), discussed at pancreatic Multidisciplinary Team (MDT) meetings. Material and Methods: All consecutive patients with PDAC, discussed at MDT meetings between from 2013 through 2017 at a single tertiary referral center, were retrospectively reviewed. Advanced stage was defined as either locally advanced PDAC or presence of distant metastases. The Kaplan-Meier method was used to estimate the OS and DFS. Prognostic factors were evaluated in uni- and multivariable Cox proportional hazard models. Approval of the local Medical Research and Ethical Committee was obtained for this study. Results: 375 patients were available for analyses, of which 151 (40.3%) patients underwent resection and 224 (59.7%) patients had advanced stage PDAC. In the total cohort, both elevated CA19-9 (>305 kU/L) and CEA (>7 μg/L) levels were significantly associated with a poor median [95% confidence interval] OS compared to lower serum levels: 8 [5.6-10.4] vs. 12 [7.7-16.3] months (P<0.001) and 5 [3.2-6.8] vs. 13 [10.2-15.8] months (P=0.009), respectively (Figure 1). Multivariable analysis showed that CA19-9 is an independent factor (Hazard Ratio (HR):1.56 [1.18-2.06]; P=0.002) for poor OS, whereas CEA did not yield a significant association anymore (HR: 1.35 [0.96 -1.89]; P=0.083). In patients who underwent resection, CA19-9>305 kU/L was significantly (P=0.012) associated with a shorter median DFS (11 [7.9-14.1] months) compared with lower levels (16 [10.1-21.9] months), which was confirmed by multivariable analysis (HR:1.86 [1.09-3.17]; P=0.023). Conclusions: Increased CA19-9 levels appeared to be an independent prognostic factor for poor survival in the total cohort and early disease recurrence in patients who underwent tumor resection.

Safety of percutaneous cholecystostomy early removal: A retrospective cohort study

Background: There are no strong recommendations regarding the management of percutaneous cholecystostomy (PC). The aim of this study was to assess the safety of early PC removal in terms of complications and recurrent disease. Material and Methods: Retrospective observational study of consecutive patients who underwent PC for acute cholecystitis from January 2012 to December 2017. We firstly evaluated PC related complications and recurrent disease in patients whose drainage was removed as inpatient (IPR) or as outpatient (OPR). Patients were then divided in two groups according to the timing of PC removal: G1 with the PC removed within the first 7 days after its collocation, and G2 after that. Results: We included 151 patients. The IPR group had the catheter removed after 8 days (6-11 days) while the OPR group after 52 days (26-67 days), p < 0.001. No difference was seen regarding complications, recurrent disease rate and readmissions. G1 included 56 patients (37.1%) while G2 95 (62.9%). When G1 was compared with G2 no differences were seen in terms of complications, however, G1 presented a shorter duration of antibiotic treatment 11 days (8-14 days) vs 15 days (12-23 days), p<0.001; a higher rate of recurrent disease 33.9% vs 15.7%, p = 0.015 and a higher rate of readmission 35,7% vs 16.8% in G2, p = 0.011. Conclusions: Early removal of PC was not associated with a higher risk of complications. However, the PC removal before 7 days could be related with an increase in recurrent disease and readmissions.

Screening diagnosis of recurrence of gastroesophageal reflux disease in patients with axial hiatal hernia after antireflux intervention by questioning on the GERD-HRQL questionnaire

Screening diagnosis of recurrence of gastroesophageal reflux disease in patients with axial hiatal hernia after antireflux intervention by questioning on the GERD-HRQL questionnaire

Prognostic Significance of Neoadjuvant Rectal Score and Indication for Postoperative Adjuvant Therapy in Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

Neoadjuvant chemoradiotherapy (CRT) is a standard treatment for patients with clinical Stage II/III rectal cancer. However, the benefit of postoperative adjuvant chemotherapy for patients after neoadjuvant CRT is uncertain. Recently, neoadjuvant rectal (NAR) score was suggested as an independent prognostic factor for patients with rectal cancer after neoadjuvant CRT. The aim of this study was to examine the prognostic significance of NAR score in rectal cancer patients who underwent neoadjuvant CRT followed by surgery, and to investigate which patients may benefit from postoperative adjuvant therapy. A total of 72 patients who underwent neoadjuvant CRT followed by R0 resection for clinical stage II /III rectal cancer were evaluated. The correlation between NAR score, various clinicopathological factors and disease recurrence were evaluated. Disease recurrence was significantly more often observed in patients with incomplete neoadjuvant CRT, tumor regression grade (TRG) 3-4, and high NAR score. Multivariate analysis revealed that NAR score was an independent predictor of disease recurrence. NAR score may be one of the predictive markers for disease recurrence in patients who underwent neoadjuvant CRT followed by surgery for rectal cancer. Patients with a low NAR score may benefit form postoperative adjuvant chemotherapy.

Identification of key pathways and genes in PTEN mutation prostate cancer by bioinformatics analysis

BackgroundProstate cancer (Pca) remains one of the leading adult malignancies. PTEN (Phosphatase and Tensin Homolog) mutant is the top common mutated genes in prostate cancer, which makes it a promising biomarker in future individualized treatment.MethodsWe obtained gene expression data of prostate cancer from TCGA (The Cancer Genome Atlas) database for analysis. We analyzed the DEGs (differentially expressed genes), and used online tools or software to analyze Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene set enrichment analysis (GSEA), Search Tool for the Retrieval of Interacting Genes/Proteins, and Molecular Complex Detection.ResultsLatest TCGA data showed PTEN mutation in about 22% patients. 1736 DEGs in total were identified. Results of gene functional enrichment analyses showed that muscle contraction, negative regulation of growth and multiple metabolic progression were significantly enriched. GNG13, ACTN2, POTEE, ACTA1, MYH6, MYH3, MYH7, MYL1, TNNC1 and TNNC2 were the top ten hub genes. Patients with PTEN mutation showed relatively decreased mRNA expression level of PTEN. Survival analysis indicated the risk of disease recurrence in patients with PTEN mutation.ConclusionsOur findings suggested that PTEN mutation in prostate cancer may induce changes in a variety of genes and pathways and affect disease progression, suggesting the significance of PTEN mutation in individualized treatment of prostate cancer.