Effect of immunonutrition on infectious complications in low skeletal muscle mass patients after pancreaticoduodenectomy.

BACKGROUND & AIMS: Sarcopenia is considered a risk factor of postoperative complications among patients undergoing abdominal surgery. However, few studies have demonstrated an effective strategy for reducing complications in sarcopenic patients. This study aimed to examine retrospectively the effect of preoperative immunonutrition on postoperative complications, especially infectious complications, in low skeletal muscle mass patients undergoing pancreaticoduodenectomy (PD). METHODS: This was a retrospective, consecutive cohort study conducted in our institution. Skeletal muscle mass was assessed using preoperative computed tomography images in 298 consecutive patients who underwent PD between May 2009 and May 2016. Cross-sectional areas at the third lumbar vertebrae normalized for stature (cm2/m2) were defined as the skeletal muscle mass index (SMI). Low SMI was defined as the lowest sex-specific quartile of SMI. Risk factors for postoperative infectious complications and the effect of preoperative immunonutrition on low SMI patients who underwent PD were evaluated. RESULTS: Results of multivariate analysis showed that the presence of low SMI and absence of preoperative immunonutrition were independent risk factors for postoperative infectious complications after PD (odds ratio [OR], 3.17 and 3.10, respectively; P < 0.001). In high SMI patients, the rate of postoperative infectious complications was significantly lower in those who received immunonutrition than in those who did not receive immunonutrition (31.9 vs. 46.1%, respectively; OR, 1.82; P = 0.045). Further, similar findings were exhibited in low SMI patients (26.3 vs. 83.6%, respectively; OR, 14.31; P < 0.001), even though OR was markedly higher in low vs. high SMI patients. CONCLUSION: There is a stronger association with reduced infectious complications in patients who have low SMI and receive immunonutrition (UMIN-CTR Identifier: UMIN000035775.).

Conversion surgery for initially unresectable pancreatic cancer: current status and unresolved issues.

Pancreatic cancer is one of the most lethal of all malignancies. One of the reasons for the dismal prognosis is that most diagnoses are made when the disease is either locally advanced or metastatic. Recent advances in chemotherapy and chemoradiotherapy (CRT) enable "conversion surgery" to be performed for selected patients with initially unresectable pancreatic cancer following favorable responses to preoperative treatment. Using FOLFIRINOX as preoperative treatment, the resection rate was reported as 6-44% of patients with locally advanced cancer and the prognosis of these patients was favorable. Even for metastasized cancer, recent reports show the effectiveness of conversion surgery, which has achieved 27-56 months of median overall survival. However, there are many unanswered questions about conversion surgery. The optimal regimen and duration of preoperative treatment remain unclear and there is still debate regarding the safety and effectiveness of vascular resection, which is often required for curative resection of locally advanced cancer. Accumulation of more data on conversion surgery is required to establish the safety and effectiveness of this treatment. In this review, we summarize the current status and unresolved issues about conversion surgery for initially unresectable pancreatic cancer.

Additional effect of perioperative, compared with preoperative, immunonutrition after pancreaticoduodenectomy: A randomized, controlled trial.

BACKGROUND: We have reported that perioperative and preoperative immunonutrition reduced infectious complications in patients undergoing pancreaticoduodenectomy; however, it is unclear whether perioperative immunonutrition has additional effects compared with preoperative immunonutrition. The present study evaluated whether perioperative, compared with preoperative, immunonutrition has additional effects on cell-mediated immunity and the infection rate after pancreaticoduodenectomy. MATERIALS AND METHODS: This was a prospective, randomized clinical trial conducted in our institution. Oral supplementation enriched with arginine, ω-3 fatty acids, and dietary nucleotides was given by enteral infusion to 30 patients before and after surgery (perioperative group); 30 patients received the same enriched formula before surgery and standard enteral nutrition following surgery (preoperative group). The primary endpoint was concanavalin (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation on postoperative day (POD) 7, which is an index of cell-mediated immunity; the secondary endpoint was the postoperative infection rate. RESULTS: There were no significant differences in Con A- or PHA-stimulated lymphocyte proliferation on POD 7 between the groups. There was no significant difference in the postoperative infection rate between the two groups. In the post hoc subgroup analysis, with respect to the effect on the infection rate, a significant interaction was found only between a long operative time and perioperative immunonutrition. CONCLUSIONS: There were no additional effects of perioperative, compared with preoperative, immunonutrition on postoperative immunity and infectious complications in patients undergoing pancreaticoduodenectomy.

Immunonutrition suppresses acute inflammatory responses through modulation of resolvin E1 in patients undergoing major hepatobiliary resection.

BACKGROUND: Although several studies have reported the effects of immunonutrition on clinical outcomes, detailed mechanisms of immunonutrition after an operation are still unclear. It was recently reported that resolvin E1, a novel lipid mediator generated from eicosapentaenoic acid (EPA), activates factors that reduce inflammation. This randomized clinical trial was designed to investigate not only the effect of immunonutrition on postoperative complications but also the participation of resolvin E1 on anti-inflammatory effects of immunonutrition in patients undergoing major hepatobiliary resection. METHODS: Forty patients who underwent major hepatobiliary resection were divided into 2 groups. Twenty patients received oral supplementation enriched with EPA, arginine, and nucleotides before the operation (group IN). Twenty patients (control group) received no artificial nutrition before the operation (group C). RESULTS: The rate of infectious complications and severity of complications in group IN was significantly lower than in group C (P < .05). Immediately after the operation, plasma resolvin E1 levels were significantly higher in group IN than in group C (P < .05), and plasma interleukin-6 levels were significantly lower in group IN than in group C (P < .05). Preoperative serum EPA levels correlated with plasma resolvin E1 levels immediately after the operation. Plasma resolvin E1 levels correlated with plasma interleukin-6 levels immediately after the operation. CONCLUSION: Preoperative immunonutrition reduced inflammatory responses and protected against the aggravation of postoperative complications in patients undergoing major hepatobiliary resection. Resolvin E1 may play a key role in the resolution of acute inflammation when immunonutrition is supplemented with EPA. (ClinicalTrials.gov Identifier: NCT01256047.).

Preoperative immunonutrition decreases postoperative complications by modulating prostaglandin E2 production and T-cell differentiation in patients undergoing pancreatoduodenectomy.

BACKGROUND: An immune-enhancing diet has been used to alter eicosanoid synthesis, cytokine production, and immune function in an attempt to limit the undesired immune reactions after injury from surgery. This prospective randomized study was designed to investigate the effect of preoperative immunonutrition on operative complications, and the participation of prostaglandin E2 (PGE2) on T-cell differentiation in patients undergoing a severely stressful surgery. METHODS: The enrolled patients who were scheduled to undergo pancreatoduodenectomy were randomized into two groups. Patients in the immunonutrition group (n = 25) received oral supplementation containing arginine, ω-3 fatty acids, and RNA for 5 days before the procedure in addition to a 50% reduction in the amount of regular food. Patients in the control group (n = 25) received no artificial nutrition and were allowed to consume regular food before surgery. All patients received early postoperative enteral infusion of a standard formula intended to provide 25 kcal/kg/day. The primary endpoint was the rate of infectious complications; the secondary endpoint was immune responses. This study is registered with ClinicalTrials.gov (NCT01256034). RESULTS: Infectious complication rate and severity of complications (Clavien-Dindo classification) were lesser in the immunonutrition group than in the control group. mRNA expression levels of T-bet were greater in the immunonutrition group than in the control group (P < .05). Serum eicosapentaenoic acid and eicosapentaenoic acid/arachidonic acid ratios were greater in the immunonutrition group than in the control group (P < .05). The levels of plasma PGE2 were lesser in the immunonutrition group than in the control group (P < .05). CONCLUSION: Preoperative immunonutrition modulates PGE2 production and T-cell differentiation and may protect against the aggravation of operative complications in patients undergoing pancreatoduodenectomy.

Effects of perioperative immunonutrition on cell-mediated immunity, T helper type 1 (Th1)/Th2 differentiation, and Th17 response after pancreaticoduodenectomy.

BACKGROUND: The mechanisms of immunonutrition on reducing infectious complications are still poorly understood. This prospective randomized study was designed to determine whether immunonutrition influences the following factors: cell-mediated immunity, differentiation of T helper type 1 (Th1) and Th2 cells, interleukin (IL)-17-producing CD4(+) helper T (Th17) cell response, and infectious complication rate after pancreaticoduodenectomy. METHODS: Thirty patients who underwent pancreaticoduodenectomy were divided into 3 groups. Ten patients in the perioperative group received immune-enhancing diets enriched with arginine, omega-3 fatty acids, and RNA for 5 days before operative resection, which was prolonged after operative resection by enteral infusion. Ten patients in the postoperative group received early postoperative enteral infusion of the same enriched formula with no artificial nutrition before operative resection. Ten patients in the control group received total parenteral nutrition postoperatively. The primary endpoint was immune responses; the secondary endpoint was the rate of infectious complications. RESULTS: Concanavalin A (Con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and natural killer cell activity were significantly higher in the perioperative group than in the other groups. Messenger RNA (mRNA) expression levels of T-bet, interferon-gamma (IFN-gamma), related orphan receptor gammat (RORgammat), and interleukin-17F (IL-17F) were significantly higher in the perioperative group than in the other groups. In the perioperative group, the rate of infectious complications was significantly reduced compared with that in the other groups. CONCLUSION: Perioperative immunonutrition reduced stress-induced immunosuppression after a major stressful operative resection. The modulation of Th1/Th2 differentiation and Th17 response may play important roles in this immunologic effect.

Guidelines for chemotherapy of biliary tract and ampullary carcinomas.

Few randomized controlled trials (RCTs) with large numbers of patients have been conducted to date in patients with biliary tract cancer, and standard chemotherapy has not been established yet. In this article we review previous studies and clinical trials regarding chemotherapy for unresectable biliary tract cancer, and we present guidelines for the appropriate use of chemotherapy in patients with biliary tract cancer. According to an RCT comparing chemotherapy and best supportive care for these patients, survival was significantly longer and quality of life was significantly better in the chemotherapy group than in the control group. Thus, chemotherapy for patients with biliary tract cancer seems to be a significant treatment of choice. However, chemotherapy for patients with biliary tract cancer should be indicated for those with unresectable, locally advanced disease or distant metastasis, or for those with recurrence after resection. That is why making the diagnosis of unresectable disease should be done with greatest care. As a rule, pathological diagnosis, including cytology or histopathological diagnosis, is preferable. Chemotherapy is recommended in patients with a good general condition, because in patients with general deterioration, such as those with a performance status of 2 or 3 or those with insufficient biliary decompression, the benefit of chemotherapy is limited. As chemotherapy for unresectable biliary tract cancer, the use of gemcitabine or tegafur/gimeracil/oteracil potassium is recommended. As postoperative adjuvant chemotherapy, no effective adjuvant therapy has been established at the present time. It is recommended that further clinical trials, especially large multi-institutional RCTs (phase III studies) using novel agents such as gemcitabine should be performed as soon as possible in order to establish a standard treatment.