Further Distance From Treating Facility is Associated With Advanced Colon Cancer at Presentation and Increased Mortality.

BACKGROUND: Colon cancer outcomes in the United States have improved over the last thirty years. However, there remain significant outcome disparities, especially in rural regions. It is unclear if distance to the treating facility has an independent effect on colon cancer mortality and outcomes. We sought to evaluate whether distance from a treating facility impacts stage at diagnosis and mortality. METHODS: The National Cancer Database (NCDB) was utilized to identify a cohort of adult patients with colon cancer between the years 2013 and 2017 in all regions of the United States. Outcomes measured included colon cancer TNM stage, time to surgery, time to chemotherapy, and overall survival. RESULTS: A total of n = 356,189 patients met inclusion criteria. When controlling for race, education status, insurance status, comorbidities, and income, distance from the treating facility was a significant predictor of stage at presentation with more advanced clinical TNM stage as distance increased (AORs 1.12-1.62, P < .001 for all groups). Longer distance significantly increased the time to surgery (between 5.06 and 14.46 days, P < .001) and overall mortality (HR 1.11-1.28, P < .001). Median survival was 82.4 months for the closest group, versus 75.1 months for the farthest group (P < .001). CONCLUSIONS: Increased distance from the treating facility resulted in a significantly higher stage at presentation, increased time to surgery, and increased mortality. These results suggest that there are significant disparities in access to cancer care for patients who live in rural areas. Targeted interventions by treating facilities are needed to improve screening and timely treatment for rural colon cancer patients.

Effect of Enhanced Recovery After Surgery Protocol Implementation on Cost and Outcomes by Type of Colectomy Performed.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are widely utilized for elective colorectal surgery to improve outcomes and decrease costs, but few studies have evaluated the impact of ERAS protocols on cost with respect to anatomic site of resection. This study evaluated the impact of ERAS protocol on elective colon resections by site and longitudinal impact over time. METHODS: A single-center retrospective cohort study of 598 consecutive patients undergoing elective colorectal resection before and after implementation of ERAS protocol from 2013 to 2017 was performed. The primary outcomes were length of stay (LOS) and cost. Comparative and multivariate inferential statistics were used to assess additional outcomes. RESULTS: A total of 598 patients (100 pre-ERAS vs 498 post-ERAS) were evaluated with an overall median LOS of 4 days for right and left colectomies and 3 days for transverse colectomies. When comparing type of resection before and after ERAS protocol introduction, an increased LOS for left hemicolectomies from 3.09 to 4.03 days (P = .047) was noted, with all other comparisons failing to reach statistical significance. Over time, an initial decrease in LOS for MIS approach after protocol introduction was observed; however, this effect diminished in the ensuing years and had no significant effect overall. Total cost of care was significantly increased post-ERAS for all cohorts except transverse colectomies. No further statistically significant differences were found. CONCLUSION: After an initial improvement in outcomes, continued utilization of ERAS protocols demonstrated no improvement in LOS compared to pre-ERAS data and increased cost overall for patients regardless of site of resection.

Laparoscopic transanal minimally invasive surgery (L-TAMIS) versus robotic TAMIS (R-TAMIS): short-term outcomes and costs of a comparative study.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) has gained worldwide popularity as a method for the local excision of rectal neoplasms. However, it is technically demanding due to limited working space. Robotic TAMIS offers potential enhanced dexterity and ability while allowing for a more aggressive resection with a stable platform. The objective of this study was to review a single institution experience between laparoscopic (L-TAMIS) and robotic TAMIS (R-TAMIS) for treatment of rectal neoplasms and determine if there are significant differences on outcomes. METHODS: Forty consecutive patients with rectal neoplasms underwent L-TAMIS or R-TAMIS by two colorectal surgeons from January 2012 to April 2017. We retrospectively reviewed a prospectively maintained database to analyze demographics, peri-operative data, pathology, post-operative complications, and cost. RESULTS: There were no significant differences between L- and R-TAMIS on patient demographics. R-TAMIS showed a statically significant increase in cost of surgery by $880. Median direct cost of L-TAMIS was $3562 compared to $4440.92 for R-TAMIS (p = 0.04). Wider range of total duration for L-TAMIS is likely due to the variability of body habitus and location of rectal neoplasm, which can significantly limit L-TAMIS compare to R-TAMIS. There was a trend toward decreased blood loss in the R-TAMIS group. Mortality was 0% in both groups. CONCLUSIONS: After reviewing our experience, we conclude there is no significant difference between L- and R-TAMIS other than total direct cost. We confirmed that both L- and R-TAMIS are safe and associated with low morbidity. The limitations of this study include its small sample size. In the future, we hope to show promising data on R-TAMIS with increased sample size and experience, which may allow for transanal resection not previously feasible. Studies with long-term follow-up assessing oncological and functional results will be mandatory.

Gut Microbiota and Colorectal Surgery: Impact on Postoperative Complications.

Colorectal anastomotic leakage is a dreaded complication after colorectal surgery and causes high morbidity and mortality. The pathophysiology of anastomotic healing remains unclear despite numerous studies. In this article, our aim is to provide different perspectives on what is known about the role of the gastrointestinal tract microbiome and its relation to anastomotic integrity.

Improved perioperative and short-term outcomes of robotic versus conventional laparoscopic colorectal operations.

BACKGROUND: Robotic assistance may offer unique advantages over conventional laparoscopy in colorectal operations. METHODS: This prospective observational study compared operative measures and postoperative outcomes between laparoscopic and robotic abdominal and pelvic resections for benign and malignant disease. RESULTS: From 2005 through 2012, 200 (58%) laparoscopic and 144 (42%) robotic operations were performed by a single surgeon. After adjustment for differences in demographics and disease processes using propensity score matching, all laparoscopic operations had a significantly shorter operative time (P < .01), laparoscopic left colectomies had a longer length of hospital stay (2009 and 2010: 6.5 vs 3.6 days, P = .01); and laparoscopic right colectomies had a higher risk for overall complications (P = .03) and postoperative ileus (P = .04). There were no significant differences in the outcomes of pelvic operations (P = .15). CONCLUSIONS: Compared with conventional laparoscopy, some types of robotic-assisted colorectal operations may offer advantages regarding postoperative length of stay and perioperative complications.

Synovial sarcoma: clinicopathologic features, treatment, and prognosis.

Synovial sarcoma is a characteristic subtype of soft tissue sarcomas with a predilection for young people. There may be a long delay in diagnosis or misdiagnosis, because of its insidious growth, varied presentation on imaging studies and associated joint pain, which can be confused with trauma. Diagnosis requires a tissue sample in the form of a needle or open biopsy. The needle biopsy may not be representative of the tumor, particular if it is biphasic, and it may be necessary to proceed to open biopsy. Ideally, the biopsy should be performed by the surgeon who will be performing the definitive surgical resection. Although treatment is predicated on surgery, adjuvant radiation and/or chemotherapy may be beneficial, particularly in high risk patients. Significant prognostic factors include: size > 5 cm, deep-seated location, adequacy of surgical margins, and history of recurrence. In the future, multi-institutional prospectively randomized, controlled studies will be needed to better define the role of adjuvant chemotherapy. Currently, outcome may be optimized by early suspicion and detection with referral to an orthopedic oncology specialist prior to the biopsy.

Chondroblastoma with associated aneurysmal bone cyst of the cuboid.

The authors describe a young adult patient with a chondroblastoma and associated aneurysmal bone cyst of the cuboid. Although chondroblastoma has been reported to occur in tarsal bones, the cuboid is a very rare location. The association of chondroblastoma with an aneurysmal bone cyst in long bones has been well documented. However, this association in the cuboid has not been reported in the English literature. A 20-year-old man with a 4-month history of foot pain localized to the lateral border of the foot and ankle presented with an expansile lesion in the cuboid bone with a nondisplaced pathologic fracture. A computed tomography scan showed an expansile lesion with discontinuity of the cortex, and magnetic resonance imaging showed marrow replacement within the cuboid with surrounding periosteal edema. An open biopsy was performed, followed by curettage and cementation of the lesion. The histology showed a chondroblastoma with an associated aneurysmal bone cyst of the cuboid.

Induction of endogenous telomerase (hTERT) by c-Myc in WI-38 fibroblasts transformed with specific genetic elements.

Elucidation of the mechanisms governing expression of the human telomerase reverse transcriptase (hTERT) is important for understanding cancer pathogenesis. Approximately 90% of tumors express hTERT, the major catalytic component of telomerase. Activation of telomerase is an early event, and high levels of this activity correlate with poor prognosis. Recent studies have shown that the transcription factors c-Myc and Mad1 activate and repress hTERT, respectively. It is not clear how these transcription factors compete for the same recognition sequence in the hTERT core promoter region. Studies have shown that the combined expression of SV40 large T antigen (T-Ag), hTERT, and H-Ras is able to transform human cells. In this study, we used a distinct human cell type, WI-38 fetal lung fibroblasts used extensively for senescence studies. We transduced cells with amphotropic retroviral constructs containing SV40 T antigen, hTERT, and activated H-ras. Transduced cells exhibited anchorage independence in soft agar and expressed increased levels of c-Myc and endogenous hTERT. These effects were observed by 25 population doublings (PDs) following the establishment of the neoplastic cell line. During the process of transformation, we observed a switch from Mad1/Max to c-Myc/Max binding to oligonucleotide sequences containing the hTERT promoter distal and proximal E-boxes. c-Myc can bind specifically to the hTERT promoter in vitro, indicating that c-Myc expression in tumors may account for the increased expression of hTERT observed in vivo. These findings indicate that the widely used model system of WI-38 fibroblasts can be employed for transformation studies using defined genetic elements and that the endogenous hTERT and c-Myc are induced in these cells during early tumorigenesis. Such studies should have important implications in the mechanisms of hTERT and c-Myc induction in the beginning stages of tumorigenesis and facilitate extension of these studies to novel models of tumorigenesis in cellular senescence.

Transcriptional control of the DNA methyltransferases is altered in aging and neoplastically-transformed human fibroblasts.

Although it has been known for quite some time that genomic methylation is significantly altered in aging and neoplastic tissues and cells, the underlying mechanisms responsible for these alterations are not yet known. Since DNA methylation affects many different cellular processes including, most significantly, gene expression, elucidation of the basis for aberrations in DNA methylation in aging and cancer is of high priority. To address this problem, we sought to analyze changes in gene expression, protein production and enzyme activity of the three major DNA methyltransferases (Dnmtl, 3a, and 3b) in aging and neoplastically-transformed WI-38 human fetal lung fibroblasts. We have found that the gene expression of each of the three Dnmts parallels changes in protein production and enzyme activity of the Dnmts not only in aging cells, but also in WI-38 fibroblasts induced to undergo neoplastic transformation using defined genetic elements. These findings strongly implicate change in gene expression as an underlying mechanism in the altered genomic methylation of these cells. Striking changes in the gene expression of the Dnmts were observed in aging cells with the mRNA of Dnmtl becoming reduced while the mRNA of Dnmt3b increased steadily in aging cells consistent with our observations in protein production and activity of these enzymes. Surprisingly, Dnmt3a actually decreased in gene expression in aging cells. We therefore propose that the transcriptional control of Dnmt1, the predominant maintenance methyltransferase, is significantly suppressed in aging cells and contributes to the reduced genomic methylation of these cells. The paradoxical sporadic gene hypermethylation in aging cells appears to be related to transcriptional up-regulation of the Dnmt3b gene. In addition, we sought to explore the coordinated changes in gene expression, protein production, and enzyme activity of these Dnmts in early cellular transformation. In these cells, the gene expression of all the three major Dnmts were up-regulated followed by marked increases in Dnmt protein and enzyme activity. These results therefore collectively indicate that changes in transcriptional control of the Dnmts are the likely cause for the known alterations in DNA methylation in aging cells and in cells undergoing tumorigenesis. They also show that changes in transcription of Dnmtl and Dnmt3b are probably most important in affecting the generalized hypomethylation and specific hypermethylation seen in aging cells while gene expression of all the Dnmts is significantly increased in cancer cells. These findings should have broad implications in elucidating the underlying causes of changes in DNA methylation in aging and tumorigenesis and point to variations in gene expression of the individual Dnmts as a likely mechanism involved in these processes.