The first case of pancreatoduodenectomy(PD) in Japan was done by Kuru in 1946, then Yoshioka in 1947, and then Honjyo performed a total pancreatectomy in 1949. Portal vein resection combined with PD was reported by Kikuchi in 1956 and by Asada in 1963. They used 70% alcohol-preserved homograft of the vein. Fortner's report of regional pancreatectomy in 1973 greatly impressed Japanese pancreatic surgeons. Then in 1981, I developed my own catheter-bypass method of the portal vein using antithrombogenic material. The isolated pancreatoduodenectomy combined with portal vein resection was completed. This bypass method made it possible to prevent portal congestion or hepatic ischemia during portal vein resection or simultaneous resection of the hepatic artery. Thus, vascular resection has become safer and easier during pancreatic surgery. Extended radical pancreatic resection was developed during the 1970s and 1980s. The high mortality rate of PD in the 1950s and 1960s decreased gradually to within 10% in the 1980s and 5% in the 1990s. Hanyu had performed a landmark 1000 PDs in 1997, and the mortality rate has been 1% since 1989.
We have performed 825 pancreatic resections, for various diseases since 1981 and mortality was observed in 14 cases (1.7%). Moreover 441 pancreatic resections for pancreatic cancer along with combined resection of the portal vein were performed in 282 cases during 1981-2009. The mortality rate of PD for pancreatic cancer was 2.7% in my series, but no mortality has been experienced in the last 11 years. However, the prognosis for pancreatic cancer is still poor and adjuvant therapy has been combined with radical surgery such as intraoperative radiotherapy using linac, and intraportal continuous infusion of 5-FU. Adjuvant chemotherapy using gemcitabine or TS-1 and clinical trial of oncolytic virus therapy using herpes simplex virus (HF10) have been performed, yet numerous problems remained to be solved.
I have devised techniques such as isolated pancreatoduodenectomy combined with portal vein resection using catheter-bypass method for the portal vein and a mesenteric approach and pancreatic head resection with segmental duodenectomy(PHRSD) for IPMN. Every day I still feel great pleasure and a sense of fulfillment in performing surgery. Surgeons are able to care for patients all the way from diagnosis and surgery through postoperative management and follow-up after the patient leaves the hospital. This sense of accomplishment is truly great, and it is a specialty that I believe we should be sure to pass down to younger people. Let me say that I am filled with gratitude to my colleagues and the younger doctors I have worked with in medical practice and research.

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Eighty-one cases of pancreas transplants from deceased, non-heart-beating, and living-related donors have been performed in Japan from April 2000 to the end of 2009, after the so-called "Organ Transplantation Law" the law regarding organ transplantation, took effect on October 16, 1997. This included the first case of simultaneous pancreas and kidney transplantation(SPK) on April 2000, 47 cases of SPK, 9 cases of PAK (pancreas after kidney transplantation) , and 3 cases of PTA (pancreas transplantation alone) were performed from deceased donors. Furthermore, two cases of SPK from non-heart-beating donors(NHBD) and 20 cases from living-related donors were also performed.
It is characteristic that pancreas transplantation in Japan was mostly marginal (73.8%). In spite of donor poor conditions, the outcome of pancreas transplants in Japan was considered comparable to that of United States and Europe. Pancreas transplant 1-year, 3-year and 5-year graft survival rates were 88.4%, 83.6%, and 73.3%, respectively.

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Pancreas transplantation and simultaneous pancreas-kidney transplantation(SPK) have been recognized as the best treatment for type 1 diabetic patients. The number of brain-death donors has been increasing in Japan since the revision of the Organ Transplantation Act on July 2010. For the transplant surgeons, appropriate operative techniques for multi-organ procurement from both brain-dead and non-heart-beating donors (from bench surgery including the inspection of the graft and vascular reconstruction) and recipient surgery are necessary in order to achieve successful outcomes.
Procurement of the pancreas from a brain-dead donor is different depending whether removal of the intestine and/or the liver is performed. We usually prioritize the small intestine and first cut the superior mesenteric vessels, proceeding next to the liver to give way to the hepatic artery, the splenic artery and the portal vein. In any case, we use the "Super Rapid Technique" combined with core cooling and surface cooling to reduce excess manipulation and to avoid organ warming during the procurement process. For the recipient operation, we usually position the pancreas graft on the right iliac fossa to anastmose the graft vessels onto the external iliac vessels and to drain pancreatic juice either to the intestine or bladder. In the case of SPK, the kidney graft is usually placed on the opposite side, left iliac fossa extraperitoneally.
Herein, the current standard and most favorable techniques for pancreas transplantation in Japan have been described.

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Outcome after pancreas and islet transplants have consistently improved. The reasons are multifactorial, including better recipient care with respect to surgical and isolation techniques, immunosuppressive regimens and preservation protocol. In this review, we summarize the recent literature regarding the current advances in pancreas preservation. A hypothermic pulsatile machine perfusion method, developed and widely used for clinical kidney transplants, was not applied for clinical pancreas transplantation. A simple cold storage method is the most widely used preservation method for all solid organs. The University of Wisconsin(UW) solution has been the standard preservation solution for the pancreas for almost 20 years. Colloid-free Celsior and histidine-tryptophan-ketoglutarate preservation solutions are equivalent to UW solution for cold storage before pancreas transplant.
A two-layer cold storage method (TL), developed at Kobe University, consists of a perfluorochemical and cold storage solution that can supply oxygen to the pancreas graft during preservation. A number of studies on human pancreas have reported the beneficial effect of TL on islet isolation outcomes since 2000. Recently, TL, using M-Kyoto solution instead of UW solution, and pancreatic ductal injection with trypsin inhibitor have reported promising outcomes in human islet isolation and transplant.
Further studies are needed to increase the availability of marginal and non-heart beating donors in pancreas transplant and to achieve single-donor islet transplantation.

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Fourteen type 1 diabetic patients with end-stage renal diseases underwent simultaneous pancreas and kidney transplantation from living donors (LDSPKs) from 2004 to 2010. All of them showed frequent hypoglycemic unawareness because of negative serum C-peptide levels (CPR; <0.03ng/ml). Six donors were ABO-incompatible for the recipients. All of them fulfilled the donor criteria for LDSPK. The donor operation was initiated with a right nephrectomy followed by distal pancreatectomy with laparoscopic procedure (HALS). LDSPK was performed by a pancreatico-cystostomy. Immunosuppression was achieved by quadruple therapy and a desensitization protocol was added for the ABO-incompatible cases. None of the donors showed any complications. One recipient developed primary non-function of the pancreas graft after transplantation. The other 13 patients immediately achieved insulin independency. The results of consecutive clinical trials demonstrated that LDSPK may therefore be a good therapeutic alternative and a potent tool for the treatment of type 1 diabetic patients with ESRD.

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Pancreas transplantation(PTx) is only established treatment to achieve insulin independency over a long period in type 1 diabetic patients. Survival rates of patient and pancreas graft in Japan were equivalent to those in the United States and Europe, but delayed endocrine pancreas graft function(DEGF) was frequently observed after PTx. Such high incidence of DEGF might relate to the high incidence of marginal donors and a high dose of immunosuppressant in the acute period after PTx. Therefore, early evaluation of endocrine graft function after PTx might be beneficial to predict insulin-independency and detect graft failure. We found that a 72-hour insulin requirement after PTx by using an artificial pancreas correlated highly with endocrine graft function at one month and one year post-transplantation. PTx also gradually ameliorated abnormal glucagon secretion in type 1 diabetic recipients, it might reduce insulin requirement after PTx. Since drug therapy for preserving pancreatic beta cells has not been established, lifestyle intervention might play an important role to persist endocrine graft function.

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The program of islet transplantation in Japan was started in 2004. Sixty-five islet isolations were performed for 34 transplantations in 18 patients with insulin-dependent diabetes mellitus. Overall graft survival defined as C-peptide level more than or equal to 0.3ng/ml was 76.5, 47.1, and 33.6% at 1, 2, and 3 years, respectively. Three of these recipients became insulin independent transiently. Clinical islet transplantation will resume as a clinical trial using mammalian-free enzyme to assess a new immunosuppression protocol.

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Islet transplantation is a cell transplantation therapy for insulin dependent diabetic patients with isolated islet cells. Invasiveness of the transplantation procedure is relatively low thus making it easier for patients; however, islet isolation technology remains challenging.
In order to improve the results of islet isolation, we introduced pancreatic ductal preservation, oxygen-charged static two-layer method and density adjusted islet purification method. With these modified technologies, our success rate of islet isolation has now reached approximately 90%. In addition, the newest protocol made it possible to perform single donor islet transplantation.
Improving the technology of islet isolation directly contributes to the improvement of clinical outcomes of islet transplantation. This is an important step to bring islet transplantation into the standard therapy.

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Pancreatic islet transplantation has now become the procedure of choice for the treatment of insulin-dependent diabetes mellitus(IDDM) since the report of successful islet transplantation by Shapiro et al in 2000. Current obstacles facing clinical islet transplantations include the inability to achieve insulin independence in IDDM recipients after islet transplantation from a single donor. One way to resolve this is to improve methods regarding donor pancreas preservation and islet isolation to afford an increase in number and viability of donor islets, and the other is to find a novel procedure to prevent loss of islets after transplantation. In this report, we refer to the latter, especially to early loss of transplanted islets within 24 hours after transplantation, and show our original findings in which islet transplantation from one donor to even two recipients becomes feasible by preventing early loss of transplanted islets in an experimental setting.

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After the success of the "Edmonton protocol", islet transplantation has been performed worldwide as a treatment for type I diabetes. The long-term outcome of islet transplantation is not satisfactory; insulin free rate at 5 years after transplantation is 10-15%. Thus, there is a strong clinical need to assess survival of transplanted islets non-invasively with clear-cut quantification. Islets are too small (≤400μm) to detect by present clinical imaging modalities, but several recent studies have confirmed the ability to localize islets by magnetic resonance image(MRI) using the iron labeling method. In this review, we introduce the current progress of MRI technology for monitoring transplanted islets with our and other published data.

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In islet transplantation, recipients need to be transplanted with islets from two to three donor pancreas, but an insulin independence thus achieved is hardly maintained for an extended period after transplantation. Specific immunological challenges to islet transplantation as well as allogenic reactions are involved in the destruction of transplanted islets. Immediately after islet infusion through the portal vein and contact with the recipients' blood, an instant blood-mediated inflammatory reaction(IBMIR) is triggered by complement-coagulation cascades and associated innate immune responses. This is followed by an early rejection reaction mediated by DNA-binding protein in the islets. Recurrence of autoimmunity also impinges on the long-term survival of the islets. To improve the success rates of islet transplantation, several methods have been designed to protect the islets from these immune reactions. Regarding an immunosuppressive regimen, the University of Minnesota has designed a new protocol, which we are planning to introduce in Japan.

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Pancreatic endocrine tumors(PETs) rarely show complete obstruction of the main pancreatic duct(MPD) compared with pancreatic ductal carcinoma on endoscopic retrograde pancreatography(ERP). We herein report 2 cases of PETs with complete MPD obstruction. The first case is a male in his 40's who was referred to our hospital for further examination of a pancreatic tumor. The other case involves a male in his 40's who visited us for the scrutiny of the MPD dilatation. On ERP, complete MPD obstruction was seen in both cases. The final diagnosis was well-differentiated endocrine carcinoma and well-differentiated endocrine tumor (uncertain behavior), respectively. Moreover, contrast-enhanced endoscopic ultrasonography(CE-EUS) presented atypical poor enhanced images in both cases. We thought the complete MPD obstruction on ERP and unusual images on CE-EUS might be important factors for predicting the malignant potential in PETs.

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A 73-year-old male was admitted to our hospital due to a sense of thirst. Elevation of HbA1c was detected, and dilatation of the main pancreatic duct was revealed by an abdominal US. An atrophic pancreas and dilatation of the main pancreatic duct from the body to tail were shown by abdominal CT, but no neoplastic lesions of pancreas. EUS images showed the dilated main pancreatic duct and an irregular, low echoic mass measuring 10mm in diameter located near to the dilated main pancreatic duct. To make a definite diagnosis, EUS-FNA was performed, and the pathological diagnosis was adenocarcinoma. Subtotal pancreatectomy was performed, and the final pathological diagnosis was invasive ductal carcinoma. However, two endocrine tumors were detected by chance in the pancreatic tail. Because their MIB-1 indexes were less than 1%, they were classified into low risk group. We had the experience of a small pancreatic carcinoma associated with endocrine tumor.

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A 63-year-old man visited a local hospital because of upper abdominal discomfort. He was diagnosed with pancreatic cystic disease, and referred to our hospital. Blood chemistry showed elevated levels of CA19-9 (90.3U/l) and Span-I (45U/ml). Abdominal CT revealed a large 10-cm cyst containing a 2-cm, node-like structure with contrast enhancement. ERCP showed that the cyst did not communicate with the main pancreatic duct, but compressed it. At surgery, a softball-sized tumor was observed in the pancreatic head. It was straightforward to dissect from the stomach, but difficult to free the pancreas, particularly a portion in the head, which was diagnosed as the site from which the cyst arose. The cyst contained a gruel-like fluid with plasma components, as well as a 2-cm nodule on its dorsal side. Histopathological examination revealed a cystic lesion containing keratinized material and lined with stratified squamous epithelium, which was immediately underlain by lymphatic tissue. These findings led to a diagnosis of lymphoepithelial cyst.

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The patient was a 46 year-old man who developed a pseudocyst and a pseudoaneurysm in it due to chronic pancreatitis. Angiography showed a blood stream into the aneurysm, therefore, transarterial embolization was conducted. Because relapsing pancreatitis was observed after that, a distal pancreatectomy was performed. Dilatation of the main pancreatic duct and relapsing pancreatitis were observed in postoperative course. Because endoscopic ultrasonography guided drainage of dilated pancreatic duct was impossible, a lateral pancreaticojejunostomy for remnant pancreas (Partington procedure) was performed. The postoperative course was uneventful and the patient was discharged on the 10th postoperative day. The patient has not suffered from recurrent pancreatitis for 1 year and 5 months after surgery. There have been no reports of a Partington procedure for recurrent pancreatitis after distal pancreatectomy for chronic pancreatitis like our case. Our case implies usefulness of surgical drainage procedure even after resection of pancreas.

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A 61-year-old man admitted for lower back pain and a malignant pancreatic tumor was suspected and later confirmed after several studies. The tumor was hypervascularized with central necrosis and was rapidly increasing in size. No metastases were found. A distal pancreatectomy and splenectomy were performed, and simultaneously, total gastrectomy and left adrenalectomy were added due to direct invasion. The specimen was a solid tumor with fibrous capsule, and the diameter was approximately 10cm. Histopathologically, the tumor was diagnosed as pleomorphic anaplastic carcinoma of the pancreas. After the surgery we have observed this case for 6 years so far without adjuvant chemotherapy, and no recurrence or metastasis has been revealed. Anaplastic carcinoma of the pancreas is a rare histologic type among pancreatic malignant neoplasms and is associated with poor prognosis. But our experience suggests that there is a possibility to achieve long term survival in cases in which a curative resection is performed.

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