Survival and cancer recurrence after short-course perioperative probiotics in a randomized trial.

BACKGROUND & AIMS: The long-term impact of perioperative probiotics remains understudied while mounting evidence links microbiome and oncogenesis. Therefore, we analyzed overall survival and cancer recurrence among patients enrolled in a randomized trial of perioperative probiotics. METHODS: 6-year follow-up of surgical patients participating in a randomized trial evaluating short-course perioperative oral probiotic VSL#3 (n = 57) or placebo (n = 63). RESULTS: Study groups did not differ in age, preoperative hemoglobin, ASA status, and Charlson comorbidity index. There was a significant difference in preoperative serum albumin (placebo group 4.0 ± 0.1 vs. 3.7 ± 0.1 g/dL in the probiotic group, p = 0.030). Thirty-seven deaths (30.8 %) have occurred during a median follow-up of 6.2 years. Overall survival stratified on preoperative serum albumin and surgical specialty was similar between groups (p = 0.691). Age (aHR = 1.081, p = 0.001), serum albumin (aHR = 0.162, p = 0.001), and surgical specialty (aHR = 0.304, p < 0.001) were the only predictors of overall survival in the multivariate model, while the placebo/probiotic group (aHR = 0.808, p = 0.726) was not predictive. The progression rate among cancer patients was similar in the probiotic group (30.3 %, 10/33) compared to the placebo group (21.2 %, 7/33; p = 0.398). The progression-free survival was not significantly different (unstratified p = 0.270, stratified p = 0.317). CONCLUSIONS: Perioperative short-course use of VSL#3 probiotics does not influence overall or progression-free survival after complex surgery for visceral malignancy.

The Future of Interventions for Stage IV Colorectal Cancers.

Future options for the management of stage IV colorectal cancer are primarily focused on personalized and directed therapies. Interventions include precision cancer medicine, utilizing nanocarrier platforms for directed chemotherapy, palliative pressurized intraperitoneal aerosol chemotherapy (PIPAC), adjunctive oncolytic virotherapy, and radioembolization techniques. Comprehensive genetic profiling provides specific tumor-directed therapy based on individual genetics. Biomimetic magnetic nanoparticles as chemotherapy delivery systems may reduce systemic side effects of traditional chemotherapy by targeting tumor cells and sparing healthy cells. PIPAC is a newly emerging option for patients with peritoneal metastasis from colorectal cancer and is now being used internationally, showing promising results as a palliative therapy for colorectal cancer. Oncolytic virotherapy is another emerging potential treatment option, especially when combined with standard chemotherapy and/or radiation, as well as immunotherapy. And finally, radioembolization with yttrium-90 ( 90 Y) microspheres has shown some success in treating patients with unresectable liver metastasis from colorectal cancer via selective arterial injection.

Impact of Medicaid Expansion on the Diagnosis, Treatment, and Outcomes of Stage II and III Rectal Cancer Patients.

BACKGROUND: Insurance status has been associated with disparities in stage at cancer diagnosis. We examined how Medicaid expansion (ME) impacted diagnoses, surgical treatment, use of neoadjuvant therapies (NCRT), and outcomes for Stage II and III rectal cancer. STUDY DESIGN: We used 2010-2017 American College of Surgeons National Cancer Database (NCDB) to identify patients ages 18-65, with Medicaid as primary form of payment, and were diagnosed with Stage II or III rectal cancer. Patients were stratified based on Census bureau division's ME adoption rates of High, Medium, Low. Overall trends were examined, and patient characteristics and outcomes were compared before and after ME date of 1/1/2014. RESULTS: Over 8 years of NCDB data examined, there was an increasing trend of Stage II and III rectal cancer diagnoses, surgical resection, and use of NCRT for Medicaid patients. We observed an increase in age, proportion of White Medicaid patients in Low ME divisions, and proportion of fourth income quartile patients in High ME divisions. Univariate analysis showed decreased use of open surgery for all 3 categories after ME, but adjusted odds ratios (aOR) were not significant based on multivariate analysis. NCRT utilization increased after ME for all 3 ME adoption categories and aOR significantly increased for Low and High ME divisions. ME significantly decreased 90-day mortality. CONCLUSIONS: Medicaid expansion had important impacts on increasing Stage II and III rectal cancer diagnoses, use of NCRT, and decreased 90-day mortality for patients with Medicaid. Our study supports increasing health insurance coverage to improve Medicaid patient outcomes in rectal cancer care.

Signet ring cell carcinoma of the gastrointestinal tract: National trends on treatment effects and prognostic outcomes.

BACKGROUND: Signet ring cell carcinoma (SRCC) is a distinct malignancy occurring across the tubular gastrointestinal tract (tGIT). We comprehensively examined the outcomes of patients diagnosed with SRCC across tGIT. METHODS: SRCC and not-otherwise-specified adenocarcinoma (NOS) patients reported to the National Cancer Database from 2004 to 2015 were included. Baseline characteristics, outcomes and site-specific adjusted hazard ratios (aHR) derived from Cox models of SRCC patients were compared to those of NOS patients. Overall survival (OS) was primary endpoint. RESULTS: A total of 41,686 SRCC (4.6%) and 871,373 NOS patients (95.4%) were included. SRCC patients were younger (63.1 ± 14.7 vs. 67.0 ± 13.4 y, p < 0.001) and more likely to present with Stage IV disease than NOS patients (42.5% vs. 24.5%, p < 0.001). Stomach (n = 24,433) and colon (n = 9,914) contributed highest frequency of SRCC. SRCC histology was associated with shorter OS (aHR = 1.377, p < 0.001) in multivariate model. There was an interaction between SRCC and chemotherapy effects on risk of death (interaction aHR = 1.072, pinteraction< 0.001) and between SRCC histology and disease site, suggesting that the effect of SRCC on OS is site-dependent, with a higher increased risk of death in patients with rectal SRCC (aHR = 2.378, pinteraction< 0.001). CONCLUSION: Significant negative prognostic effect associated with SRCC is site-dependent across the GIT. Surgical and or systemic therapy was associated with improved OS among SRCC patients, but remained lower than NOS patients. Further understanding of gastrointestinal SRCC molecular profile is needed to better inform future treatment strategies.

Systematic review and meta-analysis of the efficacy of liposomal bupivacaine in colorectal resections.

Objective: The objective of the study was to systematically investigate the outcomes of Liposomal Bupivacaine following major colorectal resections. Patients and methods: We conducted a comprehensive literature search of PubMed, Medline, Google scholar, Cochrane Central Registry and clinical trials.gov databases through May 2017 for studies published regarding liposomal bupivacaine. Studies were filtered based on relevance to perioperative analgesia in colorectal resections. Data comparing type of study, techniques of resection, mode of administration of liposomal bupivacaine, details of control group, outcomes were collected. Results: A total of 1008 patients from seven studies were included in this systematic review and meta-analysis. The studies were mostly retrospective or prospective cohort studies with one randomized controlled trial (RCT). Meta-analysis showed that liposomal bupivacaine was associated with decreased length of stay, standard mean difference in days (SMD) - 0.34, (95% confidence intervals [CI] - 0.56, -0.13, p = .001) and decreased IV opioid use (expressed as intravenous morphine equivalent in milligrams) in the first 48-72 h, SMD -0.49 (95% CI -0.69, -0.28, p < .00001). Pain scores were also significantly low in patients who received liposomal bupivacaine, SMD -0.56 (95% CI -1.07, -0.06, p = .03]. There was no significant difference in hospitalization costs between the two groups. Conclusions: Use of liposomal bupivacaine is associated with decreased IV opioid use, length of stay and lower pain scores. However, our data needs to be interpreted cautiously given the relative paucity of randomized controlled trials.

Evaluation of Quality of Life and Surgical Outcomes for Treatment of Diverticular Disease.

The prevalence of diverticular disease in the Western and industrialized nations has increased over the last century, and our understanding of this disease and its management continues to evolve. In this article, we review the literature regarding the postoperative quality of life (QOL) and functional outcomes following surgical management of diverticulitis, including information regarding bowel function, recurrence of symptoms, and other postoperative sequelae. While objective parameters, such as attacks of diverticulitis, complications, and clinical episodes have been studied, there is a paucity of data on less objective factors, such as overall patient satisfaction after operative management of diverticular disease. The literature shows improvement in QOL following surgical intervention for diverticulitis if preoperative QOL was significantly low, secondary to severe/complicated diverticulitis. However, a subset of patients does continue to have symptoms following surgical intervention for diverticulitis. Often neglected in the literature, there remains a need for prospective data evaluating preoperative function to ascertain the impact of surgery on patients' QOL and postoperative function.

Evaluation of thrombolysis using tissue plasminogen activator in lower extremity deep venous thrombosis with concomitant femoral-popliteal venous segment involvement.

OBJECTIVE: Current guidelines recommend thrombolytic therapy for iliofemoral deep venous thrombosis (DVT). Anticoagulation is the standard treatment for femoral-popliteal and tibial-level DVT. The objective of this study was to evaluate the efficacy of catheter-directed thrombolysis (CDT) using tissue plasminogen activator vs standard anticoagulation alone in patients with lower extremity DVT involving the femoral-popliteal segment. METHODS: A retrospective review was performed of patients referred to the vascular surgery service with lower extremity DVT from 2006 to 2015. Patients who had DVT involving the femoral-popliteal segment were identified, including some patients who had concomitant involvement of iliofemoral and tibial veins. Patients with pure iliofemoral and tibial vein DVT were excluded from this analysis. Review of medical records, follow-up ultrasound studies, hypercoagulable panel, and venography were performed. Comparison of outcomes between patients who received thrombolytic therapy using tissue plasminogen activator and patients who received standard anticoagulation alone was performed. The primary outcomes measured were restoration of patency of the femoral-popliteal segment at 3 months, incidence of post-thrombotic syndrome (PTS), and valvular dysfunction. Secondary outcomes were incidence of bleeding, in-hospital mortality, and pulmonary embolism. RESULTS: The study cohort was composed of 191 patients (CDT, n = 89; anticoagulation alone, n = 102) who met inclusion criteria. Most patients with thrombus involving the femoral-popliteal segment also had proximal venous segment involvement, with 93% of the patient cohort having proximal iliofemoral DVT. Patients who did not receive CDT were older (mean age of 64 years vs 51 years; P < .001) and had more associated comorbidities, such as diabetes, immobility, and cancer. A significant number of patients who received CDT had a positive family history for DVT (21.3% vs 8.8%; P = .023), and it was more likely to be their first episode of DVT (73.0% vs 55.9%; P = .016). Patients who received CDT were more likely to have restoration of patency (74.7% vs 11.1%; P < .001) and lower incidence of PTS (21.3% vs 73.4%; P < .001) and valvular dysfunction (23.0% vs 66.7%; P < .001) compared with patients who were treated with anticoagulation alone. Incidence of bleeding was significantly more for patients treated with anticoagulation alone (14.7% vs 5.6%; P = .018) compared with patients who received CDT. On multivariate analysis, age was the predominant risk factor for bleeding. There was no significant difference in mortality and pulmonary embolism. CONCLUSIONS: In patients with acute proximal DVT and concomitant femoral-popliteal venous segment involvement, CDT resulted in superior patency at 3 months and less PTS and valvular reflux. This was achieved without increase in bleeding complications compared with anticoagulation alone. Age was the major factor predictive of bleeding in either group. The results of this study may not be applicable to patients with pure femoral-popliteal venous segment DVT because only 3% of patients had this finding.

Evaluation of heparin prophylaxis protocol on deep venous thrombosis and pulmonary embolism in traumatic brain injury.

There is currently no accepted standard for deep venous thrombosis (DVT) and pulmonary embolism (PE) prophylaxis in patients with traumatic brain injury (TBI). The objective of our study was to evaluate the effects of implementing a subcutaneous heparin prophylaxis protocol for patients with TBI that began in our hospital as of June 2009. In our retrospective cohort study, we examined 3812 TBI records between January 2007 and December 2011. A significant reduction in the risk of DVT/PE development was not demonstrated by comparing DVT and PE incidences before and after protocol implementation. A clear trend between heparin use and DVT occurrence could not be determined from a review of TBI records after June 2009. The use of heparin after initiation of our protocol among operative TBI cases without intracranial hemorrhage (ICH) based on admission head computed tomography was 58 per cent. ICH complication from heparin prophylaxis was 10.6 per cent for patients with TBI with ICH on admission (five of 47 cases) compared with 0.7 per cent for those without ICH on admission (four of 535 cases).

Heterogeneity and randomness of DNA methylation patterns in human embryonic stem cells.

DNA methylation has been proposed to be important in many biological processes and is the subject of intense study. Traditional bisulfite genomic sequencing allows detailed high-resolution methylation pattern analysis of each molecule with haplotype information across a few hundred bases at each locus, but lacks the capacity to gather voluminous data. Although recent technological developments are aimed at assessing DNA methylation patterns in a high-throughput manner across the genome, the haplotype information cannot be accurately assembled when the sequencing reads are short or when each hybridization target only includes one or two cytosine-phosphate-guanine (CpG) sites. Whether a distinct and nonrandom DNA methylation pattern is present at a given locus is difficult to discern without the haplotype information, and the DNA methylation patterns are much less apparent because the data are often obtained only as methylation frequencies at each CpG site with some of these methods. It would facilitate the interpretation of data obtained from high-throughput bisulfite sequencing if the loci with nonrandom DNA methylation patterns could be distinguished from those that are randomly methylated. In this study, we carried out traditional genomic bisulfite sequencing using the normal diploid human embryonic stem (hES) cell lines, and utilized Hamming distance analysis to evaluate the existence of a distinct and nonrandom DNA methylation pattern at each locus studied. Our findings suggest that Hamming distance is a simple, quick, and useful tool to identify loci with nonrandom DNA methylation patterns and may be utilized to discern links between biological changes and DNA methylation patterns in the high-throughput bisulfite sequencing data sets.