Relative Risk Of Recurrence Research Articles

NEK2 Promotes Hepatoma Metastasis and Serves as Biomarker for High Recurrence Risk after Hepatic Resection

Introduction and aim. Developing reliable biomarkers for hepatocellular carcinoma (HCC) patients who are at a high risk of recurrence after curative hepatic resection is very important for determining subsequent therapeutic strategies. We investigated the role of the cell cycle factor NIMA-related kinase 2 (NEK2) in HCC progression in hepatoma cells and post-surgery patients.Material and methods. The effects of NEK2 on proliferation, invasion and migration of hepatoma HuH7 and SK-Hep1 cells were evaluated. In a post-surgery HCC cohort (N = 97), the Nek2 induction levels in the tumors were examined with real-time RT-PCR analysis, and the results were analyzed for their correlations with recurrence.Results. NEK2 promoted G1 to S phase cell cycle progression by causing increases in cyclin D1 and AKT phosphorylation and decreases in the cyclin-dependent kinase inhibitor p27, indicating that NEK2 plays an important role during interphase in addition to its previously identified role in M phase. NEK2 also enhanced the proliferation, migration and invasion of hepatoma cells and regulated the expression of E-cadherin and MMP9. The Nek2 mRNA levels in the tumors were highly correlated with recurrence rates in the post-surgery HCC patients. Combined evaluation of the tumor AJCC stage and the Nek2level can serve as a reliable method for predicting the relative risk of HCC recurrence in these patients. Conclusions. NEK2 plays a significant role in cell cycle progression in the inter- and M-phases. NEK2 enhances HCC metastasis and is correlated with recurrence and thus can potentially serve a promising high-risk biomarker for HCC.

Chloroquine Versus Dihydroartemisinin-Piperaquine With Standard High-dose Primaquine Given Either for 7 Days or 14 Days in Plasmodium vivax Malaria.

Primaquine is necessary for the radical cure of Plasmodium vivax malaria, but the optimum duration of treatment and best partner drug are uncertain. A randomized controlled trial was performed to compare the tolerability and radical curative efficacy of 7-day versus 14-day high-dose primaquine regimens (total dose 7mg/kg) with either chloroquine or dihydroartemisinin-piperaquine. Patients with uncomplicated P. vivax malaria on the Thailand-Myanmar border were randomized to either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine, either 0.5 mg/kg/day for 14 days or 1 mg/kg/day for 7 days. Adverse events within 42 days and 1-year recurrence rates were compared and their relationship with day 6 drug concentrations assessed. Between February 2012 and July 2014, 680 patients were enrolled. P. vivax recurrences (all after day 35) occurred in 80/654 (12%) patients; there was no difference between treatments. Compared to the 7-day primaquine groups the pooled relative risk of recurrence in the 14-day groups was 1.15 (95% confidence interval 0.7 to 1.8). Hematocrit reductions were clinically insignificant except in G6PD female heterozygotes, 2 of whom had hematocrit reductions to <23% requiring blood transfusion. Radical cure should be deployed more widely. The radical curative efficacy in vivax malaria of 7-day high-dose primaquine is similar to the standard 14-day high-dose regimen. Chloroquine and dihydroartemisinin-piperaquine are both highly effective treatments of the blood stage infection. Quantitative point of care G6PD testing would ensure safe use of the 7-day high-dose primaquine regimen in G6PD heterozygous females. NCT01640574.

Depth of invasion (DOI) as a predictor of cervical nodal metastasis and local recurrence in early stage squamous cell carcinoma of oral tongue (ESSCOT).

BackgroundThe new AJCC staging system (8th edition) incorporates depth of invasion to stage oral cancers. It is a recognized predictor for neck nodal metastasis and local recurrence, the associated risk is not well defined. The aim of this study was to explore the risk of occult neck nodal metastasis and local recurrence in relation to depth in early stage squamous cell carcinoma of oral tongue.MethodsWe have evaluated records of 179 patients with early tongue cancer treated in our unit from 2006–2015 with a mean age of 57.92 ± 11.93 years. Treatment modalities used were surgery (26%), surgery followed by radiotherapy (64%) and chemo-radiation (10%). Neck dissection was ipsilateral in 94% and bilateral in 6% of the patients. Patients were grouped according to the AJCC cut off points in 8th edition for depth; group A: 1–5 mm (35%), group B: 6–10 mm (47%) and group C: > 10 mm (18%).ResultsRisk of local recurrence and nodal metastasis for Group A was 15% (10/63) and 23% (15/63), group B 20% (17/84) and 34% (29/84), and group C 40% (13/32) and 53% (17/32).ConclusionsDepth more than 10 mm is associated with significantly increased risk of recurrence and nodal metastasis. Elective neck dissection should be a consideration for tumors having depth less than 5mm.

Coexpression of CD5 and CD43 predicts worse prognosis in diffuse large B-cell lymphoma.

Both CD5 and CD43 are expressed on the surface of B lymphocytes of definite phase and associated with the adverse outcome in diffuse large B‐cell lymphoma (DLBCL). However, the relationship between CD5 and CD43 expression and the prognostic value of CD5/CD43 coexpression in DLBCL are unknown. We herein determined the correlation between CD5 and CD43 expression, as separate factors or in combination, with the clinicopathological features and survival of 200 patients with DLBCL receiving standard chemotherapy with or without rituximab. Among these DLBCL patients, CD5 expression, CD43 expression, and CD5/CD43 coexpression were detected in 18 (9%), 57 (27%), and 10 (5%) patients, respectively, and all were positively correlated with advanced age and nongerminal cell type. CD5‐positive and CD43‐positive DLBCL patients had poorer event‐free survival (EFS, P < 0.001) and overall survival (OS, P < 0.001) than CD5‐negative and CD43‐negative patients, respectively. CD5/CD43 coexpression was correlated with a significantly worse prognosis than CD5 or CD43 expression alone. Univariate analysis showed that CD5 expression, CD43 expression, and CD5/CD43 coexpression were all adverse prognostic factors for DLBCL patient survival, and CD5/CD43 coexpression was associated with a greater relative risk for recurrence and death than either CD5 or CD43 expression alone. Multivariate analysis demonstrated that CD5/CD43 coexpression was an independent prognostic factor for EFS (P < 0.001) and OS (P < 0.001) in DLBCL. In conclusion, our data indicate that DLBCL patients with CD5/CD43 coexpression represent a specific subgroup with a significantly worse prognosis than those expressing either marker alone.

The secondary prevention of venous thromboembolism: Towards an individual therapeutic strategy.

After the anticoagulant withdrawal, a substantial proportion of patients with venous thromboembolism will develop recurrent events. Whether to consider an extended treatment depends on the risk of recurrence and bleeding risk. The assessment of the individual risk profile remains a difficult task. Several basal and post-basal factors modulate the risk of recurrence and may help clinicians to select patients who can benefit from the extended therapy. During the year 2017, new evidence regarding the post-basal factors was provided by the Morgagni and Scope studies. Another interesting novelty was the VTE-BLEED score, the first bleeding risk score that obtained the external validation in venous thromboembolism setting. In secondary prevention, the use of direct oral anticoagulants is growing instead of vitamin K antagonist. Even at lower doses, direct oral anticoagulants showed to be effective and safe, to reduce all-cause mortality and seemed to be superior to placebo for the composite outcome of fatal bleeding and fatal recurrence. After the recently published Einstein-Choice trial, the role of aspirin has become truly marginal as rivaroxaban 10 mg showed a bleeding risk similar to aspirin 100 mg but a greater effectiveness reducing the relative risk of recurrence by about 70%. Another option for secondary prevention could be sulodexide, with a lower protective effect than direct oral anticoagulants but an interesting safety profile. In conclusion, in our opinion, an individual strategy taking into account the risk of recurrence, bleeding risk, therapeutic options and patient preferences is the most appropriate approach to secondary prevention of venous thromboembolism.

Abstract 1558: STAG2 as a biomarker for prediction of recurrence in papillary non-muscle invasive bladder cancer

Abstract Purpose: Bladder cancer is the sixth most common human cancer. Most cases are early-stage tumors known as papillary non-muscle invasive bladder cancer (NMIBC). After resection, 60-70% of NMIBCs recur locally, and ~15% progress to muscle invasion and metastasis. There is an unmet need for a biomarker to stratify tumors on their likelihood of recurrence. Such a biomarker could make it possible to identify those patients most likely to benefit from adjuvant intravesical therapy such as BCG. Furthermore, lower-risk patients could become eligible for less frequent post-resection surveillance by cystoscopy than the extremely intensive current standard of care. We recently identified STAG2 as among the most commonly mutated genes in NMIBC and provided initial evidence that STAG2 mutant tumors may recur less frequently than STAG2 wild-type tumors. Here we report a STAG2 biomarker study using an independent cohort of clinically annotated papillary NMIBC tumors. Experimental Design: We identified all cases of papillary NMIBC treated at the Lombardi Comprehensive Cancer Center prior to 2013. STAG2 immunohistochemistry was performed and correlated with time to recurrence. This assay is particularly robust because (i) it utilizes a monoclonal antibody whose epitope is in the extreme carboxyl-terminus of STAG2, and ~85% of tumor-derived mutations of STAG2 are truncating; (ii) STAG2 is on the X-chromosome, so only a single mutation is required for complete gene inactivation; and (iii) STAG2 is among the most abundant proteins in the human proteome. Results: 52% of NMIBC tumors with STAG2 expression recurred, whereas only 25% of NMIBC tumors with loss of STAG2 expression recurred (p=0.017). Multivariate analysis identified STAG2 as the only significant independent predictor of recurrence (p=0.050). The relative risk of recurrence for patients with STAG2-expressing tumors was 2.408 times the risk for patients with STAG2-negative tumors. Conclusions: Here we demonstrate that a simple, robust assay for identifying STAG2-mutant tumors stratifies patients into two groups: (i) patients with retention of STAG2 expression (wild-type), ~52% of whom will recur; and (ii) patients with loss of STAG2 expression, of whom only ~25% will recur. Of note, STAG2 expression status, unlike pathologic grade–the current standard–was a significant predictor of recurrence. This information could help physicians make more informed decisions about the need for adjuvant immunotherapy/chemotherapy and also help inform the frequency of post-resection surveillance needed for individual patients. In conclusion, STAG2 is a simple, powerful, and potentially useful biomarker for prediction of recurrence in papillary NMIBC. Citation Format: Alana Lelo, Brent T. Harris, Deborah L. Berry, Krysta Chaldekas, Anagha Kumar, David Solomon, Jeffry Simko, Pritish Bhattacharyya, Ciaran Mannion, Jung-Sik Kim, George Philips, Todd Waldman. STAG2 as a biomarker for prediction of recurrence in papillary non-muscle invasive bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1558.

The association between Notch4 expression, and clinicopathological characteristics and clinical outcomes in patients with breast cancer.

Notch4, a family member of the Notch signaling pathway, has important roles in cellular developmental pathways, including proliferation, differentiation and apoptosis. The present study aimed to investigate the association between Notch4 expression and clinical outcomes with immunohistochemistry. Notch4 was expressed in 55.6% of triple-negative breast cancer (TNBC), 45.8% of Her-2-overexpressing and 25.5% of luminal breast cancer cases, with significantly higher expression occurring in TNBC (P<0.05). Furthermore, Notch4 expression was inversely associated with estrogen receptor (ER) and/or progesterone receptor positivity, and positively associated with larger tumor size, more lymph node involvement, and more advanced tumor node metastasis stage (P<0.05). No significant association was identified regarding age, menopausal status, Her-2 status or distant metastasis. Univariate survival analysis revealed that patients with low Notch4-expressing tumors exhibited a lower relative risk of cancer recurrence compared with patients with high Notch4-expressing tumors. However, in the luminal cohort, high Notch4 expression conferred significantly lower 5-year overall survival (OS) rates compared with Notch4 low-expression groups (P=0.003) but not in TNBC and Her-2-overexpressing patients. In conclusion, Notch4 expression was significantly higher in patients with TNBC and Her-2-overexpressing breast cancer compared with luminal breast cancer patients. Notch4 expression is associated with aggressive clinicopathological and biological phenotypes, and may predict poor prognosis in luminal breast cancer patients.

Evaluation of the ISL1 gene in the pathogenesis of bladder exstrophy in a Swedish cohort

Bladder exstrophy is a congenital closure defect of the urinary bladder with a profound effect on morbidity. Although the malformation is usually sporadic, a genetic background is supported by an increased recurrence risk in relatives, higher concordance rates in monozygotic twins and several associated chromosomal aberrations. Recently, the ISL1 gene was presented as a candidate gene for bladder exstrophy and epispadias complex (BEEC) development in two different studies. In our study, we screened for genetic variants in the ISL1 gene in DNA from 125 Swedish patients using Sanger sequencing and array-CGH analysis. In addition, we evaluated ISL1 expression in RNA of human bladder during embryonic and fetal weeks 5–10 relative to that in lung tissue (week 9). In total, 21 single-nucleotide variants were identified, including a potentially novel missense variant, c.137C>G p.(Ala46Gly), substituting a conserved amino acid. This variant was inherited from an unaffected mother. No structural variants were identified. RNA sequencing revealed ISL1 mRNA expression during the critical time frame of human bladder development. In conclusion, we did not detect any known or likely pathogenic variants in the ISL1 gene in 125 Swedish BEEC patients, indicating that variation in the ISL1 gene is not a common genetic mechanism of BEEC development in the Swedish population.

HELLP syndrome, risk factors in first and second pregnancy: a population-based cohort study.

HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) may have specific risk factors and risk factors varying from first to second pregnancy. The aims of the study were to estimate the risk of HELLP syndrome by potential risk factors in first and second pregnancy, respectively. A population-based cohort study including all women in Norway having their first baby (≥22 gestational weeks) during 1999 to 2014, registered in the Medical Birth Registry (n = 418 897). A subset of women with at least two births (n = 249 070) was used for estimates in second pregnancy. Relative risks with 95% CIs for HELLP syndrome were estimated using logistic regression and adjusted for maternal age and year of childbirth. Body mass index ≥30 kg/m2 and diabetes were associated with HELLP syndrome in first, but not in second pregnancy. Chronic hypertension and multiple pregnancy were associated with HELLP syndrome both in first and second pregnancy. In second pregnancy the strongest risk factors were a history of HELLP syndrome or preterm preeclampsia in the first. The risk was inversely correlated with gestational age at first delivery. The overall relative risk for recurrence of HELLP syndrome was 54.4 (95% CI 34.3-86.2) and 129.5 (95% CI 45.7-367.2) after HELLP syndrome before 29 weeks of gestation in first pregnancy. Important risk factors for HELLP syndrome differ from first to second pregnancy. HELLP syndrome in second pregnancy is rare, but the relative risk is very high in women with HELLP syndrome or preterm preeclampsia in their first pregnancy.

Prognostic Significance of Modified Residual Disease in Breast and Nodes (mRDBN) Algorithm After Neoadjuvant Chemotherapy for Breast Cancer.

We hypothesized that prognostic accuracy of the residual disease in breast and lymph nodes (RDBN) method, which is calculated using residual tumor size, nodal involvement, and tumor grade, may be improved by incorporating residual tumor cellularity. Cases included 614 patients who underwent neoadjuvant therapy for breast cancer. Tumor size was adjusted for residual cellularity of invasive carcinoma and used to calculate modified RDBN (mRDBN) and compared with unmodified gross tumor size (gRDBN). RDBN could be calculated in 428 cases. Relative risks of recurrence and death were significantly higher for RDBN-3 and RDBN-4 compared with RDBN-1. Kaplan-Meier analysis showed significant differences in disease-free survival and overall survival for estrogen receptor (ER)-negative/human epidermal growth factor receptor 2 (HER2)-negative and ER-positive/HER2-negative subgroups (P < .0001). Both mRDBN and gRDBN provide prognostic information, particularly in HER2-negative carcinoma; however, mRDBN showed better stratification of RDBN-3 and RDBN-4 patients.

Relationship Between Anthropometric Findings and Results of Corticosteroid Injections Treatment in Chronic Plantar Heel Pain.

BackgroundChronic plantar heel pain (CPHP) is one of the common, disabling, and painful problems in the foot. Obesity is one of the known causes of CPHP. The aim of this study is to investigate the relationship between the body mass and the treatment of chronic plantar heel pain.MethodsIn a cohort study, 80 CPHP patients, including 16 men and 64 women, who referred to orthopedic clinic from 2014 to 2016, were investigated. All the patients were initially treated by corticosteroid injections. A total of 80 studied patients were classified according to their body mass index (BMI) in 3 groups: obese, overweight, and ideal weight. Their pain severity, symptoms recurrence, and foot performance were examined.ResultsThe severity of morning pain was 6.6 ± 1.2 in the obese patients while it was 5.6 ± 1.7 and 5.9 ± 1.7 in overweight and ideal weight patients, respectively, which had significant difference (P = 0.005). In 57% of obese patients, symptoms recurrence was observed; this rate was 12% and 5.3% in overweight and ideal-weight patients, which showed significant difference (P = 0.001). Obese people had higher relative risk of CPHP recurrence (OR = 7.52, 95% CI = 4.28 to 16.53, P < 0.001).ConclusionsHigh BMI is a strong risk factor in recurrence of chronic plantar heel pain. There is a strong relationship between the BMI of the patients and the severity of pain in the morning.

Recurrence rates of urinary calculi according to stone composition and morphology.

Few studies have examined the relative risk of recurrence of different stone types. The object of the present study was to evaluate the tendency for stone recurrence as a function of major mineral composition of the stones and morphological characteristics of the stones. This study was carried out using 38,274 stones for which we had data available to specify if the stone was from the first or a subsequent urinary stone episode. Stones were analyzed for morphology by stereomicroscope and for composition by infrared spectroscopy. Overall, 42.7% of stones were from patients who had had a previous stone event, with these being more frequent in men (44.4%) than in women (38.9%, p < 0.0001). Age of first stone occurrence was lowest for dihydroxyadenine (15.7 ± 16.6years) and highest for anhydrous uric acid (62.5 ± 14.9years), with the average age of first stones of calcium oxalate falling in the middle (40.7 ± 14.6years for calcium oxalate dihydrate, and 48.4 ± 15.1years for calcium oxalate monohydrate, COM). By composition alone, COM was among the least recurrent of stones, with only 38.0% of COM stones coming from patients who had had a previous episode; however, when the different morphological types of COM were considered, type Ic-which displays a light color, budding surface and unorganized section-had a significantly greater rate of recurrence, at 82.4% (p < 0.0001), than did other morphologies of COM. Similarly, for stones composed of apatite, morphological type IVa2-a unique form with cracks visible beneath a glossy surface-had a higher rate of recurrence than other apatite morphologies (78.8 vs. 39-42%, p < 0.0001). Stone mineral type alone is insufficient for identifying the potential of recurrence of the stones. Instead, the addition of stone morphology may allow the diagnosis of highly recurrent stones, even among common mineral types (e.g., COM) that in general are less recurrent.

Associations between Hashimoto Thyroiditis and Clinical Outcomes of Papillary Thyroid Cancer: A Meta-Analysis of Observational Studies.

BackgroundEpidemiological studies have suggested an association between Hashimoto thyroiditis (HT) and papillary thyroid cancer (PTC) development. Other studies, however, have reported a protective role of HT against PTC progression. Through this updated meta-analysis, we aimed to clarify the effects of HT on the progression of PTC.MethodsWe searched citation databases, including PubMed and Embase, for relevant studies from inception to September 2017. From these studies, we calculated the pooled odds ratios (ORs) of clinicopathologic features and the relative risk (RR) of PTC recurrence with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Additionally, the Higgins I2 statistic was used to test for heterogeneity.ResultsThe meta-analysis included 71 published studies with 44,034 participants, among whom 11,132 had HT. We observed negative associations between PTC with comorbid HT and extrathyroidal extension (OR, 0.74; 95% CI, 0.68 to 0.81), lymph node metastasis (OR, 0.82; 95% CI, 0.72 to 0.94), distant metastasis (OR, 0.49; 95% CI, 0.32 to 0.76), and recurrence (RR, 0.50; 95% CI, 0.41 to 0.61).ConclusionIn this meta-analysis, PTC patients with HT appeared to exhibit more favorable clinicopathologic characteristics and a better prognosis than those without HT.

195: Are women with abnormal 1st and 2nd trimester serum screening markers at risk for recurrence for the same or other abnormal markers in a subsequent pregnancy?

Abnormal 1st and 2nd trimester (1T, 2T) serum markers used for aneuploidy screening are associated with other adverse pregnancy outcomes. Limited data exist on recurrence risks for elevated 2T alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG), but no such data exist for low 1T pregnancy associated plasma protein A (PAPP-A) and HCG or high 2T inhibin and low estriol. Whether women with one abnormal biomarker are at risk for a different abnormal biomarker in a subsequent pregnancy is unknown. We sought to determine the relative risks (RR) of recurrence in the next pregnancy of low PAPP-A (<0.5 MoM) and HCG (<0.5 MoM) in the 1T, and high AFP (>2.5 MoM), HCG (>3.0 MoM), inhibin (>2.0 MoM) and low estriol (<0.5 MoM) in the 2T. Using a database of 14,349 serum markers, we identified 1969 patients with 2 consecutive pregnancies screened during the 1T and 2T for AFP, PAPP-A, HCG, inhibin, and estriol, between 1/2007-12/2016. We compared women with a normal vs abnormal serum marker in the initial pregnancy to determine the rates and RR of an abnormal value for that same marker or a different abnormal marker in the subsequent pregnancy. Chi squared or Fisher's exact tests were used as appropriate. For each serum marker analyzed, we found a statistically significant increased risk for having an abnormal level in the 2nd pregnancy after having an abnormal level in the 1st. Incidence of an abnormal marker in the 1st pregnancy and RR of recurrence are shown in Table 1. There was no association between abnormal PAPP-A in the 1st pregnancy and elevated AFP or HCG in the 2nd pregnancy. Similarly, there was no association between high AFP and abnormal PAPP-A or HCG in the 2nd pregnancy. Abnormal PAPP-A, HCG, AFP, inhibin, and estriol are associated with increased risk of adverse outcomes such as preeclampsia and IUGR. Our results show that patients with an abnormal marker in their 1st pregnancy are at an increased risk for the same abnormal marker in the next pregnancy. Our findings suggest that biomarkers may be indicative of underlying maternal pathophysiology potentially driven by genetic or environmental factors. Additional studies are needed to further investigate the maternal pathophysiologic mechanisms leading to these adverse outcomes which may identify opportunities for therapeutic intervention.

Perceived recurrence risk of having another affected child: A survey on parents of children with autism spectrum disorders in Taiwan

ObjectiveAutism Spectrum Disorders (ASD) have a significant genetic predisposition. The recurrence risk of ASD ranges from 3% to 18.7% for parents having one affected child. As recurrence risk perceptions have important implications for family planning, prenatal preparation, and future children managements, absolute and relative recurrence risk perceptions of having another affected child among Taiwanese parents of children with ASD were assessed. MethodsThis study collected quantitative survey data from 415 Taiwanese parents who had one child with ASD. ResultsParticipants reported their absolute recurrence risk of having another child with ASD was 33.4%. Compared to other parents with normally-developing children, merely 49.8% of participants perceived higher relative recurrence risk. By controlling for the sociodemographic characteristics, participants’ absolute recurrence risk perceptions were significantly predicted by their perceived genetic causes of ASD and family history of ASD. Yet, participants’ relative recurrence risk perceptions were significantly associated with only the perceived genetic etiology. ConclusionTaiwanese parents of children diagnosed with ASD had an incorrect understanding of their absolute and relative recurrence risks. Practice implicationsTo facilitate informed decision-making in family planning, healthcare providers should discuss absolute and relative recurrence risks as well as genetic causes of ASD with this particular group.

A nationwide population-based study of common bile duct stone recurrence after endoscopic stone removal in Korea.

There is no consensus whether patients who underwent endoscopic common bile duct (CBD) stone removal should be followed up periodically and whether patients with gallbladder (GB) stones should undergo cholecystectomy. Thus, this study aimed to investigate the recurrence rate of CBD stones and the difference in recurrence rate according to cholecystectomy. We conducted a population-based study using the National Health Insurance database. Patients diagnosed with CBD stones and with procedure registry of endoscopic stone removal were included. The primary outcome was the recurrence rate of CBD stones. The secondary outcome was the difference in recurrence rate of CBD stones according to cholecystectomy. A total of 46,181 patients were identified. The mean follow-up was 4.2years. The first CBD stone recurrence occurred in 5228 (11.3%) patients. The cumulative first recurrence rate was low. However, the second and third recurrence rates were 23.4 and 33.4%, respectively. The cumulative second and third recurrence rates were high and gradually increased with time. The recurrence rate in the non-cholecystectomy group was higher than that in the cholecystectomy group (p<0.0001). The relative risk for CBD stone recurrence in the non-cholecystectomy group was higher in younger patients, with 3.198 in patients<50years, 2.371 in 50-59years, 1.618 in 60-69years, and 1.262 in≥70years (p<0.0001). Regular follow-up is not routinely recommended for patients with first-time endoscopic stone removal, but is recommended for patients with recurrent stones. Cholecystectomy is recommended for patients with GB stones who are younger than 70years.

Benefit of Adjuvant Radiotherapy for Local Control, Distant Metastasis, and Survival Outcomes in Patients with Localized Soft Tissue Sarcoma: Comparative Effectiveness Analysis of an Observational Cohort Study

BackgroundThis study aimed to quantify the benefit of adjuvant radiotherapy (AXRT) for local control, distant metastasis, and long-term survival outcomes in patients with localized soft tissue sarcoma (STS).MethodsThis single-center retrospective observational study enrolled 433 STS patients who underwent surgery with curative intent. An inverse probability of treatment-weighted (IPTW) analysis was implemented to account rigorously for imbalances in prognostic variables between the adjuvant treatment groups.ResultsDuring a median follow-up period of 5.5 years, the study observed 38 local recurrences (9%), 73 occurrences of distant metastasis (17%), 63 STS-related deaths (15%), and 57 deaths from other causes (13%). As expected, patients receiving AXRT (n = 258, 60%) were more likely to have high-grade G3 tumors (p < 0.0001) than patients not receiving AXRT. A crude analysis showed that AXRT was not associated with improved recurrence-free survival [hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.72–1.38; p = 0.98]. However, after IPTW, AXRT was associated with a 38% relative reduction in the risk of recurrence or death (HR 0.62; 95% CI 0.39–1.00; p = 0.05). This benefit was driven by a strong reduction in the risk of local recurrence (HR 0.42; 95% CI 0.19–0.91; p = 0.03), whereas the relative risk of distant metastasis (HR 0.69; 95% CI 0.39–1.25; p = 0.22) and overall survival (HR 0.76; 95% CI 0.44–1.30; p = 0.32) were only nonsignificantly in favor of AXRT. An exploratory analysis showed an overall survival benefit of AXRT for patients with high-grade G3 tumors (HR 0.51; 95% CI 0.33–0.78; p = 0.002). However, this finding may have been attributable to residual confounding.ConclusionIn this observational cohort, AXRT was associated with a 58% reduction in the relative risk of local recurrence. No consistent association between AXRT and lower risks of distant metastasis or death was observed.

Recurrence of Chronic Urticaria: Incidence and Associated Factors

Chronic urticaria (CU) is urticaria that has been present continuously or intermittently for at least 6 weeks. Although the prevalence and characteristics of CU are well established, little is known about recurrent CU (RCU). We sought to establish a definition, determine the frequency, and evaluate risk factors for RCU. A retrospective chart review of adult patients with CU evaluated at the University of Texas Southwestern allergy and immunology clinic was performed. RCU was defined as CU recurring at least 6 months after cessation of controller therapy and resolution of prior CU symptoms. Charts were reviewed for symptom resolution and recurrence, subtypes of CU (idiopathic, physical, and urticarial vasculitis), and medication usage (first-line agents, alternative agents, and steroid dependence). Forty-five of 341 patients (13%) had RCU. The recurrence group had a higher frequency of alternative agent use at 57.8% (n= 26) compared with the nonrecurrence group at 34.8% (n= 103), which was statistically significant (P < .01). The rate of steroid dependence was similar in both groups (13.3% in the recurrence group vs 14.5%) and not statistically significant. Individuals exposed to anti-inflammatory agents, immunosuppressants, and omalizumab had a significantly higher relative risk of recurrence compared with those who only used first-line agents (relative risk [RR] 2.32, P < .01; RR 2.69, P< .01; and RR 2.18, P= .05, respectively). RCU occurs in approximately 13% of patients with CU in our clinic population. Alternative agent use and antihistamine refractoriness appear to place patients at increased risk for recurrence compared with first-line agent use alone.

Macrometastasis in Papillary Thyroid Cancer Patients is Associated with Higher Recurrence in Lateral Neck Nodes.

The use of routine central compartment neck dissection surgery for papillary thyroid carcinoma (PTC) is controversial. Although macroscopic central neck lymph node metastasis (CNLN) in PTC is a poor prognostic factor correlated with increased loco-regional recurrence, the significance of microscopic metastasis to the central lymph nodes is not established. Herein, we aimed to assess the influence of the size of CNLN on disease recurrence among PTC patients. Data from 233 patients who underwent less than total thyroidectomy with CNLN dissection in 1989-1999 were retrospectively reviewed. The patients were assigned to three groups according to the central node metastasis: no metastasis (Group I), micrometastasis (<2mm, Group II), and macrometastasis (≥2mm, Group III). Clinicopathological features, recurrence rate, site of recurrence, and disease-free survival (DFS) were assessed. Of the 233 patients enrolled (mean follow-up period, 16.1years), 134 (57.5%) had no central neck metastasis, 37 (15.9%) had micrometastasis, and 62 (26.6%) had macrometastasis. Demographics and tumour variables were similar among the three groups. Recurrence rates were 12.7, 16.2, and 43.5% in Groups I, II, and III, respectively (p<0.001). Group III had a 3.2-fold increased relative risk of recurrence and a significantly decreased DFS compared to Group I. Group III showed significantly higher rates of lateral neck nodes metastasis than Groups I and II. In conclusion, macrometastasis significantly affects disease recurrence in PTC patients, whereas microscopic metastasis has only marginal effects. Macroscopic CNLN metastasis showed a significantly higher recurrence in the lateral neck node compared to micrometastasis.

Recurrence of Hallux Valgus Can Be Predicted from Immediate Postoperative Non-Weight-Bearing Radiographs.

The aims of this study were to identify risk factors for the recurrence of hallux valgus deformity and to clarify whether recurrence after surgery to treat hallux valgus can be predicted using radiographic parameters assessed on immediate postoperative non-weight-bearing radiographs. A proximal chevron osteotomy combined with a distal soft-tissue procedure was performed by a single surgeon to treat moderate to severe hallux valgus deformity in 93 patients (117 feet). The feet were grouped according to nonrecurrence or recurrence. Changes in the hallux valgus angle, the intermetatarsal angle, and sesamoid position over time were analyzed by comparing values measured during each postoperative period. The relative risks of recurrence as indicated by preoperative and postoperative radiographic parameters were determined. Twenty (17.1%) of the 117 feet showed hallux valgus recurrence at the time of the last follow-up. The hallux valgus angle and the intermetatarsal angle stabilized at 6 months after surgery in the nonrecurrence group. An immediate postoperative hallux valgus angle of ≥8°, an immediate postoperative sesamoid position of grade 4 or greater, a preoperative metatarsus adductus angle of ≥23°, and a preoperative hallux valgus angle of ≥40° were significantly associated with recurrence. Recurrence of hallux valgus after a proximal chevron osteotomy can be reliably predicted from immediate postoperative non-weight-bearing radiographs. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.