Faculty Bibliography

BACKGROUND:No guidelines exist for surveillance following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal and colorectal cancer. The primary objective was to define the optimal surveillance frequency after CRS/HIPEC. METHODS:The U.S. HIPEC Collaborative database (2000-2017) was reviewed for patients who underwent a CCR0/1 CRS/HIPEC for appendiceal or colorectal cancer. Radiologic surveillance frequency was divided into two categories: low-frequency surveillance (LFS) at q6-12mos or high-frequency surveillance (HFS) at q2-4mos. Primary outcome was overall survival (OS). RESULTS:Among 975 patients, the median age was 55 year, 41% were male: 31% had non-invasive appendiceal (n = 301), 45% invasive appendiceal (n = 435), and 24% colorectal cancer (CRC; n = 239). With a median follow-up time of 25 mos, the median time to recurrence was 12 mos. Despite less surveillance, LFS patients had no decrease in median OS (non-invasive appendiceal: 106 vs. 65 mos, p < 0.01; invasive appendiceal: 120 vs. 73 mos, p = 0.02; colorectal cancer [CRC]: 35 vs. 30 mos, p = 0.8). LFS patients had lower median PCI scores compared with HFS (non-invasive appendiceal: 10 vs. 19; invasive appendiceal: 10 vs. 14; CRC: 8 vs. 11; all p < 0.01). However, on multivariable analysis, accounting for PCI score, LFS was still not associated with decreased OS for any histologic type (non-invasive appendiceal: hazard ratio [HR]: 0.28, p = 0.1; invasive appendiceal: HR: 0.73, p = 0.42; CRC: HR: 1.14, p = 0.59). When estimating annual incident cases of CRS/HIPEC at 375 for non-invasive appendiceal, 375 invasive appendiceal and 4410 colorectal, LFS compared with HFS for the initial two post-operative years would potentially save $13-19 M/year to the U.S. healthcare system. CONCLUSIONS:Low-frequency surveillance after CRS/HIPEC for appendiceal or colorectal cancer is not associated with decreased survival, and when considering decreased costs, may optimize resource utilization.

INTRODUCTION:Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. MATERIALS AND METHODS:EPIC with inverse probability weighting (IPW) used for adjustment. RESULTS:<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. CONCLUSIONS:Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

BACKGROUND:Portal vein (PV) circulating tumor cells (CTCs) and elevated peripheral blood (PB) levels of biomarkers have been associated with poor outcomes in pancreatic ductal adenocarcinoma (PDAC). Although transforming growth factor-beta (TGFβ) is associated with CTCs in breast cancer, there are limited data evaluating a comprehensive biomarker panel and CTCs in PDAC patients. The authors hypothesized that tumor progression biomarkers would be associated with PV CTCs. METHODS:PDAC patients at one institution were enrolled January to August 2018 and underwent preincision PB draws (T0) and on postoperative day 1 (T3), plus intraoperative PV draws before tumor manipulation (T1) and after resection (T2). CTCs were detected using CellSearch. Plasma biomarker levels (pg/mL) were measured with a multiplex bead assay. Patients were divided into two groups: high (≥3 CTCs/7.5 mL blood) versus low (<3). Clinicopathologic variables and biomarkers were compared in the two groups. RESULTS:Fourteen had complete blood draws with PDAC resection, with five demonstrating high CTCs. Fewer patients in the high-CTC group received preoperative radiation (78 versus 20%), whereas more of the high-CTC had pT3 tumors (80 versus 11%) (all P < 0.037). High-CTC patients demonstrated higher TGFβ-2 levels (T0 [906 versus 586], T1 [1337 versus 627], T2 [1149 versus 445]), as well as higher TGFβ-3 (T0 [320 versus 173], T2 [605 versus 120]) (all P < 0.021). CONCLUSIONS:PDAC patients with high CTCs demonstrated a distinct biomarker profile with elevated PB and PV levels of immunosuppressive cytokines (TGFβ-2 and TGFβ-3). These exploratory results prompt further study into interrupting TGFβ signaling.

AIM/OBJECTIVE:To assess whether intraocular pressure (IOP) is associated with refractive error or axial length in children. METHODS:Of subjects from the Singapore Cohort Study of the Risk Factors for Myopia (SCORM), 636 Chinese children aged 9-11 years from two elementary schools underwent non-contact tonometry, cycloplegic autorefraction, and A-scan biometry during 2001. For analyses, refractive error was categorised into four groups; hypermetropia (spherical equivalent refraction (SE) > or = +1.0D), emmetropia (-0.5D<SE< +1.0D), low myopia (-3.0D<SE< or = -0.5D) and high myopia (SE< or = -3.0D). RESULTS:Of the 636 children examined, 50.6% were male. The mean IOP was 16.6 (SD 2.7) mm Hg. There were no significant IOP differences between low (mean IOP = 16.4 (2.8) mm Hg) or high myopes (16.7 (2.5) mm Hg) and emmetropes (16.7 (2.9) mm Hg), p = 0.57. IOP was not correlated with spherical equivalent refraction (Spearman correlation, r = 0.009) or axial length (r = 0.030). In regression analyses adjusting for diastolic blood pressure, neither spherical equivalent (regression coefficient = 0.014) nor axial length (regression coefficient = 0.027) were significantly associated with IOP. CONCLUSION/CONCLUSIONS:These findings do not support an association between IOP and refractive error or axial length in children. This questions postulated roles of IOP in the pathogenesis of myopia.

AIM/OBJECTIVE:To determine the prevalence and identify associated risk factors for dry eye syndrome in a population in Sumatra, Indonesia. METHODS:A one stage cluster sampling procedure was conducted to randomly select 100 households in each of the five rural villages and one provincial town of the Riau province, Indonesia, from April to June 2001. Interviewers collected demographic, lifestyle, and medical data from 1058 participants aged 21 years or over. Symptoms of dry eye were assessed using a six item validated questionnaire. Presence of one or more of the six dry eye symptoms often or all the time was analysed. Presence of pterygium was documented. RESULTS:Prevalence of one or more of the six dry eye symptoms often or all the time adjusted for age was 27.5% (95% confidence interval (CI) 24.8 to 30.2). After adjusting for all significant variables, independent risk factors for dry eye were pterygium (p<0.001, multivariate odds ratio (OR) 1.8; 95% CI 1.4 to 2.5) and a history of current cigarette smoking (p=0.05, multivariate OR 1.5; 95% CI 1.0 to 2.2). CONCLUSIONS:This population based study provides prevalence rates of dry eye symptoms in a tropical developing nation. From our findings, pterygium is a possible independent risk factor for dry eye symptoms.