Impact of Tumor-Derived DNA Testing in Peritoneal Lavage of Pancreatic Cancer Patients with and Without Occult Intra-Abdominal Metastases.

BACKGROUND: The fractional abundance of tumor-derived DNA in body fluids depends on the metastatic sites and the degree of expansion. We aimed to assess the clinical significance of tumor-derived DNA testing in the peritoneal lavage of patients with pancreatic cancer. METHODS: The prevalence and abundance of tumor-derived DNA was assessed in 204 subjects with ascites by peritoneal lavage (AS) and the evaluable paired plasma (PL) from 149 pancreatic cancer patients undergoing abdominal exploration. Genetic profiles were evaluated by next-generation sequencing, and prognostic impact was assessed using Cox proportional hazard models. RESULTS: Of 204 subjects, AS samples from patients with peritoneal dissemination (PER+) and positive cytology (CY+) showed significantly higher prevalence and abundance of tumor-derived DNA than those with negative counterparts. Tumor-derived DNA prevalence and abundance in AS were more likely to be higher than in paired PL in a subgroup of patients with PER+ and CY+, respectively. Next-generation sequencing revealed concordant or discrepant mutational patterns between the AS and PL samples. Multivariate analysis showed that both tumor-derived DNA in AS (hazard ratio [HR] 3.940, p = 0.009) and PL (HR 2.936, p = 0.026) were independently associated with poor survival in treatment-naïve patients. In patients who underwent resection, tumor-derived DNA positivity in the AS was more predictive of early recurrence than in PL. CONCLUSIONS: Tumor-derived DNA in AS can serve as characterizing the genetic profiles of tumor cells attributable to the development of PER+ and predicting the minimal residual disease and early recurrence in patients with pancreatic cancer.

Laparoscopic and robot-assisted surgery for adult congenital biliary dilatation achieves favorable short-term outcomes without increasing the risk of late complications.

PURPOSE: Minimally invasive surgery (MIS) is the optimal treatment for congenital biliary dilatation (CBD), but few studies on adults have been reported. We compared the postoperative outcomes of MIS with those of open surgery (OS) in adult patients with CBD. METHODS: The subjects of this retrospective study were 36 adult patients who underwent surgery for CBD. We compared the postoperative outcomes of 20 patients who underwent laparoscopic (n = 15) or robotic (n = 5) surgery with those of 16 patients who underwent OS. RESULTS: MIS was associated with a significantly higher rate of type I (p < 0.001), significantly less blood loss (p < 0.001), a significantly lower rate of internal stents (p = 0.048), significantly longer operation times (p = 0.009), and a significantly shorter postoperative hospital stay (p = 0.007) than OS. The postoperative outcomes of MIS for type I CBD were similar to those of the whole cohort. There were no significant differences in late complications between the groups. The robotic procedure had a significantly shorter operative time than laparoscopic surgery for hepaticojejunostomy (HJ; p = 0.029). CONCLUSIONS: MIS achieved favorable short-term outcomes without compromising mid-term outcomes compared to OS and is appropriate for adult patients with CBD. Robotic HJ may be more ideal than its laparoscopic counterpart.

Preceding Systemic Chemotherapy for Patients with Pancreatic Ductal Adenocarcinoma with Positive Peritoneal Cytology Provides Survival Benefit Compared with Up-Front Surgery.

BACKGROUND: The significance of surgical resection in pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal cytology (PPC) is controversial. This study aimed to evaluate whether preceding chemotherapy could be beneficial for patients with PDAC with PPC. METHODS: Between 2017 and 2019, 34 consecutive PDAC patients diagnosed with PPC without distant metastasis were retrospectively reviewed. Twenty-three patients did not receive neoadjuvant treatment (NAT) and 11 received NAT. All patients received systemic chemotherapy after PPC was confirmed, and they underwent surgical resection if PPC turned negative. The treatment course, ratio of conversion surgery (CS), and prognosis were evaluated. Moreover, the prognosis of PPC patients who underwent up-front surgery without NAT between 2003 and 2016 was analyzed as a comparative cohort. RESULTS: The median survival time (MST) of the patients without NAT was 31.4 months. CS was performed in 52.2% of the patients. Patients who underwent CS had better prognoses than those who did not undergo CS (p = 0.005). The CS rate was significantly higher in resectable PDAC (78.5%) than in borderline/unresectable PDAC (11.1%) (p = 0.002). The prognosis of patients with resectable PDAC was improved with preceding chemotherapy compared with up-front surgery (MST 13.0 months; p = 0.016). After NAT, the CS rate was low (27.3%), and the MST was only 14.1 months. CONCLUSIONS: As an initial treatment for PDAC patients with PPC, chemotherapy may lead to a favorable prognosis. Especially, resectable PDAC is associated with a greater chance of improved prognosis. Future studies are required to ascertain whether up-front surgery or preceding chemotherapy should be performed for these patients.

Staging laparoscopy is mandatory for the treatment of pancreatic cancer to avoid missing radiologically negative metastases.

PURPOSE: Staging laparoscopy is considered useful for determining treatment plans for advanced pancreatic cancer. However, the indications for staging laparoscopy are not clear. This study aimed to evaluate the safety of staging laparoscopy and its usefulness for detecting distant metastases in patients with pancreatic cancer. METHODS: A total of 146 patients with pancreatic cancer who underwent staging laparoscopy between 2013 and 2019 were analyzed. Staging laparoscopy was performed in all pancreatic cancer patients in whom surgery was considered possible. RESULTS: In this cohort, 42 patients (29%) were diagnosed with malignant cells on peritoneal lavage cytology, 9 (6%) had peritoneal dissemination, and 11 (8%) had liver metastases. A total of 48 (33%) had radiologically negative metastases. On a multivariate analysis, body and tail cancer [odds ratio (OR) 5.00, 95% confidence interval (CI) 2.15-11.6, p < 0.001], high CA19-9 level [OR 4.04, 95% CI 1.74-9.38, p = 0.001], and a resectability status of unresectable (OR 2.31, 95% CI 1.03-5.20, p = 0.04) were independent risk factors for radiologically negative metastases. CONCLUSIONS: Staging laparoscopy can be safely performed and is useful for the diagnosis of radiologically negative metastases. Staging laparoscopy should be routinely performed for the accurate diagnosis of pancreatic cancer patients before pancreatectomy and/or local treatment, such as radiotherapy.

Increased neutrophil-lymphocyte ratio predicts recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

BACKGROUND: The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the ability to predict the recurrence of such markers after curative resection in patients with these neoplasms. METHODS: Circulating/systemic neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet-white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan-Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals. RESULTS: Univariate analysis demonstrated that preoperative neutrophil-lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil-lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil-lymphocyte ratio (HR = 3.49 95% CI 1.05-11.7; P = 0.042) and 2017 World Health Organization classification (HR = 8.81, 95% CI 1.46-168.2; P = 0.015) were independent recurrence predictors. CONCLUSIONS: The circulating/systemic neutrophil-lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

[A Successful Case of Pancreaticoduodenectomy after Neoadjuvant Therapy for Pancreatic Head Cancer with Acute Pancreatitis Due to Iatrogenic Injury of the Pancreatic Duct].

A 64-year-old woman was referred to our hospital for treatment of pancreatic head cancer with acute pancreatitis due to iatrogenic injury of the pancreatic duct during endoscopic retrograde cholangiopancreatography. In addition to a 28 mm pancreatic head tumor, soft tissue shadow and fluid collection surrounding the superior mesenteric artery(SMA)due to pancreatitis were observed in the abdominal CT scan. The tumor was histologically diagnosed as adenocarcinoma by endoscopic ultrasound-guided fine needle aspiration. Neoadjuvant chemotherapy with gemcitabine and S-1 was performed to control the progression of the pancreatic cancer and improve the inflammatory changes for reduction of the operative risk. After 2 courses of neoadjuvant chemotherapy, abdominal CT scan revealed stable disease according to the Response Evaluation Criteria in Solid Tumors and attenuation of the inflammatory changes surrounding the SMA. Then, subtotal stomach- preserving pancreaticoduodenectomy was performed without the difficulty of peeling around the SMA in spite of the old inflammatory changes. Histological examination of the resected specimen showed R0 resection. The patient was discharged 18 days after surgery without any complications and is surviving 9 months postoperatively without any recurrence. Neoadjuvant chemotherapy was helpful for disease control and improvement of the inflammatory changes.

Prognostic impact of intraoperative peritoneal cytology after neoadjuvant therapy for potentially resectable pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NAT) is considered a potential approach to improve survival for patients with pancreatic adenocarcinoma (PA). The objective of this study was to identify the clinical implications of washing peritoneal cytology (CY) status after NAT. METHODS: Between 2005 and 2016, 151 consecutive patients with resectable (R)/borderline resectable (BR) PA underwent NAT with intention of subsequent resection at our institution. Of them, 13 and 123 patients underwent pancreatectomies with positive (CY+) and negative (CY-) cytology, respectively, while the remaining 15 patients did not undergo resection due to gross metastases at laparotomy. The clinicopathological factors influencing overall survival were clarified by the uni- and multivariate analyses. RESULTS: The postoperative overall survival (OS) and disease-free survival (DFS) were markedly worse in patients who underwent resection with CY+, compared with those who were CY- (median OS, 14.8 m vs 30.8 m, p = 0.026, and median DFS 6.0 m vs 15.1 m, p = 0.008). According to the resectability by NCCN guidelines, CY+ indicates worse prognosis than CY- in R-PA patients (mOS: 30.1 m vs 71.1 m: p = 0.080). Similarly, in BR-PA patients, CY+ showed the significantly worse prognosis than CY- (mOS: 13.8 m vs 24.5 m: p = 0.048), which prognosis is comparable with patients who did not undergo resection. The multivariate analysis revealed that resectability, CY status and the induction of adjuvant therapy were significant predictors of postoperative OS (p = 0.007: Hazard ratio 2.264, 0.040:2.094 and 0.002:3.246, respectively). CONCLUSIONS: CY+ is a significant predictor of poorer prognosis in PA patients after NAT. The subsequent pancreatectomies with CY+ after NAT do not contribute to prolonged survival.

The superior approach with the stomach roll-up technique improves intraoperative outcomes and facilitates learning laparoscopic distal pancreatectomy: a comparative study between the superior and inferior approach.

PURPOSE: We introduced a superior approach and a unique technique to retract the stomach, called the "stomach roll-up technique", to standardize laparoscopic distal pancreatectomy and increase educational effectiveness. The aim of this study was to evaluate the clinical outcomes of these procedures. METHODS: Forty-five patients who underwent laparoscopic distal pancreatectomy by surgeons-in-training between January 2015 and December 2018 were included. Twenty laparoscopic distal pancreatectomies were performed using the inferior approach, and 25 procedures were performed using the superior approach. The stomach roll-up technique was used in all cases. The perioperative outcomes were retrospectively analyzed. RESULTS: Compared with the inferior approach, the superior approach was associated with a significantly shorter operation time (p < 0.001) and lower estimated blood loss (p = 0.011), and these differences were not affected by the exclusion of cases with conversion or concomitant procedures. In the univariate analysis adjusted for other covariates, a lower body mass index (p = 0.045), pancreatic tail tumor (p = 0.0178) and the superior approach (p = 0.0176) were significantly associated with a shorter operation time. CONCLUSION: The superior approach with the stomach roll-up technique is simple and will aid in educating surgeons on performing laparoscopic distal pancreatectomy.

[A Case of Aortitis Caused by a Granulocyte-Colony-Stimulating Factor during Chemotherapy for Pancreatic Cancer].

BACKGROUND: Pegfilgrastim, a long-acting granulocyte-colony-stimulating factor(G-CSF), has been used as prophylaxis for severe hematotoxicity induced by chemotherapy. We report a case of aortitis induced by pegfilgrastim administration during modified FOLFIRINOX(mFOLFIRINOX)chemotherapy for metastatic pancreatic cancer. CASE REPORT: A 65-year-old woman underwent a distal pancreatectomy for pancreatic tail cancer. Liver metastases appeared 2 years after the surgery. mFOLFIRINOX chemotherapy was started with prophylactic administration of pegfilgrastim. Eight days after the first administration and 6 days after administration of the 8th course, the patient developed a fever. The blood test results indicated severe inflammation. Computed tomography revealed a thickened aorta indicating aortitis. The symptoms rapidly improved with antibiotic therapy. We diagnosed aortitis induced by pegfilgrastim administration. CONCLUSION: Aortitis should be considered when a patient has unidentified inflammatory findings after receiving pegfilgrastim.

Novel biomarkers distinguishing pancreatic head Cancer from distal cholangiocarcinoma based on proteomic analysis.

BACKGROUND: The differentiation between pancreatic head cancer (PHC) and distal cholangiocarcinoma (DCC) can be challenging because of their anatomical and histopathological similarity. This is an important problem, because the distinction has important implications for the treatment of these malignancies. However, there are no biomarkers for the differential diagnosis of PHC and DCC. The present study aimed to identify novel diagnostic immunohistochemical biomarkers to distinguish PHC from DCC. METHODS: Liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to detect candidate proteins. Ten PHC and 8 DCC specimens were analyzed by LC-MS/MS. Selected proteins were evaluated, using immunohistochemical analysis, to determine whether they would be appropriate biomarkers. Finally, we generated biomarker panels to improve diagnostic accuracy. We applied these panels to clinically difficult cases (cases in which different diagnoses were made before and after operation). RESULTS: Consequently, 1820 proteins were detected using LC-MS/MS. Fifteen differentially expressed proteins were selected as candidates based on semi-quantitative comparison. We first performed immunohistochemical staining on samples from the small cohort group (12 PHCs and 12 DCCs) using 15 candidates. KRT17, ANXA10, TMEM109, PTMS, and ATP1B1 showed favorable performances and were tested in the next large cohort group (72 PHCs and 74 DCCs). Based on immunohistochemical analysis, KRT17 performed best for the diagnosis of PHC as a single marker; additionally, PTMS exhibited good performance for the diagnosis of DCCs. Moreover, we indicated the KRT17+/ANXA10+/PTMS- staining pattern as a biomarker panel for the correct diagnosis of PHC and KRT17-/ANXA10-/PTMS+ for the diagnosis of DCC. After immunohistochemical staining for examining samples from the clinically difficult cases, these panels showed satisfactory diagnostic performance with 85.7% (6/7) accuracy. CONCLUSIONS: We conclude that 5 proteins and 2 biomarker panels are promising for distinguishing PHC from DCC, and patients with an equivocal diagnosis would benefit from the application of these biomarkers. Confirmatory studies are needed to generalize these findings to other populations.

Laparoscopic partial liver resection improves the short-term outcomes compared to open surgery for liver tumors in the posterosuperior segments.

PURPOSE: The aim of this study was to compare the clinical outcomes between laparoscopic partial liver resection and open partial hepatectomy for tumors in the posterosuperior segments. METHODS: The clinical outcomes of patients who underwent either laparoscopic (n = 20) or open (n = 44) resection in segments 7/8 of the liver were initially evaluated. Because of disparities in the background characteristics, a case-matched study (1:1) was conducted. In addition, a comparative study of the patients who met the institutional criteria for laparoscopic partial hepatectomy was performed. RESULTS: In the case-matched study, the laparoscopic technique required a longer operation time (p = 0.001), but was associated with less intraoperative blood loss (p = 0.021), a lower incidence of major complications (p = 0.014), higher levels of serum albumin on postoperative days 3 and 7 (p = 0.031 and p = 0.035), and earlier discharge (p = 0.001) than open resection. The results of the latter study were similar to those of the case-matched analysis. CONCLUSIONS: Laparoscopic partial hepatectomy was a feasible procedure for treating tumors in the posterosuperior segments without compromising oncological safety and yielded better short-term outcomes than open techniques. In addition, this study provides concrete selection criteria for laparoscopic partial hepatectomy for difficult lesions.

[Conversion Surgery for Locally Advanced Unresectable Pancreatic Cancer Treated with FOLFIRINOX Therapy and Proton Beam Therapy Combined with S-1 Chemotherapy-A Case Report].

We report a case of locally advanced unresectable(UR-LA)pancreatic cancer in a patient who underwent conversion surgery after FOLFIRINOX and proton beam therapy(PBT)combined with S-1. A 68-year-old woman was referred to our hospital for a pancreatic tumor. The abdominal CT scan revealed a 40mm pancreatic body tumor with an abutment(>180°) of the celiac artery and the superior mesenteric artery. Moreover, the tumor was classified as UR-LA with a contact to the abdominal aorta. The tumor was histologically diagnosed as adenocarcinoma via an endoscopic ultrasound-guided fine-nee- dle aspiration. After 2 courses of FOLFIRINOX, PBT(50 GyE/25 Fr)combined with S-1 were administered. The tumor shrunk to 30mm at the CT scan. After 5 courses of FOLFIRINOX, the tumor reduced to 20 mm. No distant metastasis or malignant cells in abdominal washing cytology was detected using staging laparoscopy. Then, distal pancreatectomy with celiac axis resection(DP-CAR)was performed. According to the General Rules for the Study of Pancreatic Cancer(7th edition)from Japan Pancreas Society, the histological findings were suggestive of ypT3, ypN0, R0, and Grade 3 histological effect. The patient had a Grade A delayed gastric emptying post-operation. He was discharged 35 days after the surgery and has been alive without recurrence on imaging for 11 months post-operation.

[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.

[Conversion Surgery Combined with Preoperative Coil Embolization of Hepatic Artery for Locally Advanced Unresectable Pancreatic Head Cancer with Hepatic Artery Invasion-A Case Report].

Here we report a case treated with conversion surgery combined with preoperative coil embolization of the hepatic artery after chemoradiation therapy for locally advanced unresectable pancreatic head cancer with hepatic artery invasion. A 63- year-old man was referred to our hospital for treatment of pancreatic cancer. Abdominal CT scan revealed a 30mm pancreatic head tumor with involvement of the common hepatic artery(CHA)and proper hepatic artery(PHA). The left hepatic artery diverged from the left gastric artery. Although S-1 with concurrent radiation therapy was performed, a follow-up CT scan revealed the progression of soft tissue shadow around the CHA. Subsequently, gemcitabine plus nab-paclitaxel(GnP)was administered 13 times. GnP helped achieve normalization of the tumor markers and long stable disease(SD)based on the Response Evaluation Criteria in Solid Tumors(RECIST). For the conversion surgery, embolization of the middle hepatic artery (MHA)was performed. Twelve days after, the right hepatic artery was embolized. Subtotal stomach-preserving pancreaticoduodenectomy was performed with resection of the CHA and PHA without arterial reconstruction 16 days after the hepatic arterial embolization. The patient was discharged from our hospital 33 days after surgery without complications related to hepatic ischemia. The patient is alive without recurrence 42 months after the initial diagnosis and 26 months after surgery.

Predictive risk factors for peritoneal recurrence after pancreatic cancer resection and strategies for its prevention.

PURPOSE: To evaluate the risk factors for peritoneal recurrence (PR) of pancreatic adenocarcinoma and to discuss the appropriate management strategies. METHODS: We reviewed the medical records of 236 patients who underwent pancreatectomy for pancreatic adenocarcinoma. We then compared the clinicopathological characteristics of patients with vs. those without PR. The independent risk factors for PR were defined using the Cox proportional hazards regression model. RESULTS: The median survival of patients with PR was 13.3 months after surgical treatment. The PR group had a significantly higher incidence of portal vein resection, longer operative time (≥648 min), greater blood loss (≥2179 mL), blood transfusion, tumor size, portal vein invasion, artery invasion, pancreatic nerve plexus invasion, and histological grade. Multivariate analysis revealed that excessive blood loss (≥2179 mL; P = 0.010), artery invasion (P = 0.025), pancreatic nerve plexus invasion (P = 0.001), and histological grade 3 (P = 0.011) were independent risk factors for PR. Excessive blood loss was also strongly related to tumor size (P = 0.018). CONCLUSIONS: Local invasion and tumor size-related factors suggested the possibility of intraoperative dissemination at the time of tumor resection. Preoperative treatment and an operative procedure to prevent tumor exposure may help prevent PR.

[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.

Novel prognostic protein markers of resectable pancreatic cancer identified by coupled shotgun and targeted proteomics using formalin-fixed paraffin-embedded tissues.

Pancreatic cancer is among the most lethal malignancies worldwide. We aimed to identify novel prognostic markers by applying mass spectrometry (MS)-based proteomic analysis to formalin-fixed paraffin-embedded (FFPE) tissues. Resectable, node positive pancreatic ductal adenocarcinoma (PDAC) with poor (n = 4) and better (n = 4) outcomes, based on survival duration, with essentially the same clinicopathological backgrounds, and noncancerous pancreatic ducts (n = 5) were analyzed. Cancerous and noncancerous cells collected from FFPE tissue sections by laser microdissection (LMD) were processed for liquid chromatography (LC)-tandem MS (MS/MS). Candidate proteins were identified by semiquantitative comparison and then analyzed quantitatively using selected reaction monitoring (SRM)-based MS. To confirm the associations between candidate proteins and outcomes, we immunohistochemically analyzed a cohort of 87 cases. In result, totally 1,229 proteins were identified and 170 were selected as candidate proteins for SRM-based targeted proteomics. Fourteen proteins overexpressed in cancerous as compared to noncancerous tissue showed different expressions in the poor and better outcome groups. Among these proteins, we found that three novel proteins ECH1, OLFM4 and STML2 were overexpressed in poor group than in better group, and that one known protein GTR1 was expressed reciprocally. Kaplan-Meier analysis showed high expressions of all four proteins to correlate with significantly worse overall survival (p < 0.05). In conclusion, we identified four proteins as candidates of prognostic marker of PDAC. The combination of shotgun proteomics verified by SRM and validated by immunohistochemistry resulted in the prognostic marker discovery that will contribute the understanding of PDAC biology and therapeutic development.

Solid pseudopapillary neoplasms of the pancreas: an 18-year experience at a single Japanese Institution.

PURPOSE: This study investigated the clinicopathological features and surgical management of solid pseudopapillary neoplasms at a single institution in Japan. METHODS: Seventeen patients (the largest series in Japan) those underwent surgery for pathologically confirmed solid pseudopapillary neoplasms were retrospectively reviewed. RESULTS: Sixteen patients were women and their mean age was 34.1 years. Most patients were asymptomatic (n = 11), and the average tumor diameter was 51.8 mm. The most common imaging characteristic was tumors of solid and cystic type (n = 10), which were most commonly located in the pancreatic body (n = 7). All patients underwent surgical exploration, i.e., distal pancreatectomies in 7 patients (laparoscopically performed in 2); middle pancreatectomies, 4; pancreaticoduodenectomies, 4; enucleation, 1; and liver resection, 1. No surgical mortalities occurred, and postsurgical complications occurred in 9 patients. Four patients had malignant tumors. One patient with liver metastases experienced recurrence, which was well controlled by paclitaxel. The remaining patients were disease free at a median follow-up of 51 months. CONCLUSIONS: Solid pseudopapillary neoplasms can be treated by complete tumor resection with limited resection or a minimally invasive approach when applicable. The combination of surgical resection and chemotherapy may therefore prolong survival, even in malignant cases.