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Background This study aimed to identify the yield of staging laparoscopy with peritoneal lavage cytology for gastric cancer patients and to track it over time. Methods The medical records of patients with gastric or gastroesophageal adenocarcinoma who underwent pretreatment staging laparoscopy at the authors’ institution from 1995 to 2012 were reviewed. The yield of laparoscopy was defined as the proportion of patients who had positive findings on laparoscopy, including those with macroscopic carcinomatosis, positive cytology, or other clinically important findings. To compare the yield of laparoscopy over time, the patients were divided into three 6-year ranges based on the date of diagnosis. Associations between clinicopathologic factors and peritoneal disease were examined using uni- and multivariate analyses. Results The study included 711 patients. Among these patients, 43.5 % had gastroesophageal junction tumors, 72.9 % had poorly differentiated adenocarcinoma, and 53 % had signet ring cell morphology. Endoscopic ultrasound had most commonly identified T3 (83.9 %) and N-positive (66.4 %) tumors. At laparoscopy, 148 (20.8 %) patients had been found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who underwent peritoneal lavage cytologic analysis, 68 (13.2 %) had positive cytology results for malignancy. The total laparoscopy yield was 36 %, which did not change over time ( p = 0.58). Multivariate analysis demonstrated that positive cytology or carcinomatosis was associated with poorly differentiated histology, linitis plastica, and equivocal computed tomography findings. Conclusions Laparoscopy remains a useful staging procedure to evaluate for peritoneal spread when treatment or surgery is considered, even with the current availability of high-quality imaging.

BackgroundWhile surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS).MethodsRetrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006–2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling.ResultsUtilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31–2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33–2.06); T3 (OR 1.51, 95% CI 1.13–2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61–0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78–0.88).ConclusionsNT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

Background Hypoparathyroidism occurs relatively frequently after thyroid surgery in children. However, few studies have reported risk factors. We aimed to identify risk factors for hypoparathyroidism that occurred after total thyroidectomy for proven or suspected malignancy in children. Methods Children (aged ≤ 18 years) who underwent total thyroidectomy for neoplasm or RET germline mutation at our institution between 1997 and 2018 were included. We retrospectively reviewed demographics, surgical indications, perioperative and follow-up laboratory results, pathologic results, and duration of calcium/calcitriol supplementation. Risk factors for hypoparathyroidism were identified by multivariate analysis. Results Of 184 consecutive patients, 111 had undergone surgery for neoplasm; these diseases were primarily malignancies (106, 95.5%), predominantly papillary carcinoma (103, 92.8%). The remaining 73 patients had undergone early thyroidectomy for RET germline mutation. Among all patients, 67 (36.4%) had hypoparathyroidism: 61 transient and 6 permanent. In a multivariate analysis, central neck dissection (odds ratio 4.3, 95% confidence interval 2.0–9.1) and gross extrathyroidal extension (odds ratio 4.9, 95% confidence interval 2.0–12.1) predicted overall hypoparathyroidism; however, no significant factors were associated with permanent hypoparathyroidism. Most patients with permanent hypoparathyroidism (5 of 6) had undergone therapeutic central neck dissection. When central neck dissection was performed, younger children had a higher risk of overall hypoparathyroidism. Conclusions In pediatric total thyroidectomies, central neck dissection and gross extrathyroidal extension were major predictors for overall hypoparathyroidism. Surgeons performing thyroidectomy in such patients should be aware of the relatively high risk, preserve parathyroid tissue to the extent possible, and be conscientious regarding postoperative calcium monitoring and replacement.

BackgroundSarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown.Patients and MethodsPatients from the National Cancer Data Base (NCDB) (2006–2016) with resected stage I–III primary extremity or trunk sarcoma were included. Predicted overall survival (pOS) was calculated using the Sarculator algorithm, which includes patient age, tumor size (cm), grade (1–3), and histology, and compared with actual overall survival (aOS). Harrell’s C-index was calculated to determine the discriminatory ability of Sarculator (0.7 = good, 0.8 = strong, 1.0 = perfect model), and calibration plots were created.ResultsIn total, 9738 patients were included. Five-year pOS was 73.7% compared with aOS of 68.9%. The C-index for the entire cohort was 0.726. By stage, the C-index was 0.730 for stage I, 0.708 for stage II, and 0.679 for stage III. By histology, C-indices were highest for leiomyosarcoma (0.745), myxofibrosarcoma (0.722), and other histologies (0.721). By sociodemographic variables, Sarculator performed better for patients < 50 years (C-index 0.722), of other/unknown race (C-index 0.781), with private insurance (C-index 0.715), treated at a center other than a community cancer programs (C-index > 0.7), and with no comorbidities (C-index 0.716). Outcomes by zip code educational attainment and income were not markedly different (all C-indices > 0.7).ConclusionsSarculator is overall a good predictor of aOS and useful tool for clinicians to aid in survival prognostication. However, clinicians should be aware of populations for whom Sarculator’s predictions may be less accurate. Future work could focus on enhancing the Sarculator algorithm specifically for US patients by including demographic variables.

Background Pathologic complete response of a primary tumor (ypT0) after preoperative therapy is associated with improved overall survival (OS). However, whether other variables are associated with outcome for gastric cancer patients with ypT0 status is unknown. Methods This study reviewed an institutional database of patients who underwent resection of gastric or gastroesophageal adenocarcinoma after preoperative therapy and identified patients with ypT0 status. Cox regression models were used to identify clinicopathologic predictors of OS. Results Of 77 patients with ypT0 status identified in this study, 36 (47%) had gastroesophageal junction tumors. At presentation, 62 patients (81%) had clinical T3 disease, and 7 (9%) had clinical T4 disease. The clinical nodal status was positive (cN+) for 45 patients (58%). Preoperative chemoradiation was administered to 75 patients (97%). The median follow-up duration was 3.54 years. The median OS was 10 years, and the 5-year OS rate was 61%. Univariable analysis identified age of 65 years or older at the time of diagnosis, histologic grade, and ypN status as significant predictors of OS. Multivariable analysis confirmed age of 65 years or older [hazard ratio (HR), 4.26; p  < 0.001] and persistent nodal disease (ypN+ status; HR, 5.12; p  < 0.001) to be independently associated with OS. Clinical stage was not associated with survival. In the subset of ypT0N0 patients, no clinicopathologic feature was predictive of survival. Conclusion For gastric or gastroesophageal adenocarcinoma patients with ypT0 status after preoperative therapy, ypN+ status substantially reduced survival. Pretreatment clinical stage had no impact on OS for patients with a pathologic complete response.

No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6–18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.

Neurofibromatosis type 1 (NF1) is a complex genetic disorder that is associated with not only neurofibromas, but also an increased susceptibility to other neoplasms. To evaluate the prevalence of neoplasia and outcomes among patients with NF1. This cohort study was conducted among patients with NF1 at a single academic cancer center from 1985 to 2020 with median (range) follow-up of 2.9 years (36 days to 30.5 years). Of 2427 patients evaluated for NF1, 1607 patients who met the National Institutes of Health consensus criteria for NF1 were included. This group was compared with estimates from Surveillance, Epidemiology, and End Results (SEER) Cancer Statistics Review 1975 to 2015 and SEER participants database unless otherwise specified. Data were analyzed from August 2018 to March 2020. Disease-specific survival (DSS) was measured from diagnosis date to date of neoplasm-specific death or censorship and calculated using the Kaplan-Meier method. Survival curves were compared using the log-rank test. Deaths from disease were considered a DSS end point; other deaths were considered censored observations. Secondary outcome measures were comparisons of (1) overall survival of patients with NF1 with neurofibroma neoplasms vs those without nonneurofibroma neoplasms, (2) neoplasm prevalence in the NF1 group vs general population estimates, and (3) age at diagnosis in the NF1 group vs general population estimates for the most common neoplasms in the NF1 group. Among 1607 patients with NF1, the median (range) age at initial visit was 19 years (1 month to 83 years) and 840 (52.3%) were female patients. Among 666 patients who developed other neoplasms in addition to neurofibromas (41.4%), 295 patients (18.4%) developed glioma and 243 patients (15.1%) developed malignant peripheral nerve sheath tumor (MPNST), the most common neoplasms. Patients with NF1, compared with the general population, developed several neoplasms at a younger mean (SD) age (low-grade glioma: 12.98 [11.09] years vs 37.76 [24.53] years; P < .0001; high-grade glioma [HGG]: 27.31 [15.59] years vs 58.42 [19.09] years; P < .0001; MPNST: 33.88 [14.80] years vs 47.06 [20.76] years; P < .0001; breast cancer: 46.61 [9.94] years vs 61.71 [13.85] years; P < .0001). Patients with NF1 developed neoplasms more frequently compared with the general population (odds ratio, 9.5; 95% CI, 8.5-10.5; P < .0001). Among patients with NF1, significantly lower 5-year DSS rates were found among those with undifferentiated pleomorphic sarcoma (1 of 5 patients [20.0%]), HGG (8 of 34 patients [23.1%]), MPNST (72 of 228 patients [31.6%]), ovarian carcinoma (4 of 7 patients [57.1%]), and melanoma (8 of 12 patients [66.7%]) compared with those who had neoplasms classified as other (110 of 119 patients [92.4%]) (all P < .001) . This cohort study found that among patients with NF1, those who developed undifferentiated pleomorphic sarcoma, HGG, MPNST, ovarian carcinoma, or melanoma had significantly lower DSS rates compared with those who developed other neoplasms. This study also found that patients with NF1 developed some neoplasms more frequently and at a younger age compared with individuals without NF1. HGGs and MPNST were noteworthy causes of death among patients NF1. This information may be useful for NF1 patient counseling and follow-up.

Background Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD) that impairs recovery and quality of life. The purpose of this study was to assess the impact risk-stratified pancreatectomy clinical pathways (RSPCPs) had on delayed gastric emptying (DGE) and identify factors associated with DGE in a contemporary period. Methods A single-institution, prospective database was queried for consecutive PDs during July 2011–November 2019. Using international definitions, DGE rates were compared between periods before and after RSPCPs were implemented in 2016, classifying patients according to their postoperative pancreatic fistula (POPF) risk. Risk factors were analyzed to identify modifiable targets. Results Among 724 elective PDs, 552 (76%) were for adenocarcinoma and 172 (24%) for other diagnoses. Of the 197 (27%) patients with DGE, 119 (16%) had type A, 41 (6%) type B, and 38 (5%) type C. In the overall cohort, DGE rates were higher with pylorus-preserving vs. classic hand-sewn reconstruction (odds ratio [OR] − 1.84; p < 0.001), postoperative abscess (OR − 2.54; p = 0.003), and non-white patients ( p = 0.007), but lower after implementation of RSPCPs (OR − 0.34, p < 0.001). In the 374 patients treated with RSPCPs, only 17% ( n = 65/374) developed DGE. Patients with protocol-compliant NGT removal ≤ 48 h were less likely to experience DGE (OR − 1.46, p = 0.042). Conclusion Our data suggest that implementation of preoperatively assigned RSPCPs as a care bundle was the most important factor in decreasing DGE. These gains were accentuated in patients who underwent early nasogastric tube removal and had a classic hand-sewn gastro-jejunostomy reconstruction. Application of these modifiable factors is generalizable with low implementation barriers.

Background Biochemical cure in normocalcemic primary hyperparathyroidism (nPHPT) is defined as parathyroid hormone (PTH) level normalization 6 months after parathyroidectomy. However, recent studies show that a significant number of nPHPT patients have persistent PTH elevation postoperatively. We sought to correlate changes in PTH levels with skeletal outcomes after parathyroidectomy in nPHPT patients. Methods Adult patients who underwent parathyroidectomy at a tertiary referral center for sporadic PHPT between 2010 and 2020 were reviewed. Pre- and postoperative (6 months, 18 months, and last follow-up) laboratory and bone mineral densities (BMD) were recorded. Primary outcome was 18-month postoperative BMD change in the lumbar spine (LS), total hip (TH) and femoral neck (FN) in normocalcemic and hypercalcemic PHPT (hPHPT) patients. Results Of 661 patients included, 68 had nPHPT. nPHPT patients frequently had multigland disease (31% vs. 18%, p  = 0.014), more bilateral cervical explorations (22% vs. 13%, p  = 0.042), and fewer achieved biochemical cure (76% vs. 95%, p  < 0.001) than hPHPT patients. Twenty-eight nPHPT patients had BMD data for comparison. Overall, nPHPT patients had improvement in the LS (1.84%, p  = 0.002) and TH (1.64%, p  = 0.014). When stratified by postoperative PTH levels, nPHPT patients with persistent PTH elevation had more BMD improvement at the TH than those who normalized PTH (3.73% vs. − 0.83%, p  = 0.017). There was no difference in improvement at the LS or FN ( p  = NS). Conclusion Parathyroidectomy is associated with improved BMD in nPHPT patients with bone disease. Although one in four nPHPT patients had elevated postoperative PTH levels persisting throughout the study, BMD improvement was still seen regardless of postoperative PTH level normalization.

BackgroundPostoperative complications (POC) are associated with poor oncologic outcomes in gastric cancer. We sought to evaluate the impact of POC on survival in patients with gastric cancer treated with upfront surgery (UpSurg) versus those treated with preoperative therapy (PreT).MethodsWe analyzed data from a prospectively maintained database of patients who had undergone resection of their gastric cancer at our institution. Patients with T1N0 or M1 lesions, recurrent disease, and mortality within 90 days were excluded. Survival was compared between patients with and without POC in the UpSurg and PreT groups. Cox regression analyses were used to examine factors associated with overall survival (OS) and disease-free survival (DFS).ResultsA total of 421 patients underwent resection of gastric cancer: 30% underwent upfront surgery, and 51% had a POC. Among patients who had POCs, 71% were infectious and 53% were Clavien–Dindo grade III or IV. UpSurg patients with a POC had shorter OS (5-year, 47 vs. 85%; p < 0.001) and DFS (5-year, 46 vs. 76%; p < 0.001) than those without a POC. In contrast, there was no difference in OS (5-year, 57 vs. 63%; p = 0.77) and DFS (5-year, 52 vs. 52%; p = 0.52) between PreT patients with and without POC. Multivariable Cox regression model demonstrated that a POC in UpSurg patients had significant impact on DFS (2.6 [95% confidence interval (CI) 1.48–4.74]), whereas it did not in PreT patients (0.9 [95% CI 0.70–1.33]).ConclusionsThe use of preoperative therapy negated the impact of POCs on OS and DFS in patients undergoing resection for gastric cancer.