Fibroblast growth factor receptor 2 (FGFR2) fusions in Japanese patients with intrahepatic cholangiocarcinoma.

OBJECTIVE: Fibroblast growth factor receptor gene alterations have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer that has a poor prognosis. This study evaluated the frequency of fibroblast growth factor receptor 2 fusions in clinical specimens from Japanese patients with iCCA. METHODS: This study enrolled 116 patients who had histologically or cytologically confirmed adenocarcinoma and been diagnosed as relapsing after resection or with unresectable intrahepatic cholangiocarcinoma. We evaluated the frequency of fibroblast growth factor receptor 2 fusions-positive cells in their specimens using break-apart fluorescent in situ hybridization 'for 114 patients who met the study protocol'. RESULTS: Of a total of 114 cases, six (5.3%) were identified as fibroblast growth factor receptor 2 fusions-positive with a high frequency (87% or more) of fibroblast growth factor receptor 2 fusions-positive tumour cells whereas the remainder, with the exception of three cases with indeterminate results, were identified as fibroblast growth factor receptor 2 fusions-negative. The patients' baseline characteristics as well as their objective response rates, disease control rates, times to progression, and times to treatment failure with previous or ongoing first-line chemotherapy did not have any obvious relationship to the proportion of fibroblast growth factor receptor 2 fusions-positive case. CONCLUSIONS: Further detailed elucidation of fibroblast growth factor receptor 2 fusion status is expected to contribute to the development of promising therapeutic options for patients suffering from recurrent or unresectable intrahepatic cholangiocarcinoma.

Silencing of LRRFIP1 enhances the sensitivity of gemcitabine in pancreatic cancer cells by activating JNK/c-Jun signaling.

BACKGROUND: The epithelial-mesenchymal transition (EMT) in cancer cells has been shown to closely associate with the survival and drug resistance of cancer cells. We recently provided evidence that Wnt signal activator leucine-rich repeat in flightless-1-interacting protein 1 (LRRFIP1) regulates EMT in pancreatic cancer. LRRFIP1 silencing inhibits the translocation of ß-catenin to the nucleus, which led to reverse EMT in cancer cells. It was suggested that LRRFIP1 was implicated in gemcitabine sensitivity by regulating EMT signaling. METHODS: Gemcitabine chemosensitivity was investigated in LRRFIP1-knockdown pancreatic cancer cells (PANC-1 and MIA Paca-2). In addition, the effects of LRRFIP1 knockdown on JNK/SAPK (stress activated-protein kinase) signaling and apoptosis were evaluated. RESULTS: LRRFIP1 silencing accelerates gemcitabine-induced caspase activity and cell death in pancreatic cancer cells. It was also revealed that gemcitabine-induced phosphorylation of c-Jun N-terminal kinase (JNK) and c-Jun were increased in LRRFIP1 knockdown cells. The activation of JNK/c-Jun in LRRFIP1-knockdown cells was significantly diminished by the inhibition of Rac activity. It was confirmed that the acquisition of gemcitabine sensitivity by LRRFIP1 silencing largely depends on the stimulation of JNK/SAPK (stress activated-protein kinase) signaling. CONCLUSIONS: Our findings suggest that reversing EMT and transient activation of JNK might be essential for the gemcitabine sensitivity in LRRFIP1 knockdown pancreatic cancer cells. Our discoveries highlight the potential role of LRRFIP1 in the chemosensitivity related to the regulation of EMT signaling.

Preoperative biliary drainage of the hepatic lobe to be resected does not affect liver hypertrophy after percutaneous transhepatic portal vein embolization.

BACKGROUND: In patients with malignant perihilar biliary strictures, preoperative biliary drainage (PBD) of the hepatic lobe to be resected may decrease the liver volume of the future liver remnant (FLR) after percutaneous transhepatic portal vein embolization (PVE). However, evidence of its application is insufficient. This study aimed to clarify the effects of PBD on liver hypertrophy after PVE. METHODS: Between January 2008 and December 2017, 169 patients with malignant perihilar biliary strictures underwent major hepatectomy or palliative surgery at our hospital. Of these, 76 patients who underwent PVE were categorized into two groups: group A (n = 29) who received unilateral PBD of the FLR and group B (n = 47) who received bilateral PBD, including that of the hepatic lobe to be resected. FLR ratios after PVE and liver hypertrophy ratios were retrospectively compared in both groups. RESULTS: Group B exhibited significantly severe biliary stenosis (p = 0.0038) and high serum bilirubin before biliary drainage (p = 0.0037). After PVE, the total liver volumes were 1287 ± 260 ml and 1340 ± 257 ml (p = 0.39), respectively. FLR volumes were 555 ± 135 and 577 ± 113 ml (p = 0.45), respectively. FLR ratios were 43.4 ± 8.2% and 43.4 ± 6.4%, respectively (p = 0.98). Liver hypertrophy ratios were 124.2 ± 17.7% and 129.2 ± 20.9%, respectively (p = 0.28). In addition, an examination which excluded patients with Bismuth type I obtained similar result. CONCLUSIONS: PBD of the hepatic lobe to be resected did not decrease the FLR ratios and hypertrophy ratios. Thus, in patients with poor biliary drainage, additional PBD of the target lobe is acceptable.

Metastasis of ovarian cancer to the bile duct: a case report.

BACKGROUND: Ovarian cancer typically spreads along the peritoneum or metastasizes through the blood or lymphatic stream. The bile duct is an extremely rare site of ovarian cancer-associated metastases. CASE PRESENTATION: A 55-year-old female underwent surgery for advanced left ovarian cancer 2 years ago. She was diagnosed with ovarian serous adenocarcinoma with multiple peritoneal metastases. She received chemotherapy for the residual peritoneal metastases. She achieved a clinical complete response and was followed up with imaging examinations for 1 year. She then complained of dark urine, yellowish discoloration of the eyes, and weight loss. Computed tomography showed an approximately 10-mm solid tumor at the hepatic hilum. Simultaneously, multiple peritoneal metastases were detected in the abdominal and pelvic cavity. Intraductal ultrasonography suggested that the hepatic hilum tumor was located in the bile duct wall. Tumor biopsy and brush cytology of the bile duct indicated atypical cells suspicious for carcinoma. After percutaneous transhepatic portal embolization, she underwent right hepatectomy and extrahepatic bile duct resection for the hepato-hilar tumor. The histopathological features were dysplastic cells with hyperchromatic nuclei and no dysplastic cells in the native biliary epithelium. Immunohistochemical staining revealed that the tumor cells were positive for CK-7 and WT-1 and negative for CK-20 and ER. These results suggested that the tumor was a metastasis of the ovarian serous adenocarcinoma. CONCLUSION: This may be the first case of ovarian cancer metastasis to the bile duct. While it is extremely rare, ovarian cancer may metastasize to the hepatic duct, mimicking hilar cholangiocarcinoma.

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.

18-Fluorodeoxyglucose Positron Emission Tomography Predicts Recurrence in Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: We aimed to determine whether treatment should be stratified according to 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) maximum standardized uptake values (SUVmax) in pancreatic ductal adenocarcinoma. METHODS: Patients who underwent preoperative 18F-FDG PET/CT between 2006 and 2014 (n = 138) were stratified into high (≥ 4.85) and low (< 4.85) PET groups. The clinicopathological characteristics and prognostic outcomes were analyzed retrospectively. RESULTS: The primary tumor SUVmax was positively correlated with preoperative CA19-9 levels (P < 0.001). The high PET group failed to achieve postoperative CA19-9 normalization (P = 0.014). Disease-specific (P < 0.001), recurrence-free (P < 0.001), liver recurrence-free (P < 0.001), and peritoneal recurrence-free (P = 0.020) survivals were significantly shorter in the high PET group. The primary tumor SUVmax was an independent predictive risk factor for liver metastasis (hazard ratio 3.46, 95% confidence interval 1.61-7.87; P = 0.001) and peritoneal recurrence (hazard ratio 3.36, 95% confidence interval 1.18-10.89; P = 0.023). CONCLUSIONS: Surgical resection failed to achieve CA19-9 normalization in the high PET group and distant recurrence was frequent. This suggests the potential for residual cancer at distant sites, even after curative resection. Stronger preoperative systemic chemotherapy is preferred for the high PET group patients.

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.

Application of Quantitative Targeted Absolute Proteomics to Profile Protein Expression Changes of Hepatic Transporters and Metabolizing Enzymes During Cholic Acid-Promoted Liver Regeneration.

Preoperative administration of cholic acid (CA) may be an option to increase the liver volume before elective liver resection surgery, so it is important to understand its effects on liver functionality for drug transport and metabolism. The purpose of this study is to clarify the absolute protein expression dynamics of transporters and metabolizing enzymes in the liver of mice fed with CA-containing diet for 5 days (CA1) and mice fed with CA-containing diet for 5 days followed by diet without CA for 7 days (CA2), in comparison with non-CA-fed control mice. The CA1 group showed the increased liver weight, cell proliferation index, and oxidative stress, but no increase in apoptosis. Quantitative targeted absolute proteomics revealed (1) decreases in basolateral bile acid transporters Na+-taurocholate cotransporting polypeptide, anion transporting polypeptide (oatp) 1a1, and oatp1b2, bile acid synthesis-related enzymes cyp7a1 and cyp8b1, and drug transporters breast cancer resistance protein, multidrug resistance-associated protein 6, ent1, and oatp2b1; and (2) increases in glutathione biosynthetic enzymes and drug-metabolizing enzyme cyp3a11. Liver concentrations of reduced and oxidized glutathione were both increased. In the CA2 group, the increased liver weight was maintained, whereas the biochemical features and protein profiles were restored to the non-CA-fed control levels. These findings suggest that CA administration alters liver functionality per body during liver regeneration and restoration.

A case of adult undifferentiated embryonal sarcoma of the liver successfully treated with right trisectionectomy: a case report.

BACKGROUND: Undifferentiated embryonal sarcoma of the liver (UESL) is a rare malignant mesenchymal tumor that usually occurs in children and is rarely diagnosed in adults. CASE PRESENTATION: Here, we describe the case of a 65-year-old woman who presented with a huge cystic lesion in the liver. Laboratory studies performed on admission showed modest inflammation, poor nutrition, and elevated levels of total bilirubin, alkaline phosphatase, and γ-glutamyl transferase. Computed tomography showed a well-defined, heterogeneous tumor with multiple cysts involving the right lobe and the medial segment of the liver, with a maximum diameter of 16 cm. Positron emission tomography/computed tomographic scans showed the uptake of 2-(fluorine-18)-fluoro-2-deoxy-D-glucose in a part of the cyst. The patient was diagnosed with mucinous cystadenocarcinoma or sarcoma of the liver and underwent right trisectionectomy. Histopathological studies revealed that the tumor was composed of pleomorphic and polynuclear dyskaryotic cells with eosinophilic globules in the cytoplasm. Mesenchymal hamartoma-like tissue was observed in the peripheral part of the tumor. Immunohistochemical analyses showed the tumor stained with vimentin, α-smooth muscle actin, desmin, α1-antitrypsin, and α1-antichymotripsin. Therefore, a histological diagnosis of UESL was made. Eighteen months following treatment, two recurrent tumors in the remnant liver were detected and resection of the recurrent tumors was performed. CONCLUSIONS: A UESL should be considered in the differential diagnosis of large cystic hepatic lesions. Although the prognosis of UESL is extremely unfavorable, aggressive surgical resection should be the most important factor for ensuring long-term survival.

MK2461, a Multitargeted Kinase Inhibitor, Suppresses the Progression of Pancreatic Cancer by Disrupting the Interaction Between Pancreatic Cancer Cells and Stellate Cells.

OBJECTIVES: Platelet-derived growth factor receptor beta (PDGFRß) and hepatocyte growth factor receptor (MET) expressed on pancreatic stellate cells (PSCs) are suggested as important components modulating the interactions between pancreatic cancer cells (PCCs) and PSCs. The objective of this study is to clarify the effect of MK2461, a multikinase inhibitor targeting MET and PDGFRß, on the interaction between PCCs and PSCs. METHODS: In this study, we profiled the expression of receptor tyrosine kinases (including PDGFRß and MET) in pancreatic cancer with quantitative targeted absolute proteomics using liquid chromatography tandem mass spectrometry. In addition, the effect of MK2461 on PCC-PSC interaction was investigated using PSCs prepared from pancreatic cancer tissues. RESULTS: In PSCs, PDGFRß and MET were upregulated compared with other receptor tyrosine kinases. Conditioned medium from PSCs promoted the proliferation of PCCs, and vice versa. Moreover, MK2461 suppressed the effects of conditioned medium on PCCs and PSCs. Finally, MK2461 significantly inhibited tumor growth in mice coinjected with PCCs and PSCs. CONCLUSIONS: The PDGFRß and MET may play a critical role in the interaction between PCCs and PSCs, which was modulated by MK2461. Therefore, MK2461 may have therapeutic potential in the treatment of pancreatic cancer.

Locally advanced pancreatic cancer successfully treated by distal pancreatectomy with celiac axis resection (DP-CAR) after S-1 with radiation therapy followed by gemcitabine/nab-paclitaxel therapy: a case report.

BACKGROUND: The prognosis for pancreatic cancer remains dismal because many patients are diagnosed with unresectable cancer at the initial diagnosis. Recently, conversion surgery was reported as an effective treatment for initially unresectable pancreatic cancer with a favorable response to non-surgical treatment lasting over 240 days. Here, we describe a case of locally advanced pancreatic cancer (LAPC) successfully resected after treatment with S-1 and radiation followed by gemcitabine/nab-paclitaxel therapy. CASE PRESENTATION: A 73-year-old man with LAPC was referred to our hospital. Computed tomography findings revealed a 2.5-cm mass in the pancreatic body that had invaded the celiac artery, common hepatic artery, and splenic artery. Superior mesenteric artery (SMA) encasement was not observed, but tumor abutment over 180° with the main tumor was detected. Staging laparoscopy showed no findings of distant metastasis, and washing cytology revealed no malignancy. He was diagnosed with unresectable pancreatic cancer. Treatment with S-1 with radiation therapy followed by gemcitabine with nab-paclitaxel was performed. Six months after the initial treatment, the tumor size had decreased to 1.2 cm, and encasement of the main artery was diminished. Though abutment to the main artery, including the SMA, was still detected, distal pancreatectomy with celiac artery resection was performed. The histopathological findings around the celiac artery revealed fibrous changes with an Evans classification of grade IIb. There was no residual cancer at the periphery; thus, R0 resection was achieved. The patient has been healthy and without recurrence for more than 12 months since the initial treatment. CONCLUSIONS: Gemcitabine/nab-paclitaxel therapy revealed high response rate for metastasic pancreatic cancer (PC), but the effect for LAPC proposing conversion surgery was not well discussed. In this case, we achieve R0 resection combined with chemoradiation therapy and gemcitabine/nab-paclitaxel therapy. This regimen was also effective for LAPC and may be used to increase the population of conversion surgery by its high response rate.

[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 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.

Silencing of LRRFIP1 reverses the epithelial-mesenchymal transition via inhibition of the Wnt/ß-catenin signaling pathway.

The canonical Wnt/ß-catenin signaling pathway has been shown to promote the epithelial-mesenchymal transition (EMT), which is a crucial process in multiple embryonic developmental processes and the progression of carcinomas. We recently provided evidence that leucine-rich repeat flightless-1-interacting protein 1 (LRRFIP1) promotes cancer metastasis and invasion. In the present study, we identified the signaling elements targeted by LRRFIP1 for promotion of the EMT in pancreatic and lung cancer. LRRFIP1 silencing reversed the EMT, as shown by increased expression of E-cadherin (an epithelial marker) and decreased expression of vimentin (a mesenchymal marker). Silencing of LRRFIP1 up-regulated phosphorylation of ß-catenin and decreased its nuclear localization by targeting the ß-catenin destruction complex. The expression of ß-catenin and E-cadherin in the plasma membrane fraction was increased in LRRFIP1 silenced cancer cells, and the migration and invasion capabilities were strongly inhibited. In addition, this protein was highly expressed at the invasion front of malignant tissue collected from pancreatic cancer patients. Consequently, our data strongly suggested that LRRFIP1 played an important role in the invasion of carcinoma cells. Our data provide experimental evidence that LRRFIP1 is an attractive candidate for targeted therapy in human cancers.

Long-term outcomes after extrahepatic excision of congenital choladocal cysts: 30 years of experience at a single center.

BACKGROUND/AIMS: Congenital choladocal cysts are generally treated by resection of the dilated extrahepatic biliary duct followed by hepaticojejunostomy, but it is associated with postoperative complications, including postoperative cholangitis, intrahepatic calculi, pancreatitis, and carcinogenesis, in the remnant bile duct. We investigated the most common long-term complications and identified the factors implicated in their development. METHODOLOGY: We conducted a retrospective review and analysis of the long-term complications of 65 patients surgically treated for congenital choledochal cysts between 1978 and 2008 at one institute. The risk factors for intrahepatic calculi were identified based on the odds ratios of the implicated variables. RESULTS: Cholangitis with high fever or abdominal pain was reported in 14 patients (21.5%), intrahepatic calculi in 12 (18.5%), pancreatitis in 3 (4.6%), and cholangiocarcinoma in 3 (4.6%). Diagnosis with type IVa choledochal cysts was the most significant risk factor, followed by age ≥30 years at the time of treatment, and the presence of preoperative intrahepatic calculi. CONCLUSIONS: While precise and thorough surgical treatment is necessary to prevent the long-term development of complications after surgical excision of congenital choledochal cysts, it must be accompanied by long-term postoperative follow-up, especially of elderly patients and those with type IVa cysts.

[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.

[A case of successful R0 resection after neoadjuvant therapy for locally advanced unresectable pancreatic cancer].

Adjuvant surgery for initially unresectable pancreatic cancer with a favorable response to chemotherapy or chemoradiation therapy often contributes to a better prognosis than non-surgical treatment alone. We encountered a sexagenarian woman with cancer of the pancreatic body involving the celiac trunk, common hepatic artery, and gastroduodenal artery, which are normally indicative of an unresectable tumor. After systemic chemotherapy (gemcitabine plus S-1 following chemoradiation therapy [S-1 plus irradiation, total 56 Gy]), the level of carbohydrate antigen 19-9 (CA19-9) decreased to within the normal range and the radiological findings showed a slight regression of the tumor without evidence of metastases. Ten months after the initial treatment, distal pancreatectomy with celiac axis resection was performed. Histopathologically, the tumor was almost replaced by marked fibrosis, including the nerve plexus around the adjacent arteries. Viable cells were observed in a part of the nerve plexus of the common hepatic artery alone. S-1 was administered after the surgery, and the patient has survived without recurrence for 17 months since the initial therapy. Here, we report a case of successful R0 resection after chemoradiation therapy for locally advanced unresectable pancreatic cancer.

[Efficacy of neoadjuvant chemotherapy for resectable pancreatic carcinoma].

Surgery followed by adjuvant chemotherapy is standard care for resectable pancreatic carcinoma. The maximum estimated 2-year survival rate associated with this strategy is nearly 50%. The use of neoadjuvant therapy for pancreatic cancer remains controversial, and its efficacy has not been elucidated. To evaluate the efficacy of neoadjuvant chemotherapy for planned pancreatic cancer resection, the oncological outcomes of neoadjuvant gemcitabine plus S-1 combination therapy( GS therapy) and a surgery-first approach were retrospectively compared. Patients with planned pancreatic cancer resection and without major artery abutments were enrolled in this study. There were 39 cases of neoadjuvant GS therapy (N group) and 93 cases of the surgery-first approach( S group). Survival and surrogate markers, including the R0 rate, the "true R0 rate"( R0 with tumor marker normalization after resection), and N0 rate, were compared. The groups did not differ significantly in terms of age, gender, or tumor location. The resection rates of the N and S groups were similar (92% and 86%, respectively). The median survival of the N group (39.4 months) was significantly longer than that of the S group (20.8 months) in intention-to-treat analysis (p=0.0009). The R0, true R0, and N0 rates of the N group (85%, 69%, and 44%, respectively) were higher than those of the S group( 72%, 48%, and 24%, respectively). In conclusion, this retrospective analysis showed that neoadjuvant GS therapy might be more effective than the standard surgery-first strategy in terms of oncological outcomes for resectable pancreatic cancer. A prospective randomized study, Prep-02/JSAP-05, which compares neoadjuvant therapy to the surgery-first approach, is ongoing (UMIN-No. 000009634).