Xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells improves diabetic wound healing by promoting angiogenesis and lymphangiogenesis.

BACKGROUND: Some clinical trials have shown the usefulness of stem cell therapy for diabetic foot ulcers. However, the donor supply is limited, and the process is time consuming and expensive. This study assessed the therapeutic effects of neonatal porcine bone marrow-derived mesenchymal stem cell (npBM-MSC) xenotransplantation using diabetic wound model mice. METHODS: All layers of back skin were removed from streptozotocin-induced diabetic mice. In the npBM-MSCs group, npBM-MSCs were transplanted to the wound, and syngeneic mouse bone marrow-derived mesenchymal stem cells (mBM-MSCs) were transplanted to the wound in the mBM-MSCs group. The control group comprised diabetic mice that did not receive cellular therapy. The therapeutic effects of the transplantation were evaluated according to the rate of wound closure and the promotion of neovascularization in the wound. RESULTS: The wound closure rate was significantly improved in the npBM-MSCs group compared with the control group (p < .001 at postoperative day [POD] 4 and p < .01 at POD 7) and mBM-MSCs groups (p < .05 at POD 4). Prominent promotion of both angiogenesis and lymphangiogenesis was observed in the npBM-MSCs group. Furthermore, the expression of murine Prox1 and both porcine and murine Vegfs and Tgfb1 in the wounds was enhanced until POD 4 by npBM-MSCs transplantation. The amounts of vascular endothelial growth factor (VEGF) A, VEGFC, and transforming growth factor ß1 secreted from npBM-MSCs were higher than those from mBM-MSCs (p < .05). CONCLUSION: Xenotransplantation of npBM-MSCs improved diabetic wound healing by promoting both angiogenesis and lymphangiogenesis.

Intravenous injection of human multilineage-differentiating stress-enduring cells alleviates mouse severe acute pancreatitis without immunosuppressants.

INTRODUCTION: We examined the effect of intravenously injected human multilineage-differentiating stress-enduring (Muse) cells, non-tumorigenic endogenous reparative stem cells already used in clinical trials, on a severe acute pancreatitis (SAP) mouse model without immunosuppressants. METHODS: Human Muse cells (1.0 × 105 cells) collected from mesenchymal stem cells (MSCs) as SSEA-3(+) were injected into a C57BL/6 mouse model via the jugular vein 6 h after SAP-induction with taurocholate. The control group received saline or the same number of SSEA-3(-)-non-Muse MSCs. RESULTS: Edematous parameters, F4/80(+) macrophage infiltration and terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was the lowest and the number of proliferating endogenous pancreatic progenitors (CK18(+)/Ki67(+) cells) the highest in the Muse group among the three groups, with statistical significance, at 72 h. An enzyme-linked immunosorbent assay and quantitative polymerase chain reaction demonstrated that in vitro production of VEGF, HGF, IGF-1, and MMP-2, which are relevant to tissue protection, anti-inflammation, and anti-fibrosis, were higher in Muse cells than in non-Muse MSCs, particularly when cells were cultured in SAP mouse serum. Consistently, the pancreas of animals in the Muse group contained higher amounts of those factors according to Western blotting at 18 h than that in the non-Muse MSCs and control groups. CONCLUSIONS: Intravenous injection of human Muse cells was suggested to be effective for attenuating edema, inflammation and apoptosis in the acute phase of SAP.

Xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells improves murine hind limb ischemia through lymphangiogenesis and angiogenesis.

BACKGROUND: The clinical utility of stem cell therapy for peripheral artery disease has not been fully discussed, and one obstacle is limited donor supplies. In this study, we attempted to rescue mouse ischemic hind limb by xenotransplantation of neonatal porcine bone marrow-derived mesenchymal stem cells (npBM-MSCs). METHODS: Neonatal porcine bone marrow-derived mesenchymal stem cells were transplanted to ischemic hind limbs of male C57BL/6J mice (npBM-MSCs group). Mice with syngeneic transplantation of mouse BM-MSCs (mBM-MSCs group) were also prepared for comparison. The angiogenic effects were evaluated by recovery of blood flow on laser Doppler imaging, histologic findings, and genetic and protein levels of angiogenic factors. RESULTS: Regarding laser Doppler assessments, blood flow in the hind limb was rapidly recovered in the npBM-MSCs group, compared with that in the mBM-MSCs group (P = .016). Compared with the mBM-MSCs group, the npBM-MSCs group had early and prominent lymphangiogenesis [P < .05 on both post-operative days (PODs) 3 and 7] but had similar angiogenesis. Regarding genomic assessments, xenotransplantation of npBM-MSCs enhanced the expressions of both porcine and murine Vegfc in the hind limbs by POD 3. Interestingly, the level of murine Vegfc expression was significantly higher in the npBM-MSCs group than in the mBM-MSCs group on PODs 3 and 7 (P < .001 for both). Furthermore, the secreted VEGFC protein level was higher from npBM-MSCs than from mBM-MSCs (P < .001). CONCLUSION: Xenotransplantation of npBM-MSCs contributed to the improvement of hind limb ischemia by both angiogenesis and lymphangiogenesis, especially promotion of the latter. npBM-MSCs may provide an alternative to autologous and allogeneic MSCs for stem cell therapy of critical limb ischemia.

Lymphangiogenesis and angiogenesis rescue murine ischemic hindlimb via transient receptor potential vanilloid 4.

In this study, we assessed the regulation of transient receptor potential vanilloid 4 (TRPV4) promoting lymphangio/angiogenesis to improve the ischemic hindlimb animal model, and revealed that (1) a TRPV4 agonist improved the blood flow of ischemic hindlimbs by inducing both angiogenesis and lymphangiogenesis; (2) excessive TRPV4 expression was detected on lymphatic endothelial cells (LECs) in the ischemic hindlimb; and (3) hypoxic conditions promoted Ca2+ influx into LECs via TRPV4. It is considered that the upregulation of both lymphatic and blood vessels by activating TRPV4 would be a promising therapeutic strategy for peripheral artery disease.

Combination of longitudinal pancreaticojejunostomy with coring-out of the pancreatic head (Frey procedure) and distal pancreatectomy for chronic pancreatitis.

PURPOSE: The Frey procedure is an effective surgery for chronic pancreatitis (CP) patients who have pancreatic head lesions with dilation of the main pancreatic duct. However, pancreatic tail lesions can cause relapsing pancreatitis after the procedure. Therefore, additional distal pancreatectomy (DP) might complement the therapeutic effect of the Frey procedure in controlling inflammation of the pancreatic tail. The Frey procedure with DP (Frey + DP) is indicated for inflammatory lesions in the pancreatic head and tail. In this study, we assessed the usefulness of Frey + DP using the retrospective clinical data of our cases. METHODS: The clinical outcomes were compared between CP patients who underwent the Frey procedure (N = 44) and Frey + DP (N = 13) from January 2005 to April 2016. RESULTS: Frey + DP showed similarly good therapeutic effects to the Frey procedure with regard to the postoperative stay, morbidity, mortality, pain relief and nutrition, although the Frey + DP had a longer operative time, more bleeding and higher incidence of diabetes mellitus than the Frey procedure because of the additional DP. One patient in the Frey group received additional DP because of recurrent pain due to the tail lesion. CONCLUSION: Frey + DP can be a promising treatment for CP patients with pancreatic head and tail lesions.

Development and Characteristics of Pancreatic Epsilon Cells.

Pancreatic endocrine cells expressing the ghrelin gene and producing the ghrelin hormone were first identified in 2002. These cells, named ε cells, were recognized as the fifth type of endocrine cells. Differentiation of ε cells is induced by various transcription factors, including Nk2 homeobox 2, paired box proteins Pax-4 and Pax6, and the aristaless-related homeobox. Ghrelin is generally considered to be a "hunger hormone" that stimulates the appetite and is produced mainly by the stomach. Although the population of ε cells is small in adults, they play important roles in regulating other endocrine cells, especially ß cells, by releasing ghrelin. However, the roles of ghrelin in ß cells are complex. Ghrelin contributes to increased blood glucose levels by suppressing insulin release from ß cells and is also involved in the growth and proliferation of ß cells and the prevention of ß cell apoptosis. Despite increasing evidence and clarification of the mechanisms of ε cells over the last 20 years, many questions remain to be answered. In this review, we present the current evidence for the participation of ε cells in differentiation and clarify their characteristics by focusing on the roles of ghrelin.

FBXW7 modulates malignant potential and cisplatin-induced apoptosis in cholangiocarcinoma through NOTCH1 and MCL1.

The ubiquitin ligase F-box and WD repeat domain-containing 7 (FBXW7) is responsible for degrading diverse oncoproteins and is considered a tumor suppressor in many human cancers. Inhibiting FBXW7 enhances the malignant potential of several cancers. In this study, we aimed to investigate the role of FBXW7 in cholangiocarcinoma. We found that FBXW7 expression was associated with clinicopathological outcomes in cholangiocarcinoma patients. Both disease-free and overall survival were significantly worse in the low-FBXW7 group than in the high-FBXW7 group (P = .001 and P < .001, respectively). Multivariate analysis with the Cox proportional hazards model indicated that FBXW7 was the most important independent prognostic factor for disease-free (P = .006) and overall (P = .0004) survival. We also showed that the two FBXW7 substrates, NOTCH1 and myeloid cell leukemia sequence 1 (MCL1), regulate cholangiocarcinoma progression. Depletion of FBXW7 resulted in NOTCH1 accumulation and increased cholangiocarcinoma cell migration and self-renewal. Interestingly, when cells were stimulated with cis-diamminedichloridoplatinum(II) (cisplatin), FBXW7 suppression induced MCL1 upregulation, which reduced the sensitivity of cholangiocarcinoma cells to apoptosis, indicating that FBXW7-mediated ubiquitylation is context-dependent. These results indicate that FBXW7 modulates the malignant potential of cholangiocarcinoma through independent regulation of NOTCH1 and MCL1.

Frey's procedure for chronic pancreatitis improves the nutritional status of these patients.

PURPOSE: The aim of surgical intervention for chronic pancreatitis (CP) is to relieve symptoms and improve quality of life. However, the precise effect of surgery on the nutritional status of CP patients, which is often impaired by exocrine and endocrine pancreatic dysfunction, has not been elucidated. We conducted this study to evaluate whether Frey's procedure improves the nutritional status of CP patients. METHODS: The nutritional status of 35 patients who underwent Frey's procedure for CP at our institute between April 2005 and December 2014, was assessed by the controlling nutritional status (CONUT) scoring before and 1 year after the surgery, and compared with that of seven CP patients who underwent pancreatoduodenectomy. The occurrence of postoperative hepatic steatosis was also monitored. RESULTS: The nutritional status improved after Frey's procedure, but not after pancreatoduodenectomy. The median postoperative CONUT score after Frey's procedure was significantly lower than the preoperative score (1.0 ± 0.5 vs. 4.0 ± 2.5; p < 0.001). CONCLUSION: Frey's procedure is superior to pancreatoduodenectomy for improving the nutritional status of CP patients.

Lymph nodes around the posterior gastric artery: their existence, frequency, and clinical implications.

PURPOSE: The lymphatic flow along the posterior gastric artery (PGA) is considered of possible clinical importance in terms of lymphatic metastasis; however, little is known about the lymph nodes (LNs) around this artery. The purpose of this study was to establish if LNs exist around the PGA and to evaluate their clinical implications. METHODS: We examined the tissues surrounding the PGA from 21 cadavers to search for LNs. We also investigated the patterns of lymphatic metastases in patients who underwent surgery for gastric neoplasms at our institute to detect their presence along the PGA. RESULTS: The PGA was identified in 11 cadavers, and LNs around the PGA were detected microscopically in 2 of these. Lymphatic metastasis directly to the LNs at the splenic artery without any metastases was regarded as skip metastasis along the PGA. Skip metastasis was found in two of ten patients who underwent surgery for remnant gastric cancer. CONCLUSIONS: The existence of LNs around the PGA was confirmed, and based on our findings, lymphatic metastasis through the PGA is possible in patients with remnant gastric cancer.

The Spleen as an Optimal Site for Islet Transplantation and a Source of Mesenchymal Stem Cells.

This review demonstrates the unique potential of the spleen as an optimal site for islet transplantation and as a source of mesenchymal stem cells. Islet transplantation is a cellular replacement therapy used to treat severe diabetes mellitus; however, its clinical outcome is currently unsatisfactory. Selection of the most appropriate transplantation site is a major factor affecting the clinical success of this therapy. The spleen has long been studied as a candidate site for islet transplantation. Its advantages include physiological insulin drainage and regulation of immunity, and it has recently also been shown to contribute to the regeneration of transplanted islets. However, the efficacy of transplantation in the spleen is lower than that of intraportal transplantation, which is the current representative method of clinical islet transplantation. Safer and more effective methods of islet transplantation need to be established to allow the spleen to be used for clinical transplantation. The spleen is also of interest as a mesenchymal stem cell reservoir. Splenic mesenchymal stem cells contribute to the repair of damaged tissue, and their infusion may thus be a promising therapy for autoimmune diseases, including type 1 diabetes mellitus and Sjogren’s syndrome.

[Conversion Surgery for Pancreatic Head Cancer with Peritoneal Dissemination Following Chemotherapy for Two Years - A Case Report].

Here we report a case of pancreatic cancer(PC)with peritoneal dissemination, underwent conversion surgery following chemotherapy for 2 years. A5 5-year-old woman was referred to our hospital for treatment of PC. Abdominal CT scan revealed 3.0 cm of a pancreatic head tumor with abutment of the portal vein and the hepatic artery, classified as borderline resectable. Staging laparoscopy(SL)showed positive peritoneal cytology(CY). Gemcitabine(Gem)plus S-1 therapy(GS) was performed. Ten months after initial GS, SL revealed the disseminated nodule and positive CY. The regimen was changed to Gem plus nab-paclitaxel therapy(Gem plus nab-PTX). Since right ovarian tumor was detected by CT scan 6 months after initial Gem plus nab-PTX, laparoscopic oophorectomy was performed. Histological findings showed positive CY and ovarian metastasis of PC. Afterward, Gem plus nab-PTX has been continued for 8 months. Since SL after 2 years from initial chemotherapy showed negative CY and no metastatic lesion, pancreaticoduodenectomy with portal vein resection was performed as conversion surgery. According to General Rules for the Study of Pancreatic Cancer the 7th edition by Japan Pancreas Society, histological findings showed ypT3, ypN0, R0, and Grade 1b of histological effect. The patient is alive without recurrence 6 months after the resection.

PHLDA3 is a novel tumor suppressor of pancreatic neuroendocrine tumors.

The molecular mechanisms underlying the development of pancreatic neuroendocrine tumors (PanNETs) have not been well defined. We report here that the genomic region of the PHLDA3 gene undergoes loss of heterozygosity (LOH) at a remarkably high frequency in human PanNETs, and this genetic change is correlated with disease progression and poor prognosis. We also show that the PHLDA3 locus undergoes methylation in addition to LOH, suggesting that a two-hit inactivation of the PHLDA3 gene is required for PanNET development. We demonstrate that PHLDA3 represses Akt activity and Akt-regulated biological processes in pancreatic endocrine tissues, and that PHLDA3-deficient mice develop islet hyperplasia. In addition, we show that the tumor-suppressing pathway mediated by MEN1, a well-known tumor suppressor of PanNETs, is dependent on the pathway mediated by PHLDA3, and inactivation of PHLDA3 and MEN1 cooperatively contribute to PanNET development. Collectively, these results indicate the existence of a novel PHLDA3-mediated pathway of tumor suppression that is important in the development of PanNETs.

[Multidisciplinary Therapy with Gemcitabine and Nab-Paclitaxel for Unresectable Pancreatic Cancer].

Gemcitabine with nab-paclitaxel(GN)shows promisinganti -tumor effect and has been established standard regimen for metastatic pancreatic cancer(PC). Conversion surgery(CS), recently reported about initially unresectable PC with favorable response to non-surgical treatment, might provide long-term survival. The aim of this study is to evaluate the efficacy of multi-modal treatment includingCS after GN therapy for initially unresectable PC. From 2015 to 2016, 29 initially unresectable PC treated with chemotherapy includingGN were eligible for the retrospective analysis. Unresectability was defined over 180- degree abutment to major arteries(UR-LA)or suspicious small metastases(UR-M). CS was planed after clinical favorable response over 6 months of treatment duration. Median age of the patients was 62.5 years old, including 18 males and 11 females. Tumor in the pancreas head(n=20)was dominant. Eighteen patients were UR-LA and remaining1 1 were UR-M. CS was performed in 9 cases(31%)with no significant difference between UR-LA and UR-M. CS showed significant better survival with 67%of 2-year survival rate, compared to without CS(p=0.039). GN regimen effectively induced CS for initially unresectable PC. Multidisciplinary therapy includinginduction GN and CS might have survival impact on unresectable PC.

[A Case of Successful Adjuvant Surgery for the Pancreas Head Cancer with Peritoneal Metastasis].

We report a case of the pancreas head cancer with peritoneal metastasis, which was resected curatively after chemotherapy. A6 6-year-old male was referred to our hospital for the treatment of biliary stenosis. The serum CA19-9 level was elevated and abdominal CT scan showed stenosis of distal bile duct. By laparotomy, we noticed mass in the head of the pancreas with 8mm of the seeding nodule in a diameter at jejunal mesentery which was diagnosed as adenocarcinoma by intraoperative frozen sections. Therefore, the patient was diagnosed as pancreas head cancer with peritoneal metastasis. After hepaticojejunostomy, we started chemotherapy planning adjuvant surgery if the clinical response was observed. Systemic chemotherapy with gemcitabine and nab-paclitaxel was administrated on days 1, 8 and 15 every 4 weeks. After 5 courses, therapeutic effect was stable disease(SD)in response evaluation criteria in solid tumor(RECIST). All of tumor markers were normalized. Subtotal stomach-preserving pancreatoduodenectomy(SSPPD)was performed 6 months after the initial surgery. Histopathologically, most cancer cells showed degeneration and eliminated in the head of the pancreas. R0 resection was achieved with diagnosis of ypT3, ypN1, pM1(PER), Stage IV . Histological therapeutic effect was Grade III according to the Evans classification. The patient is alive, with no sign of recurrence 8 months after surgery. Adjuvant surgery was suggested to be one of the therapeutic options for pancreatic cancer with peritoneal metastasis.

[A Case of Successful Stomach-Preserving Pancreaticoduodenectomy with Celiac Artery Resection after Neoadjuvant Chemoradiation Therapy for Pancreatic Cancer with Hepatic Arterial Variation].

Here we report a case of successful stomach-preserving pancreaticoduodenectomy with celiac artery resection for pancreatic cancer with hepatic arterial variation. A 70-year-old woman was referred to our hospital for examination and treatment of pancreatic cancer. A CT scan showed a tumor with suspected portal vein invasion at the body and head of the pancreas, in contact with the common hepatic artery and the splenic artery with 360°involvement. Contact with the celiac artery and left gastric artery was less than1 80°. CT and angiography revealed hepatic arterial variation in which the right hepatic artery and the left hepatic artery arose from the superior mesenteric artery and the left gastric artery, respectively. Resectability status was considered as borderline resectable. After neoadjuvant chemoradiation therapy, the levels of the serum tumor markers declined remarkably and a CT scan showed SD(RECIST). Subtotal stomach-preserving pancreaticoduodenectomy with celiac artery resection(SSPPD-CAR)was performed without resectionof the left gastric artery and a pathological R0 resectionwas achieved. The significance of performing combination resection and reconstruction of a major artery in pancreatic cancer is unclear. However, there may be cases with vascular variants that enable radical resection without reconstruction of the common hepatic artery. Therefore, it is important to preoperatively evaluate the configuration of the artery accurately and to select the optimal surgical procedures onthe basis of these variations.

Clinicopathological features and surgical outcomes of adenosquamous carcinoma of the pancreas: a retrospective analysis of patients with resectable stage tumors.

PURPOSE: Adenosquamous carcinoma of the pancreas is a rare subtype of pancreatic cancer. We herein describe the clinicopathological features of surgically resected cases of adenosquamous carcinoma of the pancreas. METHODS: From 2001 to 2011, 132 patients underwent R0 resection for Stage IIA or IIB pancreatic cancer. The survival rate, pathological features and recurrence status were reviewed. RESULTS: Out of 132 patients, 121 patients had tubular adenocarcinoma, and only seven had adenosquamous carcinoma (ASC). The incidence of ASC increased with the tumor size. The overall survival and disease-free survival periods of the patients with ASC were significantly shorter than those of patients with tubular adenocarcinoma (p = 0.0153 and p = 0.0045). The histological findings revealed more marked venous invasion in ASC compared to tubular adenocarcinoma (G1, G2 and G3). The proportion of v3 cases, which denotes the most severe venous invasion, was 31.3 % in G1, 47.3 % in G2, 60.0 % in G3 and 71.4 % in ASC cases, respectively. Other factors, including lymphatic and nerve invasion, were not correlated with the histological subtypes. The incidence of ASC was 11.1 % in the tumors more than 6 cm in diameter, and 0 % in those less than 2 cm in diameter. CONCLUSIONS: We revealed that adenosquamous carcinoma of the pancreas is associated with a poor outcome, and also clarified its clinicopathological features.

[A Patient with Three-Year Relapse-Free Survival after Surgical Resection for Lung and Liver Metastases of Cholangiocarcinoma].

We report of a patient with 3-year relapse-free survival after surgical resection for lung and liver metastases of distal cholangiocarcinoma (DCC). A quinquagenarianman was taken to a local hospital in October 2009 for yellow urine. He was diagnosed with DCC and was referred to our hospital for surgery. Pancreaticoduodenectomy was performed, and there was no residual tumor on histological examination. He did not receive any adjuvant therapy. One year 7 months after surgery, an isolated lung metastasis was identified on CT and was surgically removed. Six months after resection of the lung metastasis, a solitary liver metastasis was detected. Although systematic chemotherapy (gemcitabine plus S-1; 2 weeks treatment, 1 week drug free) was administered, the treatment was abandoned because of grade 3 (CTCAE v4.0) of skin disorders during the third course. Partial resection of the liver was performed in April 2012. Alternate-day treatment with S-1 was performed after resection of liver metastasis and is ongoing without adverse events. He has survived for more than 3 years without recurrence after liver resection. In this case of DCC metastasis, prognosis improved with surgical resection.

Strategy for clinical setting in intramuscular and subcutaneous islet transplantation.

Intraportal islet transplantation has a long history as a procedure for clinical islet transplantation. However, many recent studies revealed that the intraportal procedure has some disadvantages in transplant efficiency and safety. Many candidates as an optimal transplant site for islets have been assessed, but further studies and clinical trials are still necessary. Intramuscular and subcutaneous spaces are important candidates, because the transplant and biopsy procedures are simple approaches with minimal invasion and few complications. Although they are sites with hypovascularity and hypoxia, which contribute to the poor transplant efficiency, many experimental trials for improving the outcome in intramuscular and subcutaneous islet transplantations have been performed, focusing on early angiogenesis and scaffolds for engrafting transplanted islets. We review current progress in intramuscular and subcutaneous islet transplantations and discuss ways to develop them as optimal transplant sites for islets.

The best surgical approach for perforated gastric cancer: one-stage vs. two-stage gastrectomy.

BACKGROUND: Surgery for perforated gastric cancer has a dual purpose: treating life-threatening peritonitis and curing gastric cancer. An emergent one-stage gastrectomy may place an undue burden on patients with a poor general status and could impair long-term survival even if the gastric malignancy is curable. A two-stage gastrectomy, in which the initial treatment of peritonitis is followed by elective gastrectomy, can accomplish both desired purposes. METHODS: We retrospectively analyzed 514 Japanese cases of perforated gastric cancer. 376 patients underwent a one-stage gastrectomy and 54 patients underwent a two-stage gastrectomy. We evaluated patient characteristics, surgical outcomes, postoperative complications, and survival rates in both groups. RESULTS: The two-stage gastrectomy group saw a 78.4% rate of curative R0 resection and 1.9% hospital mortality rate, while corresponding rates in the one-stage gastrectomy group were 50 and 11.4%, respectively. Among cases in which curative R0 resection was performed, there was no significant difference in overall survival between 136 one-stage gastrostomies and 40 two-stage gastrostomies. In a multivariate analysis, curative R0 resection [hazard ratio (HR) 2.937, p = 0.001] and depth of tumor invasion (HR 1.179, p = 0.016) were identified as independent prognostic factors. CONCLUSIONS: Regardless of whether patients underwent a one-stage or two-stage gastrectomy, curative R0 resection improved survival in patients with perforated gastric cancer. When curative R0 resection cannot be performed in the initial treatment phase due to diffuse peritonitis, non-curative and palliative gastrectomy should be avoided, and a two-stage gastrectomy should be planned following peritonitis recovery and detailed examinations.

[A case of pancreatic cancer with local recurrence and liver metastases eight years after surgery].

Here we report a rare case of late recurrence of pancreatic cancer 8 years after surgery. A woman in her mid-fifties was hospitalized for examination of epigastralgia. Computed tomography (CT) revealed a 4 cm nodule at the pancreatic head with suspected invasion of the superior mesenteric vein. She underwent pancreaticoduodenectomy with wedge resection of superior mesenteric vein and intraoperative radiation therapy. Pathological findings showed moderately differentiated tubular adenocarcinoma and T3N1M0, Stage IIB according to The Union for International Cancer Control (UICC) TNM classification. As adjuvant chemotherapy, 56 courses of gemcitabine (GEM) were administered in 3.5 years. Because of long-term use of GEM, common terminology criteria for adverse events (CTCAE) Grade 3 anemia occurred, and chemotherapy was discontinued. Tumor markers were evaluated every month and CT scans were taken every 6 months for 5 years. Subsequently, CT was performed annually. The patient was hospitalized for high-grade fever, 8.5 years after surgery. CT, magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) detected local recurrence with liver metastases. GEM was administered again, but was ineffective. The patient died 9 years after surgery. In conclusion, even if long-term survival is achieved in pancreatic cancer, follow-ups should not be stopped.