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Background Plexiform schwannoma is one of the least common variants of schwannoma, accounting for only 5% of all schwannoma cases. It generally occurs in the skin and subcutaneous tissues and is uncommon in deep soft tissue or viscera. We present an extremely rare case of plexiform schwannoma arising from the peripancreatic plexus. Case presentation A 29-year-old man presented with hyperglycemia detected during a medical checkup. He was diagnosed with type 1 diabetes based on the clinical findings and laboratory tests. During the diagnostic process for diabetes, a 2.5 cm mass was incidentally detected in the pancreas by abdominal ultrasound. Contrast-enhanced computed tomography revealed a mass that was gradually enhanced at the body and tail of the pancreas. Magnetic resonance imaging revealed low signal intensity of the mass on T1-weighted images and high signal intensity on T2-weighted and diffusion-weighted images. Magnetic resonance cholangiopancreatography showed no abnormal findings in the main pancreatic duct. Endoscopic ultrasonography (EUS) showed a lobulated, low-echoic mass with a clear boundary. EUS-guided fine needle biopsy was performed, and spindle-shaped cells that were diffusely immunopositive for S-100 and negative for c-kit and desmin were detected, resulting in a diagnosis of a neurogenic tumor arising from the pancreas or the peripancreatic nerve plexus. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. Although the tumor was connected to the splenic plexus, the splenic artery could be divided along its adventitial plane. Macroscopic findings of the excised tumor consisted of multiple yellowish-white nodules, and its histopathological features were consistent with plexiform schwannoma. There was no pancreatic tissue on the dorsal surface of the tumor, which suggested that the tumor arose from the peripancreatic nerve plexus. Conclusions The findings documented herein can aid in the differential diagnosis of peripancreatic schwannoma and in planning appropriate treatment.

Background Prospective studies are needed to understand the safety and feasibility of laparoscopic pancreatectomy. The aim of the present study was to describe laparoscopic pancreatectomy currently undertaken in Japan, using a prospective registration system. Methods Patient characteristics and planned operations were registered preoperatively, and then the performed operation and outcomes were reported using an online system. Collected data were also compared between institutions based on their level of experience. This study was registered with UMIN000022836. Results Available data were obtained from 1,429 patients at 100 Japanese institutions, including 1,197 laparoscopic distal pancreatectomies (LDPs) and 232 laparoscopic pancreatoduodenectomies (LPDs). The rates of completion for planned operations were 92% for LDP and 91% for LPD. Postoperative complication rates after LDP and LPD were 17% and 30%, and 90-day mortality rates were 0.3% and 0.4%, respectively. Shorter operation time, less blood loss, and lower incidence of pancreatic fistula were observed in institutions experienced in LDP. A higher rate of pure laparoscopic procedure and shorter operation time were noted in institutions experienced with LPD. Conclusion LDPs and LPDs are performed safely in Japan, especially in experienced institutions. Our data could support the next challenges in the field of laparoscopic pancreatectomy.

A 61-year-old man was examined for cervical pain and CT showed a 9 cm tumor to the third part of the duodenum and proximal jejunum. CT /MRI showed that the tumor was separated from the pancreas body. We scheduled a laparoscopic partial resection of the intestine with a suspected diagnosis of GIST of the intestine. The tumor was adhered to both the proximal jejunum and uncinate process of the pancreas. Therefore, we converted to an open surgery and resected part of the pancreas, duodenum, and proximal jejunum including the tumor. Histopathological examination showed the tumor capsule included the tissue of the pancreas and that the border between the intestine and the tumor was clear, suggesting that the origin of the tumor was the pancreas. We diagnosed the patient as having a grade 2 pancreatic neuroendocrine tumor based on the tumor growth pattern and immunohistochemistry findings. We examined the preoperative CT images retrospectively and found that the tumor had adhered to the uncinate process of the pancreas, which extends over the left side of the superior mesenteric artery. When GIST close to the proximal jejunum is suspected, the possibility of pancreatic neuroendocrine tumor should be considered.

A 73-year-old man visited our hospital with the chief complaints of anorexia and weight loss. Computed tomography showed a 5 cm tumor(diameter)in the sigmoid mesocolon. We performed laparoscopic Hartmann operation; however, because of sacral invasion of tumor, curative surgery was difficult. Therefore, the tumor was excised together with the sigmoid colon. Histopathological examination of the tumor confirmed the diagnosis of epithelioid sarcoma. Postoperatively, the patient received heavy-particle radiotherapy at another facility as treatment for the residual tumor. The size of the residual tumor decreased 6 months after the surgery. Up until 1 year after surgery, the patient's condition has remained stable without any disease progression. Epithelioid sarcoma is a rare soft-tissue tumor and often leads to a poor prognosis. We present a case of epithelioid sarcoma occurring in the sigmoid mesocolon.

Background Postpancreatectomy hemorrhage (PPH) is a life-threatening complication of pancreatic surgery. The shift from surgical to radiological intervention was recently reported in retrospective cohort studies, but it has remained controversial as to which emergent intervention provides optimal management. Methods All 553 patients who underwent standard pancreatic resection at Kobe University Hospital between January 2003 and December 2013 were included. Patient data and complication data were identified from a prospective database. Results The overall incidence of PPH was 6% (35 of 553 patients). Ten patients underwent endoscopic intervention or observation monitoring, or suffered hemorrhagic sudden death. Among the remaining 25 PPH patients, primary surgical intervention was successful in the 6 hemodynamically unstable PPH patients. Primary radiological intervention could successfully stop the bleeding in 15 of the 17 patients with late-PPH. Nine patients who had bleeding from the hepatic artery after pancreaticoduodenectomy were rescued by endovascular embolization of the artery-trunk. The in-hospital mortality of PPH was 20% (7 of 35). Four of the 5 PPH patients who died following any intervention eventually died due to the other complications associated with prolonged pancreatic fistula. Conclusions The leading treatment has been radiological intervention. Endovascular embolization of the hepatic artery-trunk can be securely performed only if blood flow to the liver by an alternate route is confirmed. To reduce mortality of PPH patients, it is necessary to prevent other complications associated with pancreatic fistula following hemostasis. Proactive surgical intervention such as abscess drainage or remnant pancreatectomy is a key consideration.

A 72-year-old man underwent endoscopic submucosal dissection for early gastric cancer at antrum in July 2015. The histopathological examination revealed an adenocarcinoma invading the deep submucosal layer(SM2)with lymphatic invasion, consistent with the diagnosis of non-curative resection. Additional surgery was recommended, and he underwent laparoscopic distal gastrectomy in August 2015. The histopathological examination of resected specimen revealed there were no lymph node metastases, and postoperative diagnosis was Stage I A. However, 8 months after the surgery, abdominal enhanced computed tomography(CT)revealed an enlargement of para-aortic lymph node. Positron emission tomography-CT showed high accumulation at the enlarged lymph node. A para-aortic lymph node metastasis was suspected, and laparoscopic lymph node dissection was performed in July 2016. The histopathological examination revealed lymph node metastasis of gastric cancer. He was given systematic chemotherapy using S-1 plus cisplatin after the surgery, and has been followed-up without recurrences for 21 months after the first operation. Although recurrence of the para-aortic lymph nodes was assumed as part of a systemic metastasis, some population certainly benefit from multidisciplinary treatment including surgical approach.

Although surgical resection remains the only chance for cure in patients with pancreatic ductal adenocarcinoma (PDAC), postoperative early recurrence (ER) is frequently encountered. The purpose of this study is to determine the preoperative predictive factors for ER after upfront surgical resection.Between 2001 and 2012, 968 patients who underwent upfront surgery with R0 or R1 resection for PDAC at seven high-volume centers in Japan were retrospectively reviewed. ER was defined as relapse within 6 months after surgery. Study analysis stratified by resectable (R) and borderline resectable (BR) PDACs was conducted according to the National Comprehensive Cancer Network guidelines.ER occurred in 239 patients (25%) with a median survival time (MST) of 8.8 months. Modified Glasgow prognostic score = 2 (odds ratio (OR) 2.06, 95% confidence interval (CI) 1.05-3.95; P = 0.044), preoperative CA19-9 ≥300 U/ml (OR 1.94, 1.29-2.90; P = 0.003), and tumor size ≥30 mm (OR 1.72, 1.16-2.56; P = 0.006), were identified as preoperative independent predictive risk factors for ER in patients with R-PDAC. In the R-PDAC patients, MST was 35.5, 26.3, and 15.9 months in patients with 0, 1 and ≥2 risk factors, respectively. There were significant differences in overall survival between the three groups (P0.001). No preoperative risk factors were identified in BR-PDAC patients with a high rate of ER (39%).There is a high-risk subset for ER even in patients with R-PDAC and a simple risk scoring system is useful for prediction of ER.

The therapeutic strategy for borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) has remained unestablished because the preoperative prognostic factors have not been determined. One hundred eighty-four consecutive PDAC patients who underwent upfront surgery with a curative resection between January 2000 and June 2013 at Kobe University Hospital were retrospectively studied. The PDAC patients were stratified into resectable (R)-PDAC (n = 147) and BR-PDAC patients (n = 37). We evaluated the independent prognostic significance of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) in the BR-PDAC patients. BR-PDAC patient survival was significantly worse than R-PDAC patient survival (median survival time: 22.1 months vs. 24.3 months; 5-year survival rate 6 vs. 21 %; P = 0.042). The median survival in BR-PDAC patients with a preoperative NLR of >3 (n = 12) was 10.2 months, while that in patients with preoperative NLR of ≤3 (n = 25) was 24.9 months (P = 0.002). Moreover, the median survival in BR-PDAC patients with a preoperative PLR of >225 (n = 8) was 10.2 months, while that in patients with a preoperative PLR of ≤225 (n = 29) was 24.7 months (P = 0.003). Preoperative NLR >3 (HR = 2.980, 95 % CI 1.251–6.920; P = 0.015) and PLR >225 (HR = 3.050, 95 % CI 1.169–7.468; P = 0.024) were independent prognostic factors in BR-PDAC patients. Higher preoperative NLR and PLR can be independent predictive risk factors in BR-PDAC patients following curative resection.

A 63-year-old woman had recurrences of metastatic rectal cancer in the lung, peritoneum, and ovary. Regorafenib was administered at 160mg/day as third-line chemotherapy. The patient developed Grade(Gr)3 hand-foot syndrome(HFS) and Gr 2 rash, but the abdominal distension and pain were relieved by the 1st course. Analgesics could be reduced and regorafenib was administrated at reduced dosage. The patient received keishi-bukuryo-gan(EK-25)and sai-rei-tou(TJ-114) for HFS. At the beginning of therapy, ovarian metastases were not reduced and showed poor contrast enhancement on CT. Serum levels of lactate dehydrogenase(LDH)and tumor markers were increased. During the 4th course of therapy, ovarian metastases tended to shrink and serum levels of LDH and tumor markers were decreased. Ovarian metastases showed a partial response(PR)after the 6th course. Lung metastases showed a progressive disease during the 2nd course, but a PR after the 3rd course, and were not apparent after the 6th course. Reduction of metastases was maintained at 16 months after the start of therapy, and HFS was assessed at Gr 2 or lower. Physical, laboratory, and imaging findings should be carefully evaluated prior to long-term administration of regorafenib.

Acute graft-versus-host-disease (aGVHD) is a rare complication in the setting of pancreas-kidney transplantation (PKT). We herein describe the case of a 37-year-old male with severe type 1 diabetes with chronic renal failure who received simultaneous PKT from a female donor. Diarrhea developed on postoperative day (POD) 10. Subsequently, fever and liver dysfunction occurred on POD 32. Skin rashes appeared with pain and itching on his trunk and extremities on POD 40. As pancytopenia occurred on POD 63, bone marrow biopsies demonstrated profound hypoplastic marrow. On POD 69, we eventually made a definitive diagnosis of aGVHD because skin biopsies revealed the XX chromosome signal in a fluorescence in situ hybridization analysis. Thereafter, 100 mg of prednisolone was administered for 5 days. Although every symptom was temporarily improved, on POD 156, the patient expired from the septic pneumonia without any effects of antibiotics. Clinician should be aware that PKT has the potential to induce aGVHD.

Background and Objectives Pylorus-preserving pancreatoduodenectomy (PPPD) has been associated with a high incidence of delayed gastric emptying (DGE). There are few studies comparing DGE associated with PPPD and subtotal stomach-preserving pancreatoduodenectomy (SSPPD). Moreover, differences between the procedures with respect to long-term results have not been reported. A prospective randomized study was conducted to compare perioperative complications and long-term nutritional status with PPPD and SSPPD. Methods One hundred patients with periampullary lesions were randomized to receive either PPPD (n = 50) or SSPPD (n = 50). All patients were followed up for 3 years after surgery or to the time of recurrence to evaluate nutritional status for the study. The effects of the procedure, age, and malignancy on changes in nutritional indicators were estimated with linear mixed models. This study was registered at UMIN Clinical Trials Registry (UMIN 000012337). Results The incidence of DGE assessed by the International Study Group of Pancreatic Surgery was 20% with PPPD and 12% with SSPPD (P = 0.414). There were no significant differences between the two procedures on postoperative serum albumin levels, serum total cholesterol levels, and body mass index during the 3-year follow-up period. Conclusions SSPPD is equally effective in DGE occurrence rate and long-term nutritional status comparing to PPPD. J. Surg. Oncol 2014; 109:690–696. © 2014 Wiley Periodicals, Inc.

Background & Aims There are no accurate and reliable tools for diagnosis of early stage pancreatic ductal adenocarcinoma (PDA) or small metastatic lesions. It is also a challenge to differentiate PDA from focal mass-forming pancreatitis (FMP). There is controversy regarding the efficacy of 18-fluorodeoxyglucose positron-emission tomography (FDG-PET) in the diagnosis of PDA. We investigated whether FDG-PET provides information that, combined with data from other imaging techniques, can aid in decision making for patients with suspected PDA. Methods We performed a retrospective analysis of data collected from 232 consecutive patients with suspected PDA at Kobe University Hospital from January 2006 through June 2012. All patients underwent a diagnostic imaging protocol that included multidetector row computed tomography, superparamagnetic iron oxide–enhanced magnetic resonance imaging, and FDG-PET. Based on endoscopic ultrasonography, fine-needle aspiration biopsy, or endoscopic retrograde cholangiopancreatography analyses, 218 patients had PDA (89 underwent resection and 129 did not) and 14 patients had FMP (8 had focal mass-forming chronic pancreatitis and 6 had focal mass-forming autoimmune pancreatitis). Results FDG-PET detected 50% of stages 0 and I, 91.9% of stage II, 100% of stage III, and 96.8% of stage IV tumors. Detection was affected significantly by tumor size ( P = .024) and T stage ( P = .023) in resected tumors. Multidetector row computed tomography detected significantly more liver metastases than FDG-PET. Few para-aortic lymph node or peritoneal metastases were detected by FDG-PET. FDG-PET correctly identified 11 of the 14 patients with FMP (5 of 8 with focal mass-forming chronic pancreatitis and 6 of 6 with focal mass-forming autoimmune pancreatitis). Conclusions FDG-PET is not effective in detecting early stage PDA and small metastases, or in differentiating PDA from FMP. Combining FDG-PET with current diagnostic techniques for PDA did not provide any decisive information, therefore it should not be included in this analysis.

Introduction Pancreatogenic diabetes after pancreatectomy is of growing importance due to the increasing life expectancy of pancreatectomized patients. Although reduction of pancreatic volume is thought to affect glucose metabolism, a consistent relationship has yet to be determined. This study aimed to investigate functional consequences of distal pancreatectomy (DP) in preoperatively non-diabetic patients. Methods This study included 61 non-diabetic patients who underwent DP. Clinical data were obtained, and the percent resected volume (PRV) of each pancreas was determined via multi-detector row computed tomography volumetry. Results During the follow-up period (median 26 months), 22 patients (36 %) developed new-onset diabetes within a median onset time of 8 months (range 0.5–42 months) postoperatively. The remaining 39 patients also showed impaired glucose metabolism. Multivariate analysis identified preoperative hemoglobin A1c ≥ 5.7 % (odds ratio 15.6, p = 0.001) and PRV > 44 % (odds ratio 11.3, p = 0.004) as independent risk factors for new-onset diabetes. Conclusions Key determinants of postoperative glycemic control include preoperative functional reserve of the endocrine pancreas and the volume reduction of pancreatic parenchyma. Our findings enable reliable preoperative evaluation of the risk of postoperative diabetes and appropriate postoperative surveillance, which is helpful for early intervention in high risk patients.

症例は51歳女性．検診の腹部USで膵腫瘤を指摘され紹介となった．EUSでは膵頭体部移行部に内部に嚢胞成分を有する10mmの低エコー腫瘤を認め，ダイナミックCTでは腫瘤は指摘できず5mmの嚢胞のみを認めた．ERPでは膵管像に異常はなく膵液細胞診はclass IIIであった．IDUSでは10mmの腫瘤内に5mmの嚢胞を認めた．以上より術前診断は確定できず，膵内分泌腫瘍，Solid-pseudopapillary neoplasm，浸潤性膵管癌（膵癌）などの疑診にて膵中央切除を行った．術中迅速病理検査は膵癌であったため，亜全胃温存膵頭十二指腸切除術に術式を変更した．病理診断は中分化型管状腺癌でpTS1（15mm）pT1 pN0 cM0 fStage Iであり，嚢胞部分は拡張した腫瘍腺管であった．嚢胞を伴う小膵癌の診断は困難であるが，常に念頭に置き診療にあたることが重要と考えられた．

臓器保存法は歴史的に主に腎移植の領域で研究，開発が進められ，灌流保存法（hypothermic pulsatile perfusion）が提唱され，臓器保存液による単純浸漬保存法（simple cold storage）がそれに続いた．膵保存では灌流保存法は臨床応用に至らず，1980年代に開発されたUniversity of Wisconsin solution（UW液）による単純浸漬保存法は長期膵保存を可能とし，現在でも標準的保存法である．いくつかの新規保存液が開発され臨床応用されているが，現時点でUW液を凌駕するエビデンスはない．本学で開発されたPerfluorochemical（PFC）と臓器保存液を用いた二層法膵保存は，PFCにより保存中の臓器に酸素を供給できるという特性を有する．二層法は主に膵島移植において2000年以降北米を中心に臨床応用され，優れた成績を示した．近年，従来のUW液の代わりにM-Kyoto液を用いた二層法や膵管内注入保存法などによりさらに優れた成績が報告されている． マージナルドナーや心停止ドナーからの膵臓移植，1ドナー1レシピエントでの膵島移植の実現など，今後も臓保存法が果たす役割は大きく，さらなる研究，発展が望まれる．

症例は61歳の男性で，膵頭部癌に対して膵頭十二指腸切除術（Pancreatoduodenectomy；以下，PDと略記）を施行した．術後10日目に膵空腸吻合部ドレーンから大量出血を認め，出血性ショックとなった．血管造影検査で上腸間膜動脈（Superior mesenteric artery；以下，SMAと略記）根部に径1 cmの仮性動脈瘤を認め，同部からの出血と判明した．仮性動脈瘤がSMA根部にあったため，Interventional radiology（以下，IVRと略記）による止血は不可能と判断し，緊急手術を施行した．手術は残膵全摘，SMA縫合閉鎖，左大伏在静脈による右総腸骨動脈-SMAバイパス術を施行した．術後CTではSMA本幹からの血流はなく，腸管血流はグラフト経由で供給されていた．PD術後の仮性動脈瘤大量出血に対しIVR施行困難例では躊躇なく積極的な外科手術を考慮すべきと考えられた．

Bile acid has an important role in protecting immune systems related to gut-associated lymphoid tissue. This study was designed to evaluate the effects of internal biliary drainage after a pancreaticoduodenectomy (PD) on postoperative nutrition and complications in a randomized study.The authors compared the morbidity, mortality, and postoperative nutritional status of 46 patients who had a hepaticojejunostomy (HJ) with a stented external biliary drainage (group E) or with a non-stented internal biliary drainage (group I) after a PD.Systemic infection was recognized in four patients in group E, while no patients in group I. Transthyretin at postoperative 28 days in group I was 15.6 +/- 6.2, higher than that in group E. Retinol-binding protein at postoperative 28 days in group I was 2.6 +/- 1.0 and also higher than that in group E.HJ with no-stented internal biliary drainage was not associated with systemic infections and mortality, but showed the possibility of improving nutritional status.

重症急性膵炎モデルとしてラット胆汁酸膵管内注入モデルなどが頻用されるが，in vivoのモデルだけでは分子機構の解析や再構成実験として限界がある．我々は重症急性膵炎の臓器障害におけるアポトーシスの関与と分子機構を解明するため，ラットDCA（デオキシコール酸）膵炎の腹水（pancreatitis-associated ascitic fluid；PAAF）を培養細胞（肝細胞，腎尿細管細胞，腸管上皮細胞）に添加するin vitroの実験系を確立している．最近では，in vivoにおいて腸管粘膜上皮のアポトーシスが加速し，アポトーシスを抑制することにより腸管粘膜上皮が保護され, bacterial translocationが減少することを明らかにした．実際，PAAFをT84細胞（ヒト腸管上皮）に添加するとアポトーシスが増強し，電気抵抗が減弱（透過性が亢進）していることが確認できた．PAAFを用いた実験系は，重症急性膵炎に特異的な臓器障害機構や感染成立機構の解明に有用である．

69歳，女性．黄疸を主訴に近医受診し肝門部胆管癌と診断され，精査加療目的にて当科紹介入院となったが，肝転移を認めたため手術適応外と判断し，gemcitabine（GEM）を投与開始し外来継続投与を行った．投与開始後148日目に下肢脱力感を訴え，両側下肢近位筋の軽度筋力低下を認めたが，血液検査で異常なく経過観察となった．しかし，両下肢疼痛・筋力低下が進み，投与開始後162日目に両下肢疼痛・近位筋筋力低下，発熱，乏尿を主訴に当院救急外来受診となった．血液検査で炎症反応，筋原性逸脱酵素の上昇を認め，急性腎不全の所見で入院となったが，安静，輸液にてcreatine kinase（CK）は低下を示し，利尿を得た．疼痛，筋力低下は徐々に改善し入院後13日目からリハビリテーションを開始し，症状発現後約2カ月で症状消失した．原因精査の結果，GEMによる横紋筋融解症が最も強く推測された．

In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications. Immunosuppressive acidic protein (IAP) is an immunosuppressive factor to be present in serum and ascites of cancer patients, and it is used as a tumor marker and an index of immune status of cancer hosts.We measured serum IAP levels in 42 patients with SAP (Japanese severity score [JSS]or = 2) on admission and analyzed the relationships with disease severity, pancreatic necrosis, blood biochemical parameters on admission, and clinical outcome (infection and death).Serum IAP level increased 791 +/- 285 microg/mL (range, 159-1430 microg/mL) on admission and recognized abnormal high level (normal range,500 microg/mL) in 37 patients (88.1%). Serum IAP level was significantly lower in patients of stages 3 and 4 (JSSor = 9) (678 +/- 187 microg/mL) than that in patients of stage 2 (2or = JSSor = 8) (848 +/- 311 microg/mL). It was also significantly lower in patients whose Ranson score was 5 or higher (674 +/- 287 microg/mL) than that in patients whose Ranson score was 4 or less (910 +/- 287 microg/mL). Moreover, it was significantly lower in patients with pancreatic necrosis (693 +/- 194 microg/mL) than that in patients without pancreatic necrosis (922 +/- 336 microg/mL). Among the blood biochemical parameters on admission, serum IAP was significantly negatively correlated with hematocrit, serum lipase, and serum interferon gamma and was significantly positively correlated with serum total protein. Serum IAP levels in patients of stage 2 reached higher peak at 7 days after admission and decreased more rapidly than those in patients of stages 3 and 4.Serum IAP levels were elevated in patients with SAP but were significantly lower in patients with higher grade of severity or pancreatic necrosis. These results suggest that serum IAP levels may be related to systemic inflammatory response and reflect the immunoresponsiveness in patients with SAP.

Sepsis due to infected pancreatic necrosis is the most serious complication in the late phase of severe acute pancreatitis (SAP). Bacterial translocation from the gut is thought to be the main cause of pancreatic infection. The possibility has recently been reported that selective digestive decontamination (SDD) and enteral nutrition (EN) may alleviate the complications and reduce the mortality rate in patients with SAP. We analyzed the treatment outcome of SDD and EN in patients with SAP.We divided 90 patients with SAP into three groups: SDD(-)EN(-),group A; SDD(+)EN(-), group B; and SDD(+)EN(+), group C. Clinical outcome was analyzed retrospectively. The effect of SDD was compared in groups A and B, and the effect of EN was compared in groups B and C.The background of patients was not significantly different between the groups. SDD reduced the incidence of organ dysfunction (from 70% to 59%) and the mortality rate (from 40% to 28%), but the differences were not significant. EN reduced the incidence of infected pancreatic necrosis (from 31% to 24%) and the frequency of surgery for pancreas (from 28% to 18%), and further reduced the mortality rate (from 28% for SDD to 16%), but the differences were not significant. The peripheral lymphocyte count was significantly increased in patients with EN.SDD and EN did not significantly affect the treatment outcome in SAP. However, the results in this study raise the possibility that SDD and EN may decrease the complications and reduce the mortality rate in SAP. The efficacy of SDD and EN for SAP should be evaluated in a randomized controlled trial.

In severe acute pancreatitis, multiple organ dysfunction syndrome and infectious complications are contributors to high mortality. Interleukin (IL)-15 is a novel cytokine that shares many biologic properties with IL-2. Serum IL-15 levels have not yet been determined in SAP.Serum IL-15 concentrations were measured in 54 patients with severe acute pancreatitis on admission. The relationships with severity, organ dysfunction, infection, and prognosis were analyzed. Utility of IL-15 for the prediction of clinical outcome was evaluated by receiver operator characteristic (ROC) curve analysis.Serum IL-15 levels were increased significantly in severe acute pancreatitis (5.8 +/- 0.5 pg/mL), and they were correlated with Ranson, APACHE II, and Japanese severity score. Serum IL-15 levels were greater in patients with organ dysfunction, patients with infection, and nonsurvivors (P05 each). Incidences of organ dysfunction in patients whose IL-15 levels were less than 3.0, 3.0-5.3, and greater than or equal to 5.3 pg/mL, were 8%, 31%, and 89%, respectively (P.001). Usefulness of IL-15 for the prediction of organ dysfunction was superior to CRP, IL-6, and IL-8, and it was similar to Ranson, APACHE II, and Japanese severity score. Incidences of infection in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 7%, 25%, and 50%, respectively (P.05). Mortality rates in patients whose IL-15 levels were less than 5.5, 5.5-9.0, and greater than or equal to 9.0 pg/mL, were 11%, 25%, and 80%, respectively (P.001). Usefulness of IL-15 for the prediction of death was superior to CRP, IL-6, and IL-8.Serum IL-15 level is a useful predictor of the complications (especially organ dysfunction) and mortality in severe acute pancreatitis.

In severe acute pancreatitis (SAP), infectious complications are the main contributors to high mortality. Since 1995, we have performed continuous regional arterial infusion of protease inhibitor and antibiotics (CRAI) and enteral nutrition (EN) as prevention therapies against infection. When infected pancreatic necrosis was proven, surgical intervention was adapted. The aim of this study was to investigate the clinical outcome of these treatments. We examined the relationship between the historical change of treatment strategy and clinical outcome. We divided 84 patients with acute necrotizing pancreatitis into two groups, CRAI (−) and CRAI (+), and compared the outcome. We divided 145 patients with SAP into two groups, EN (−) and EN (+), and compared the outcome. We also analyzed the outcome of surgical treatment. In the CRAI (+) group, the incidence of infection, the frequency of surgery, and the mortality rate were lower than those in CRAI (−) group: 34% versus 51%, 27% versus 63% (P < 0.05), and 37% versus 54%, respectively. In the EN (+) group, the frequency of surgery and the mortality rate were lower than those in the EN (−) group: 23% versus 32% and 19% versus 35% (P < 0.05), respectively. These improvement effects were manifest in stage 3 (9 ≤ Japanese Severity Score ≤ 14). Treatment outcome of necrosectomy for infected pancreatic necrosis was still poor. Bleeding and abscess–gut fistula were postoperative life-threatening complications. CRAI and EN may improve the clinical outcome of SAP, reducing infection and averting pancreatic surgery.

Objectives Bacterial translocation (BT) plays an important role in systemic complications in severe acute pancreatitis (SAP). We recently demonstrated that accelerated apoptosis of intestinal mucosa might have a role in BT. Effects of vascular endothelial growth factor (VEGF) on intestinal epithelial cell apoptosis and BT were investigated in SAP. Methods Severe acute pancreatitis was induced by retrograde injection of sodium deoxycholate into the biliopancreatic duct in rats. Recombinant rat VEGF (2 microg) was injected, and SAP was immediately induced. Eight hours after the induction, serum amylase/lipase levels and apoptosis of ileal mucosa were evaluated. After 18 hours, the villous height of ileum was examined. After 22 hours, hematocrit, pancreatic water content, BT to the mesenteric lymph nodes, plasma plasminogen activator inhibitor 1 levels, and microvessel density in the small intestine were investigated. Results Amylase/lipase levels were significantly elevated in SAP, but VEGF did not affect them. Apoptosis of ileal mucosa was accelerated in SAP, and VEGF significantly reduced the apoptosis. Villous height was significantly decreased in SAP, and VEGF significantly improved it. Vascular endothelial growth factor did not affect the hematocrit or pancreatic water content. Bacterial translocation occurred in the SAP group, and VEGF significantly prevented that. Plasminogen activator inhibitor 1 levels were significantly elevated in SAP, and VEGF significantly improved the elevation. Microvessel counts were significantly reduced in SAP, and VEGF significantly increased them. Conclusion These results suggest that VEGF inhibits intestinal epithelial cell apoptosis and subsequent BT in SAP.

Background and aim Endotoxin/bacterial translocation (E/BT) plays an important role in systemic complications in severe acute pancreatitis (SAP). The breakdown of intestinal integrity is considered to be implicated in E/BT. We recently demonstrated that accelerated apoptosis of intestinal mucosa may have a part in E/BT. On the other hand, caspase is believed to play a central role in apoptosis. The aim of this study was to investigate the efficacy of caspase inhibitor on intestinal integrity and E/BT in SAP. Methods SAP was induced by retrograde injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats. At the same time, polycaspase inhibitor (Z-VAD-fmk) was administered intraperitoneally. Caspase activation in the intestine was evaluated by immunohistochemical staining and Western blotting. Apoptosis of intestinal mucosa was detected by TdT-mediated dUTP-biotin nick end labeling staining and DNA fragmentation enzyme-linked immunosolvent assay. Intestinal permeability was assayed ex vivo by measuring the leaked amount of FITC-dextran. Blood endotoxin level, bacterial culture of the ascites and mesenteric lymph nodes, and 24-h mortality rate were evaluated. Results Immunoreactivities for activated caspase-10, -9, and -3 were increased 2 h after induction of SAP. Apoptosis and permeability of ileum were significantly increased 6 h after induction of SAP. Caspase inhibitor significantly improved the increasing apoptosis and permeability. It did not prevent the bacterial translocation but improved the disorder of intestinal mucosa and elevation of blood endotoxin 18 h after induction of SAP. Moreover, caspase treatment significantly improved the 24-h mortality rate. Z-VAD-fmk indeed inhibited the caspase-3 activation in intestinal mucosa of SAP. Conclusions These results suggest that caspase activation has a key role in the accelerated apoptosis of intestinal epithelial cells in SAP and that breakdown of intestinal mucosa via accelerated apoptosis causes the increase in intestinal permeability following endotoxin translocation in SAP.

OBJECTIVE The aim of this study was to reappraise the clinical role of total pancreatectomy with curative intent in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS In 2001 to 2011 database from 7 institutions in Japan, 45 (3.1%) of 1451 patients with PDAC underwent total pancreatectomy (TP group), and 885 patients underwent pancreaticoduodenectomy (PD group). A matched-pairs group consisted of 45 patients matched for age, sex, year, resectability status, and neoadjuvant therapy (matched-PD group). Clinicopathological data, overall survival, and disease-free survival were compared between groups. RESULTS Clinical features of the TP group revealed higher-stage disease, greater surgical stress, a higher frequency of lymph node metastasis, and a lower adjuvant chemotherapy completion rate compared with the PD group (P < 0.05). Overall survival and disease-free survival in the TP group were significantly worse than those in the PD group (P < 0.05). Multivariate analysis revealed resectability status, neoadjuvant therapy, blood transfusion, lymph node metastasis, and adjuvant therapy to be significant prognostic factors. No differences in mortality and morbidity rates were observed between the 2 groups. A matched-pairs analysis revealed similar surgical outcomes and overall survival. CONCLUSIONS The surgical outcome of total pancreatectomy for patients with PDAC is acceptable. When margin-negative resection is expected, total pancreatectomy should not be abandoned in the modern era.

A 38-year-old man underwent right hepatectomy for a huge hepatocellular carcinoma(HCC)in the right hepatic lobe. Four months later, recurrent and metastatic disease were observed in the remnant liver and right lung, respectively. We performed a hepatectomy for the recurrent lesion because transcatheter arterial chemoembolization (TACE) was not effective. After surgery, we initiated sorafenib treatment for the lung metastases. One year later, the lung metastases worsened and metastases were observed in the mediastinal lymph nodes, and both metastatic lesions were resected. Seven months later, para-aortic lymph nodal metastasis was observed and dissected. Three months later, metastasis to the supraclavicular lymph node was observed. We performed particle radiation therapy and a complete response was achieved. One year later, metastases in both lungs were observed and resected. Despite continued sorafenib administration throughout the clinical course, a metastasis to the left adrenal gland was observed. This lesion was extirpated because no other recurrent lesions were detected. At 4 years and 6 months after the first operation, no other recurrences have occurred. Currently, sorafenib is the initial drug of choice for HCC with extrahepatic metastases. It is possible to improve the prognosis of patients with HCC and extrahepatic metastases by applying surgical treatment during the course of sorafenib administration.

The aim of this study was to evaluate the validity of preoperative resectability status, as defined by the National Comprehensive Cancer Network (NCCN), from the viewpoint of overall survival.A total of consecutive 704 patients with pancreatic head carcinoma who underwent pancreatoduodenectomy with upfront surgery at seven Japanese hospitals between 2001 and 2012 were evaluated retrospectively. According to the NCCN definition of preoperative resectability status, tumors were divided into resectable tumors without vascular contact (R group), resectable tumors with portal or superior mesenteric vein (PV/SMV) contact of ≦180° (R-PV group), borderline resectable(BR) tumors with PV/SMV contact of180° (BR-PV group), and BR tumors with arterial contact (BR-A group). The relationship between the NCCN definition of preoperative resectability status and overall survival was analyzed.Of the 704 patients, 389, 114, 145, and 56 were classified into the R group, the R-PV group, the BR-PV group, and the BR-A group, respectively. Overall survival of the BR-PV and BR-A groups was significantly worse than that of the R group and R-PV groups (P0.05), although there was no significant difference in overall survival between the R group and the R-PV group (P = 0.310). Multivariate analysis revealed that PV/SMV contact of180° (P = 0.008) and arterial contact (P0.001) were independent prognostic factors of overall survival.From the viewpoint of overall survival, the NCCN definition of preoperative resectability status was valid.

The benefits of re-resection for recurrent intrahepatic cholangiocarcinoma (IHC) are unknown.We evaluated the comparative efficacy of different treatment schema for recurrent IHC following curative resection.Among 46 patients, 26 underwent R0 resection, while 20 underwent R1 resection. There were 13 cases of recurrence in R1 patients (65%), and 19 in R0 patients (61%). Recurrent IHC cases were divided into 3 groups based on the treatment received after recurrence: re-resection (n=5), chemotherapy (n=13), and best supportive care (BSC) (n=8). Survival times were evaluated for each group; median survival times (MSTs) after recurrence were 26, 14, and 4 months for the re-resection, chemotherapy, and BSC groups, respectively (p=0.030). Next, we examined the patients who only had intrahepatic recurrence; MSTs after recurrence for re-resection, chemotherapy, and BSC groups were 26, 14, and 5 months, respectively (p=0.0018).In recurrent IHC, survival time improves with re-resection or chemotherapy, when compared to BSC. In patients with intrahepatic recurrence only, re-resection is especially effective in prolonging survival.

The patient was a 79-year-old man diagnosed with a single 9.3-cm hepatocellular carcinoma (HCC) in the medial segment of the liver, and left iliac bone metastasis. Initially, the patient was treated with a hepatic arterial infusion of low-dose FP (cisplatin/5-fluorouracil) at another hospital. Here, the patient received particle therapy for the left iliac bone metastasis at a total dose of 52.8 Gy in 4 fractions. Subsequently, he underwent medial segmentectomy of the liver to treat the primary HCC. Eleven months later, the first intrahepatic recurrence occurred, and the tumor was treated with percutaneous radiofrequency ablation (RFA). A second intrahepatic recurrence was detected 39 months later, which was also treated with percutaneous RFA. The patient remains well, with no evidence of tumor recurrence.

A 70-year-old woman was admitted to a near by hospital with complaints of epigastric pain and fever. Endoscopic retrograde cholangiopancreatography (ERCP) and magnetic resonance cholangiopancreatography (MRCP) revealed stenosis of the hilar bile duct and multiple stenoses in the intrahepatic bile duct; bile cytological analysis indicated adenocarcinoma. The levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were within normal limits. It was very difficult to evaluate the extent of tumor invasion; therefore, we concluded that the tumor was unresectable. The patient underwent systemic chemotherapy with gemcitabine. After 5 years, she developed obstructive jaundice and cholangitis. The patient underwent endoscopic retrograde biliary drainage (ERBD), with 3 incidents of cholangitis recurrence. Although systemic chemotherapy with gemcitabine was performed for a long time, she died 6 years after the initiation of chemotherapy. Gemcitabine was administered 140 times in total, with a total dose of 203.744 g.

A 67-year-old man was admitted to our hospital with a complaint of epigastric discomfort. A 29-mm hypovascular tumor was detected in the head of the pancreas by abdominal computed tomography imaging. As the superior mesenteric artery (SMA) was also involved, we diagnosed the tumor as unresectable pancreatic cancer. With S-1 chemotherapy, a radiological partial response was seen. After 4 courses of chemotherapy, a subtotal-stomach-preserving-pancreatoduodenectomy with dissection of the nerve plexus surrounding the SMA was performed. Although the tissue surrounding the SMA was hard, invasion of the SMA was not detected. Microscopic investigation revealed a few moderately differentiated adenocarcinoma cells in the fibrous tissue and the nerve fibers of pancreas. No cancer cells were found at the edges of the surgical specimen. The patient underwent R0 resection and a pathological evaluation showed Grade III tumor according to the Evans classification. After surgery, S-1 was interrupted because of diarrhea and local recurrence appeared 4 months postoperatively. For improving the prognosis of patients with pancreatic cancers, surgical intervention is often performed in patients with initially unresectable pancreatic cancers who have "long-term" favorable responses to chemotherapy or chemoradiotherapy. However, because of the possibility of relatively good prognosis with nonsurgical treatment for such patients and also the demerits of surgical stress, it is important to carefully consider the adjuvant surgery option.

Here, we report a case of Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy. A 69-year old man underwent pancreatoduodenectomy for pancreatic cancer in 2006 in which the splenic vein was ligated near the portal vein and then divided. The patient suffered repeated episodes of anemia between 2010 and 2013. However, we could not identify the bleeding site at that time. In 2011, local recurrence was detected. Disease progression occurred despite chemotherapy treatment, which was then discontinued. The left-sided portal hypertension gradually progressed, and the collateral vessels became dilated. In 2014, he was examined in our department for gastrointestinal bleeding. An upper gastrointestinal endoscopy revealed bleeding from gastric varices. Gastrointestinal bleeding ceased after endoscopic injection sclerotherapy ( EIS) was performed; however, the bleeding recurred. Balloon retrograde transvenous occlusion (BRTO) could not be performed because blood flow was not detected within the gastro-renal shunt. An emergency surgery was performed. Surgical splenectomy and devascularization (Hassab's operation) were performed. After surgery, the gastric body varices and gastrointestinal anastomosis disappeared and the bleeding did not occur. He is currently receiving outpatient treatment.

Recently, the indications for particle beam therapy have been expanded to include metastatic liver tumors. However, its adverse effects on the treated liver are unclear, and the possibility of local recurrence after treatment should not be ignored. A 65-year-old man with advanced rectal carcinoma underwent low anterior resection. Resectable metastatic liver tumors were detected after adjuvant chemotherapy; however, he opted to undergo particle beam therapy. Nine months after treatment, a local recurrence was detected around the treated area, and central bisegmentectomy of the liver was performed as a salvage operation. The operation was technically complicated owing to severe adhesions and inflammatory changes in the liver parenchyma around the treated area. Pathological examination revealed advanced liver fibrosis at the treated area, in contrast with normal parenchyma in the untreated area. Although the procedure requires advanced surgical techniques, salvage surgery is a feasible option for recurrent liver tumors after particle beam therapy.

Multiple organ failure because of systemic inflammatory response in the early phase and sepsis in the late phase is the main contributor to high mortality in severe acute pancreatitis (SAP). High-mobility group box chromosomal protein 1 (HMGB1) was recently identified as a potent proinflammatory mediator and increases in various pathological conditions such as sepsis. The aim of this study was to investigate contributions of HMGB1 in SAP.We measured serum HMGB1 concentrations by an enzyme-linked immunosorbent assay in 45 patients with SAP at the time of admission. Furthermore, relationship between their serum HMGB1 levels and clinical factors was analyzed.The mean value of serum HMGB1 levels was significantly higher in patients with SAP (5.4 +/- 1.3 ng/mL) than that in healthy volunteers (1.7 +/- 0.3 ng/mL). Serum HMGB1 levels were significantly positively correlated with the Japanese severity score and Glasgow score. Serum HMGB1 levels were significantly positively correlated with lactate dehydrogenase, C-reactive protein, and total bilirubin. The HMGB1 levels were higher in patients with organ dysfunction and infection during the clinical course. The HMGB1 levels in nonsurvivors were higher than those in survivors. Serum HMGB1 levels gradually declined after the admission.Serum HMGB1 levels were significantly increased in patients with SAP and were correlated with disease severity. These results suggest that HMGB1 may act as a key mediator for inflammation and organ failure in SAP.

Fig 1. Dynamic CT imaging showing pancreatic tissue completely encircling the superior mesenteric vein (SMV; arrow) and a dilated main pancreatic duct in the tissue behind the SMV (arrow head). A PREVIOUSLY HEALTHY 81-YEAR-OLD WOMAN with general fatigue was admitted to our hospital in June 2009. Her blood chemistry data were within normal limits except for slightly elevated liver function values. Serum levels of carbohydrate antigen 19-9 and carcinoembryonic antigen were both normal. Gastroduodenoscopy showed an erosive tumor in the ampulla of Vater. Dynamic computed tomography (CT) revealed bilateral intrahepatic biliary dilatation, and the superior mesenteric vein (SMV) circumferentially embedded in the body of the pancreas, as well as a slightly dilated main pancreatic duct (MPD) in the tissue behind the SMV (Fig 1). The MPD was found posteriorly to the SMV and the accessory pancreatic duct (APD) was seen anteriorly to the SMV. The 2 ducts joined in the body of the pancreas to the left side of the

Pancreatic stellate cells (PSCs) are thought to be responsible for pancreatic fibrosis. Although fibrosis is a major characteristic of chronic pancreatitis (CP) induced by pancreatic duct obstruction, it is unclear whether pancreatic duct obstruction itself activates PSCs.To test the hypothesis that pancreatic duct obstruction activates PSCs, clinical and experimental analyses were performed using alpha smooth muscle actin (alpha-SMA) as a marker of their activation. In clinical analysis, surgical specimens from the patients with pancreatic cancer or cancer of the papilla Vater were classified into two groups with or without duct obstruction. alpha-SMA expression was examined on these specimens, and the difference between two groups was evaluated. In animal experiment, duct ligation-induced pancreatitis was developed in rats by ligating the secondary pancreatic duct in duodenal segment, and the expression of alpha-SMA was examined.In clinical analysis, the specimens from the pancreas with duct obstruction (14 cases) expressed alpha-SMA significantly stronger than those from the pancreas without duct obstruction (7 cases). All specimens in the former expressed alpha-SMA, but 4 specimens from the latter did not at all (P0.05). In animal experiment, alpha-SMA expression was detected 7 days after the ligation and was increased on the 10th day.We can assume that pancreatic duct obstruction itself activates PSCs. This mechanism may play roles in the development of CP from multiple origins.

The study aim was to determine the short- and long-term results of surgical drainage procedure for chronic pancreatitis at a single center in Japan.The records of 28 consecutive patients were retrospectively reviewed. All patients underwent surgery at Kobe University Hospital between June 1999 and April 2013. Long-term follow-up was performed in all patients for a median period of 77 months.The 26 men (93%) and 2 women (7%) had a mean age of 47 years. The etiology of pancreatitis was chronic alcohol abuse in 24 patients (86%). The major indication for surgery was persistent symptoms (97%). Modified Frey's procedure in 21 patients, lateral pancreaticojejunostomy (LPJ) in 6 patients, LPJ and distal pancreatectomy in one patient, were performed. There was no postoperative mortality. Postoperative morbidity occurred in 6 patients (21%). The percentage of pain-free patients after surgery was 97%, and further acute exacerbation was prevented in 97%. Two patients (6%) required subsequent surgery for infectious pancreatic cyst and intraabdominal abscess. Of the patients that completed follow-up, 13 (46%) had diabetes mellitus, including 5 patients (19%) with new-onset diabetes, and 6 patients (19%) developed pancreatic exocrine insufficiency.Modified Frey's procedure is safe, feasible, and effective to manage chronic pancreatitis. The technique prevents further exacerbations and maintains appropriate pancreatic endocrine and exocrine function.

Adjuvant chemotherapy (AC) is recommended as a standard treatment after curative resection in patients with pancreatic adenocarcinoma (PA). Although patients who failed to complete AC had significantly worse survival compared with those who completed AC for cancers in various organs, the effects of complete AC on survival in patients with PA have not been investigated. The purpose of this study was to clarify the impact of complete AC on PA patient survival and to identify independent risk factors for incomplete AC. Medical records of 236 consecutive PA patients who planned to undergo surgical resection with curative intent between January 2000 and September 2012 at Kobe University Hospital were retrospectively reviewed. Of these, the complete AC (n = 75) and the incomplete AC (n = 30) groups due to adverse events were compared. Patient survival was significantly better in the complete AC group than in the incomplete AC group (median survival time 48.9 vs. 17.9 months; 5-year survival rate 42.7 vs. 17.1 %; p

The objective of the present study was to reappraise the clinical value of peritoneal washing cytology (CY) in 984 pancreatic ductal adenocarcinoma patients who underwent margin-negative resection. In a 2001–2011 database from seven high-volume surgical institutions in Japan, 69 patients (7 %) had positive CY (CY+ group) indicative of M1 disease and 915 patients had negative CY (CY− group). Clinicopathological data and survival were compared between groups. Significant correlations between CY+ and high CA19-9 level, pancreatic body and tail cancer, lymph node metastasis, and a lower frequency of R0 resection were observed. Overall survival (OS) of CY+ patients was significantly worse than that of CY− patients (median survival time [MST], 16 vs. 25 months; 3-year OS rate, 6 vs. 37 %; p

Here, we report the efficacy of dual treatment with hepatic resection and percutaneous isolated hepatic perfusion (PIHP) for advanced hepatocellular carcinoma( HCC). Recently, we introduced treatment with combined particle therapy and PIHP for unresectable HCC in cases of insufficient liver function. The purpose of this study was to evaluate the safety and efficacy of PIHP for local control in the liver after particle therapy. From 2006 to 2013, 6 patients underwent particle therapy for the main lesion and subsequent PIHP for remnant liver lesions. Their mean age was 64 years, and the mean size of the main lesion was 6.2 cm (range, 2.0-10.8 cm). All patients had liver cirrhosis. After particle therapy, PIHP was performed by hepatic arterial infusion of 100 mg/m2 of doxorubicin and 30 mg/m2 of mitomycin C. With regard to side effects, neutropenia occurred in all patients but no serious hepatobiliary injury was observed. The response rate for PIHP was 50% (partial response: 3 and stable disease: 3). The mean overall survival time was 26.9 months after particle therapy. In conclusion, even after particle therapy, PIHP is a safe treatment and is associated with a good local control rate for remnant HCCs. Further accumulation of data is needed to evaluate the efficacy of this treatment strategy in terms of prognosis.

A 55-year-old woman underwent subtotal stomach-preserving pancreaticoduodenectomy for pancreatic ductal adenocarcinoma( PDAC) in July 2008. The final diagnosis was Stage I PDAC according to the Union for International Cancer Control( UICC) TNM classification. After the operation, adjuvant chemotherapy with gemcitabine was administered for 6 months. The tumor marker level increased at 49 months after the operation, and 18-fluoro-deoxyglucose (FDG)-positron emission tomography( PET) showed FDG accumulation in the remnant pancreas. A hypovascular tumor was revealed in the remnant pancreas on computed tomography( CT). As PDAC was diagnosed without distant metastasis, completion pancreatectomy was performed. Histopathological investigation revealed PDAC with invasion into the muscularis propria of the anastomosed jejunum and splenic plexus. The final diagnosis was T3N0M0 UICC Stage IIA metachronous PDAC. The postoperative course was uneventful. However, multiple liver metastases and local recurrence were detected on CT 2 months after resection, and the patient died 3 months after resection. Most reported cases of metachronous PDACs were diagnosed at an advanced stage despite regular follow-ups after the initial resection. Further investigation is needed to determine the adequate surveillance time and novel therapeutic strategies.

Complete resection of advanced bile duct cancer is difficult due to the anatomical location of the tumor and invasion into other organs. Even if a complete resection is achieved, the survival rates of patients with bile duct cancer after surgery are lower as compared to those associated with other gastrointestinal tumors. Certain cases with para-aortic lymph node metastasis have a poor prognosis. In the present report, we describe a case involving long-term survival following bile duct cancer that was treated by multidisciplinary therapy (particle radiotherapy, surgical resection, chemotherapy). In the present case, we detected lymph node (LN) metastasis only in LN#16, but not in LN#13 or LN#17. We believe that particle radiotherapy, consisting of proton and carbon-ion, can be used to control the lymphatic metastasis around the pancreas head and hepatoduodenal ligament. Our findings suggest that particle radiotherapy can be a standard neoadjuvant therapy for bile duct cancer.

A 75-year-old woman was admitted to our hospital with elevated serum hepatic enzyme levels. After evaluation with imaging studies, she was diagnosed as having gallbladder cancer, which had invaded the liver and hepatic artery, with lymph node metastases. The tumor was considered unresectable, and the patient received chemotherapy with gemcitabine (GEM)alone. Six months later, computed tomography(CT)indicated shrinkage of the gallbladder tumor and disappearance of lymph node metastases. Surgical resection was planned. However, liver metastasis was suspected on the basis of macroscopic findings, and the patient underwent gallbladder bed resection. Pathological examination indicated that almost all of the tumor cells in the gallbladder were viable; however, there were no tumor cells in the liver nodule and lymph node. The postoperative course was uneventful. The patient received adjuvant chemotherapy with GEM and was alive without recurrence 17 months after tumor resection. Immunohistochemical analysis showed that 80.9% of the tumor cells were positive for CD133, a cancer stem cell marker. This case illustrates a possible relationship between cancer stem cells and chemoresistance.