Intensive Surveillance Protocol Research Articles

Effect of concomitant variant histology on the prognosis of patients with upper urinary tract urothelial carcinoma after radical nephroureterectomy

ObjectiveTo evaluate the prognostic effect of concomitant variant histology (CVH) on survival outcomes in patients with upper urinary tract urothelial carcinoma (UTUC) after radical nephroureterectomy. Materials and methodsData on 417 patients with UTUC treated with radical nephroureterectomy without preoperative adjuvant therapy were retrospectively reviewed with a focus on CVH. Clinicopathological features and prognostic factors were compared between patients with pure UTUC and patients with UTUC with CVH. The primary end points were cancer-specific survival (CSS), disease recurrence-free survival (DFS), and overall survival (OS). ResultsUTUC with CVH was present in 90 (21.6%) of 417 patients. At a median follow-up of 26 months, 153 (36.7%) had died of UTUC, 161 (38.6%) had experienced a relapse, and 176 (42.2%) had died of other causes. UTUC with CVH was significantly associated with advanced tumor stage, high tumor grade, tumor diameter, lymphovascular invasion, lymph node metastasis, positive surgical margins, and tumor architecture compared with pure UTUC (all P<0.01). The estimated 5-year CSS, DFS, and OS rates were 64.9%, 61.1%, and 62.1%, respectively, in the pure UTUC group, compared with 36.3%, 34.3%, and 26.5%, respectively, in the UTUC with CVH group (P<0.001). Multivariate analysis demonstrated that CVH was an independent predictor of CSS (hazard ratio [HR] = 1.594; 95% CI: 1.125–2.259; P = 0.009), DFS (HR = 1.549; 95% CI: 1.077–2.152; P = 0.017), and OS (HR = 1.685; 95% CI: 1.212–2.343; P = 0.002). ConclusionsApproximately one-fifth of the specimens of patients with UTUC were observed to exhibit CVH. CVH was an independent prognostic factor for CSS, DFS, and OS in patients with UTUC on both univariate and multivariate analyses. Genitourinary pathologists should look for potential CVH components in UTUC specimens and report this in routine pathological practice. The presence of CVH should identify patients as candidates for consultation regarding early adjuvant therapy and intensive surveillance protocols.

History, Pathogenesis, and Management of Familial Gastric Cancer: Original Study of John XXIII's Family

Background. Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma. Methods. In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines. Results. Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN) was classified as cT4bN3a (IV stage). In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively. Conclusions. Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer's development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members.

The influence of metabolic syndrome on hemodialysis access patency

The natural history of patients with metabolic syndrome (MetS) undergoing hemodialysis access placement is unknown. MetS has previously been found as a risk factor for poor outcomes for vascular surgery patients undergoing other interventions. The aim of this is study is to describe the outcomes of MetS patients undergoing primary hemodialysis access placement. The medical records of the 187 patients who underwent hemodialysis access placement between 1999 and 2009 at the Veterans Administration Connecticut Healthcare System were reviewed. Survival, primary patency, and secondary patency were evaluated using the Gehan-Breslow test for survival. MetS was defined as the presence of three or more of the following: blood pressure≥130/90 mm Hg; triglycerides≥150 mg/dL; high-density lipoprotein≤50 mg/dL for women and ≤40 mg/dL for men; body mass index≥30 kg/m2; or fasting blood glucose≥110 mg/dL. Of the 187 patients who underwent hemodialysis access placement, 115 (61%) were identified to have MetS. The distribution of MetS factors among all patients was hypertension in 98%, diabetes in 58%, elevated triclyceride in 39%, decreased high-density lipoprotein in 60%, elevated body mass index in 36%, and 39% were currently receiving hemodialysis. Patients were a mean age of 66 years. The median length of follow-up was 4.2 years. The forearm was site of fistula placement in 53%; no difference existed between groups (MetS, 57%; no MetS, 50%; P=.388). The median time to primary failure was 0.46 years for all patients (MetS, 0.555 years; no MetS, 0.436 years; P=.255). Secondary patency was 50% at 1.18 years for all patients (no MetS, 1.94 years; MetS, 0.72 years; P=.024). Median survival duration for all patients was 4.15 years (no MetS, 5.07 years; MetS, 3.63 years; P=.019). MetS is prevalent among patients undergoing hemodialysis access placement. Patients with MetS have equivalent primary patency rates; however, their survival and cumulative patency rates are significantly lower than in patients without MetS. Patients with MetS form a high-risk group that needs intensive surveillance protocols.

Improvement in 2-year survival for ventricular assist device patients after implementation of an intensive surveillance protocol

This study was conducted to determine the effect of a disease-management model termed an "intensive surveillance protocol" (ISP) on survival in ventricular assist device (VAD) patients. This intervention consisted of a formalized, protocol-driven, multi-disciplinary team approach to VAD patient follow-up initiated August 1, 2006. The goal was to attain an internal program benchmark of 70% survival at 2 years. Historically, 2-year survival after VAD implant has been sub-optimal, and no patient management algorithms have been formally tested to determine their effect on 2-year survival. The study comprised 76 patients, of whom 26 had a VAD as destination therapy (DT) and 50 as a bridge to transplant (BTT), from July 1, 2003, to June 30, 2008. Survival before and after initiation of ISP was compared. A parametric hazard multivariable analysis, with a time-varying covariable for implementation of ISP, was used to evaluate of other factors affecting survival. Survival at 16 months was 100% for DT patients who received a VAD after August 1, 2006 vs 64% for the earlier era (p = 0.06). For BTT, 16- month survival was 71% vs 43% (p = 0.03). Predicted 2-year survival before and after implementation of the ISP improved from 30% to 87% for DT (p = 0.02) and from 20% to 61% for BTT patients (p = 0.01). Predictors of midterm survival by multivariable analysis included ISP (p = 0.004), younger age (p = 0.03), non-emergent implant (p < 0.0001), and isolated left ventricular VAD (p < 0.0001). After adjustment for covariables, the ISP was associated with a 70% reduction in the hazard for death for the entire cohort (p = 0.004). The effect of ISP was also significant in the patients who received the HeartMate XVE (Thoratec, Pleasanton, CA), which spanned both eras of the study. Survival improved for DT and BTT VAD patients after implementation of the ISP, with a dramatic decrease in hazard for death. Although the transition from pulsatile to axial flow technology occurred during the study period and likely contributed to improved outcomes, the institution of the ISP provided an important and significant contribution to improved survival through a proactive approach to patient management, allowing earlier identification of potential adverse events. For optimal outcomes, VAD patients require intensive follow-up surveillance protocols that have previously become standard in the care of heart transplant patients.

One to 2-Year Surveillance Intervals Reduce Risk of Colorectal Cancer in Families With Lynch Syndrome

Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program. The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy. After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without. With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.

In-depth investigation of the molecular pathogenesis of bladder cancer in a unique 26-year old patient with extensive multifocal disease: a case report

BackgroundThe molecular characteristics and the clinical disease course of bladder cancer (BC) in young patients remain largely unresolved. All patients are monitored according to an intensive surveillance protocol and we aim to gain more insight into the molecular pathways of bladder tumors in young patients that could ultimately contribute to patient stratification, improve patient quality of life and reduce associated costs. We also determined whether a biomarker-based surveillance could be feasible.Case PresentationWe report a unique case of a 26-year-old Caucasian male with recurrent non-muscle invasive bladder tumors occurring at a high frequency and analyzed multiple tumors (maximal pTaG2) and urine samples of this patient. Analysis included FGFR3 mutation detection, FGFR3 and TP53 immunohistochemistry, mircosatellite analysis of markers on chromosomes 8, 9, 10, 11 and 17 and a genome wide single nucleotide polymorphism-array (SNP). All analyzed tumors contained a mutation in FGFR3 and were associated with FGFR3 overexpression. None of the tumors showed overexpression of TP53. We found a deletion on chromosome 9 in the primary tumor and this was confirmed by the SNP-array that showed regions of loss on chromosome 9. Detection of all recurrences was possible by urinary FGFR3 mutation analysis.ConclusionsOur findings would suggest that the BC disease course is determined by not only a patient's age, but also by the molecular characteristics of a tumor. This young patient contained typical genetic changes found in tumors of older patients and implies a clinical disease course comparable to older patients. We demonstrate that FGFR3 mutation analysis on voided urine is a simple non-invasive method and could serve as a feasible follow-up approach for this young patient presenting with an FGFR3 mutant tumor.

415: Improvement in Two Year Survival for Ventricular Assist Device Patients after Implementation of an Intensive Surveillance Protocol

To determine the effect of an intensive surveillance protocol (ISP) on survival in ventricular assist device (VAD) patients. ISP consisted of multi-disciplinary clinic visits and monitoring by weekly phone calls initiated 8/1/06. The goal was to attain an internal program benchmark of 70% two-year survival to justify VADs as a long-term treatment option.

The Seattle Protocol Does Not More Reliably Predict the Detection of Cancer at the Time of Esophagectomy Than a Less Intensive Surveillance Protocol

The optimal management of high-grade dysplasia in Barrett's esophagus remains controversial. A biopsy protocol consisting of 4 quadrant jumbo biopsies (every 1 cm) with biopsies of mucosal abnormalities (the Seattle protocol) is considered to be the optimal method for detecting early cancers in patients with high-grade dysplasia, although it has never been validated. This study aimed to determine the frequency of unsuspected carcinoma at esophagectomy in Barrett's esophagus patients with high-grade dysplasia who underwent the Seattle protocol and to compare the findings with those of a less rigorous biopsy protocol. Thirty-three patients with high-grade dysplasia underwent esophagectomy. None had obvious mass lesions at preoperative endoscopy. Patients were divided into group 1 (preoperative surveillance biopsies according to Seattle protocol) and group 2 (4 quadrant biopsies every 2 cm). Preoperative and postoperative diagnoses were confirmed by 2 expert gastrointestinal pathologists. Unsuspected intramucosal cancer was found in 8 of 20 (40%) patients in group 1 versus 4 of 13 (30%) in group 2 (P = .6). Preoperative mucosal nodularity was observed in 4 of 8 (50%) postoperative intramucosal cancers from group 1 versus 3 of 4 (75%) from group 2. Multifocal high-grade dysplasia was seen preoperatively in 7 of 8 (87.5%) postoperative intramucosal cancers in group 1 versus 2 of 4 (50%) in group 2. No patient had submucosal cancer or lymph node metastases at surgery. Intense preoperative biopsy sampling by the Seattle protocol does not more reliably predict the detection of cancer at the time of esophagectomy than a less intensive surveillance protocol. This calls into question the concept that extensive sampling with the Seattle protocol consistently detects early cancers arising in Barrett's esophagus patients with high-grade dysplasia.

The Role of Postoperative Surveillance in Colorectal Cancer

Postoperative surveillance for recurrent and/or metachronous disease is an important component of the treatment of patients with colorectal cancer. The optimal schedule of follow-up investigations remains controversial. Several randomized trials have suggested a moderate improvement in 5-year survival and earlier detection of cancer recurrence with the implementation of intensive surveillance protocols. Whether these protocols are cost-effective has yet to be determined. Current guidelines from the American Society of Colon and Rectal Surgeons recommend periodic patient follow-up with office visits, carcinoembryonic antigen (CEA) measurement, and endoscopy following potentially curative resection of colorectal cancer.

Prevention of Pulmonary Embolism by Combined Modalities of Thromboprophylaxis and Intensive Surveillance Protocol.…Mukesh Misra, M.D., Ben Roitberg, M.D., Koji Ebersole, B.A., Fady T. Charbel, M.D.

Prevention of Pulmonary Embolism by Combined Modalities of Thromboprophylaxis and Intensive Surveillance Protocol.…Mukesh Misra, M.D., Ben Roitberg, M.D., Koji Ebersole, B.A., Fady T. Charbel, M.D.

Prevention of Pulmonary Embolism by Combined Modalities of Thromboprophylaxis and Intensive Surveillance Protocol.???Mukesh Misra, M.D., Ben Roitberg, M.D., Koji Ebersole, B.A., Fady T. Charbel, M.D.

Prevention of Pulmonary Embolism by Combined Modalities of Thromboprophylaxis and Intensive Surveillance Protocol.???Mukesh Misra, M.D., Ben Roitberg, M.D., Koji Ebersole, B.A., Fady T. Charbel, M.D.

The Incidence of Thromboembolism in the Surgical Intensive Care Unit

The clinical diagnosis of deep venous thrombosis (DVT) is unreliable. Studies have been performed examining the utility of frequent duplex scans. However, these studies included patients outside of the intensive care unit. The incidence of venous thromboembolism and the effect of a less intense surveillance protocol was prospectively examined at a level-1 urban trauma center for a 6 month period. During the study period there were 726 admission to the surgical intensive care unit. Sequential compression devices (SCDs) were used for DVT prophylaxis in 93 per cent of the admissions. A total of 114 duplex scans were ordered: 42 per cent for surveillance and the rest for evaluation of a clinical indication. Twelve DVTs were discovered (11% overall DVT rate). No patient on subcutaneous heparin or low-molecular-weight heparin developed a DVT or pulmonary embolism (PE). Four patients suffered a PE; however, none were found to have a lower extremity DVT on duplex ultrasound and all received SCD prophylaxis. Overall, proper use of DVT prophylaxis for intensive care unit days 1-14 was 77 per cent. The incidence of venous thromboembolism in a group of patients at overall high risk was low. A program of DVT surveillance with duplex ultrasound was not cost-effective.