Nonclosure technique with saline-coupled bipolar electrocautery in management of the cut surface after distal pancreatectomy

金沢大学医学部附属病院肝胆膵・移植外科　Background/Purpose: Management of the pancreatic remnant after distal pancreatectomy is still debated, the most serious complication is development of a pancreatic fistula. We developed a nonclosure technique with saline-coupled bipolar electrocautery for preventing fistula formation after distal pancreatectomy as an alternative to traditional stump closure methods. Methods: The distinguishing feature of this technique is nonclosure of the stump, relying instead upon dependable ligation of the main pancreatic duct and sealing of the cut surface by shrinkage accomplished by low-temperature coagulation using saline-coupled bipolar electrocautery. A recent addition has been intraoperative stenting of the remnant pancreatic duct. Results: To date we have used the nonclosure technique in 40 cases, among which 5 (12.5%) developed fistulas: 4 in the nonstenting subgroup (14.8%) and 1 in the stenting subgroup (7.7%). According to a recent classification, 4 fistulas were considered grade A; 1, grade B; and 0, grade C. The grade B patient did not undergo stenting. Conclusion: Our preliminary experience should prompt more widespread evaluation of the nonclosure technique. © Springer Japan 2008

MDCT findings of extrapancreatic nerve plexus invasion by pancreas head carcinoma: correlation with en bloc pathological specimens and diagnostic accuracy

金沢大学医薬保健研究域Objective: To elucidate the multi-detector row computed tomography (MDCT) findings of extrapancreatic nerve plexus (PLX) invasion by pancreas head carcinoma (PhC) by "point-by-point" correlation with en bloc pathological specimens and to assess their diagnostic accuracy. Methods: Each pathological section of PhC and adjusted double oblique multiplanar reconstruction MDCT images were correlated in 554 sections from 37 patients. The diagnostic accuracy of the MDCT patterns derived was assessed by blind reading. Results: PLX invasion with fibrosis showed mass or strand shape (85.6%) or coarse reticula (13.3%). The CT findings were divided into fine reticular and linear, coarse reticular, mass and strand, and nodular patterns. PLX invasion was revealed pathologically in 92% of the regions of investigation showing the mass and strand pattern and 63% of the coarse reticular pattern (all continuous with PhC), and they were highly suggestive of PLX invasion by PhC on MDCT images (p < 0.001). Sensitivity, specificity, accuracy, and positive and negative predictive values of these MDCT findings in the diagnosis of PLX invasion were 100% (25/25), 83.3% (10/12), 94.6% (35/37), 92.6% (25/27) and 100% (10/10), respectively. Conclusion: The mass and strand pattern and the coarse reticular pattern continuous with PhC on MDCT images were highly suggestive of PLX invasion by PhC. © 2010 European Society of Radiology

Results of video-assisted thoracoscopic surgery for esophageal cancer during the induction period

金沢大学医学部附属病院胃腸外科Objective. The attainment of proficiency in thoracoscopic radical esophagectomy for thoracic esophageal cancer requires much experience. We aimed to master this procedure safely with our regular surgical team members under the direction of an experienced surgeon. We evaluated the efficacy of instruction during the induction period and the significance of our results. Methods. We compared the results of 12 thoracic esophageal cancer patients who underwent thoracoscopic radical esophagectomy in our institution (group A) to those of the initial 17 patients who underwent the same operation at the director\u27s institution (group B). Results. We were able to perform complete thoracoscopic radical esophagectomies without any direction after experiencing 10 cases that were performed under adequate direction. The number of dissected lymph nodes and the duration of the procedure were similar in the two groups: 34 (22-53) vs. 26 (9-55) nodes, P = 0.23; and 327.5 (230-455) vs. 315 (190-515) min, P = 0.947, respectively. The amount of thoracic blood loss was significantly less in group A than in group B: 185 (110-380) g vs. 440 (110-2360) g, P = 0.0035. Postoperative pneumonia and atelectasis were observed in 25.0% of group A patients and in 17.6% of group B patients. The incidence of recurrent nerve palsy was 30.7% in group A and 11.7% in group B, but there was no statistically significant difference (P = 0.19). The morbidity rates in group A and group B were 41.6% and 29.4%, respectively (P = 0.694). Conclusion. Thoracoscopic radical esophagectomy can be mastered relatively quickly and safely under the direction of an experienced surgeon and a regular surgical team. © 2008 The Japanese Association for Thoracic Surgery

Learning of thoracoscopic radical esophagectomy: How can the learning curve be made short and flat?

金沢大学附属病院胃腸外科Attainment of proficiency in video-assisted thoracoscopic radical esophagectomy (VATS) for thoracic esophageal cancer requires much experience. We have mastered this procedure safely under the direction of an experienced surgeon. After adoption of the procedure, the educated surgeon directed induction of this surgical procedure at another institution. We evaluated the efficacy of instruction during the induction period by comparing the results at the two institutions in which VATS had been newly induced. We defined the induction period as the time from the beginning of VATS to the time when the last instruction was carried out. From January 2003 to December 2007, 53 patients were candidates for VATS at Kanazawa University (institution 1). Of these, 46 patients underwent curative VATS by a single operator. We divided this period into three parts: the induction period of VATS, post-induction period, and proficient period when the educated surgeon of institution 1 directed the procedure at Maebashi Red Cross Hospital (institution 2). At institution 1, 12 VATS were scheduled, and nine procedures (75%) (group A) including eight instructions were completed during the induction period (from January 2003 to August 2004). Thereafter, VATS was performed without instruction. In the post-induction period, nine VATS were scheduled, and eight procedures (88.8%) (group B) were completed from September 2004 to August 2005. Subsequently, 32 VATS were scheduled, and 29 procedures (90.6%) (group C) were completed during the proficient period (from September 2005 to December 2007). The surgeon at Maebashi Red Cross Hospital (institution 2) started to perform VATS under the direction of the surgeon who had been educated at institution 1 from September 2005. VATS was completed in 13 (76.4%) (group D) of 17 cases by a single surgeon including seven instructions during the induction period at institution 2 from September 2005 to December 2007. No lethal complication occurred during the induction period at both institutions. We compared the results of VATS among four groups from the two institutions. There were no differences in the background and clinicopathological features among the four groups. The number of dissected lymph nodes and amount of thoracic blood loss were similar in the four groups (35 [22-52] vs 41 [26-53] vs 32 [17-69] vs 29 [17-42] nodes, P = 0.139, and 170 [90-380] vs 275 [130-550] vs 220 [10-660] vs 210 [75-543] g, P = 0.373, respectively). There was no difference in the duration of the thoracic procedure during the induction period at the two institutions. However, the duration of the procedure was significantly shorter in the proficient period of institution 1 (group C: 266 [195-555] minutes) than in the induction period of both institutions (group A: 350 [280-448] minutes [P = 0.005] and group D: 345 [270-420] mL [P = 0.002]). There were no surgery-related deaths in any of the groups. The incidence of postoperative complications did not differ among the four groups. Thoracoscopic radical esophagectomy can be mastered quickly and safely with a flat learning curve under the direction of an experienced surgeon. The educated surgeon can instruct surgeons at another institution on how to perform thoracoscopic esophagectomy. The operation time of thoracoscopic surgery is shortened by experience. © 2010 Copyright the Authors. Journal compilation © 2010, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus

Management of postoperative hemorrhage associated with factor VIII inhibitor: report of a case

This report presents a case that was successfully treated for acquired factor VIII inhibitor after extensive visceral surgery. A 71-year-old male who underwent surgery for bile duct cancer had active bleeding in the abdominal drainage tube on postoperative day (POD) 5, and prolonged activated partial thromboplastin time (aPTT) was detected (83.1 s) on POD 7. An extensive coagulation work-up revealed factor VIII deficiency (1 %), and a diagnosis of an acquired factor VIII deficiency was established when a factor VIII inhibitor of 8 Bethesda units was demonstrated. The patient was treated with activated prothrombin complex concentrate (aPCCs) and bloody discharge was stopped within 3 days. Inhibitor elimination was started using prednisolone on POD 20; rituximab, was administered on POD 74 and 81. Factor VIII inhibitor had disappeared by POD 124, and factor VIII (72 %) and aPTT recovered to 45.9 s. This case report demonstrated the efficacy of aPCCs and rituximab in the treatment of acquired hemophilia associated with visceral surgery. © 2012 Springer

P53, hTERT, WT-1, and VEGFR2 are the most suitable targets for cancer vaccine therapy in HLA-A24 positive pancreatic adenocarcinoma

Cancer vaccine therapy is one of the most attractive therapies as a new treatment procedure for pancreatic adenocarcinoma. Recent technical advances have enabled the identification of cytotoxic T lymphocyte (CTL) epitopes in various tumor-associated antigens (TAAs). However, little is known about which TAA and its epitope are the most immunogenic and useful for a cancer vaccine for pancreatic adenocarcinoma. We examined the expression of 17 kinds of TAA in 9 pancreatic cancer cell lines and 12 pancreatic cancer tissues. CTL responses to 23 epitopes derived from these TAAs were analyzed using enzyme-linked immunospot (ELISPOT), CTL, and tetramer assays in 41 patients, and factors affecting the immune responses were investigated. All TAAs were frequently expressed in pancreatic adenocarcinoma cells, except for adenocarcinoma antigens recognized by T cells 1, melanoma-associated antigen (MAGE)-A1, and MAGE-A3. Among the epitopes recognized by CTLs in more than two patients in the ELISPOT assay, 6 epitopes derived from 5 TAAs, namely, MAGE-A3, p53, human telomerase reverse transcriptase (hTERT), Wilms tumor (WT)-1, and vascular endothelial growth factor receptor (VEGFR)2, could induce specific CTLs that showed cytotoxicity against pancreatic cancer cell lines. The frequency of lymphocyte subsets correlated well with TAA-specific immune response. Overall survival was significantly longer in patients with TAA-specific CTL responses than in those without. P53, hTERT, WT-1, and VEGFR2 were shown to be attractive targets for immunotherapy in patients with pancreatic adenocarcinoma, and the induction of TAA-specific CTLs may improve the prognosis of these patients. © 2014 Springer-Verlag Berlin Heidelberg

Carcinomas of the ventral and dorsal pancreas exhibit different patterns of lymphatic spread

金沢大学医学部附属病院肝胆膵・移植外科　In patients with carcinoma of the head of the pancreas with positive lymph nodes, the extent of an adequate lymph node dissection beyond peripancreatic area has remained controversial. Based on the two anlagens, the ventral or dorsal pancreas, we assessed the lymphatic spread pattern in 58 primary adenocarcinoma of head of the pancreas. Detection of lymph node mestastasis was based on microscopic detection of carcinoma in consecutive serial sections of resected specimens including lymph nodes. When the tumor was confined to the ventral pancreas domain (n=20), the lymph node metastases were limited to areas along the superior mesenteric artery (SMA) besides peripancreatic lymph nodes. When the tumor was in the dorsal pancreas domain (n=6), the lymph node metastases were limited to areas along the common hepatic artery (CHA) and the hepatoduodenal ligament besides peripancreatic lymph nodes. When the tumor was extended into both domains (n=32), the lymph node metastases were distributed widely in areas along the SMA, CHA and the hepatoduodenal ligament besides peripancreatic lymph nodes. Based on these findings, the lymphatic spread of carcinomas of the head of the pancreas can be divided into two patterns by tumor location based on the two anlagens of the pancreas

A pure invasive micropapillary carcinoma of the pancreatic head: Long disease-free survival after pancreatoduodenectomy and adjuvant chemotherapy with gemcitabine [4]

金沢大学医学部附属病院肝胆膵・移植外科

Angiotensin II induces tumor progression and fibrosis in intrahepatic cholangiocarcinoma through an interaction with hepatic stellate cells

富山県立中央病院金沢大学医薬保健研究域医学系金沢大学附属病院胃腸外科Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis