Kazuyasu Takizawa

Left Posterior Approach to the Superior Mesenteric Vascular Pedicle in Pancreaticoduodenectomy for Cancer of the Pancreatic Head

CONTEXT Dissection of the superior mesenteric artery is the most important part of a pancreaticoduodenectomy for pancreatic cancer. Since 2005, we have used the left posterior approach for superior mesenteric vascular pedicle dissection, in which the superior mesenteric artery and the superior mesenteric vein are dissected first in a clockwise fashion. OBJECTIVE This article presents the technique of a left posterior approach and the clinical outcome. PATIENTS Forty patients underwent a left posterior approach and were compared to 35 patients treated with a conventional dissection. MAIN OUTCOME MEASURES The differences in surgical technique between the left posterior approach and the conventional method were described, and the short- and long-term surgical results compared patients who underwent the left posterior approach to those who were treated with the conventional method. INTERVENTION The superior mesenteric vascular pedicle was first dissected from the left lateral border of the superior mesenteric artery. The superior mesenteric vein was also dissected from the left side. Then, the uncinate process and perivascular soft tissue were separated en bloc from the vasculature. RESULTS No life-threatening complications occurred after the pancreaticoduodenectomies using a left posterior approach. Diarrhea requiring the administration of antidiarrheal agents occurred in 65% of patients; however, planned adjuvant chemotherapy was completed in all patients who did not have an early tumor recurrence. Survival rate was 52.8% at 3 years after surgery. CONCLUSION After a pancreaticoduodenectomy with a left posterior approach, most patients had various degrees of diarrhea, but the adjuvant chemotherapy was able to be continued with close monitoring. The left posterior approach facilitates understanding of the topographic anatomy in the superior mesenteric vascular pedicle.

Successful Super-Small-for-Size Graft Liver Transplantation by Decompression of Portal Hypertension via Splenectomy and Construction of a Mesocaval Shunt: A Case Report

We performed a successful super-small-for-size graft liver transplantation by decompressing portal hypertension via splenectomy and a mesocaval shunt. A 46-year-old woman with Child-Pugh class C liver cirrhosis associated with Wilsons disease underwent a living donor liver transplantation (LDLT). The donor had an anomalous portal vein, hepatic vein, and bile duct, so we had to use the right lateral segment for the graft. Preoperative computed tomographic (CT) volumetry showed the volume of this area to be 433 mL; graft-to-recipient weight ratio (GRWR) was 0.72; and graft-to-standard liver volume (GV/SLV) was 39.0%. However, the real volume of the resected right lateral segment was 281 g; GRWR was 0.47; and GV/SLV was 25.3%--a super-small-for-size graft. After implantation, congestion of the small graft was severe due to excessive portal hypertension. Therefore, we tried decompressing the portal vein. First, we performed splenectomy which reduced the portal pressure which remained excessive. Second, a mesocaval shunt was constructed decreasing the portal pressure from 38 to 30 cm H2O. Additionally, we initiated continuous portal injection of prostaglandin E1. The postoperative course was not smooth, but the general status slowly recovered. Over 25 cm H2O of portal hypertension was observed until postoperative day 21 when it improved. At last, the recipient was discharged on postoperative day 156. Accurate preoperative CT volumetry is important to obtain sufficient graft volume. Our case may be one of the smallest-for-size grafts that was successfully transplanted. Management of excessive portal hypertension is important for LDLT, especially using a small-for-size graft. Splenectomy and construction of a mesocaval shunt may be useful strategies to decompress the portal vein.

Splenic-intrahepatic left portal shunt in an adult patient with extrahepatic portal vein obstruction without recurrence after pancreaticoduodenectomy

In the last decade, a superior mesenteric-intrahepatic left portal shunt (Rex shunt) has been reported for successful management of extrahepatic portal vein obstruction in children. However, in adults, a mesocaval shunt has been generally performed for the surgical management of extrahepatic portal vein obstruction because of the complexity of the underlying disease and the difficulty of the superior mesenteric-intrahepatic left portal shunt. We herein report an adult patient who was successfully treated by splenic-intrahepatic left portal shunt with an artificial graft (6-mm polytetrafluoroethylene) for complete obstruction of the extrahepatic portal vein following pancreaticoduodenectomy. The shunt procedure not only relieved portal hypertension but also restored hepatic portal flow. In the near future, the Rex shunt should be considered for a beneficial management of extrahepatic portal vein obstruction, even in adults.

The long term follow-up of laparoscope-assisted living donor hepatectomy

BACKGROUND We have introduced and performed laparoscope-assisted surgery in living donor hepatectomy. The objective of this study was to investigate the long-term results of laparoscope-assisted living donor hepatectomy. METHODS From 2006 to 2016, laparoscope-assisted living donor hepatectomy was performed in 11 patients (laparoscopic group), and conventional open living donor hepatectomy was performed in 40 patients (conventional group). Intraoperative and postoperative complications were evaluated according to the Clavien-Dindo classification and analyzed in the laparoscopic group for comparison with the conventional group. RESULTS The median postoperative follow-up period was 88 months (range, 58-120 months) in the laparoscopic group. One donor in the conventional group died from a motor vehicle crash 16 months after surgery. All others were alive and returned to their preoperative activity level. Regarding intraoperative and early (≤90 days after surgery) postoperative complications, 1 patient (1/11, 9%) showed biliary fistula (Grade IIIa) in the laparoscopic group. In the conventional group, 6 patients (6/40, 15%) showed surgical complications of Grade I in 2 patients and Grade II in 4 patients. Regarding late (>90 days after surgery) postoperative complications, biliary stricture was observed in 1 patient of the laparoscopic group; this patient developed hepatolithiasis 6 years after surgery, and endoscopic lithotomy and extracorporeal shockwave lithotripsy were performed, resulting in successful treatment. Late complications were not observed in the conventional group. CONCLUSION One donor in the laparoscopic group showed Grade IIIa late complications. The introduction of laparoscopic surgery to living donor hepatectomy should be performed carefully.

Development of the Total Pancreatectomy and Autologous Islet Transplantation Models as the Step for Allogenic Islet Transplantation Experiments in the Swine

Background Islet transplantation has been established as a treatment for type 1 diabetes mellitus (DM). However, there are some problems to overcome, such as the necessity of transplantation from multiple donors repeatedly and the difficulty of achievement of the long term insulin independence. Creating an experimental model with large animal is extremely important as a preclinical study aiming to overcome those problems. We successfully established the total pancreatectomy combined with autologous islet transplantation model in the swine. Materials and Methods Thirteen swine weighing 10-20 kg underwent total pancreatectomy under general anesthesia. [Experiment 1] Eight swine underwent only total pancreatectomy (TP group), and the results of body weight, fasting blood glucose (FBS) and intravenous glucose tolerance test (IVGTT) before and after total pancreatectomy were compared and analyzed. [Experiment 2] Five swine underwent total pancreatectomy, then 50% of the excised pancreas were isolated by Ricordi method. Isolated pancreatic islets were autologously transplanted from portal vein into the liver (Islet Tx group) and their postoperative data was compared with that of TP group. Results [Experiment 1] Loss of body weight was significantly severer (+0.8 kg vs -1.9 kg, p=0.032) in 7 days after total pancreatectomy than in 7 days before total pancreatectomy. The value of FBS (49.4 mg/dl vs 327.0 mg/dl, p=0.001)) and IVGTT 120 min (84.0 mg/dl vs 364.7 mg/dl, p=0.044) were increased significantly after total pancreatectomy. Insulin secretion after glucose injection was not detected in this series. [Experiment 2] Compared with TP group, the loss of body weight was mild (-1.9 kg vs -0.1 kg, p=0.22), and the survival rate was significantly increased (38% vs 100%, p=0.035) in Islet Tx group. The value of postoperative FBS (327.0 mg/dl vs 97.4 mg/dl, p=0.001) and IVGTT 120 min (364.7 mg/dl vs 153.5 mg/dl, p=0.016) were significantly lower in the Islet Tx group. In the Islet Tx group, insulin secretion after glucose injection was detected. This is because transplanted islets were survive and functioning. Pathological specimens on the 7th day after islet transplantation showed the engraftment of transplanted pancreatic islets into the intrahepatic portal vein. Conclusions We successfully established the insulin dependent DM model by using total pancreatectomy in the swine. We also successfully established the total pancreatectomy and islet autotransplantation model in the swine. Improvement in the outcomes of islet transplantation would be expected by developing this model to allogeneic islet transplantation experiments.

Pathogenic Germline BRCA1/2 Mutations and Familial Predisposition to Gastric Cancer

Most gastric cancers (GCs) are considered sporadic, however familial aggregation occurs in 10% of cases1, 2. Approximately 5% of GCs are caused by an autosomal dominant inherited trait, with carriers having a strongly increased risk of GC and other cancers3. Clinical criteria for this entity were defined by the International Gastric Cancer Linkage Consortium (IGCLC)4. Among these, hereditary diffuse gastric cancer (HDGC) is a well-known type of familial GC (FGC). About 40% of families fulfilling the clinical criteria for HDGC have germline CDH1 mutations5. A subset of the remaining families of HDGC, and ones fulfilling the criteria of other familial GC, harbor pathogenic germline mutation in other genes which associated with hereditary cancer predisposition syndromes4. Hereditary breast and ovarian cancer (HBOC) is one of the best-described inherited cancer predisposition syndromes, caused by pathogenic germline BRCA1 or BRCA2 (BRCA1/2) mutations6–9. The increased risks of cancers other than breast and ovarian cancers were observed in the carriers10. The association between germline BRCA1/2 mutation and increased risk of GC were demonstrated in previous studies for HBOC families11–14. Regarding FGC, a recent large-scale study demonstrated that germline BRCA2 mutations were identified in patients who had a family history which fulfilled the criteria of HDGC, but lacking CDH1 mutations15. Therefore, it is possible that germline BRCA1/2 mutations may cause familial predisposition to GC. Recent advances of comprehensive genomic analysis enable us to identify the genomic alterations in GC16. BRCA1/2 mutations were shown in the subset of GC tumor tissues, however the association between germline BRCA1/2 mutations and familial predisposition to GC were not fully understood. Previously we performed genomic sequencing of 207 Japanese GCs using 435-gene panel, and identified BRCA1/2 mutations in tumor17. In this study, we conducted BRCA1/2 genetic testing in seven Japanese GC patients whose tumor had BRCA1/2 mutations. We identified pathogenic germline BRCA1/2 mutations in three patients, who have a familial component of GC.

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor

Duodenal gastrointestinal stromal tumors (GISTs) are extremely rare disease entities, and the extraluminal type is difficult to diagnose. These tumors have been misdiagnosed as pancreatic tumors; hence, pancreaticoduodenectomy has been performed, although partial duodenectomy can be performed if accurately diagnosed. Developing a diagnostic methodology including endoscopic ultrasonography (EUS) and fine-needle aspiration (FNA) has allowed us to diagnose the tumor directly through the duodenum. Here, we present a case of a 50-year-old woman with a 27-mm diameter tumor in the pancreatic uncus on computed tomography scan. EUS showed a well-defined hypoechoic mass in the pancreatic uncus that connected to the duodenal proper muscular layer and was followed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Histological examination showed spindle-shaped tumor cells positively stained for c-kit. Based on these findings, the tumor was finally diagnosed as a duodenal GIST of the extraluminal type, and the patient underwent successful mass resection with partial resection of the duodenum. This case suggests that EUS and EUS-FNA are effective for diagnosing the extraluminal type of duodenal GISTs, which is difficult to differentiate from pancreatic head tumor, and for performing the correct surgical procedure.

Successful Endoscopic Management of Acute Necrotic Pancreatitis and Walled Off Necrosis After Auxiliary Partial Orthotopic Living-Donor Liver Transplantation: A Case Report

Endoscopic management of acute necrotic pancreatitis and walled off necrosis is less invasive than surgical treatment and has become the 1st choice for treating pancreatic necrosis and abscess. We treated a case of acute necrotic pancreatitis and walled off necrosis after auxiliary partial orthotopic living-donor liver transplantation (APOLT). A 24-year-old woman was admitted to our university hospital for removal of the internal biliary stent, which had already been placed endoscopically for the treatment of biliary stricture after APOLT. She had been treated for acute liver failure by APOLT 10 years before. After we removed the internal stent with the use of an endoscopic retrograde approach, she presented with severe abdominal pain and a high fever. Her diagnosis was severe acute pancreatitis after endoscopic retrograde cholangiography (ERC). Her symptoms worsened, and she had multiple organ failure. She was transferred to the intensive care unit (ICU). Immunosuppression was discontinued because infection treatment was necessary and the native liver had already recovered sufficiently. After she had been treated for 19 days in the ICU, she recovered from her multiple organ failure. However, abdominal computerized tomography demonstrated the formation of pancreatic walled off necrosis and an abscess on the 20th day after ERC. We performed endoscopic ultrasonography-guided abscess drainage and repeated endoscopic necrosectomy. The walled off necrosis diminished gradually in size, and the symptoms disappeared. The patient was discharged on the 87th day after ERC. This is the 1st report of a case of acute necrotic pancreatitis and walled off necrosis that was successfully treated by endoscopic management after APOLT.

Study of Immune Tolerance Cases in Adult Living Donor Liver Transplantation

BACKGROUND Complete immune tolerance is the chief goal in organ transplantation. This study aimed to evaluate patients who successfully withdrew from immunosuppressive (IS) agents after living donor liver transplantation (LDLT). MATERIALS AND METHODS A retrospective review of all adult LDLT from July 1999 to March 2012 was conducted. In patients who acquired immune tolerance after LDLT, their background and the course of surgical procedures were evaluated. RESULTS Of a total of 101 adult LDLT patients, 8 patients were completely free of IS agents. Six of these patients (75%) were female, and the median age at the time of transplantation was 56 years (range, 31-66 years). The primary disease causing liver failure was type C liver cirrhosis (50%), fulminant hepatitis (25%), type B liver cirrhosis (12%), and alcoholic liver cirrhosis (12%). The median Child-Pugh score and MELD score were 13 points (range, 8-15 points) and 19 points (range, 10-18 points), respectively. The living related donor was the recipients child (75%), sibling (12%), or parent (12%). ABO compatibility was identical in 62%, compatible in 25%, and incompatible in 12%. CONCLUSIONS In this study, we evaluated the adult patients who successfully withdrew from IS agents after LDLT. In most cases, it took more than 5 years to reduce IS agents. Because monitoring of the serum transaminase level is not adequate to detect chronic liver fibrosis in immune tolerance cases, further study is required to find appropriate protocols for reducing IS agent use after LDLT.

The Role of Wide Excision of Occult Cancer Tissue Harbored Posteriorly to the Superior Mesenteric Artery

We would like to thank Drs. Dumitrascu and Popescu for their letter. A major point of comment regarding our article is the question that “the surgical outcome was improved but status of positive surgical margin was not changed”. As shown in our article [1], postoperative survival after a pancreaticoduodenectomy using left posterior approach was improved as compared with that after a pancreaticoduodenectomy using conventional methods in “univariate analysis”, but the difference was not shown in “multivariate analysis”. It is well known the nerve bundle arising from the celiac ganglia forms the superior mesenteric plexus and then ramifies into the secondary plexus consisting of pancreatic branches and intestinal branches. The superior mesenteric plexus is thin and located in the innermost layer. Although the excision of the superior mesenteric plexus or the intestinal branches causes severe diarrhea after surgery, excision of the pancreatic branches alone does not influence intestinal motility. Regardless of the dissection techniques, the principal variable affecting postoperative intestinal motility is whether or not dissection of the superior mesenteric plexus was performed, and whether the dissection was performed partially or extensively. In the control group of our study [1], the right half of the superior mesenteric plexus was resected. Accordingly, it is thought that the incidence of diarrhea did not differ significantly between the two groups. From the point of view of the pathological examination, the resected margin of the plexus showed a complicated and irregular shape in the left posterior approach rather than in the conventional dissection (dissection on the right side of the superior mesenteric artery). Considering the mode of tumor extension involved in perineural invasion, the cancer cells spread continuously along the perineural space as reported previously by Nagakawa et al. [2]. However, on the mapping of the tumor extension in our study (Figure 3) [1], the deposit of the perineural invasion was far from the main tumor in some cases. The continuity of the perineural spread of the tumor was divided by the dissection of the plexus. In addition, the resected plexus was sampled and underwent intraoperative frozen section examination in some cases. Accordingly, the identification of the true surgical margins, especially the medial margin, may sometimes be difficult. The method of pathologically examining the evaluation of the status of the medial margin was altered gradually during the study period. In our study, the plexus invasion-positive case was taken as the margin-positive case [1]. The more detailed pathology examination was conducted in the left posterior approach group as compared to the control group. It may be one of the possible reasons that the positive rate in medial margin status did not decrease. However, we believe that the occult cancer tissue which was harbored posteriorly to the superior mesenteric artery was widely excised using the left posterior approach, and that local recurrence around the artery was reduced. Nowadays, gemcitabine-based chemotherapy is the most popular therapy in a postoperative adjuvant setting. The preoperative imaging diagnosis for patient selection and postoperative management, including adjuvant chemotherapy, have improved rapidly. Liver perfusion chemotherapy [3] was performed more frequently in the left posterior approach group as compared to the control group [1], although its Received August 9, 2011