A Review of Quality Improvement Process Measures for Colorectal Surgery in the United States Using the American College of Surgeons National Surgical Quality Improvement Program Database - Have We Made Progress?

Numerous guidelines have been published regarding Enhanced Recovery Programs (ERP) following colorectal surgery over the past decade. Participation in these guidelines at a national level is unclear. We hypothesize that the adaptation of ERP for patients undergoing elective colorectal surgery is limited but the use of quality improvement measures has increased and while outcomes have improved over the past several years. A total of 86 402 patients were evaluated undergoing elective colectomy between 2013-2018 using the ACS-NSQIP database. Over a 5-year period, there was a significant increase in the use of quality improvement process measures: mechanical and oral bowel preparation and minimally invasive approach. During this time, there was a significant decrease in overall perioperative morbidities (P <.001). These encouraging results from a large national database suggest that evidence-based, quality improvement guidelines are being embraced and that overall outcomes for patients undergoing elective colectomy are improving.

The Accuracy of Point-of-Care Ultrasound in the Diagnosis of Acute Cholecystitis.

PURPOSE: Acute cholecystitis (AC) affects 50-200 000 patients per year. Early surgery is the treatment of choice for AC. Therefore, timely diagnosis is important to begin proper management. Recently, emergency departments have adopted point-of-care ultrasound (POCUS) for the initial evaluation of AC. The accuracy of POCUS for AC has not been well studied. METHODS: Patients receiving POCUS for evaluation of AC in the emergency department at our tertiary care institution for 2 years were considered. Patients with previous biliary diagnoses were excluded. Patients were deemed to have AC from a recorded POCUS result or 2/3 of the following POCUS findings: pericholecystic fluid, gallbladder wall hyperemia, and sonographic Murphy's sign. Formal ultrasound and final diagnosis from surgical and pathology reports were used as gold standards for comparison. RESULTS: In total, 147 patients met inclusion criteria. POCUS had a sensitivity and specificity of .4 (95% CI: .1216-.7376) and .99 (.9483-.9982), respectively, when compared to a final diagnosis and .33 (.0749-.7007) and .94 (.8134-.9932) when compared to formal US. The modified Tokyo guidelines for suspicion of AC had a sensitivity of .2 (.0252-.5561) and specificity of .88 (.8173-.931) compared to the final diagnosis. CONCLUSION: Point-of-care ultrasound was not a better screening test than the modified Tokyo guidelines. We recommend a simplified screening approach for AC using clinical findings and laboratory data, followed by confirmatory formal imaging. This strategy could prevent unnecessary delays in surgical management and use of physician resources.

A chemokine/chemokine receptor signature potentially predicts clinical outcome in colorectal cancer patients.

BACKGROUND: Differential expression of chemokines/chemokine receptors in colorectal cancer (CRC) may enable molecular characterization of patients' tumors for predicting clinical outcome. OBJECTIVE: To evaluate the prognostic ability of these molecules in a CRC cohort and the CRC TCGA-dataset. METHODS: Chemokine (CXCL-12α, CXCL-12ß, IL-17A, CXCL-8, GM-CSF) and chemokine receptor (CXCR-4, CXCR-7) transcripts were analyzed by RT-qPCR in 76 CRC specimens (normal: 27, tumor: 49; clinical cohort). RNA-Seq data was analyzed from the TCGA-dataset (n= 375). Transcript levels were correlated with outcome; analyses: univariate, multivariable, Kaplan-Meier. RESULTS: In the clinical cohort, chemokine/chemokine receptor levels were elevated 3-10-fold in CRC specimens (P⩽ 0.004) and were higher in patients who developed metastasis (P= 0.03 - < 0.0001). CXCR-4, CXCR-7, CXCL-12α, CXCL-8, IL-17 and GM-CSF levels predicted metastasis (P⩽ 0.0421) and/or overall survival (OS; P⩽ 0.0373). The CXCR-4+CXCR-7+CXCL-12 marker (CXCR-4/7+CXCL-12 (α/b) signature) stratified patients into risk for metastasis (P= 0.0014; OR, 2.72) and OS (P= 0.0442; OR, 2.7); sensitivity: 86.67%, specificity: 97.06%. In the TCGA-dataset, the CXCR-4/7+CXCL-12 signature predicted metastasis (P= 0.011; OR, 2.72) and OS (P= 0.0006; OR: 4.04). In both datasets, the signature was an independent predictor of clinical outcome. CONCLUSIONS: Results of 451 specimens from both cohorts reveal that the CXCR-4/7+CXCL-12 signature potentially predicts outcome in CRC patients and may allow earlier intervention.

Clinical and epidemiological factors associated with suicide in colorectal cancer.

PURPOSE: While increased suicidal tendencies among cancer patients have been well documented, this study aims to examine suicide rates and factors associated with suicide specifically in patients with colorectal cancer (CRC). METHODS: Patients diagnosed with CRC between the years of 1988-2010 were selected from the Surveillance, Epidemiology, and End Result (SEER) database. Comparisons with the general population were done using the National Center for Disease Control registry. RESULTS: One thousand three hundred eighty-one suicides among 884,529 patients were identified, with a standardized mortality ratio (SMR) of 1.53 (95% CI, 1.13-1.33) compared to the general population. No statistically significant difference in suicide rate was found with respect to age, marital status, socio-economic status, surgical intervention, histologic subtype, or stage at diagnosis. Within the CRC population, Whites were significantly more likely to commit suicide than non-Whites (OR, 2.28; 95% CI, 1.89-2.75; P < 0.001), and males were significantly more likely than females (OR, 5.635; 95% CI, 4.85-6.54; P < 0.001). Most suicides occurred in patients with distal lesions in the sigmoid/rectosigmoid junction (P < 0.001). SMRs for CRC patients were 4.24 for females (95% CI, 3.69-4.86), 1.35 for males (95% CI, 1.28-1.43), 0.38 for African-Americans (95% CI, 0.28-0.52), 1.77 for Whites (95% CI, 1.68-1.87), and 0.90 for other races (95% CI, 0.72-1.12). CONCLUSION: Identification of risk factors associated with suicide among patients with CRC is an important step in developing screening strategies and management of psychosocial stressors. These results could be helpful in formulating a comprehensive suicide risk scoring system for screening all cancer patients.

A case report of a patient with gallbladder agenesis resulting in a common bile duct injury.

INTRODUCTION: Congenital agenesis of the gallbladder is a rare embryological defect of the biliary system. While occurring equally in men and women, gallbladder agenesis is found clinically twice as often in women. Patients present with symptoms suggesting biliary colic. Abdominal ultrasound and cholecintigraphy or HIDA scan are usually inconclusive and, in some cases, may be read as positive for biliary colic. Patients can undergo surgery based on characteristics of pain. PRESENTATION OF CASE: We report the case of a 60-year-old female presenting with symptoms of recurrent biliary colic and subsequently undergoing laparoscopic cholecystectomy after inconclusive workup. DISCUSSION: We offer a review of past reported cases as well as a new approach to such patients during the intraoperative period. An intraoperative decision should be made whether to continue and search for a possible ectopic gallbladder or investigate further with imaging studies. CONCLUSION: Gallbladder agenesis is a rare clinical presentation that the surgeon must be aware of. With inconclusive studies, the surgeon should consider congenital absence of the gallbladder and pursue further imaging if the gallbladder cannot be localized during the intraoperative period.

Colorectal Cancer Screening and Prevention.

Colorectal cancer is a common cause of morbidity and mortality in the United States. Most colorectal cancers arise from preexisting adenomatous or serrated polyps. The incidence and mortality of colorectal cancer can be reduced with screening of average-risk adults 50 to 75 years of age. Randomized controlled trials show evidence of reduced colorectal cancer-specific mortality with guaiac-based fecal occult blood tests and flexible sigmoidoscopy. There are no randomized controlled trials on the effectiveness of colonoscopy to reduce colorectal cancer-specific mortality; however, several randomized controlled trials comparing colonoscopy with other strategies are in progress. The best available evidence supporting colonoscopy is from prospective cohort studies that demonstrate decreased incidence of colorectal cancer and colorectal cancer-related mortality in individuals undergoing colonoscopy. Other screening options include fecal immunochemical testing, computed tomographic colonography, and multitargeted stool DNA testing combined with fecal immunochemical testing. There is good evidence that aspirin, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, and hormone therapy decrease the risk of colorectal cancer and adenomatous polyps, but potential harms limit their usefulness. There is good evidence that calcium supplementation, moderate dairy consumption, reduced red meat consumption, increased physical activity, decreased body mass index, and statin use decrease the risk of colorectal cancer and adenomatous polyps. Although increased alcohol intake and tobacco use are associated with an increased risk of colorectal cancer, there is no direct evidence that reducing alcohol consumption or smoking cessation decreases the risk.

Molecular Characterization of Renal Cell Carcinoma: A Potential Three-MicroRNA Prognostic Signature.

Background: Aberrantly expressed miRNAs promote renal cell carcinoma (RCC) growth and metastasis and are potentially useful biomarkers for metastatic disease. However, a consensus clinically significant miRNA signature has not been identified. To identify an miRNA signature for predicting clinical outcome in RCC patients, we used a four-pronged interconnected approach.Methods: Differentially expressed miRNAs were identified and analyzed in 113 specimens (normal kidney: 59; tumor: 54). miRNA profiling was performed in matched normal and tumor specimens from 8 patients and extended to 32 specimens. Seven aberrantly expressed miRNAs were analyzed by qPCR, and their levels were correlated with RCC subtypes and clinical outcome. miRNA signature was confirmed in The Cancer Genome Atlas RCC dataset (n = 241).Results: Discovery phase identified miR-21, miR-142-3p, miR-142-5p, miR-150, and miR-155 as significantly upregulated (2-4-fold) and miR-192 and miR-194 as downregulated (3-60-fold) in RCC; miR-155 distinguished small tumors (<4 cm) from benign oncocytomas. In univariate and multivariate analyses, miRNA combinations (miR-21+194; miR-21+142-5p+194) significantly predicted metastasis and/or disease-specific mortality; miR-21+142-5p+194 (for metastasis): P = 0.0017; OR, 0.53; 95% confidence interval (CI), 0.75-0.33; 86.7% sensitivity; 82% specificity. In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21+142-5p+194: P < 0.0001; OR, 0.37; 95% CI, 0.58-0.23).Conclusions: The interconnected discovery-validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients.Impact: With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients. The three-miRNA signature discovered and validated may potentially at an early stage detect and predict metastasis, to allow early intervention for improving patient prognosis. Cancer Epidemiol Biomarkers Prev; 27(4); 464-72. ©2018 AACR.

Colorectal Cancer Screening and Surveillance in Individuals at Increased Risk.

Individuals at increased risk of developing colorectal cancer include those with a personal or family history of advanced adenomas or colorectal cancer, a personal history of inflammatory bowel disease, or genetic polyposis syndromes. In general, these persons should undergo more frequent or earlier testing than individuals at average risk. Individuals who have a first-degree relative with colorectal cancer or advanced adenoma diagnosed before 60 years of age or two first-degree relatives diagnosed at any age should be advised to start screening colonoscopy at 40 years of age or 10 years younger than the earliest diagnosis in their family, whichever comes first. In individuals with ulcerative colitis or Crohn disease with colonic involvement, colonoscopy should begin eight to 10 years after the onset of symptoms and be repeated every one to three years. Individuals who have a first-degree relative with hereditary nonpolyposis colorectal cancer should begin colonoscopy at 25 years of age and repeat colonoscopy every one to two years. In persons with a family history of adenomatous polyposis syndromes, screening should begin at 10 years of age or in a person's mid-20s, depending on the syndrome; repeat colonoscopy is typically required every one to two years. Screening colonoscopy should begin at eight years of age in individuals with Peutz-Jeghers syndrome. If results are normal, colonoscopy can be repeated at 18 years of age and then every three years. Persons with sessile serrated adenomatous polyposis should begin annual colonoscopy as soon as the diagnosis is established.

Demographic and clinical factors associated with suicide in gastric cancer in the United States.

While increased suicidal tendencies among cancer patients have been well documented, there has been no specific examination of suicide and gastric cancer. The purpose of this study is to characterize suicide incidence among patients diagnosed with gastric cancer from 1973 to 2013 and identify variables associated with higher suicide rates. Patients with gastric cancer were identified in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The study included clinical and demographic data from 1973 to 2013. Standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs) were calculated. Comparisons with the general US population were based on mortality data collected by the Centers for Disease Control and Prevention's National Center for Injury Prevention and Control using the Web-based Injury Statistics Query and Reporting System. Multivariable logistic regression models generated odds ratios (ORs) to assess factors associated with increased suicide in gastric malignancy. There were 210 suicides for patients with gastric cancer (SMR, 3.21; 95% CI: 2.80-3.67). Female gender (SMR 8.54), White race (SMR 4.08), age ≤39 years (SMR 3.06), and age 70-79 years (SMR 2.90), were found to be significant for an increased incidence of suicide compared with the general population. There was not a statistically significant relationship between suicide and marital status, income, mode of radiation therapy, and the role of surgical intervention. Approximately 77% of deaths by suicide occurred within the first year following diagnosis. Female gender, White race, age ≤39 years, and age 70-79 years are factors associated with increased risk of suicide in patients with gastric cancer. These results, coupled with further studies and analyses, will be used to formulate a comprehensive suicide risk factor scoring system for screening all cancer patients.

Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia.

The prevalence of gallstones is 10% to 15% in adults. Individuals with acute cholecystitis present with right upper quadrant pain, fever, and leukocytosis. Management includes supportive care and cholecystectomy. The prevalence of choledocholithiasis is 10% to 20%, and serious complications include cholangitis and gallstone pancreatitis. The goal of management in individuals with choledocholithiasis consists of clearing common bile duct stones. Acute ascending cholangitis is a life-threatening condition involving acute inflammation and infection of the common bile duct. Treatment includes intravenous fluids, analgesia, intravenous antibiotics, and biliary drainage and decompression. Biliary dyskinesia includes motility disorders resulting in biliary colic in the absence of gallstones.

Hyaluronic acid family in bladder cancer: potential prognostic biomarkers and therapeutic targets.

BACKGROUND: Molecular markers of clinical outcome may aid in designing targeted treatments for bladder cancer. However, only a few bladder cancer biomarkers have been examined as therapeutic targets. METHODS: Data from The Cancer Genome Atlas (TCGA) and bladder specimens were evaluated to determine the biomarker potential of the hyaluronic acid (HA) family of molecules - HA synthases, HA receptors and hyaluronidase. The therapeutic efficacy of 4-methylumbelliferone (4MU), a HA synthesis inhibitor, was evaluated in vitro and in xenograft models. RESULTS: In clinical specimens and TCGA data sets, HA synthases and hyaluronidase-1 levels significantly predicted metastasis and poor survival. 4-Methylumbelliferone inhibited proliferation and motility/invasion and induced apoptosis in bladder cancer cells. Oral administration of 4MU both prevented and inhibited tumour growth, without dose-related toxicity. Effects of 4MU were mediated through the inhibition of CD44/RHAMM and phosphatidylinositol 3-kinase/AKT axis, and of epithelial-mesenchymal transition determinants. These were attenuated by HA, suggesting that 4MU targets oncogenic HA signalling. In tumour specimens and the TCGA data set, HA family expression correlated positively with ß-catenin, Twist and Snail expression, but negatively with E-cadherin expression. CONCLUSIONS: This study demonstrates that the HA family can be exploited for developing a biomarker-driven, targeted treatment for bladder cancer, and 4MU, a non-toxic oral HA synthesis inhibitor, is one such candidate.

Thoracic Trauma in the Oldest of the Old: An Analysis of the Nationwide Inpatient Sample.

Thoracic trauma (TT) has the second highest mortality rate in the geriatric population. These injuries cause significant morbidity in elderly patients. Little has been done to describe the demographics and mortality of specific injuries in these patients. ICD-9 codes corresponding with thoracic trauma for patients aged >80 years were extracted from the Nationwide Inpatient Sample database from 2000 to 2010. Characteristics including gender, race, Charlson Comorbidity Index (CCI), length of stay (LOS), and in-hospital mortality (IHM) were analyzed. For females and males, mean CCI was 4.84 and 4.93, respectively (P < 0.0001), and IHM was 5.49 and 2.44 per cent, respectively (P < 0.0001). For white and non-white patients, mean CCI was 4.88 and 4.84, respectively (P < 0.05), and IHM was 3.5 and 3.19 per cent, respectively. This difference was not statistically significant (P = 0.149). Logistic regression revealed correlation coefficient between CCI and mortality was 0.314 (P < 0.0001). Fitting a regression of CCI on LOS adjusting for gender and race, the adjusted effect was 0.146 (P < 0.0001). LOS was significantly less for patients surviving hospitalization. Males had higher CCI and mortality than females. Although whites had a higher CCI than non-whites, there was no difference in IHM between these two groups.

JAK-STAT-mediated chronic inflammation impairs cytotoxic T lymphocyte activation to decrease anti-PD-1 immunotherapy efficacy in pancreatic cancer.

Human pancreatic cancer does not respond to immune check point blockade immunotherapy. One key feature of pancreatic cancer is the association between its progression and chronic inflammation. Emerging evidence supports a key role for the JAK-STAT pathway in pancreatic cancer inflammation. We aimed at testing the hypothesis that sustained JAK-STAT signaling suppresses cytotoxic T lymphocyte (CTL) activation to counteract anti-PD-1 immunotherapy-induced CTL activity in pancreatic cancer. We show that human pancreatic carcinomas express high level of PD-L1 and exhibit low level of CTL infiltration. JAK-STAT inhibitor Ruxolitinib selectively inhibits STAT1 and STAT3 activation and increases CTL infiltration to induce a Tc1/Th1 immune response in the tumor microenvironment in an orthotopic pancreatic cancer mouse model. Ruxilitinib-mediated tumor suppressive efficacy diminishes in T-cell-deficient mice. Pancreatic tumor grows significantly faster in IFNγ-deficient mice. However, neutralizing IFNγ does not alter tumor growth but diminishes Ruxolitinib-induced tumor suppression in vivo, indicating that lymphocytes and IFNγ are essential for Ruxolitinib-induced host antitumor immune response. Both type I and type II interferons upregulate PD-L1 expression through the JAK-STAT signaling pathway in mouse pancreatic tumor cells. Tumor cells respond to activated T cells by activating STAT3. The inhibition of STAT3 downregulates immune suppressive cytokines production by tumor cells, resulting in increased T cell activation and effector function. Consequently, Ruxolitinib significantly improves the efficacy of anti-PD-1 immunotherapy. Our data demonstrate that Ruxolitinib is effective in the inhibition of systemic inflammation in the tumor microenvironment and therefore upregulates CTL infiltration and activation to overcome pancreatic cancer resistance to anti-PD-1 immunotherapy.

Racial disparities in the use of laparoscopic surgery to treat colonic diverticulitis Are not fully explained by socioeconomics or disease complexity.

BACKGROUND: Several studies have demonstrated favorable outcomes for laparoscopic surgery over open surgery for the treatment of diverticular disease. This study was designed to analyze the relationship between race, socioeconomic status and the use of laparoscopy to address diverticulitis. METHODS: A retrospective analysis of 53,054 diverticulitis admissions was performed using data from the 2009-2013 National Inpatient Sample (NIS). The primary outcome was the use of laparoscopic versus open colectomy. Bivariate analysis and multivariable logistic regression were used to determine the raw and adjusted odds by race, insurance status, and median household income. RESULTS: Overall, 41.6% of colectomies involved the use of laparoscopy. Black patients were 19% less likely than White patients to undergo laparoscopic surgery. Hispanic patients were no more or less likely to undergo laparoscopic colectomy. Lacking private insurance was a strong predictor of undergoing open surgery. Lower income patients were 33% less likely to receive minimally invasive colectomies. CONCLUSIONS: These results demonstrate disparities in surgical treatment. Further research is warranted to understand and ameliorate treatment differences which can contribute to outcome disparities.