The Utility of ctDNA in Lung Cancer Clinical Research and Practice: A Systematic Review and Meta-Analysis of Clinical Studies.

This systematic review with embedded meta-analysis aimed to evaluate the clinical utility of circulating tumor DNA (ctDNA) in lung cancer. After screening and review of the Embase database search, 111 studies from 2015 to 2020 demonstrated ctDNA's value in prognostication/monitoring disease progression, mainly in patients with advanced/metastatic disease and non-small cell lung cancer. ctDNA positivity/detection at any time point was associated with shorter progression-free survival and overall survival, whereas ctDNA clearance/decrease during treatment was associated with a lower risk of progression and death. Validating these findings and addressing challenges regarding ctDNA testing integration into clinical practice will require further research.

Metastatic non-small-cell lung cancer without driver mutations: projections by therapy line in Western Europe, 2021-2026.

Aim: To estimate the incidence, prevalence and treated prevalence by line of therapy (LOT) for non-small-cell lung cancer (NSCLC) patients without driver mutations from 2021 to 2026. Materials & methods: Country-specific registry data for Western Europe were used to project incidence and prevalence of NSCLC; LOT information was obtained from CancerMPact® Treatment Architecture physician surveys. Results: Incidence, prevalence and treated prevalence across LOTs for NSCLC are projected to increase across five WE countries, including for stage IV patients without driver mutations (184,966 cases [2021] to 197,925 [2026]). Pembrolizumab monotherapy is utilized by ∼50% of NSCLC patients with programmed death-ligand 1 expression ≥50%. Conclusion: Improved treatment options for NSCLC patients without known driver mutations are important for combating the projected increase in prevalence.

Lung cancer is the leading cause of cancer-related death in Europe. This study estimated how the number of patients living with, and being treated for, lung cancer is projected to change between 2021 and 2026 in Western Europe by collecting past data on lung cancer in France, Germany, Italy, Spain and the UK, and analyzing the trends to create estimates for the future. The number of new cases of lung cancer is projected to increase each year from 2021 to 2026, and in line with this, the number of patients receiving treatment for their disease will increase. Improving treatment options for lung cancer will be an important step to combat the expected increase in cancer cases.

The Negative Impact of Body Mass Index on the Tumor Microenvironment in Colon Cancer: Results of a Prospective Trial.

BACKGROUND: The association between tumor mismatch repair status and obesity in colon cancer is not well understood. The authors of this study hypothesized that mismatch repair deficiency in colon cancer may be associated with a lower Body Mass Index (BMI) and improved patient outcome due to an enhanced tumor immune microenvironment. METHODS: For this study, 70 patients were randomly selected from a prospective trial evaluating nodal ultrastaging for colon cancer. The mismatch repair status of tumors and immunomarker expression were correlated with clinicopathologic characteristics and evaluated for disease-free survival. RESULTS: Patients with mismatch repair-deficient tumors (n = 11) had a lower mean BMI than those with mismatch repair-proficient tumors (n = 59) (22.16 vs. 26.30 kg/m2, respectively; p = 0.029).The findings showed that CD3+ T cells were inversely associated with mismatch repair proficiency (p = 0.048). Mismatch repair-proficient tumors in nonobese patients (BMI < 30 kg/m2) versus obese patients had a higher density of CD8+ (p = 0.008) and FOXP3+ (p = 0.005) T cells. Multivariable analysis linked CD4+ (hazard ratio [HR] 0.52; 95% confidence interval [CI] 0.35-0.76), CD8+ (HR 0.67; 95% CI 0.50-0.89), and number of tumor-positive lymph nodes (HR 1.19; 95% CI 1.03-1.36) to disease-free survival for patients with mismatch repair-proficient tumors. CONCLUSIONS: Tumor mismatch repair status and obesity are correlated in patients with colon cancer. Increased intratumoral T cells in nonobese patients suggests an unexplored link between tumor mismatch repair and immunoprofile.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis.

Although gastric cancer with peritoneal carcinomatosis is associated with poor prognosis and is generally treated with palliative systemic therapy, recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may prove to be an efficacious treatment option. In addition to reviewing the natural history of gastric cancer with peritoneal carcinomatosis, this mini-review examines literature on the efficacy of CRS and HIPEC as compared to chemotherapy and surgical options. Both randomized and non-randomized studies were summarized with the emphasis focused on overall survival. In summary, CRS and HIPEC are indeed a promising treatment option for gastric cancer with peritoneal carcinomatosis and large randomized clinical trials are warranted.

Colon cancer lymph node evaluation among military health system beneficiaries: an analysis by race/ethnicity.

BACKGROUND: The number of lymph nodes examined during colon cancer surgery falls below nationally recommended guidelines in the general population, with Blacks and Hispanics less likely to have adequate nodal evaluation in comparison to Whites. The Department of Defense's (DoD) Military Health System (MHS) provides equal access to medical care for its beneficiaries, regardless of racial/ethnic background. This study aimed to investigate whether racial/ethnic treatment differences exist in the MHS, an equal-access medical care system. METHODS: Linked data from the DoD cancer registry and administrative claims databases were used and included 2,155 colon cancer cases. Multivariate logistic regression assessed the association between race/ethnicity and the number of lymph nodes examined (<12 and ≥12) overall and for stratified analyses. RESULTS: No overall racial/ethnic differences in the number of lymph nodes examined was identified. Further stratified analyses yielded similar results, except potential racial/ethnic differences were found among persons with poorly differentiated tumors, where non-Hispanic Blacks tended to be less likely to have ≥12 lymph nodes dissected (odds ratio 0.34; 95 % confidence interval 0.14-0.80; p = 0.01) compared with non-Hispanic Whites. CONCLUSION: Racial/ethnic disparities in the number of lymph nodes evaluated among patients with colon cancer were not apparent in an equal-access healthcare system. However, among poorly differentiated tumors there might be racial/ethnic differences in nodal yield, suggesting the possible effects of factors other than access to healthcare.

Value of primary tumor gene signatures in colon cancer when national quality standards are adhered to: preliminary results of an international prospective multicenter trial.

BACKGROUND: The purpose of this study was to determine if gene signatures are informative in colon cancer (CC) when National Quality Standards (NQS) are adhered to. Several studies have demonstrated the prognostic potential of gene signatures in primary CC. This has never been evaluated prospectively with adherence to NQS. METHODS: This was a prospective, international, multicenter trial. Eligibility criteria were: no distant metastasis, ≥12 lymph nodes (LNs), and no adjuvant chemotherapy for LN-negative CC. RNA from frozen tumor samples was considered reliable if RNA Integrity Number >9. Using an Agilent whole human genome array, 44,000 genes were analyzed in primary tumors for differential gene expression (DGE). ANOVA applied at 2-fold expression level was performed in at least 8 experiments to obtain the DGEs. RESULTS: Molecular analysis was completed in 113 of 128 patients. With median follow-up of 27 months, 11.5 % recurred within 3 years after surgery. Significant DGE was identified in recurrent tumors reflected by upregulation (UR) in cellular proliferation and by downregulation (DR) in prodifferentiating panel of 9 genes, independent of T or N classification. By multivariate analysis 3-year disease-free survival was 12.5 % in the UR/DR group versus 93.4 % in the non-UR/DR group (p < .0001; HR = 24.2; 95 % CI 4.8-120.4). CONCLUSIONS: This is the first prospective trial to evaluate gene signatures in CC with adherence to a 12-node minimum quality standard. Certain molecular pathways may be prognostically relevant if both surgery and pathology are standardized, regardless of T or N classification. Careful consideration should be made to include surgical quality measures when planning clinical trials to evaluate the true effect of molecular markers in CC.

Surgical cure of primary hyperparathyroidism ameliorates gastroesophageal reflux symptoms.

OBJECTIVE: Gastroesophageal reflux disease (GERD) symptoms are commonly reported in primary hyperparathyroidism (pHPT). Although a calcium-mediated cause-and-effect relationship has been suggested, it remains unknown if parathyroidectomy improves GERD symptoms. METHODS: Over a 22-month period, 1,175 (39%) of 3,000 consecutive adult patients with pHPT and symptomatic GERD (on prescription reflux medications daily for ≥2 years) undergoing parathyroidectomy were entered into a prospective study. Standardized Frequency Scale for Symptoms of GERD (FSSG) questionnaire was used to assess symptoms before, 1 and 2 years after parathyroidectomy. RESULTS: Daily prescription medication was used by 81%, while 19% used daily non-prescription drugs, both for a mean of 2.9 ± 0.7 years. GERD symptoms improved (26%) or resolved completely (36%) in 62% of patients (p < 0.0001 vs. preoperative baseline) 1 year after parathyroidectomy. Prescription medications for GERD decreased from 81% of enrolled patients to 26% (p < 0.0001) 12 months postoperatively, with 39% having complete symptom relief and taking no medications (p < 0.0001). Daily use of prescription GERD medications decreased to occasional over-the-counter drug use in 35% after parathyroidectomy (p < 0.0001). Mean FSSG scores decreased significantly postoperatively (pre-op: 18.0 ± 8.0 vs. post-op: 10.0 ± 5.0; p < 0.0001), with significant improvements in all 12 FSSG categories, including motility (pre-op: 7.3 ± 3.0 vs. post-op: 4.4 ± 3.0; p < 0.0001) and acid reflux symptoms (pre-op: 10.8 ± 5.0 vs. post-op: 5.9 ± 4.0; p < 0.0001). Symptomatic improvements were durable 2 years after parathyroidectomy. CONCLUSION: Symptomatic GERD is common in pHPT. Parathyroidectomy provides significant, durable relief of both motility and acid reflux symptoms allowing discontinuation of prescription drug use for GERD in most (74%) patients providing yet another indication for parathyroidectomy in pHPT.

Role of multi-modality therapy in peritoneal carcinomatosis and visceral metastasis: a case report and review of the literature.

INTRODUCTION: Treatment for advanced stage colorectal cancer with synchronous peritoneal carcinomatosis (PC) and hepatic metastasis (HM) has progressed significantly over the past 10 years. CASE REPORT: We present the case of a 39-year-old female patient with stage IV colorectal cancer with bilateral HM, pulmonary oligometastatic disease, and diffuse PC who underwent hyperthermic intraperitoneal chemotherapy (HIPEC) and complete cytoreductive surgery (CRS) for her intra-abdominal disease. The patient had an uneventful immediate post-operative recovery, and subsequently tolerated multiple cycles of adjuvant chemotherapy and percutaneous radiofrequency ablation of pulmonary lesions. At her 22-month follow-up assessment, the patient remains alive with disease. CONCLUSION: Current recommendations for surgical management of synchronous colorectal cancer PC and HM indicate that patients with less than three HMs, a low peritoneal cancer index (PCI), and good functional status will benefit most from CRS and HIPEC. Our patient had an elevated PCI of 12 as measured by computed tomography imaging, and five HMs (all less than 3 cm in size); however, given that her life expectancy on systemic chemotherapy was estimated to be approximately 12 months, we have observed carefully selected patients to benefit from an aggressive multi-modality approach. This case report demonstrates an all too common scenario for surgeons managing patients with advanced CRC, and highlights the importance of patient selection for surgical management as part of multidisciplinary cancer care in this patient population.

The impact of age on colorectal cancer incidence, treatment, and outcomes in an equal-access health care system.

BACKGROUND: Inferior outcomes in younger patients with colorectal cancer may be associated with multiple factors, including tumor biology, delayed diagnosis, disparities such as access to care, and/or treatment differences. OBJECTIVE: This study aims to examine age-based colorectal cancer outcomes in an equal-access health care system. DESIGN: This study is a retrospective large multi-institutional database analysis. PATIENTS: Patients with colorectal cancer included in the Department of Defense Automated Central Tumor Registry (January 1993 to December 2008) were stratified by age <40, 40 to 49, 50 to 79, and ≥80 years to determine the effect of age on incidence, treatment, and outcomes. MAIN OUTCOME MEASURES: The primary outcomes measured were the stage at presentation, adjuvant therapy use, 3- and 5-year disease-free survival, and overall survival. RESULTS: Some 7948 patients were identified; most (77%) patients were in the 50- to 79-year age group. Overall, 25% presented with stage III disease. Compared with patients aged 50 to 79 and ≥80 years, patients aged <40 and 40 to 49 years presented more frequently with advanced disease (stage III (35% and 35% vs 28% and 26%) and stage IV (24% and 21% vs 18% and 15%); all p < 0.001). Adjuvant chemotherapy use in stage III patients was 62%; those patients ≥80 and 50 to 79 years had decreased use (p < 0.001). Overall recurrence was 8.1% at 3 years and 9.7% at 5 years, with the highest rates in patients <40 years (11.8%; p = 0.007). Overall survival was worse in patients ≥80 years, whereas the remaining cohorts were similar. For stage III disease, patients 40 to 49 years had the highest survival among all cohorts (p < 0.001). LIMITATIONS: This study was limited by the lack of specific comorbid information and the limitations inherent to large database reviews. CONCLUSIONS: In an equal-access system, young age at presentation (<50 years) was associated with advanced stage and higher recurrence of colorectal cancer, but similar survival in comparison with older patients. Although increased adjuvant therapy use in younger patients may partially account for stage-specific increases in survival, the relative decreased chemotherapy use overall requires further evaluation.

Colon cancer treatment: are there racial disparities in an equal-access healthcare system?

BACKGROUND: In the general US population, blacks and whites have been shown to undergo colon cancer treatment at disproportionate rates. Accessibility to medical care may be the most important factor influencing differences in colon cancer treatment rates among whites and blacks. OBJECTIVE: We assessed whether racial disparities in colon cancer surgery and chemotherapy existed in an equal-access health care system. In addition, we sought to examine whether racial differences varied according to demographic and tumor characteristics. DESIGN AND SETTING: Database research using the Department of Defense Military Health System. PATIENTS: Patients included 2560 non-Hispanic whites (NHW) and non-Hispanic blacks (NHB) with colon cancer diagnosed from 1998 to 2007. MAIN OUTCOME MEASURES: Logistic regression was used to assess the associations between race and the receipt of colon cancer surgery or chemotherapy while controlling for available potential confounders, both overall and stratified by age at diagnosis, sex, and tumor stage. RESULTS: After multivariate adjustment, the odds of receiving colon cancer surgery or chemotherapy for NHBs versus NHWs were similar (OR, 0.75 [95% CI, 0.37-1.53]; OR, 0.79 [95% CI, 0.59-1.04]). In addition, no effect modifications by age at diagnosis, sex, and tumor stage were observed. LIMITATIONS: Treatment data might not be complete for beneficiaries who also had non-Department of Defense health insurance. CONCLUSIONS: When access to medical care is equal, racial disparities in the provision of colon cancer surgery and chemotherapy were not apparent. Thus, it is possible that the inequalities in access to care play a major role in the racial disparities seen in colon cancer treatment in the general population.

Prospective validation of a surgical complications grading system in a cohort of 2114 patients.

BACKGROUND: We recently reported a grading system for surgical complications. This system proved to have a high sensitivity for recording minor but meaningful complications prolonging hospital stay in patients after colorectal surgery. We aimed to prospectively validate the complication grading system in a general surgery department over 1 year. METHODS: All surgical procedures and related complications were prospectively recorded between January 1st and December 31st, 2009. Surgical complications were graded on a severity scale of 1-5. The system classifies short-term outcome by grade emphasizing intensity of therapy required for treatment of the defined complication. RESULTS: During the study period, 2114 patients underwent surgery. Elective and oncological surgeries were performed in 1606 (76%) and 465 (22%) patients, respectively. There were 422 surgical complications in 304 (14%) patients (Grade 1/2: 203 [67%]; Grade 3/4: 90 [29%]; Grade 5: 11 [4%]). Median length of stay correlated significantly with complication severity: 2.3 d for no complication, 6.2 and 11.8 d for Grades 1/2 and 3/4, respectively (P < 0.001). Older age (OR 2.75, P < 0.001), comorbidities (OR 1.44, P = 0.02), American Society of Anesthesiology score >2 (OR 2.07, P < 0.001), contamination Grade (OR 1.85, P = 0.001), oncological (OR 2.82, P < 0.001), open (OR 1.22, P = 0.03), prolonged >120 min (OR 2.08, P < 0.001), and emergency surgery (OR 1.42, P = 0.02) independently predicted postoperative complications. CONCLUSIONS: This system of grading surgical complications permits standardized reporting of surgical morbidity according to the severity of impact. Prospective validation of this system supports its use in a general surgery setting as a tool for surgical outcome assessment and quality assurance.

Impact of maximal cytoreductive surgery plus regional heated intraperitoneal chemotherapy (HIPEC) on outcome of patients with peritoneal carcinomatosis of gastric origin: results of the GYMSSA trial.

BACKGROUND: A prospective randomized trial was conducted to compare the impact of systemic chemotherapy versus multi-modality therapy (complete cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and systemic chemotherapy) on overall survival (OS) in patients with gastric carcinomatosis. METHODS: Patients with measurable metastatic gastric adenocarcinoma involving the peritoneum, and resectable to "no evidence of disease" were randomized to gastrectomy, metastasectomy, HIPEC, and systemic FOLFOXIRI (GYMS arm) or FOLFOXIRI alone (SA arm). RESULTS: Seventeen patients were enrolled (16 evaluable); 7 of 9 patients in the multi-modality GYMS arm achieved complete cytoreduction (CCR0). Median OS was 11.3 months in the GYMS arm and 4.3 months in the SA arm. Four patients in the GYMS arm survived >12 months, 2 patients close to 2 years at last follow-up, and 1 patient more than 4 years, with 2 of these patients still alive. No patient in the SA arm lived beyond 11 months. All patients surviving beyond 12 months in the surgery arm achieved complete cytoreduction and had an initial Peritoneal Cancer Index (PCI) of ≤ 15. CONCLUSION: Maximal cytoreductive surgery combined with regional (HIPEC) and systemic chemotherapy in selected patients with gastric carcinomatosis and limited disease burden can achieve prolonged survival.

Label-retaining liver cancer cells are relatively resistant to sorafenib.

OBJECTIVE: The standard therapy for advanced hepatocellular carcinoma (HCC) is sorafenib, with most patients experiencing disease progression within 6 months. Label-retaining cancer cells (LRCC) represent a novel subpopulation of cancer stem cells (CSC). The objective was to test whether LRCC are resistant to sorafenib. METHODS: We tested human HCC derived LRCC and non-LRCC before and after treatment with sorafenib. RESULTS: LRCC derived from human HCC are relatively resistant to sorafenib. The proportion of LRCC in HCC cell lines is increased after sorafenib while the general population of cancer cells undergoes growth suppression. We show that LRCC demonstrate improved viability and toxicity profiles, and reduced apoptosis, over non-LRCC. We show that after treatment with sorafenib, LRCC upregulate the CSC marker aldehyde dehydrogenase 1 family, wingless-type MMTV-integration-site family, cell survival and proliferation genes, and downregulate apoptosis, cell cycle arrest, cell adhesion and stem cells differentiation genes. This phenomenon was accompanied by non-uniform activation of specific isoforms of the sorafenib target proteins extracellular-signal-regulated kinases and v-akt-murine-thymoma-viral-oncogene homologue (AKT) in LRCC but not in non-LRCC. A molecular pathway map for sorafenib treated LRCC is proposed. CONCLUSIONS: Our results suggest that HCC derived LRCC are relatively resistant to sorafenib. Since LRCC can generate tumours with as few as 10 cells, our data suggest a potential role for these cells in disease recurrence. Further investigation of this phenomenon might provide novel insights into cancer biology, cancer recurrence and drug resistance with important implications for the development of novel cancer therapies based on targeting LRCC.

Utility of cell-based vaccines as cancer therapy: Systematic review and meta-analysis.

Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the natural immune process and stimulate an adaptive immune response against tumor antigens. The primary objective of this study is to perform a systematic literature review with an embedded meta-analysis of all published Phase 2 and 3 clinical trials of cell-based cancer vaccines in human subjects. The secondary objective of this study is to review trials demonstrating biological activity of cell-based cancer vaccines that could uncover additional hypotheses, which could be used in the design of future studies. We performed the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final review included 36 studies - 16 single-arm studies, and 20 controlled trials. Our systematic review of the existing literature revealed largely negative trials and our meta-analysis did not show evidence of clinical benefit from cell-based cancer-vaccines. However, as we looked beyond the stringent inclusion criteria of our systematic review, we identified significant examples of biological activity of cell-based cancer vaccines that are worth highlighting. In conclusion, the existing literature on cell-based cancer vaccines is highly variable in terms of cancer type, vaccine therapies and the clinical setting with no overall statistically significant clinical benefit, but there are individual successes that represent the promise of this approach. As cell-based vaccine technology continues to evolve, future studies can perhaps fulfill the potential that this exciting field of anti-cancer therapy holds.

Technical effects of adding 1 % lidocaine to technetium sulfur colloid for sentinel lymphatic mapping in early breast cancer: analysis of data from a double-blind randomized controlled trial.

BACKGROUND: A practice standard in sentinel lymph node (SLN) mapping in breast cancer is intradermal injection of technetium-99m sulfur colloid (Tc-99m), resulting in significant patient discomfort and pain. A previous randomized controlled trial showed that adding lidocaine to Tc-99m significantly reduced radioisotope injection-related pain. We tested whether 1 % lidocaine admixed with Tc-99m affects feasibility of SLN mapping. METHODS: Between January 2006 and April 2009, 140 patients with early breast cancer were randomly assigned (1:1:1:1) to receive standard topical 4 % lidocaine cream and intradermal Tc-99m (control) or to one of three other study groups: topical placebo cream and injection of Tc-99m containing sodium bicarbonate (NaHCO3), 1 % lidocaine, or both. All SLN data were collected prospectively. RESULTS: Study groups were comparable for clinicopathological parameters. As previously reported, the addition of 1 % lidocaine to the radioisotope solution significantly improved patient comfort. Overall SLN identification rate in the trial was 93 %. Technical aspects of SLN biopsy were similar for all groups, including time from injection to operation, first SLN (SLN 1) gamma probe counts, ex vivo counts for SLN 1 and SLN 2, and axillary bed counts. SLN identification rates were comparable statistically: control (96 %), lidocaine (90 %), sodium bicarbonate (97 %), and sodium bicarbonate-lidocaine (90 %). The control group had a significantly higher SLN 2/SLN 1 ex vivo count ratio, and the number of SLNs detected was significantly reduced in the lidocaine versus no-lidocaine groups (p < 0.05). CONCLUSIONS: Addition of 1 % lidocaine to standard radioisotope solution for SLN mapping in breast cancer is associated with fewer SLNs detected, but it does not appear to compromise SLN identification.

Clinical decision support and individualized prediction of survival in colon cancer: bayesian belief network model.

BACKGROUND: We used a large population-based data set to create a clinical decision support system (CDSS) for real-time estimation of overall survival (OS) among colon cancer (CC) patients. Patients with CC diagnosed between 1969 and 2006 were identified from the Surveillance Epidemiology and End Results (SEER) registry. Low- and high-risk cohorts were defined. The tenfold cross-validation assessed predictive utility of the machine-learned Bayesian belief network (ml-BBN) model for clinical decision support (CDS). METHODS: A data set consisting of 146,248 records was analyzed using ml-BBN models to provide CDS in estimating OS based on prognostic factors at 12-, 24-, 36-, and 60-month post-treatment follow-up. RESULTS: Independent prognostic factors in the ml-BBN model included age, race; primary tumor histology, grade and location; Number of primaries, AJCC T stage, N stage, and M stage. The ml-BBN model accurately estimated OS with area under the receiver-operating-characteristic curve of 0.85, thereby improving significantly upon existing AJCC stage-specific OS estimates. Significant differences in OS were found between low- and high-risk cohorts (odds ratios for mortality: 17.1, 16.3, 13.9, and 8.8 for 12-, 24-, 36-, and 60-month cohorts, respectively). CONCLUSIONS: A CDSS was developed to provide individualized estimates of survival in CC. This ml-BBN model provides insights as to how disease-specific factors influence outcome. Time-dependent, individualized mortality risk assessments may inform treatment decisions and facilitate clinical trial design.

A novel nomogram for peritoneal mesothelioma predicts survival.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare disease treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Estimation of personalized survival times can potentially guide treatment and surveillance. METHODS: We analyzed 104 patients who underwent CRS and cisplatin-based HIPEC for MPM. By means of 25 demographic, laboratory, operative, and histopathological variables, we developed a novel nomogram using machine-learned Bayesian belief networks with stepwise training, testing, and cross-validation. RESULTS: The mean peritoneal carcinomatosis index (PCI) was 15, and 66 % of patients had a completeness of cytoreduction (CC) score of 0 or 1. Eighty-seven percent of patients had epithelioid histology. The median follow-up time was 49 (1-195) months. The 3- and 5-year overall survivals (OS) were 58 and 46 %, respectively. The histological subtype, pre-CRS PCI, and preoperative serum CA-125 had the greatest impact on OS and were included in the nomogram. The mean areas under the receiver operating characteristic curve for the 10-fold cross-validation of the 3- and 5-year models were 0.77 and 0.74, respectively. The graphical calculator or nomogram uses color coding to assist the clinician in quickly estimating individualized patient-specific survival before surgery. CONCLUSIONS: Machine-learned Bayesian belief network analysis generated a novel nomogram predicting 3- and 5-year OS in patients treated with CRS and HIPEC for MPM. Pre-CRS estimation of survival times may potentially individualize patient care by influencing the use of systemic therapy and frequency of diagnostic imaging, and might prevent CRS in patients unlikely to achieve favorable outcomes despite surgical intervention.

Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence.

BACKGROUND: The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis. METHODS: Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). RESULTS: Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. CONCLUSION: CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process.

Spectral-cepstral estimation of dysphonia severity: external validation.

OBJECTIVES: The current study applied an acoustic algorithm incorporating measures from cepstral and spectral analyses, the Cepstral Spectral Index of Dysphonia (CSID), in an attempt to externally validate the CSID as an acoustic estimate of dysphonia severity. METHODS: Correlation (Pearson's r) between the CSID and trained listener-perceived severities as rated on the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) was calculated from sentence and sustained vowel samples from 56 patients before or after they underwent thyroid surgery. RESULTS: A strong correlation was identified between the mean CSID values calculated across CAPE-V sentences and vowels and the median rating of perceived overall severity (r = 0.82; p < 0.001). The CSID values did not differ significantly from their corresponding auditory-perceptual ratings of dysphonia severity for these samples (CSID: mean, 15.54, SD, 16.63; CAPE-V Severity: mean, 17.33, SD, 13.61; p = 0.16). CONCLUSIONS: Independent testing of an acoustic algorithm incorporating measures from cepstral and spectral analyses (the CSID) confirmed a strong correlation of the CSID to perceptual ratings of overall voice quality. This study provides external validation of the CSID as a robust correlate of dysphonia severity as rated by trained listeners.