Background: Colorectal cancer is the third most deadly cancer among African Americans (AA). When compared to Caucasian Americans (CA), AA present with more advanced disease and lower survival rates. Here, we investigated if differences in tumor immunology could be contributive to disparities observed between these populations. Methods: We examined gene expression of tumor and non-tumor adjacent tissues from AA and CA by whole transcriptome sequencing, and generated scores for immune cell populations by NanoString. In addition, we utilized “The Cancer Genome Atlas” (TCGA) database from AA and CA as a validation cohort. Finally, we measured the secretion of cytokines characteristic of effector T helper cell (T h ) subsets by ELISA using plasma from each AA and CA participant. Results: Colon tumors from AA patients showed significant fold-change increase in gene expression when compared to CA for FOXP3 (6.22 vs. 3.22), IL1B (103 vs. 11.4) and IL8 (220 vs. 28.9) ( p < 0.05). In contrast, among CA we observed statistically higher gene expression of markers associated with antitumor activity such as GZMB (Granzyme B), IFNG and the immunotherapy targets PDL1 ( CD274 ) and CTLA4 ( p < 0.05). TCGA data validated our observed higher gene expression of GZMB and PDL1 in CA patients when compared to AA. Notably, our observations on immune cell populations show that AA tumors have significantly higher number of exhausted CD8+ cells ( p < 0.01), mast cells ( p < 0.02) and increased T regulatory cells when compared to CA. AA colon cancer patients differed from CA in cytokine production patterns in plasma (i.e., reduced IL-12). Conclusions: Our study demonstrates significant differences of the immunological profiles of colon tumors from AA compared to CA that suggest a deficiency of appropriate immune defense mechanisms in terms of gene expression, recruitment of immune cells and systemic secretion of cytokines. As such, these immune differences could be mitigated through population-specific therapeutic approaches.
Acute pancreatitis (AP) is an inflammatory disorder of pancreatic tissue initiated in injured acinar cells. Severe AP remains a significant challenge due to the lack of effective treatment. The widely-accepted autodigestion theory of AP is now facing challenges, since inhibiting protease activation has negligible effectiveness for AP treatment despite numerous efforts. Furthermore, accumulating evidence supports a new concept that malfunction of a self-protective mechanism, the unfolded protein response (UPR), is the driving force behind the pathogenesis of AP. The UPR is induced by endoplasmic reticulum (ER) stress, a disturbance frequently found in acinar cells, to prevent the aggravation of ER stress that can otherwise lead to cell injury. In addition, the UPR’s signaling pathways control NFκB activation and autophagy flux, and these dysregulations cause acinar cell inflammatory injury in AP, but with poorly understood mechanisms. We therefore summarize the protective role of the UPR in AP, propose mechanistic models of how inadequate UPR could promote NFκB’s pro-inflammatory activity and impair autophagy’s protective function in acinar cells, and discuss its relevance to current AP treatment. We hope that insight provided in this review will help facilitate the research and management of AP.
In contrast to adult colonic intussusception in which malignancy is the dominant cause, small bowel intussusceptions are mostly benign. Although surgery is the accepted standard treatment, its necessity in small bowel intussusceptions identified by CT scan is unknown. Twenty-three patients from 2005 to 2008 (16 males; median age, 44 years) with acute abdominal pain and CT-proven small bowel intussusception were studied. Factors associated with the necessity for surgery were determined. Among 11 patients who were managed operatively, surgery was deemed unnecessary in two patients based on negative explorations. Follow up in 10 of 12 patients managed nonoperatively was not associated with any recurrence of intussusception or malignancy (median follow up, 14 months). The only predictor of the need for surgery was CT evidence of small bowel obstruction and/or a radiologically identified lead point, which was present in 7 of 9 (78%) patients having a necessary operation and absent in 12 of 14 (86%) with no indication for surgery (P = 0.008). All small bowel intussusceptions found on CT scan in patients with acute abdominal pain do not require operative management. CT findings of small bowel obstruction and/or presence of a lead point are indications for surgery.
Background and Objectives:Ventral hernia repair is one of the most commonly performed general surgery procedures, and minimally invasive approaches are increasingly preferred. The physiologic repair offered by the preperitoneal approach is favorable, with reduced complications, but it remains a technical challenge. The robotic platform allows for enhanced instrument flexibility and ease of operation. We conducted a retrospective review of our experience with robotic transabdominal preperitoneal repair (rTAPP) versus robotic intraperitoneal onlay mesh (rIPOM) at a tertiary care hospital in an urban setting.Methods:We reviewed the records of patients undergoing minimally invasive ventral hernia repair from March 2014 through March 2017. Demographics, complication rates, and operative time were compared by t test and Chi square test, as applicable.Results:Sixty-three patients met the criteria for inclusion in the study. Of those, 27 underwent ventral hernia repair with rIPOM and 36 with rTAPP, with no major intraoperative complications. There were no significant differences in demographics between the 2 groups in age, BMI, and sex. The difference in mean operative time was not significant (rIPOM 167.26 [SD 51.76] minutes vs rTAPP 158.84 minutes [SD 61.5]; P = .57), whereas mean console time was significantly different (rIPOM 70.88 minutes [SD 32.88] vs rTAPP 90.26 [SD 31.17]; P = .018). Postoperative complications occurred only with rIPOM and included urinary retention, seroma, and fever.Conclusions:rTAPP is a promising alternative to rIPOM, with reduced complications without adding significant operative time, and may allow for reduced costs.
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