Faculty Bibliography

Background/UNASSIGNED:There is recent interest in treating locally advanced rectal cancer (LARC) patients with total neoadjuvant therapy (TNT). However, whether TNT is associated with improved overall survival (OS) remains unknown. This study compares outcomes following TNT and following neoadjuvant chemoradiation therapy (nCRT) in patients with LARC, clinically defined cT3/4 or node positive disease, using the National Cancer Database. Methods/UNASSIGNED:LARC patients diagnosed between 2004-2015 were included. TNT was defined as multi-agent chemotherapy given at least 2 months before RT followed by pre-operative chemoradiation therapy and definitive surgery without adjuvant chemotherapy. nCRT was defined as pre-operative RT and chemotherapy started within 2 weeks from each other followed by definitive surgery with or without adjuvant chemotherapy. Kaplan-Meier curve with logrank test and multivariable Cox proportional hazards regression modelling were used to analyse the primary endpoint of overall survival (OS). Multivariable logistic regression modelling was used for secondary outcomes to determine if TNT is associated with pathological complete response (pCR), defined as ypT0N0, and negative circumferential resection margin (CRM). Findings/UNASSIGNED: = 0•19) in multivariable logistic regression modelling. Interpretation/UNASSIGNED:With results from current clinical trials pending, our data suggested that TNT and nCRT resulted in similar survival, while TNT led to higher pCR and CRM negative rate, albeit not statistically significant.

Purpose: To determine if anal cancer patients with HPV positive disease have different overall survival (OS) compared to those with HPV negative disease, and to elucidate differences in the association between radiation dose and OS. Patients and methods: We utilized the National Cancer Database (NCDB) registry to identify a cohort of non-metastatic anal cancer patients treated with curative intent between 2008 and 2014. Propensity score matching was used to account for potential selection bias between patients with HPV positive and negative disease. Multivariable Cox regression was used to determine the association between HPV status and OS. Kaplan-Meier methods were used to compare actuarial survival estimates. Results: We identified 5927 patients with tumor HPV status for this analysis, 3523 (59.4%) had HPV positive disease and 2404 (40.6%) had HPV negative disease. Propensity-matched analysis demonstrated that patients with HPV positive locally advanced (T3-4 or node positive) anal cancer had better OS (HR = 0.81 (95%CI: 0.68-0.96), p=.018). For patients with early stage disease (T1-2 and node negative) there was no difference in OS (HR = 1.11 (95%CI: 0.86-1.43), p=.43). In the unmatched cohort, we found a significant improvement in OS with increasing radiation dose only for patients with locally advanced, HPV negative disease (p<.001). In those patients, significant improvement in OS compared to the group receiving 30-45 Gy was seen for increasing doses up to 55-60 Gy, but not beyond 60 Gy. Conclusion: We found HPV to be a significant prognostic marker in anal tumors, especially for locally advanced disease. We further found that higher radiation dose up to 55-60 Gy was associated with better OS, but only for patients with locally advanced, HPV negative disease.

BACKGROUND:Rectovaginal fistula in Crohn's disease is challenging for both healthcare providers and patients. The impact of immunomodulation therapy on healing after surgery is unclear. OBJECTIVE:The purpose of this study was to examine whether immunomodulation therapy impacts healing after surgery for rectovaginal fistula in Crohn's disease. DESIGN/METHODS:This was a retrospective analysis with a follow-up telephone survey. SETTINGS/METHODS:The study was conducted at two major tertiary referral centers. PATIENTS/METHODS:All of the patients who underwent rectovaginal fistula repair from 1997 to 2013 at our centers were included. MAIN OUTCOME MEASURES/METHODS:A χ test and logistical regression analysis were used to study treatment outcomes according to type of procedure, recent use of immunosuppressives, and number of previous attempted repairs. Age, BMI, smoking, comorbidities, previous vaginal delivery/obstetric injury, use of probiotics, diverting stoma, and use of seton were also analyzed. RESULTS:A total of 120 (62%) patients were contacted, and 99 (51%) of them agreed to participate in the study. Mean follow-up after surgical repair was 39 months. Procedures included advancement flap (n = 59), transvaginal repair (n = 14), muscle interposition (n = 14), episioproctotomy (n = 6), sphincteroplasty (n = 3), and other (n = 3); overall, 63% of patients experienced healing. Sixty-eight patients underwent recent immunomodulation therapy but did not exhibit statistical significance in outcome after surgical repair. In the subset of patients with fistula related to obstetric injury, a 74% (n = 26) healing rate after surgical repair was observed. Age, BMI, diabetes mellitus, use of steroids, probiotics, seton before repair, fecal diversion, and number of repairs did not affect healing. LIMITATIONS/CONCLUSIONS:This was a retrospective analysis; the high volume tertiary referral inflammatory bowel disease centers studied may not be reflective of rectovaginal fistula presentation, treatment, or results in all patients, and the 3-year follow-up may not be sufficiently long. CONCLUSIONS:Despite a relatively low success rate (63%) in healing after surgical repair of a rectovaginal fistula, the recent use of immunomodulation therapy did not negatively impact healing. However, tissue interposition techniques had the highest success rates.

IMPORTANCE/OBJECTIVE:The management of care for rectal cancer has undergone many changes and improvements in recent decades. A multidisciplinary approach to this complex disease is essential to ensure high-quality treatment and outcomes. OBJECTIVE:To present a current, evidence-based approach to the multidisciplinary team management of rectal cancer with a review of the diagnosis, staging, and treatment of the disease by radiologists, oncologists, surgeons, and pathologists. EVIDENCE REVIEW/METHODS:The literature review was conducted through online searches of MEDLINE and PubMed. Articles published between January 1, 2000, and June 2014 and pertaining to staging modalities, surgical approaches, pathologic assessment, and medical treatments of rectal cancer were considered. All studies were reviewed, with preferential inclusion of larger or randomized trials. The review focused on changing paradigms and current controversies in rectal cancer management. FINDINGS/RESULTS:A multidisciplinary approach to the patient with rectal cancer includes many health care professionals. Although treatments continue to evolve and improve, clear evidence-based principles have been well studied. The important roles of various specialists must be acknowledged and utilized. Within each role, new and emerging treatment approaches require critical review by experts in their fields. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Many new technologies and treatment options will continue to advance the treatment of rectal cancer, further emphasizing the need for a multidisciplinary approach to achieve optimal care.

The knowledge of the vascular anatomy of the concerned region is an important prerequisite for planning surgical intervention. The awareness of the existing vascular anomalies enhances the insight regarding that region. We report a patient undergoing preoperative evaluation with CTA finding of Superior Mesenteric Artery (SMA) originating from the celiac artery. This celiac-mesenteric trunk is rare (<1%).

Actinomyces species has been described as an opportunistic pathogen, particularly in the oral cavity; however, in rare cases these bacteria can cause actinomycosis which is characterized by formation of abscesses in the mouth, lungs, or gastrointestinal tract. Actinomycosis was commonly present in the pre-antibiotic era; however, it has a low prevalence now days. It has been recognized since 150 years ago, but because of its variable clinical presentation and indolent course, its recognition is difficult and patients are often misdiagnosed. Here we present a case of primary hepatic actinomycosis presenting as a metastatic liver tumor.

Therapeutic cancer vaccines rely on the immune system to eliminate tumor cells. In contrast to chemotherapy or passive (adoptive) immunotherapies with antibodies or ex vivo-expanded T cells, therapeutic vaccines do not have a direct anti-tumor activity, but aim to reset patients' immune systems to achieve this goal. Recent identification of effective ways of enhancing immunogenicity of tumor-associated antigens, including the use of dendritic cells and other potent vectors of cancer vaccines, provide effective tools to induce high numbers of circulating tumor-specific T cells. However, despite indications that some of the new cancer vaccines may be able to delay tumor recurrence or prolong the survival of cancer patients, their ability to induce cancer regression remains low. Recent reports help to identify and prospectively remove the remaining obstacles towards effective therapeutic vaccination of cancer patients. They indicate that the successful induction of tumor-specific T cells by cancer vaccines is not necessarily associated with the induction of functional cytotoxic T lymphocytes, and that current cancer vaccines may promote undesirable expansion of Treg cells. Furthermore, recent studies also identify the tools to counteract such phenomena, in order to assure the desirable induction of Th1-cytotoxic T lymphocytes, NK-mediated type-1 immunity and appropriate homing of effector cells to tumors.