Katsunori Furukawa

Usefulness of intraoperative fluorescence imaging to evaluate local anatomy in hepatobiliary surgery.

BACKGROUND/PURPOSE One of the major complications encountered in hepatobiliary surgery is the incidence of bile duct and blood vessel injuries. It is sometimes difficult during surgery to evaluate the local anatomy corresponding to hepatic arteries and bile ducts. We investigated the potential utility of an infrared camera system as a tool for evaluating local anatomy during hepatobiliary surgery. METHODS An infrared camera system was used to detect indocyanine green fluorescence in vitro. We also employed this system for the intraoperative fluorescence imaging of the arteries and biliary system in a pig. Further, we evaluated blood flow in the hepatic artery, portal vein, and liver parenchyma during a human liver transplant and we investigated local anatomy in patients undergoing cholecystectomy. RESULTS Fluorescence confirmed that indocyanine green was distributed in serum and bile. In the pig study, we confirmed the fluorescence of the biliary system for more than 1 h. In the liver transplant recipient, blood flow in the hepatic artery and portal vein was confirmed around the anastomosis. In most of the patients undergoing cholecystectomy, fluorescence was observed in the gallbladder, cystic and common bile ducts, and hepatic and cystic arteries. CONCLUSIONS Intraoperative fluorescence imaging in hepatobiliary surgery facilitates better understanding of the anatomy of arteries, the portal vein, and bile ducts.

Influences of soybean oil emulsion on stress response and cell-mediated immune function in moderately or severely stressed patients

OBJECTIVES We previously reported that omega-6 fat emulsion increases cytokine production in burned rats. Effects of soybean oil emulsion on surgical stress responses and lymphocyte function according to the surgical severity have not been studied in detail. We investigated the effects of soybean oil emulsion, which contains 50% omega-6 fatty acid, on postoperative stress responses and cell-mediated immune function according to the severity of surgical stress. METHODS Eight patients who underwent gastric or colorectal surgery and nine who underwent esophagectomy were fed fat-free total parenteral nutrition. Ten patients who underwent gastric or colorectal surgery and seven who underwent esophagectomy were fed total parenteral nutrition with soybean oil emulsion. Total parenteral nutrition provided 1.5 g of protein and 40 kcal per kilogram every day from 7 d before surgery to postoperative day 14. Soybean oil emulsion (Intralipid) accounted for 20% of the total calories. Serum interleukin-6, C-reactive protein, glucagon, and concanavalin A- or phytohemagglutinin-stimulated lymphocyte proliferation were determined. RESULTS In the group of moderately stressed patients, soybean oil emulsion did not amplify the measured levels. In the group of severely stressed patients, soybean oil emulsion amplified the level of serum interleukin-6 and decreased concanavalin A- or phytohemagglutinin-stimulated lymphocyte proliferation. CONCLUSIONS Soybean oil emulsion amplifies the stress responses and possibly suppresses cell-mediated immune function induced by surgical stress in severely stressed patients, but not in moderately stressed patients.

n-3 Versus n-6 Polyunsaturated Fatty Acids in Critical Illness

The effects of n-6 and n-3 polyunsaturated fatty acids (PUFA) on protein metabolism, cell-mediated immunity, and production of cytokines and prostanoids were studied in experimental animals and patients with esophageal cancer. In the experimental study using a rat burn model, n-6 PUFA increased serum interleukin-6 (IL-6) and tumor necrosis factor (TNF), alpha (P < 0.05), and decreased nitrogen balance (NB) (P < 0.05), when compared with a fat-free control. But addition of n-3 PUFA reduced TNF-alpha and IL-10 (P < 0.05) and improved NB (P < 0.05). Suppressed delayed type hypersensitivity (DTH) induced by burn injury, which was not influenced by n-6 PUFA, was significantly improved by the administration of n-3 PUFA. n-6 PUFA tended to increase, and n-3 PUFA significantly decreased the endotoxin translocation. DTH, granulocyte-macrophage colony-stimulating factor, and eicosapentaenoic acid (EPA) content increased proportionately with the intravenous dose of fish oil emulsion. The effects of n-6 and n-3 PUFA were studied in the patients who underwent surgery for esophageal cancer. In the group of patients fed by total parenteral nutrition with soybean oil emulsion, the serum IL-6 significantly increased at 2 and 6 h after operation (P < 0.05). Oral/enteral supplementation of EPA ethyl ester (1.8 g/d) significantly reduced the postoperative IL-6 production (P < 0.05 at 1, 2, and 6 h after operation), and improved cell-mediated immune function 3 wk after operation (P = 0.05). During the chemoradiation therapy, cell-mediated immune function was improved significantly in the patients fed enterally with EPA ethyl ester (n = 5), when compared with the patients without EPA (n = 14).

Aggressive Surgical Resection for Hilar Cholangiocarcinoma of the Left-Side Predominance: Radicality and Safety of Left-Sided Hepatectomy

Objectives:To evaluate the clinicopathologic outcomes in patients with hilar cholangiocarcinoma (HC) after left-sided hepatectomy (L-H). Summary Background Data:L-H is indicated as radical surgery for HC, predominantly involving left hepatic duct. However, several reports have demonstrated that L-H often results in tumor-positive margin and unfavorable prognosis compared with right-sided hepatectomy (R-H). Methods:A total of 224 patients with HC underwent surgical resection with curative intent at our institution: L-H for Bismuth-Corlette (B-C) type IIIb tumors in 88 patients (39.3%) including 75 left hemihepatectomies and 13 left trisectionectomies, and R-H mainly for B-C type IIIa and IV tumors in 84 patients (37.5%). In this study, clinicopathologic outcomes and perioperative morbidity and mortality rates after L-H were investigated and compared with those after R-H. Results:Histologically negative margin (R0) resection was achieved in 56 cases (63.6%) with L-H, similar to the results for R-H (58/84, 69.1%). However, the R0 resection rate in L-H cases with portal vein (PV) resection was lower (11/25, 44.0%), and various types of PV reconstruction were required. Proximal ductal stumps and excisional surface at periductal structures were the most common sites of positive margins. However, when curative resection was achieved, 5-year survival was comparable to that in R-H cases. Furthermore, lower mortality was noted in L-H cases, even with left trisectionectomy. Multivariate analysis indicated curability and hepatic artery resection as independent prognostic factors. Conclusions:Since L-H is a safe procedure and represents the only curative resectional option for type IIIb tumor, aggressive surgical resection should be performed even in cases with PV involvement, if R0 resection is possible.

Similarities and differences between intraductal papillary tumors of the bile duct with and without macroscopically visible mucin secretion.

Intraductal papillary neoplasms of the bile duct (IPNB) have been recently proposed as the biliary counterpart of intraductal papillary mucinous neoplasms of the pancreas (IPMN-P). However, in contrast to IPMN-P, IPNB include a considerable number of the tumors without macroscopically visible mucin secretion. Here we report the similarities and differences between IPNB with and without macroscopically visible mucin secretion (IPNB-M and IPNB-NM). Surgically resected 27 consecutive cases with IPNB were divided into IPNB-M (n=10) and IPNB-NM (n=17), and their clinicopathologic features were examined. Clinically, both tumors were similar. Pathologically, the most frequent histopathologic types were pancreatobiliary in IPNB-NM and intestinal in IPNB-M. Various degrees of cytoarchitectural atypia within the same tumor were exhibited in 8 IPNB-M, but only 3 in IPNB-NM. Although the tumor size was similar, 9 IPNB-NM were invasive carcinoma, whereas all but 1 IPNB-M with carcinoma were in situ or minimally invasive. Immunohistochemically, positive MUC2 expression was significantly more frequent in IPNB-M than in IPNB-NM, whereas MUC1 tended to be more frequently expressed in IPNB-NM compared with IPNB-M. Among IPNB-NM with positive MUC1 expression, 3 had negative MUC2 and MUC5AC expressions. These tumors showed a tubulopapillary growth with uniform degree of cytoarchitectural atypia. All IPNB-M were negative for p53, and the frequency of positive p53 protein in IPNB-NM was at the middle level of that in IPNB-M and nonpapillary cholangiocarcinoma. In conclusion, IPNB-M showed striking similarities to IPMN-P, but IPNB-NM contained heterogeneous disease groups.

Effects of Soybean Oil Emulsion and Eicosapentaenoic Acid on Stress Response and Immune Function After a Severely Stressful Operation

OBJECTIVE To investigate the effects of soybean oil emulsion and oral or enteral administration of eicosapentaenoic acid (EPA) on stress response, cytokine production, protein metabolism, and immune function after surgery for esophageal cancer. SUMMARY BACKGROUND DATA It has been reported that safflower oil, rich in n-6 polyunsaturated fatty acid (n-6 PUFA), affects the survival rate of septic animals and decreases the immune function. It has also been reported that the administration of fish oil, in contrast, reduces these stress responses and stress-induced immunosuppression. In humans, the effects of soybean oil emulsion and the administration of EPA on stress response and immune function after surgery have not been established. METHODS Patients who underwent esophagectomy with thoracotomy were divided into three groups. Seven patients were fed by total parenteral nutrition (TPN) with soybean oil emulsion, which accounted for 20% of total calories. Seven patients were given oral or enteral administration of 1.8 g/day EPA, in addition to TPN with soybean oil emulsion. Nine patients served as the control group; these patients received fat-free TPN. Serum interleukin-6 (IL-6), C-reactive protein, concanavalin A (con A)- or phytohemagglutinin (PHA)-stimulated lymphocyte proliferation, natural killer cell activity, and stress hormones were measured. RESULTS The postoperative level of serum IL-6 was significantly higher in the group receiving soybean oil emulsion than in the fat-free group. Oral or enteral supplementation of EPA with soybean oil emulsion significantly reduced the level of serum IL-6 compared with the patients receiving soybean oil emulsion. Con A- or PHA-stimulated lymphocyte proliferation decreased significantly on postoperative day 7 in all groups of patients. The supplementation of EPA with soybean oil emulsion significantly improved the lymphocyte proliferation and natural killer cell activity on postoperative day 21 compared with the group receiving soybean oil emulsion. CONCLUSIONS Soybean oil emulsion amplifies, and the supplementation of EPA reduces, the stress response and stress-induced immunosuppression.

Changes in immune function following surgery for esophageal carcinoma.

Changes in immune function due to surgical injury have been well-documented. Immunosuppression is one of the causes of infectious complications leading to organ dysfunction in critical illness. It is not known what kind of surgery in the daily clinical practice causes immunosuppression. Stress response and immune function following surgery for esophageal carcinoma, assuming a highly-stressed operation, were studied and then compared with the stress response and immune function following gastric surgery, a moderately-stressed procedure. Forty patients who underwent esophagectomy and 39 patients receiving gastric operation were studied. The concentrations of serum interleukin-6 (IL-6) were measured preoperatively, at 1, 2, and 6 h, and at 1, 3, and 10 d after operation. Total protein, serum albumin, rapid turnover protein, serum CRP, and cortisol were measured before operation and at 1, 3, 7, and 21 d after operation. ConA- and PHA-stimulated lymphocyte proliferation, IgA, IgG, and IgM were also measured preoperatively, and on 7 and 21 d following surgery. The patients were fed exclusively by total parenteral nutrition (TPN). A striking rise of IL-6 was observed, with a peak in both groups at 1 to 6 h following operation. The peak values were 419+/-30 pg/mL, which was approximately twice as high in the esophagectomy patients as in the gastrectomy patients (195+/-40 pg/mL). CRP and cortisol also increased after operation, and these increases were also significantly greater in the esophagectomy patients. ConA- and PHA-stimulated lymphocyte proliferation decreased significantly 7 d after esophagectomy (P<0.05), but was unchanged in the patients receiving gastrectomy. Suppression of cellular immunity correlated significantly with serum cortisol, and was preceded by a rise in serum IL-6. The IgA, IgG, and IgM levels, however, remained unchanged from their preoperative values throughout the study in both groups. Nutritional status in terms of serum protein, albumin, and rapid turnover protein, decreased postoperatively, but there was no difference between the two groups. It is, therefore, concluded that cell-mediated immunosuppression, preceded by a hyperinflammatory response, is an observable reaction in patients following esophageal surgery, but not in patients undergoing gastric surgery.

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.

One hundred seven consecutive surgical resections for hilar cholangiocarcinoma of Bismuth types II, III, IV between 2001 and 2008.

Many authors at high-volume centers all over the world have reported improved outcomes of hilar cholangiocarcinoma by several aggressive surgical approaches such as extended hepatic resection, combined vascular resection, and hepatopancreaticoduodenectomy in recent years. There has been great progress in the surgical treatment of hilar cholangiocarcinoma with these previous efforts by aggressive hepatobiliary surgeons. In particular, surgical techniques, diagnostic modalities, and perioperative management have been remarkably improved as compared with before. Herein we report the surgical outcome for both hilar cholangiocarcinoma of Bismuth types II, III, and IV and intrahepatic cholangiocarcinoma involving the hepatic duct confluence during the recent 8-year period between 2001 and 2008 at our institution, the Department of General Surgery at Chiba University. From our recent experienced results, it can be concluded that the surgical strategy for hilar cholangiocarcinoma has been improved remarkably, and major surgical hepatectomy can be done with relative safety, and these aggressive surgical approaches, including combined vascular resection, may be warranted for the surgical treatment of hilar cholangiocarcinoma. However, the adoption of new innovative therapeutic approaches might be required for further improvement of surgical outcome of hilar cholangiocarcinoma.

Repeat pancreatectomy for pancreatic ductal cancer recurrence in the remnant pancreas after initial pancreatectomy: Is it worthwhile?

BACKGROUND The clinical implications of repeat completion pancreatectomy for recurrent pancreatic cancer in the remnant pancreas after initial pancreatectomy have not been clarified. We retrospectively analyzed our patients and evaluated the clinical implications of repeat pancreatectomy for isolated local recurrence in the remnant pancreas after initial resection for pancreatic cancer. METHODS One-hundred seventy patients who had recurrence of pancreatic cancer out of 326 patients who had initially undergone resection for pancreatic cancer were included in this study. Sixty-seven of 170 recurrent patients were diagnosed as having isolated local recurrence of pancreatic cancer. Eleven of these 67 patients with isolated local recurrence only in the remnant pancreas underwent repeat pancreatectomy. Characteristics and operative outcomes for these 11 patients with repeat pancreatectomy were analyzed and evaluated in comparison with other recurrent patients. RESULTS Among 170 patients with recurrence after initial resection for pancreatic cancer, the median survival time was 78.2 and 20.3 months after initial resection, in the repeat pancreatectomy group and the unresectable group, respectively (P < .001), and the 2- and 5-year survival probability rates after initial resection were 91%, and 82% vs 42%, and 13%, respectively. Among 67 patients with isolated local recurrence, the median survival time after repeat resection or diagnosis of recurrence was 25.0 and 9.3 months, and the 2- and 5-year survival probability rates after repeat resection or diagnosis of recurrence were and 61% and 46% vs 19% and 6.2% in the repeat pancreatectomy group and the unresectable group, respectively (P < .01). There was no difference in survivals between the unresectable isolated local recurrence group and the unresectable nonlocal recurrence group. CONCLUSION Repeat pancreatectomy might bring about beneficial effects on prognosis in selected patients with isolated local recurrence in the remnant pancreas after initial pancreatectomy for pancreatic cancer without increased operative morbidity or mortality.