Evolution of Computed Tomographic Characteristics of Spontaneous Isolated Superior Mesenteric Artery Dissection During Conservative Management.

BACKGROUND: Spontaneous isolated superior mesenteric artery (SMA) dissection is a rare condition, and its clinical and angiographic courses are poorly defined. We aimed to monitor the morphological characteristics of spontaneous isolated SMA dissection using computed tomography (CT) over 2 years of follow-up, including the recovery process via vascular remodeling, and identify the factors that affect vascular remodeling using univariate analysis. METHODS AND RESULTS: We retrospectively reviewed the medical records and morphological findings of 59 consecutive patients with spontaneous isolated SMA dissection between October 2007 and July 2014, which included 36 symptomatic and 23 asymptomatic patients. Surgical intervention with open laparotomy was required in 3 patients during the follow-up period; 41 patients who received conservative treatment were followed up over 2 years with regular CT. Complete remodeling was achieved in 16 of 25 symptomatic patients who were treated conservatively (64.0%). A patent false lumen and aneurysmal formation on an initial CT scan were identified as negative factors that affected remodeling in patients with spontaneous isolated SMA dissection. CONCLUSIONS: Conservative management of spontaneous isolated SMA dissection is associated with a good prognosis, both clinically and morphologically. Surgical intervention is only required in patients with severe intestinal ischemia or rapid aneurysmal enlargement. (Circ J 2016; 80: 1452-1459).

Effects of laparoscopic surgery on the patterns of death in elderly colorectal cancer patients: competing risk analysis compared with open surgery.

PURPOSE: The effects of laparoscopic colorectal surgery (LAC) on the long-term outcomes of elderly patients remain unclear. This study aimed to assess the short- and long-term outcomes of LAC in elderly colorectal cancer patients and to quantify the effects of LAC on the patient death patterns. METHODS: The clinicopathological data of elderly colorectal cancer patients aged ≥80 years old who were treated between 2006 and 2014 were extracted. The relationships between the clinicopathological factors and overall survival (OS) were assessed using the Cox proportional hazards model and Kaplan-Meier analyses. The risk factors for the types of death were estimated using a competing risk analysis. RESULTS: A total of 107 patients were included. Fifty-two patients underwent LAC, whereas 55 underwent open surgery (OC). There were no significant differences in the American Society of Anesthesiologists grade or comorbidity rate between the groups. The postoperative complication rate was significantly lower with LAC than OC (p < 0.001). After adjustment for covariates, laparoscopic surgery was not a significant risk factor for any of the types of death. CONCLUSIONS: LAC is an effective and safe technique for elderly patients with colorectal cancer. Furthermore, there was no significant association between the surgical procedure and the pattern of death.

Liver allografts are toleragenic in rats conditioned with posttransplant total lymphoid irradiation.

BACKGROUND: Posttransplant total lymphoid irradiation (TLI) treatment has been applied to tolerance induction protocols in heart and kidney transplantation models. METHODS: We examined the efficacy and mechanism of posttransplant TLI treatment in the induction and maintenance of tolerance in a rat orthotopic liver transplantation model. RESULTS: Posttransplant TLI prolonged ACI (RT1(a)) liver allograft survival in Lewis (RT1(b)) hosts, with 50% long-term engraftment without immunosuppression and without evidence of chronic rejection. Injection of donor-type liver mononuclear cells (LMCs) facilitated the prolongation of graft survival, with more than 70% of grafts in LMC recipients surviving more than 100 days without chronic rejection. Recipients with long-term liver allograft survival accepted ACI but not PVG skin grafts. In TLI-conditioned recipients with accepted grafts, apoptosis occurred predominantly in graft-infiltrating leukocytes. In contrast, there were few apoptotic leukocytes in rejecting grafts. Recipients with long-term graft acceptance (>100 days of survival) demonstrated evidence of immune deviation; mixed lymphocyte reaction to ACI stimulator cells was vigorous, but secretion of interferon-gamma and interleukin-2 was reduced. In tolerant recipients, the number of Foxp3(+) CD25(+) CD4(+) regulatory T cells was increased in the liver allograft as well as in the peripheral blood. CONCLUSION: We conclude that posttransplant TLI induces tolerance to liver allografts via a mechanism involving apoptotic cell-deletion and immunoregulation.

Mutations to bid cleavage sites protect hepatocytes from apoptosis after ischemia/reperfusion injury.

BACKGROUND: Apoptosis of hepatocytes contributes to many forms of liver pathology and can compromise liver function. Hepatocytes have been shown to require mitochondrial disruption to execute apoptosis, a process that is controlled by members of the Bcl-2 family. Bid is a proapoptotic Bcl-2 family member that is cleaved to its active form, tBid, by caspase 8 and granzyme B. Studies in the Bid-deficient mouse have established that hepatocytes require Bid to undergo apoptosis. METHODS: We generated aspartic acid to glutamic acid mutations in the rat Bid protein, at the caspase 8 and granzyme B cleavage sites, and utilized recombinant adenoviruses to express this protein in hepatoma cells and in the livers of rats. RESULTS: Cells transduced with recombinant adenoviruses encoding Bid containing mutations to the caspase 8 and granzyme B cleavage sites are significantly protected from both tumor necrosis factor-alpha-induced and cell-mediated apoptosis. Protection occurs through a mechanism that includes decreased Bid cleavage, caspase activation, and mitochondrial membrane damage. Further, after warm ischemia/reperfusion injury, we show that rats expressing cleavage-resistant Bid in the liver display significantly less hepatocyte apoptosis as compared to control rat livers and this results in improved liver function and survival. CONCLUSION: Our results suggest that reagents that prevent the cleavage of Bid would be an effective strategy to inhibit hepatocyte apoptosis and decrease liver injury.

NKp30 is a functional activation receptor on a subset of rat natural killer cells.

NKp30 is a stimulatory receptor on human NK cells implicated in tumor immunity, and is capable of promoting or terminating dendritic cell maturation. To gain a better understanding of NKp30 biology, we have investigated the expression and function of rat NKp30 (rNKp30). We generated stable transfectants of rNKp30 in RNK16 cells, a rat NK lymphoma line, and used a novel panel of mAb against rNKp30 to study this receptor. Using agonistic rNKp30 mAb, we demonstrated that rNKp30 mediates robust IFN-gamma production and cytolytic responses from rNKp30-transfected RNK16 cells. We determined by flow cytometry that rNKp30 is expressed by a subset of primary NK cells isolated from the blood and spleen, and to a lesser extent also on liver NK cells. Stimulation of rNKp30 on primary NK cells led to IFN-gamma production. Liver NK cells expressed low levels of NKp30 and had reduced rNKp30-mediated IFN-gamma responses. During an alloimmune response in vivo, the proportion of the rNKp30(+) NK cell subset in the peripheral blood significantly increased, suggesting that rNKp30 may play an important role during alloactivation. Thus, our data demonstrate that NKp30 is indeed expressed in rodents and is a functional stimulatory receptor in a subset of rat NK cells.

IFN-gamma, produced by NK cells that infiltrate liver allografts early after transplantation, links the innate and adaptive immune responses.

The role of NK cells following solid organ transplantation remains unclear. We examined NK cells in acute allograft rejection using a high responder model (DA-->Lewis) of rat orthotopic liver transplantation. Recipient-derived NK cells infiltrated liver allografts early after transplantation. Since chemokines are important in the trafficking of cells to areas of inflammation, we determined the intragraft expression of chemokines known to attract NK cells. CCL3 was significantly increased in allografts at 6 h post-transplant as compared to syngeneic grafts whereas CCL2 and CXCL10 were elevated in both syngeneic and allogeneic grafts. CXCL10 and CX3CL1 were significantly upregulated in allografts by day 3 post-transplant as compared to syngeneic grafts suggesting a role for these chemokines in the recruitment of effector cells to allografts. Graft-infiltrating NK cells were shown to be a major source of IFN-gamma, and IFN-gamma levels in the serum were markedly increased, specifically in allograft recipients, by day 3 post-transplant. Accordingly, in the absence of NK cells the levels of IFN-gamma were significantly decreased. Furthermore, graft survival was significantly prolonged. These data suggest that IFN-gamma-producing NK cells are an important link between the innate and adaptive immune responses early after transplantation.

One-stage surgical management of concomitant abdominal aortic aneurysm and gastric or colorectal cancer.

One-stage surgical management of concomitant abdominal aortic aneurysm (AAA) and gastric or colorectal cancer should provide certain benefits. We reviewed the records of 21 patients with both AAA and gastric or colorectal cancer who underwent one-stage surgical management. Four had distal gastrectomy, 2 had total gastrectomy, and 5 had abdominoperineal rectal resection transperitoneally; 3 had total gastrectomy transperitoneally and AAA repair extraperitoneally. Two underwent right hemicolectomy and thromboexclusion of the AAA. Two had creation of a temporary ileostomy and implantation of an interposition graft. Two underwent left hemicolectomy, creation of a temporary transversostomy, and implantation of an interposition graft. One had a Hartmann's procedure and implantation of a bifurcated prosthetic interposition graft for AAA. There were no operative deaths or serious postoperative complications. One patient had colorectal ischemia that resolved with conservative treatment. Eighteen of the 21 patients (85.7%) were alive 10 months to 14 years postoperatively. In conclusion, one-stage surgical treatment of concomitant AAA and gastric or colorectal cancer is well tolerated and can avoid the time, financial costs, and patient anxiety involved in a second operation.

Effects of preinjury administration of corticosteroids on pseudointimal hyperplasia and cytokine response in a rat model of balloon aortic injury.

Restenosis occurs in approximately one-third of patients with coronary or peripheral vascular disease who undergo balloon angioplasty or a surgical bypass procedure primarily because of the development of pseudointimal hyperplasia (PIH). Corticosteroids were effective in suppressing PIH in several experimental studies, but no clinical studies have been reported. To resolve this discrepancy, we studied the effects of preinjury administration of several doses of methylprednisolone (MP) at targeted times in a rat model of balloon aortic injury. Rats were given either no treatment or an intravenous injection of MP (0.5, 5.0, 50, or 500 mg/kg) 2 hours before aortic injury. Four hours later interleukin-6 (IL-6), IL-10, and macrophage migration inhibitory factor (MIF) concentrations in serum and tissue of injured aortas were assessed. Two weeks after injury, damaged aortas were harvested and studied histopathologically. Compared with results in controls, MP at a dose of 5 mg/kg significantly inhibited increases in plasma and tissue levels of IL-6 and significantly reduced the pseudointimal area, pseudointimal/medial area ratio, and proliferating cell nuclear antigen index in injured vessels. Administration of MP had no significant effect on the IL-10 or MIF level. Thus in a rat model of balloon aortic injury, preinjury administration of MP 5 mg/kg mitigated the development of PIH and cell proliferation and suppressed the postinjury increase in serum and tissue IL-6 concentrations. These results suggest that there is an appropriate dosage as well as appropriate timing for MP administration to suppress PIH.