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.

Prospective Case Series of a Novel Minimally Invasive Bipolar Coagulation System in the Treatment of Grade I and II Internal Hemorrhoids.

Background Existing nonsurgical procedures for the treatment of grade I and II internal hemorrhoids are often painful, technically demanding, and often necessitate multiple applications. This study prospectively assessed the safety and efficacy of the HET Bipolar System, a novel minimally invasive device, in the treatment of symptomatic grade I and II internal hemorrhoids. Methods Patients with symptomatic grade I or II internal hemorrhoids despite medical management underwent hemorrhoidal ligation with the HET Bipolar System. Endpoints included resolution or improvement of hemorrhoidal bleeding and/or prolapse from baseline, recurrent or refractory symptoms, and pain. Results Twenty patients were treated with the HET Bipolar System. Two were lost to follow-up. Refractory or recurrent bleeding was present in 8 of 18 (44.4%), 4 of 11 (36.4%), and 4 of 8 (50.0%) patients, and prolapse was reported by 1 of 18 (5.6%), 4 of 11 (36.4%), and 1/7 (14.3%) of patients at 1, 3, and 6 months, respectively. Bleeding improved from baseline in 88.2%, 81.8%, and 87.5% of patients, and resolution of baseline prolapse was seen in 11 of 11 (100%), 4 of 7 (57.1%), and 5 of 5 (100%) patients at the same intervals. Thirteen of 18 (72.2%) patients did not require additional treatment for their symptoms. Conclusions The HET Bipolar System is safe and easy to use with short-term effectiveness comparable to that of currently used techniques for the treatment of symptomatic grade I and II internal hemorrhoids. It may be an effective alternative to rubber band ligation in patients with larger internal hemorrhoids and those with hemorrhoids close to the dentate line in which banding may produce debilitating pain.

Failing to Prepare Is Preparing to Fail: A Single-Blinded, Randomized Controlled Trial to Determine the Impact of a Preoperative Instructional Video on the Ability of Residents to Perform Laparoscopic Right Colectomy.

BACKGROUND: Laparoscopic colorectal resection is an index case for advanced skills training, yet many residents struggle to reach proficiency by graduation. Current methods to reduce the learning curve for residents remain expensive, time consuming, and poorly validated. OBJECTIVE: The purpose of this study was to assess the impact of the addition of a preprocedural instructional video to improve the ability of a general surgery resident to perform laparoscopic right colectomy when compared with standard preparation. DESIGN: This was a single-blinded, randomized control study. SETTINGS: Four university-affiliated teaching hospitals were included in the study. PARTICIPANTS: General surgery residents in postgraduation years 2 through 5 participated. INTERVENTION: Residents were randomly assigned to preparation with a narrated instructional video versus standard preparation. MAIN OUTCOME MEASURES: Resident performance, scored by a previously validated global assessment scale, was measured. RESULTS: Fifty-four residents were included. Half (n = 27) were randomly assigned to view the training video and half (n = 27) to standard preparation. There were no differences between groups in terms of training level or previous operative experience or in patient demographics (all p > 0.05). Groups were similar in the percentage of the case completed by residents (p = 0.39) and operative time (p = 0.74). Residents in the video group scored significantly higher in total score (mean: 46.8 vs 42.3; p = 0.002), as well as subsections directly measuring laparoscopic skill (vascular control mean: 11.3 vs 9.7, p < 0.001; mobilization mean: 7.6 vs. 7.0, p = 0.03) and overall performance score (mean: 4.0 vs 3.1; p < 0.001). Statistical significance persisted across training levels. LIMITATIONS: There is potential for Hawthorne effect, and the study is underpowered at the individual postgraduate year level. CONCLUSIONS: The simple addition of a brief, narrated preprocedural video to general surgery resident case preparation significantly increased trainee ability to successfully perform a laparoscopic right colectomy. In an era of shortened hours and less exposure to cases, incorporating a brief but effective instructional video before surgery may improve the learning curve of trainees and ultimately improve safety.

High-resolution anoscopy or expectant management for anal intraepithelial neoplasia for the prevention of anal cancer: is there really a difference?

BACKGROUND: High-resolution anoscopy has been shown to improve identification of anal intraepithelial neoplasia but a reduction in progression to anal squamous-cell cancer has not been substantiated when serial high-resolution anoscopy is compared with traditional expectant management. OBJECTIVE: The aim of this study was to compare high-resolution anoscopy versus expectant management for the surveillance of anal intraepithelial neoplasia and the prevention of anal cancer. DESIGN: This is a retrospective review of all patients who presented with anal squamous dysplasia, positive anal Pap smears, or anal squamous-cell cancer from 2007 to 2013. SETTING: This study was performed in the colorectal department of a university-affiliated, tertiary care hospital. PATIENTS: Included patients had biopsy-proven anal intraepithelial neoplasia from 2007 to 2013. INTERVENTIONS: Patients were treated with high-resolution anoscopy with ablation or standard anoscopy with ablation. Both groups were treated with imiquimod and followed every 6 months indefinitely. MAIN OUTCOME MEASURES: The incidence of anal squamous-cell cancer in each group was the primary end point. RESULTS: From 2007 to 2013, 424 patients with anal squamous dysplasia were seen in the clinic (high-resolution anoscopy, 220; expectant management, 204). Three patients (high-resolution anoscopy, 1; expectant management, 2) progressed to anal squamous-cell cancer; 2 were noncompliant with follow-up and with HIV treatment, and the third was allergic to imiquimod and refused to take topical 5-fluorouracil. The 5-year progression rate was 6.0% (95% CI, 1.5-24.6) for expectant management and 4.5% (95% CI, 0.7-30.8) for high-resolution anoscopy (p = 0.37). LIMITATIONS: This was a retrospective review. There is potential for selection and referral bias. Because of the rarity of the outcome, the study may be underpowered. CONCLUSIONS: Patients with squamous-cell dysplasia followed with expectant management or high-resolution anoscopy rarely develop squamous-cell cancer if they are compliant with the protocol. The cost, morbidity, and value of high-resolution anoscopy should be further evaluated in lieu of these findings.

Preoperative classification of pancreatic cystic neoplasms: the clinical significance of diagnostic inaccuracy.

BACKGROUND: The potential for malignant transformation varies among pancreatic cystic neoplasms (PCN) subtypes. Imaging and cyst fluid analysis are used to identify premalignant or malignant cases that should undergo operative resection, but the accuracy of operative decision-making process is unclear. The objective of this study was to characterize misdiagnoses of PCN and determine how often operations are undertaken for benign, non-premalignant disease. METHODS: A retrospective analysis of patients undergoing pancreatic resection for the preoperative diagnosis of PCN was undertaken. Preoperative and pathological diagnoses were compared to measure diagnostic accuracy. RESULTS: Between 1999 and 2011, 74 patients underwent pancreatic resection for the preoperative diagnosis of PCN. Preoperative classification of mucinous vs. non-mucinous PCN was correct in 74%. The specific preoperative PCN diagnosis was correct in 47%, but half of incorrect preoperative diagnoses were clinically equivalent to the pathological diagnoses. The likelihood that the pathological diagnosis was of higher malignant potential than the preoperative diagnosis was 7%. In 20% of cases, the preoperative diagnosis was premalignant or malignant, but the pathological diagnosis was benign. Diagnostic accuracy and the rate of undercall diagnoses and overcall operations did not change with the use of EUS or during the time period of this analysis. CONCLUSIONS: Precise, preoperative classification of PCN is frequently incorrect but results in appropriate clinical decision-making in three-quarters of cases. However, one in five pancreatic resections performed for PCN was for benign disease with no malignant potential. An appreciation for the rate of diagnostic inaccuracies should inform our operative management of PCN.

Memory T cells are uniquely resistant to melanoma-induced suppression.

We have previously observed that in vivo exposure to growing melanoma tumors fundamentally alters activated T cell homeostasis by suppressing the ability of naïve T cells to undergo antigen-driven proliferative expansion. We hypothesized that exposure of T cells in later stages of differentiation to melanoma would have similar suppressive consequences. C57BL/6 mice were inoculated with media or syngeneic B16F10 melanoma tumors 8 or 60 days after infection with lymphocytic choriomeningitis virus (LCMV), and splenic populations of LCMV-specific T cells were quantified using flow cytometry 18 days after tumor inoculation. Inoculation with melanoma on post-infection day 8 potentiated the contraction of previously activated T cells. This enhanced contraction was associated with increased apoptotic susceptibility among T cells from tumor-bearing mice. In contrast, inoculation with melanoma on post-infection day 60 did not affect the ability of previously established memory T cells to maintain themselves in stable numbers. In addition, the ability of previously established memory T cells to respond to LCMV challenge was unaffected by melanoma. Following adoptive transfer into melanoma-bearing mice, tumor-specific memory T cells were significantly more effective at controlling melanoma growth than equivalent numbers of tumor-specific effector T cells. These observations suggest that memory T cells are uniquely resistant to suppressive influences exerted by melanoma on activated T cell homeostasis; these findings may have implications for T cell-based cancer immunotherapy.

Melanoma-induced suppression of tumor antigen-specific T cell expansion is comparable to suppression of global T cell expansion.

We have observed that in vivo interaction between melanoma and resting T cells promotes suppression of antigen-driven proliferative T cell expansion. We hypothesized that this suppression would affect tumor antigen-specific T cell populations more potently than tumor-unrelated T cell populations. A B16F10 cell line was stably transfected to express low levels of the lymphocytic choriomeningitis virus (LCMV) glycoprotein GP33 (B16GP33). Mice bearing B16F10 or B16GP33 tumors were infected with LCMV, and proliferative expansion of LCMV epitope-specific T cell populations was quantified. In vitro and in vivo assays confirmed low levels of antigenic GP33 expression by B16GP33 tumors. Suppressed expansion of GP33-specific T cells was equivalent between mice bearing B16F10 and B16GP33 tumors. These observations suggest that the ability of growing melanoma tumors to impair antigen-driven proliferative expansion of activated T cells is global and not antigen-specific, and provide further insight into the influence of cancer on activated T cell homeostasis.

Suppression of T-cell expansion by melanoma is exerted on resting cells.

BACKGROUND: Immunotherapeutic cancer protocols often rely on the ability to promote proliferative expansion of tumor-specific T-cell, but the influence of cancer on in vivo T-cell expansion remains largely undefined. METHODS: The ability of control and B16F10 melanoma-bearing C57BL/6 mice to expand lymphocytic choriomeningitis virus antigen-specific T-cell populations in response to acute viral infection was compared by using flow cytometric assays of splenocytes. RESULTS: The ability to expand virus-specific CD8+ and CD4+ T-cells was globally and markedly suppressed in tumor-bearing mice. Expanded cytotoxic T lymphocytes (CTLs) retained in vivo and in vitro functionality, suggesting that melanoma growth did not induce T-cell anergy. The magnitude of suppressed proliferative expansion was proportional to the extent of tumor burden. Melanoma-induced suppression of CTL expansion was correlated with upregulated apoptotic activity and hampered the induction of memory precursor effector cells. Adoptive transfer of resting LCMV antigen-specific T-cells before or after tumor establishment demonstrated that a critical period of in vivo exposure of resting T-cells to growing melanoma was responsible for the induction of suppressed expansion. This suppression was durable; surgical resection of melanoma after in vivo exposure to resting T-cells but before antigenic stimulation did not restore full expansion. CONCLUSIONS: These data suggest that growing melanoma tumors exert a global, antigen-independent influence on resting T-cells that fundamentally reprograms their ability to undergo proliferative expansion in response to subsequent antigenic stimulation. This finding may have direct implications for T-cell-based immunotherapeutic strategies.

Functional implications of long-term pain following outpatient inguinal herniorrhaphy--a prospective evaluation.

BACKGROUND: The purpose of the present study is to assess pain and functional outcomes at 1 y following inguinal herniorrhaphy in which patients were randomized to receive a continuous wound infusion of bupivacaine to receiving a saline infusion. METHODS: Patients received saline or bupivacaine prior to incision and then for 60 h postoperatively. The incidence, severity, and functional interference of pain were assessed for five postoperative days, and at 1 y. RESULTS: Seventy patients completed a survey 1 y following herniorrhaphy. Four percent (3/72) of patients were in moderate to severe pain "almost always" or "often". Twenty-one percent (15/72) of patients experienced pain with ambulation. There was no difference between groups at 1 y. CONCLUSIONS: The incidence of moderate or severe pain is concerning 1 y following surgery. Functional aberrations associated with pain should be assessed in all studies evaluating long-term pain after herniorrhaphy.

Laparoscopy improves short-term outcomes after surgery for diverticular disease.

BACKGROUND & AIMS: Observational studies and small randomized controlled trials have shown that the use of laparoscopy in colon resection for diverticular disease is feasible and results in fewer complications. We analyzed data from a large, prospectively maintained, multicenter database (National Surgical Quality Initiative Program) to determine whether the use of laparoscopy in the elective treatment of diverticular disease decreases rates of complications compared with open surgery, independent of preoperative comorbid factors. METHODS: The analysis included data from 6970 patients who underwent elective surgeries for diverticular disease from 2005 to 2008. Patients with diverticular disease were identified by International Classification of Diseases, 9th revision codes and then categorized into open or laparoscopic groups based on Current Procedural Terminology codes. Preoperative, intraoperative, and postoperative data were analyzed to determine factors associated with increased risk for postoperative complications. RESULTS: Data were analyzed from 3468 patients who underwent open surgery and 3502 patients who underwent laparoscopic procedures. After correcting for probability of morbidity, American Society of Anesthesiology class, and ostomy creation, overall complications (including superficial surgical site infections, deep incisional surgical site infections, sepsis, and septic shock) occurred with significantly lower incidence among patients who underwent laparoscopic procedures compared with those who received open operations. CONCLUSIONS: The use of laparoscopy for treating diverticular disease, in the absence of absolute contraindications, results in fewer postoperative complications compared with open surgery.

Impact of selection bias on the utilization of adjuvant therapy for pancreas adenocarcinoma.

BACKGROUND: Improved outcomes have been associated with the use of adjuvant therapy after resection of pancreas adenocarcinoma. However, the frequency with which patients receive adjuvant therapy and the factors impacting its use remain largely undefined. We hypothesized that nonutilization of adjuvant therapy was primarily associated with patient comorbidity and onset of postoperative complications. METHODS: A prospectively maintained database was reviewed to identify patients who underwent potentially curative resection of histologically confirmed pancreas adenocarcinoma at our institution from January 1996 to May 2007. Clinicopathological data and postoperative treatment history were collected to identify variables associated with receipt of adjuvant therapy. RESULTS: Of 119 patients, 33% did not receive adjuvant therapy. The frequency with which patients underwent adjuvant therapy did not change over time. On multivariate analysis, patient age 70 years or greater, major postoperative complications, distal pancreatectomy, absence of nodal metastases, and absence of perineural invasion were associated with decreased utilization of adjuvant therapy. DISCUSSION: One-third of patients in this contemporary dataset of patients did not go on to receive adjuvant therapy. The likelihood of receiving adjuvant treatment is negatively impacted by the course of postoperative recovery. Moreover, the fact that adjuvant therapy was undertaken less often for older patients and patients with favorable pathological features highlights the selection bias impacting the decision to pursue postoperative therapy for this disease. This selective utilization of postoperative therapy for patients with adverse oncological characteristics is likely to bias any retrospective analysis attempting to measure the efficacy of adjuvant treatment for pancreas adenocarcinoma.

Role of platelet-rich plasma in acceleration of bone fracture healing.

Platelet-rich plasma (PRP) is a common therapy for acceleration of maxillofacial and spinal fusion bone-graft healing. This study analyzes the therapeutic role of PRP during long-bone fracture healing evaluated Lewis rats. Following creation of unilateral open femur fractures, either 500 microL thrombin-activated PRP (PRP treated group) or 500 microL saline (control group) were applied once to the fracture site. Fracture healing was analyzed after 1 and 4 weeks. Following 4 weeks of fracture healing, radiographic analysis demonstrated higher callus to cortex width ratio (P < 0.05) in the PRP group (PRP: 1.65 +/- 0.06; control: 1.48 +/- 0.05). Three-point load bearing showed increased bone strength following PRP treatment (PRP: 60.85 +/- 6.06 Newton, control: 47.66 +/- 5.49 Newton). Fracture histology showed enhanced bone formation in the PRP group. Immunohistochemistry and Western-blotting demonstrated healing-associated changes in transforming growth factor (TGF)-beta1 and bone morphogenetic protein (BMP)-2. Our results suggest that PRP accelerates bone fracture healing of rat femurs via modulation of TGF-beta1 and BMP-2 growth factor expression.