Harmsen, William S.

Abstract Background The prognostic value of pathological lymph node status following neoadjuvant radiotherapy (ypN) remains unclear. This study was designed to determine whether ypN status predicted overall survival. Methods Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant long-course radiation between 2005 and 2014 were identified from the National Cancer Data Base, and divided into ypN0, ypN1 and ypN2 groups. The primary outcome was overall survival. Univariable and multivariable analyses were used to determine factors associated with overall survival. Results Of 12 271 patients, 3713 (30·3 per cent) were found to have residual nodal positivity. A majority of patients with ypN1 (1663 of 2562) and ypN2 (878 of 1151) disease had suspected lymph node-positive disease before neoadjuvant therapy, compared with 3959 of 8558 with ypN0 tumours (P < 0·001). Moreover, ypN1 and ypN2 were significantly associated with ypT3–4 disease (65·7 and 83·0 per cent respectively versus 39·4 per cent for ypN0; P < 0·001). In unadjusted analyses, survival differed significantly between ypN groups (P < 0·001). Five-year survival rates were 81·6, 71·3 and 55·0 per cent for patients with ypN0, ypN1 and ypN2 disease respectively. After adjustment for confounding variables, ypN1 and ypN2 remained independently associated with overall survival: hazard ratio (HR) 1·61 (95 per cent c.i. 1·46 to 1·77) and 2·63 (2·34 to 2·95) respectively (P < 0·001). Overall survival was significantly longer in patients with ypN1–2 combined with ypT0–2 status than among those with ypT3–4 tumours even with ypN0 status (P = 0·031). Clinical nodal status before neoadjuvant therapy was not significantly associated with overall survival (HR 1·05, 0·97 to 1·13; P = 0·259). Conclusion Both ypT and ypN status is of prognostic significance following neoadjuvant therapy for rectal cancer.

This study examined the potential correlation between pulmonary embolism (PE) attenuation on computed tomography pulmonary angiography (CTPA) and pulmonary artery hemodynamic response to catheter-directed thrombolysis (CDT) in 10 patients with submassive PE. Treatment parameters, PE attenuation, clot burden, computed tomography signs of right ventricle dysfunction and right ventricular systolic pressure at echocardiography were retrospectively analyzed to determine correlation with pulmonary artery pressure improvement using Spearman correlation. A single reader, blinded to the treatment results, measured PE attenuation of all patients. There was a significant positive correlation between PE attenuation and absolute pulmonary artery pressure improvement with a Spearman correlation of 0.741, p=0.014. When attenuation was greater than or equal to the median (44.5 HU, n=5), CDT was associated with significantly better pulmonary artery pressure improvement ( p=0.037). Clot attenuation at CTPA may be a potential imaging biomarker for predicting pulmonary artery pressure improvement after CDT.

Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs. placebo on gastric emptying of solids (by scintigraphy) with a 320-kcal meal, gastric volumes (GVs; fasting and accommodation by single photon emission-computed tomography ), satiation [maximum tolerated volume (MTV)], and symptoms after a dyspeptogenic meal of Ensure. Aprepitant (125 mg on day 1, followed by 80 mg on days 2–5) or placebo, one tablet daily, was administered for 5 consecutive days. Statistical analysis was by unpaired rank sum test, adjusted for sex difference and body mass index. To assess treatment effects on symptoms, we incorporated MTV in the model. Aprepitant increased fasting, postprandial, and accommodation GV and tended to increase volume to fullness and MTV by ~200 kcal. However, aprepitant increased aggregate symptoms, nausea, and pain scores after ingestion the MTV of Ensure. There was no significant effect of aprepitant on gastric half-emptying time of solids. We conclude that NK1 receptors are involved in the control of GV and in determining postprandial satiation and symptoms. Further studies of the pharmacodynamics and therapeutic role of NK1 receptor antagonists in patients with gastroparesis and dyspepsia are warranted. NEW & NOTEWORTHY Aprepitant increases fasting, postprandial, and accommodation gastric volumes. Aprepitant increases volume to fullness and maximum tolerated volume during a nutrient drink test. NK1 receptors are involved in the control of gastric volume and in determining postprandial satiation and symptoms.

Background: Although obesity is associated with increased complication rates after lower-extremity arthroplasty, there is a relative paucity of studies examining the effect of body mass index (BMI) on shoulder arthroplasty. The purpose of this investigation was to evaluate the effect of BMI on implant survival and the rate of complications after shoulder arthroplasty. Methods: Using an institutional total joint registry, 4,567 consecutive shoulder arthroplasty cases from 1970 to 2013 were studied. The mean BMI was 29.7 kg/m 2 (range, 14 to 66 kg/m 2 ), with 1,622 patients (36%) with a BMI of 30 to 40 kg/m 2 and 297 patients (7%) with a BMI of >40 kg/m 2 . There were 2,493 female patients (55%). BMI was dichotomized after examination of the smoothing spline curve. The associations of factors and complications were assessed using Cox proportional hazard regression analysis. Results: Increasing BMI was associated with an increased risk of a revision surgical procedure, reoperation, revision for mechanical failure, and superficial infection, and it was negatively associated with risk of a periprosthetic fracture. The risk of a revision surgical procedure increased in a linear fashion with increasing BMI (hazard ratio [HR], 1.05, or a 5% increased risk per 1 unit of BMI; p = 0.03). Increased BMI was also associated with an increased risk of revision for mechanical failure (HR, 1.05; p = 0.004). In a multivariate model, the association of BMI and risk of a revision for any reason, revision for mechanical failure, and reoperation maintained significance (p ≤ 0.02). The most marked association between increasing BMI and any complication in shoulder arthroplasty was its association with superficial wound infection (HR, 1.09; p = 0.03). Conclusions: Increasing BMI is strongly associated with increased rates of revision surgical procedures and postoperative complications after shoulder arthroplasty. It is important to consider these findings when counseling patients, estimating risks, and estimating complication risks in policy decisions. Level of Evidence: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background/Aim: The epidemiology of hepatocellular carcinoma (HCC) has changed in the United States recently. The aim of this study is to evaluate the recent trends of HCC epidemiology in Olmsted County, MN. Methods: Residents aged over 20 with newly diagnosed HCC were identified using the Rochester Epidemiology Project database. Clinical information was compared among patients diagnosed between 2000 and 2009 (era 1) and 2010 to 2014 (era 2). Results: Over 1.6 million person years of follow-up, 93 residents were diagnosed with HCC. The mean age was 67 and 71% were male. The age-adjusted and sex-adjusted incidence rates were 6.3 and 7.0 per 100,000 person years in the first and second eras (P=0.64). The proportion with hepatitis B virus etiology increased from 4% to 21% between the 2 eras (P<0.01), whereas there was a trend toward a decreasing proportion of hepatitis C virus etiology from 42% to 29% (P=0.20). Only 39% of HCC surveillance candidates had HCCs detected under surveillance and 41% of cirrhotic patients had unrecognized cirrhosis at the time of HCC diagnosis. Nonalcoholic fatty liver disease was associated with unrecognized cirrhosis and absence of cirrhosis at HCC diagnosis. More than half (56%) of patients presented at Barcelona Clinic Liver Cancer stage C or D and the median survival was 9.7 months. The overall survival had not changed over time. Conclusions: The incidence of HCC remained stable after 2010 in Olmsted County. The proportion of hepatitis B virus-induced HCC increased, whereas there was a trend of decreasing proportion of hepatitis C virus-induced HCC. The overall survival in community residents with HCC remains poor.

Background and ObjectivesCurrent randomized controlled trials are investigating the outcomes of non‐surgical treatment for patients with ductal carcinoma in situ (DCIS). We sought to evaluate pre‐operative factors associated with no residual disease at definitive resection following a core needle biopsy (CNB) diagnosis of DCIS.MethodsEight hundred and thirty‐four operations for DCIS were performed at our institution between January 2004 and October 2014. We evaluated patient and biopsy tumor characteristics to determine pre‐operative factors associated with no residual disease at surgical resection using uni‐ and multivariable analyses.ResultsSixty‐nine patients (8%) had no residual disease on final pathology. On multivariable analysis, low‐ or intermediate‐grade lesions, <1 cm in size on mammography, and lesions where ≥90% of calcifications were removed correlated with finding no residual disease on final pathology, c‐statistic 0.84. Of the 14 patients with all three low‐risk factors, 36% had no residual disease on final pathology.ConclusionsAlthough our multivariable analysis performed well, its clinical utility would be limited as we were unable to identify a subset of patients with DCIS in whom the probability of finding no residual disease is low enough to consider routine use of non‐surgical management.

711 Background: For patients with stage IVA rectal cancer with liver metastases treated with curative-intent chemotherapy and surgery, the role of adjuvant pelvic radiotherapy (RT) is unclear. The purpose of this study was to evaluate the impact of pelvic RT on oncologic outcomes in this patient population. Methods: We retrospectively reviewed medical records of all patients with stage IVA rectal adenocarcinoma with liver metastases treated with curative-intent resection of the primary tumor and all liver metastases at our institution between 1991 and 2010. Patient and treatment characteristics were compared between patients who did or did not receive pelvic RT using chi-square and unpaired ttests. Survival and recurrence estimates were calculated from date of initial diagnosis using the Kaplan-Meier method. Local recurrence (LR) was defined as recurrence in the pelvis occurring at or before distant recurrence (DR). Cox regression was used to compare rates of freedom from LR (FFLR), freedom from DR (FFDR), and overall survival (OS) between patients who did or did not receive pelvic RT. Results: The analysis included 65 patients. Median patient age at diagnosis was 59 years (range, 27-87). Tumor stage was T2 (n = 4), T3 (n = 53), or T4 (n = 8). The median number of liver metastases was 2 (range, 1-14). Surgery was low anterior resection (n = 54) or abdominoperineal resection (n = 11). All patients received perioperative fluoropyrimidine based chemotherapy. Pelvic RT was administered to 35 patients (54%), either preoperatively (n = 22) or postoperatively (n = 13). Median RT dose was 50.4 Gy (range 25-58). Patient characteristics were similar for those who did or did not receive pelvic RT. Median follow-up was 3.7 years. The 3-year estimates of FFLR, FFDR and OS were 81% vs 58% (p =.056), 35% vs 29% (p =.75), and 66% vs 71% (p =.81) for RT vs no RT, respectively. Conclusions: In this analysis of patients with stage IVA rectal cancer with liver metastases undergoing curative intent therapy, pelvic RT (vs. no pelvic RT) was associated with a trend to lower rates of LR and similar rates of DR and OS.

Background: High body mass index (BMI) is associated with increased rates of complications after total knee arthroplasty. To date, to our knowledge, studies have examined risk as a dichotomous variable using specific BMI thresholds. The purpose of this investigation was to quantify implant survival and the risk of common complications after total knee arthroplasty using BMI as a continuous variable. Methods: Using prospectively collected data from our institutional total joint registry, we analyzed 22,289 consecutive knees, in 16,136 patients, treated with primary total knee arthroplasty from 1985 to 2012. The mean BMI of these patients at the time of the surgical procedure was 31.3 kg/m 2 (range, 11 to 69 kg/m 2 ). The Kaplan-Meier survival method was used to estimate survivorship, reoperations, and common complications, with associations of outcomes assessed using a Cox regression model. Results: Utilizing smoothing spline parameterization, we found that reoperation (p < 0.001) and implant revision or removal rates (p < 0.001) increased with increasing BMI after total knee arthroplasty. Increasing BMI also was associated with increased rates of wound infection (hazard ratio [HR], 1.07; p < 0.001) and deep infection (HR, 1.08; p < 0.001) per unit of BMI over 35 kg/m 2 . A BMI of 35 to 40 kg/m 2 was associated with a higher rate of implant revision for aseptic loosening (p < 0.001) and for polyethylene wear (p < 0.001) compared with a BMI of 18 to 24.99 kg/m 2 . There was no correlation between BMI and risk of venous thromboembolism, tibiofemoral instability, or need for knee manipulation. Conclusions: The rates of reoperation, implant revision or removal, and many common complications after total knee arthroplasty were strongly associated with BMI. Level of Evidence: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AimsThe purpose of this study was to determine the lifetime risk of revision surgery for patients undergoing Charnley cemented total hip arthroplasty (THA), with 40-year follow up, using death as a competing risk.Materials and MethodsWe retrospectively reviewed 2000 cemented Charnley THAs, with 51 living hips available at 40 years.ResultsThe cumulative risk of revision or removal for any reason was 13% (95% confidence interval (CI) 12 to 15). Patients aged under 50 years at the time of surgery had a 35% (95% CI 28 to 42) risk of revision or removal for any reason (Hazard Ratio (HR) 3.6; 95% CI 2.5 to 5.2; p < 0.001), patients 50 to 59 years old had a 20% risk (95% CI 16 to 24) (HR 2.1; 95% CI 1.5 to 2.8; p < 0.0001), patients aged 60 to 69 years had a 9% risk (95% CI 7 to 11) (reference point), and patients ≥ 70 years old had a 5% risk (95% CI 4 to 7) (HR 0.96; 95% CI 0.6 to 1.5; p = 0.86) during their lifetime. Men had a higher risk of revision or removal for any reason (HR 2.1; 95% CI 1.7 to 2.7; p < 0.001).ConclusionWith almost all the patients in this series followed up till either death or revision, we have been able to develop a ‘rule of thumb’ for lifetime likelihood of revision or implant removal for the Charnley THA: one in three for patients < 50 years, one in five for patients 50 to 59 years, one in ten for patients 60 to 69 years, and one in 20 for patients ≥ 70 years. The results provide a benchmark for comparison of outcomes, for the newer designs of THA. Cite this article: Bone Joint J 2016;98-B:1436–40.