Liver tolerance and the manipulation of immune outcomes

In recent years it has become apparent that the liver holds a distinct immunological position. Previously described as a "graveyard" for T cells activated in the periphery, emerging evidence indicates that this organ may have a more active role in mediating tolerance. Attenuated immune responses in the liver can be beneficial in the transplantation setting, as liver transplants are more readily accepted than other organ allografts even in the absence of immunosuppressive drugs. However, the ability of the liver to induce immunological unresponsiveness could be exploited by some pathogens, such as the hepatitis C virus (HCV), to establish chronic infections with potentially fatal outcomes. Understanding the mechanisms controlling the balance between intrahepatic tolerance and immunity is critical in order to design new strategies to enhance acceptance of solid organ allografts and to promote efficient immune responses against HCV. In this article, we will review current knowledge of the mechanisms regulating intrahepatic immunity and discuss how these mechanisms might potentially be targeted to achieve advantageous clinical outcomes in transplantation and persistent hepatotropic infections.     

Different approaches for complete mobilization of the splenic flexure during laparoscopic rectal cancer resection

Purpose

Laparoscopic resection of rectal cancer has already become the standard procedure in many hospitals. The splenic flexure mobilization (SFM) is an important preparational step. Several methods are used for laparoscopic SFM; however, studies comparing different approaches are lacking. In the present study, three different approaches for SFM have been compared to each other.

Methods

Between January 1998 and December 2010, 415 patients with rectal adenocarcinoma underwent laparoscopic rectal resection at one center. Of these, 303 patients received complete splenic flexure mobilization. The SFM was performed using either a medial (SFM-M; n?=?41), lateral (SFM-L; n?=?214), or anterior (SFM-A; n?=?48) approach.

Results

There was a significantly higher rate of intraoperative complications in the SFM-L group as compared to the SFM-M or the SFM-A group (p?=?0.038). Postoperative surgical complications occurred in 5 (10.6?%) patients of the SFM-A group compared to 38 patients (17.7?%) in the SFM-L group (p?=?0.002) and 5 (12.1?%) patients in the SFM-M group (p?=?0.037). SFM-L was also associated with a higher frequency of overall postoperative morbidity which was mainly due to wound infection rates (p?=?0.001).

Conclusions

The anterior approach for SFM in laparoscopic surgery seems to be associated with lower frequency of intra- and postoperative morbidity.     

Predictors of delayed referral to a pediatric rheumatology center

Objective

To report on referral patterns of primary physicians for children subsequently diagnosed with juvenile idiopathic arthritis (JIA) and to identify predictors of delayed referral to a pediatric rheumatology center.

Methods

A retrospective cohort study of consecutive patients with JIA referred to a pediatric rheumatology center over a 15‐year period was performed. Variables included age, sex, JIA subtype, the physician's subspecialty, and distance to the pediatric rheumatology center. Outcome parameters were the time to first presentation to a primary physician, the time to the first rheumatology visit, and the total time to referral. Putative predictors were evaluated by analysis of variance, resulting in regression models.

Results

A total of 132 patients with JIA were included; 83 (63%) were female. The median age at the onset of symptoms was 4.5 years (range 1.0–15.8 years). Most frequently, children were referred by pediatricians (49.4%) or orthopedic surgeons (34.1%). The median time to first presentation was short at 10 days (range 0–1,610 days). In contrast, the median time to first rheumatology visit was 60 days (range 0.0–2,100.0 days), resulting in a long median total time to referral of 90 days (range 0.0–2,160.0 days). Statistically significant predictors for delayed referral were the primary physician's subspecialty (P = 0.016) and the distance to the pediatric rheumatology center (P = 0.001). Children living in remote areas or referred by orthopedic surgeons had the longest referral times.

Conclusion

Despite free access to health care in Germany, children with JIA are referred to pediatric rheumatology centers with significant delay. Educational interventions targeting primary physicians and orthopedic surgeons may contribute to earlier referral to pediatric rheumatology centers and improve outcome in patients with JIA.