Hepatic artery resection in distal cholangiocarcinoma.

PURPOSE: This study aimed to elucidate the safety and oncological outcomes of surgery with hepatic artery resection (HAR) for patients with distal cholangiocarcinoma. METHODS: The clinical data of patients with distal cholangiocarcinoma who underwent curative intent surgery at Hiroshima University between March 2009 and January 2021 were retrospectively analyzed. Eligible patients were classified according to the presence or absence of HAR (HAR and non-HAR group), and clinicopathological features and disease-free survival rates were compared between the two groups. RESULTS: Among the 60 patients analyzed, eight patients had received HAR, and the remaining 52 patients had not. The rate of portal vein resection, T stage, and the number of metastasized lymph nodes in the HAR group were significantly greater than those in the non-HAR group (p < 0.001, p = 0.00695, and p = 0.0480, respectively). Postoperative severe complication was confirmed in one patient, and there were no in-hospital deaths in the HAR group. Seven of 8 patients in the HAR group showed recurrence during follow-up, and of those, six patients showed early recurrence within 1 year postoperatively. The disease-free survival time in the HAR group was significantly shorter than that in the non-HAR group (median: 7.4 m vs. 34.2 m, respectively) (p < 0.001). Multivariate analysis revealed that lymph node metastasis and HAR were significant risk factors for predicting the adverse disease-free survival time (hazard ratio (HR), 3.21; p = 0.0142; HR, 4.47; p = 0.0346, respectively). CONCLUSIONS: Patients with distal cholangiocarcinoma who underwent surgery with HAR tended to show early recurrences, although HAR could be performed safely.

Preoperative risk factors for positivity of peritoneal lavage cytology in patients with pancreatic ductal adenocarcinoma in the era of neoadjuvant therapy.

BACKGROUND: The preoperative risk factors for positive peritoneal lavage cytology (CY) are unknown, especially in patients who received neoadjuvant therapy. In addition, the optimal indications for staging laparoscopy (SL) are still unclear. The aim of this study was to investigate the preoperative risk factors of CY positivity in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection and to determine the optimal indications for SL. METHODS: We retrospectively analyzed 493 patients with PDAC, including 356 treated with upfront surgery and 137 treated with neoadjuvant chemotherapy (NAC). The preoperative risk factor for CY positivity was investigated along with stratification according to NAC. RESULTS: Among the 493 patients, 36 (7.3%) were CY-positive. The CY-positive frequency in patients who received and did not receive NAC was 9 (6.6%) and 27 (7.6%), respectively. In the multivariate analyses, no independent preoperative predictive factor was found in patients who received NAC, whereas body and tail PDAC were identified as an independent risk factor for CY positivity in patients who did not receive NAC. CONCLUSIONS: The preoperative risk factors of CY-positive PDAC are body and tail PDAC in 356 patients who did not receive NAC. However, there is no useful predictive factor for CY positivity in patients treated with NAC. Based on these results, it was difficult to determine the optimal indication for SL especially in NAC cases.

Impact of disintegrin and metalloproteinase domain-containing protein 12 on pancreatic ductal adenocarcinoma treated with surgical resection and perioperative chemotherapy.

BACKGROUND/OBJECTIVES: A disintegrin and metalloproteinase domain-containing protein 12 (ADAM12) has been reported to influence tumor progression and chemosensitivity in human cancers. We assessed the prognostic impact of ADAM12 and its predictive value for neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC) treated with surgical resection. METHODS: ADAM12 expression was immunohistochemically examined in 428 patients with PDAC who underwent surgical resection. The association of ADAM12 expression with clinicopathological factors and survival was also analyzed. RESULTS: Patients with high ADAM12 expression exhibited significantly shorter median disease-free survival (DFS) (high ADAM12: 17.8 vs. low ADAM12: 37.9 months; P < 0.001) and overall survival (OS) (high ADAM12: 33.1 vs. low ADAM12: 65.0 months; P < 0.001). A multivariate analysis revealed that high ADAM12 expression was an independent risk factor for poor DFS (P < 0.001) and OS (P < 0.001) in all eligible patients. Of 100 patients who received neoadjuvant chemotherapy (NAC), high ADAM12 expression was significantly associated with poor DFS in a subset of patients treated with the nab-paclitaxel (PTX) neoadjuvant regimen (P = 0.03), whereas the prognostic value of ADAM12 was not evident in patients not treated with nab-PTX (P = 0.12). CONCLUSIONS: A negative prognostic value of high ADAM12 expression was observed in patients with PDAC treated with surgical resection, which was enhanced in patients treated with NAC, including nab-PTX. These results suggested that ADAM12 expression can predict nab-PTX chemosensitivity in PDAC and reflect PDAC progression.

Increased clostridium difficile infection in the era of preoperative chemotherapy for pancreatic cancer.

BACKGROUND: In recent trend of preoperative chemotherapy, postoperative clostridium difficile infection (CDI) might be increasing in pancreatic ductal adenocarcinoma (PDAC) patients. This study aimed to elucidate the inducement of postoperative CDI in the new era of preoperative chemotherapy. METHODS: Eligible patients were those who received pancreaticoduodenectomy for PDAC. Patients were classified into two groups according to the presence or absence of postoperative CDI, and the independently associated factors for postoperative CDI were investigated. Additionally, eligible patients were classified using the identified associated factors, and the duration of preoperative antimicrobial administration and incidence of CDI were compared between the groups. RESULTS: Two hundred PDAC patients were eligible for this study, and postoperative CDI was detected in 15 (7.5%) patients. Multivariate analysis revealed that preoperative biliary tract infection (BTI) and chemotherapy (Chemo) were independently associated with postoperative CDI (OR, 4.05; 95% CI, 1.25-13.1; p = 0.0200 and OR, 3.64; 95% CI, 1.14-11.6; p = 0.0209, respectively). The patients were classified into four groups according to the presence or absence of preoperative BTI and Chemo (BTI-/Chemo-, BTI-/Chemo+, BTI+/Chemo- and BTI+/Chemo + group). The median durations of preoperative antimicrobial administration were 0, 2, 8 and 15 days in each group, respectively. Postoperative CDI was detected in 3.7%, 10.0%, 10.5% and 31.3% in each group, respectively, and patients in BTI+/Chemo + group suffered CDI more frequently compared to those in BTI-/Chemo-group (p = 0.00778). CONCLUSIONS: Preoperative BTI and chemotherapy might induce postoperative CDI for PDAC patients.

Clinicopathological features of gastric cancer after pancreaticoduodenectomy: reporting of three institutional cases and review of the global literature.

PURPOSE: Gastric cancer after pancreaticoduodenectomy was firstly reported in 1995, and the number of reports about this topic has increased in the past years. This review aimed to elucidate the clinicopathological features of this disease. METHODS: Data for 32 cases were obtained using literature search, and three cases in our institution were added. RESULTS: Twenty cases were reported from Japan, and fifteen cases were from the Western countries (Germany: 1 case, France: 2 cases, USA: 12 cases). In Japanese and the Western cases, the most dominant indication for pancreaticoduodenectomy was distal bile duct cancer and pancreatic ductal adenocarcinoma, respectively. The most frequently applied procedure of pancreaticoduodenectomy was pylorus-preserving pancreatoduodenectomy with pancreaticogastrostomy and pancreaticoduodenectomy with pancreaticojejunostomy, respectively. The median length of time interval from pancreaticoduodenectomy to GC detection tended to be shorter in the Japanese cases (61.5 months vs. 115 months). Of all cases, thirteen (37.1%) patients with gastric cancer showed no abdominal symptoms, and eight were diagnosed at regular gastroscopy. Surgical gastrectomy was performed in 30 patients, and among them, concomitant pancreatectomy was performed in six patients. Four patients received reanastomosis of remnant pancreas using pancreaticojejunostomy. Twenty-two (73.3%) patients had undifferentiated carcinomas, and stage 1, 2, 3, and 4 cancer was identified in 14, six, six, and four patients, respectively. All eight patients who had received routine gastroscopy were T1N0M0 stage 1. CONCLUSION: Gastric cancers after pancreaticoduodenectomy including newly reported Japanese cases and our institutional cases were reviewed to make Japanese studies available to a broader scientific audience. Further investigation is necessary to elucidate the most important carcinogens among the various potential local and systemic factors.

Neoadjuvant therapy contributes to nodal downstaging of pancreatic cancer.

PURPOSE: This study aimed to assess the impact of neoadjuvant therapy (NAT) for borderline resectable or locally advanced pancreatic cancer (BR/LAPC) on the American Joint Commission on Cancer (AJCC) nodal status. METHODS: The medical records of BR/LAPC patients who underwent surgery with curative intent were retrospectively reviewed. The nodal status was compared between patients who underwent upfront surgery (UFS) and those who received NAT. Moreover, clinicopathological factors and prognostic factors for overall survival were analyzed. RESULTS: In all, 200 patients with BR/LAPC, 78 with UFS, and 122 with NAT were enrolled. The nodal status was significantly lower in patients after NAT than after UFS (p = 0.011). A multivariate analysis of overall survival showed that UFS (hazard ratio (HR) 1.61, p = 0.024) and N2 status (HR 2.69, p < 0.001) were independent poor prognostic factors. The median serum carbohydrate antigen (CA) 19-9 level after NAT in N2 patients was 105 U/mL, which was significantly higher than that of patients with N0 (p = 0.004) and N1 (p = 0.008) status. CONCLUSION: Patients with BR/LAPC who underwent surgery after NAT had significantly lower N2 status and better prognosis than patients who underwent UFS. Elevated CA19-9 levels after NAT indicated a higher nodal status.

Optimal lymph-node dissection for pancreatic tail cancer.

PURPOSE: The optimal range of lymph-node dissection for pancreatic tail cancer remains unclear. We investigated the location and frequency of lymph-node metastases to identify the correct range of lymph-node dissection for pancreatic tail cancer. METHODS: We analyzed clinical data retrospectively, on patients who underwent distal pancreatectomy for resectable left-sided pancreatic cancer, between February, 2006 and March, 2021. Eligible patients were divided into two groups according to the tumor location: those with pancreatic tail cancer (Pt group) and those with pancreatic body or body and tail cancer (non-Pt group). RESULTS: Of the 96 patients analyzed, 61 (64%) were assigned to the Pt group and 35 (36%) were assigned to the non-Pt group. Metastases to stations 7, 8, 9, 10, 11, 14, and 18 were found in 0 (0%), 0 (0%), 0 (0%), 4 (7%), 18 (30%), 2 (4%), and 10 (17%) patients in the Pt group, and in 1 (3%), 4 (12%), 2 (6%), 1 (3%), 18 (51%), 3 (9%), and 6 (17%) patients in the non-Pt group, respectively. CONCLUSION: Lymph-node dissection at stations 7, 8, and 9 might not be necessary in patients with resectable pancreatic cancer confined to the pancreatic tail.

Clinical Implications of Pre- and Postoperative Circulating Tumor DNA in Patients with Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The clinical implications of pre- and postoperative KRAS-mutated circulating tumor DNA (ctDNA) present in patients with pancreatic ductal adenocarcinoma (PDAC) have remained an unresolved issue. This study sought to investigate the clinical significance of pre- and postoperative ctDNA analyses and their impact on the prognosis of PDAC patients. METHODS: Digital droplet polymerase chain reaction detected ctDNA in pre- and postoperative plasma samples prospectively obtained from patients with resectable and borderline-resectable PDAC. Its associations with recurrence-free survival (RFS) and overall survival (OS) were analyzed. The patients were sorted according to the presence of pre- and postoperative ctDNA, and its ability to stratify prognosis was evaluated. RESULTS: The study analyzed 97 patients. Both pre- and postoperative ctDNA were detected in 9 patients, and neither was detected in 55 patients. Whereas 15 patients harbored only preoperative ctDNA, 18 patients had only postoperative ctDNA. The multivariate analysis showed that the presence of preoperative ctDNA was associated with poorer OS (P = 0.008) and that postoperative ctDNA was not associated with either RFS or OS. Survival did not differ significantly between the patients with a positive shift in ctDNA status and those without detectable pre- or postoperative ctDNA. CONCLUSIONS: For the patients with PDAC, the presence of preoperative ctDNA was significantly associated poor OS, whereas postoperative ctDNA was not associated with poor survival. A positive change in ctDNA did not affect patients' survival.

Survival impact of distal pancreatectomy with en bloc celiac axis resection combined with neoadjuvant chemotherapy for borderline resectable or locally advanced pancreatic body carcinoma.

BACKGROUND: The survival benefit associated with distal pancreatectomy with en bloc celiac axis resection (DP-CAR) for patients with borderline resectable or locally advanced pancreatic body carcinoma is controversial. The aim of this study was to evaluate the impact of DP-CAR following neoadjuvant chemotherapy on survival in patients with borderline resectable or locally advanced pancreatic body carcinoma. METHODS: Medical records of patients with pancreatic ductal adenocarcinoma who underwent distal pancreatectomy (DP, n = 102) and DP-CAR following neoadjuvant chemotherapy (n = 32) between 2008 and 2019 were analyzed retrospectively. Short- and long-term outcomes were compared between the two groups. RESULTS: All patients who underwent DP-CAR had tumor contact with the celiac axis. Of these, 30 patients underwent preoperative embolization of the common hepatic artery. The pretreatment tumor size of patients who underwent DP-CAR was larger (P < 0.001), and rates of blood transfusion (P = 0.003) and postoperative complications (P = 0.016) were higher in patients who underwent DP-CAR compared with patients who underwent DP. The 5-year survival rate of patients who underwent DP and DP-CAR were 50.6% and 41.1%, respectively (median survival time, 65.9 vs 37.0 months). For all 134 patients, pretreatment serum CA19-9 levels (P < 0.001), adjuvant chemotherapy (P < 0.001), and lymph node status (P = 0.035) were independent prognostic factors of overall survival by multivariate analysis. CONCLUSIONS: DP-CAR following neoadjuvant chemotherapy for patients with borderline resectable or locally advanced pancreatic body carcinoma may bring the same survival impact as DP, despite increased morbidity.

Preoperative risk factors for para-aortic lymph node positivity in pancreatic cancer.

PURPOSE: This study aimed to identify the preoperative risk factors for para-aortic lymph node (PALN) positivity, including micrometastasis, in pancreatic cancer. METHODS: Medical records of patients with pancreatic cancer who underwent curative resection were retrospectively reviewed, and the relationships between preoperative risk factors and PALN positivity were identified. Clinicopathological and prognostic factors for overall survival were analyzed. Micrometastasis was investigated by immunohistochemistry. RESULTS: 400 patients were enrolled. PALN positivity by hematoxylin and eosin staining, micrometastasis, and negative were found in 46 (11%), 32 (8%), and 322 (81%) patients, respectively. The median overall survival times of patients with PALN positivity, including micrometastasis, was 22.5 months. Multivariate logistic regression identified borderline or locally advanced status (p=0.037), elevated preoperative carbohydrate antigen (CA) 19-9 level (p<0.001), larger tumor size ≥30 mm (p=0.001) and larger PALN size ≥10 mm (p=0.019) as independent preoperative risk factors of PALN positivity. Multivariate overall survival analysis demonstrated borderline or locally advanced status (p=0.013), elevated preoperative CA19-9 level (p<0.001) and PALN positivity (p=0.048) were independent poor prognostic factors. CONCLUSIONS: Borderline or locally advanced status, elevated preoperative CA19-9 level, and larger tumor and PALN size were risk factors for PALN positivity, and thus, they may contribute to the optimization of preoperative treatments for patients with potential PALN positivity.

Identification of Preoperative Risk Factors for Poor Survival in Patients with Resectable Pancreatic Cancer Treated with Upfront Surgery.

INTRODUCTION: The aim of this study was to identify preoperative risk factors for poor survival in patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with upfront surgery. METHODS: Medical records of 268 patients with resectable PDAC defined by resectability status who underwent upfront surgery were reviewed retrospectively. Multivariate analyses were performed to identify preoperative risk factors for recurrence-free survival (RFS) and overall survival (OS). Moreover, a binary logistic regression model was built to determine preoperative independent risk factors of 2- and 3-year recurrence and survival. RESULTS: Multivariate analyses identified CA19-9 (≥100 U/mL, p < 0.001) as an independent risk factor for poor RFS, and worse performance status (1 or 2, p = 0.03), platelet:lymphocyte ratio (<150, p = 0.04), and preoperative CA19-9 (≥100 U/mL, p < 0.001) as independent risk factors for poor OS. Moreover, preoperative CA19-9 (≥100 U/mL) was the only independent risk factor identified for 2- and 3-year recurrence and survival. DISCUSSION/CONCLUSION: Preoperative CA19-9 (≥100 U/mL) was the most reliable preoperative predictive factor for poor survival in resectable PDAC treated with upfront surgery. These findings warrant further clinical trials investigating efficacy of neoadjuvant therapy targeting the subset of patients with resectable PDAC who have elevated preoperative CA19-9, namely, those with high risk of poor prognosis.

Prognostic significance of dissecting the nerve plexus around the common hepatic artery in pancreatic cancer.

PURPOSE: This study aims to investigate the positivity rate of the nerve plexus (NPL) around the common hepatic artery (CHA), as well as the impact of dissecting the NPL-CHA, during surgical resection of pancreatic cancer. METHODS: Clinicopathological factors, including hematoxylin and eosin (H&E) staining and immunohistochemistry, were compared between the resectable pancreatic cancer (RPC) and borderline resectable PC (BRPC) groups. Moreover, the relationship between the NPL-CHA status and overall survival (OS) was investigated. RESULTS: In this study, 136 eligible patients were divided into the RPC (72) and BRPC (64) groups. In the RPC group, all patients were negative for H&E staining and microinvasion, whereas 13 (20%) and five patients (8%) were positive for H&E staining and microinvasion, respectively, in the BRPC group. The median OS times in the NPL-CHA-positive and -negative groups were 29.8 and 60.2 months, respectively (p = 0.088). The multivariate analysis of OS indicated an elevated initial carbohydrate antigen 19-9, lymph node (LN) metastasis, and lack of adjuvant chemotherapy (AC), which independently predicted poor outcomes. In the BRPC subgroup, contact with the CHA on preoperative computed tomography (CT) was a high-risk factor for NPL-CHA positivity. CONCLUSION: NPL-CHA positivity was only present in the BRPC group. In the absence of CT evidence of CHA contact, NPL-CHA dissection may not have survival benefits.

Is surgery justified for elderly patients with extrahepatic cholangiocarcinoma? Reappraisal from a viewpoint of comorbidity and organ function.

PURPOSE: The benefit of surgery for older patients with extrahepatic cholangiocarcinoma (EHCC) has not been established and the differences in the general condition of younger vs. older patients remain unclear. METHODS: Patients who underwent curative surgery for EHCC were divided into two groups according to age: those younger than 75 years old (younger group) and those aged 75 years or older (older group). We analyzed the clinical data of the two groups retrospectively. RESULTS: Among the 116 patients analyzed, 45 (38.8%) were in the older group. Regarding comorbidity, only cardiac disease was significantly more common in the older patients; however, the cardiac function of the two groups was identical. There were no significant differences in the prevalence of kidney and lung disease, but renal function was significantly deteriorated and the incidence of the mixed ventilatory defect was significantly greater in the older group. The overall 5-year survival rates for the younger and older groups were 52.4% vs. 50.4% of all cholangiocarcinoma patients (p = 0.458), 42.4% vs. 51.3% of those with hilar cholangiocarcinoma (p = 0.718), and 69.0% vs. 49.1% of those with distal cholangiocarcinoma (p = 0.534), respectively. CONCLUSIONS: Improved survival after surgery can be expected in well-selected older cholangiocarcinoma patients. Comorbidities were not necessarily reflected in organ function, with precise organ function assessment being more important when selecting surgical candidates.

The prognostic impact of peritoneal washing cytology for otherwise resectable extrahepatic cholangiocarcinoma patients.

The clinical importance of peritoneal washing cytology (PWC) for cholangiocarcinoma patients remains unclear. The clinical data of 137 extrahepatic cholangiocarcinoma patients who received PWC and curative surgery were retrospectively analyzed. Among the 137 patients analyzed, five (3.6%) had positive PWC, and 132 (96.4%) had negative PWC. The median survival time in patients with negative PWC was 6.45 years, and the overall 1-, 2-, and 5-year survival rates were 86.5%, 75.3%, and 51.6%, respectively. The median survival time in patients with positive PWC was 2.56 years, and the overall 1-, 2-, and 5-year survival rates were 60.0%, 60.0%, and 40.0%, respectively. A multivariate analysis revealed that positive lymph node metastasis (P < 0.001), positive perineural invasion (P = 0.014) and no use of adjuvant chemotherapy (P < 0.001), but not positive PWC were independently associated with a worse overall survival. In conclusion, surgery and subsequent chemotherapy might be a therapeutic option for cholangiocarcinoma patients with positive PWC.

Clinical characteristics of initial recurrence in lung after surgical resection for pancreatic ductal adenocarcinoma.

BACKGROUND: The clinical characteristic differences at the initial recurrence site after resection for pancreatic ductal adenocarcinoma (PDAC) remain unknown. We investigated the clinical characteristics in patients with lung recurrence after surgical resection and evaluated the outcome of resection for isolated lung recurrence. METHODS: Of 442 consecutive PDAC patients who underwent surgical resection between 2002 and 2018, 229 had recurrence on imaging. Initial recurrence sites were the liver, lung, local, peritoneal, multiple organs, and others. We analyzed the clinicopathologic factors and outcomes, comparing by initial recurrence site, and investigated the outcomes of resection for isolated lung recurrence. RESULTS: Liver recurrences were the most frequent (n = 60, 26%), followed by lung recurrence (n = 48, 21%). The interval from surgery to recurrence was significantly longer in lung recurrence (P = 0.0001). Patients with lung recurrence had significantly longer overall survival after diagnosis (P < 0.0001). Patients who underwent surgical resection of lung recurrence had a significantly prolonged overall survival rate after recurrence diagnosis (P = 0.004). CONCLUSIONS: Patients with lung recurrence had significantly prolonged survival than those with other recurrence patterns. Resection for isolated lung recurrence represented relatively good prognosis, and possibly may be beneficial in highly-selected patients.

Flooring the Major Vessels with Falciform Ligament to Prevent Post-Pancreatectomy Hemorrhage.

BACKGROUND: One of the most severe pancreatic surgery complications is post-pancreatectomy hemorrhage (PPH). This study's aim was to evaluate the efficacy of flooring the major vessels with falciform ligament in preventing PPH after pancreatoduodenectomy (PD). METHODS: This study was a retrospective review of 500 consecutive patients who underwent PD between Jan 2010 and Dec 2019 at Hiroshima University. Morbidities, including postoperative pancreatic fistula (POPF) or PPH and 90-day mortality, were analyzed. The study cohort was divided into two groups based on the time of surgery (2010-2016 and 2017-2019), i.e., before and after implementation of falciform ligament flooring method. The patient characteristics, operative parameters, clinicopathological factors, morbidity, and mortality were compared between the two periods. RESULTS: Morbidity and mortality rates in the entire cohort were 21% and 1.4%, respectively. The incidence of Grade B/C POPF and PPH was 9.0% and 3.8%, respectively. There was no significant difference between the two periods with respect to Grade B/C POPF, morbidity rate, and mortality rate; however, the rate of Grade B/C PPH significantly decreased from 5.2 to 1.6% p = .027. On multivariate analysis, the absence of the falciform ligament flooring method was an independent PPH risk factor p = .003. CONCLUSIONS: Falciform ligament flooring method may help decrease the incidence of PPH after PD.

Neoadjuvant therapy for pancreatic cancer: an intention-to-treat analysis.

PURPOSE: This study aimed to reassess the duration of neoadjuvant therapy (NAT) for patients with borderline resectable pancreatic cancer (BRPC). METHODS: The medical records of patients with BRPC who received NAT before intended curative resection were retrospectively reviewed. Patient demographics, clinicopathological factors, and prognostic factors for overall survival were analyzed. The serum carbohydrate antigen (CA) 19-9 level was examined monthly during NAT. RESULTS: A total of 118 patients with BRPC were enrolled. The median survival time and 5-year overall survival were 28.0 months and 31%, respectively. Three months after NAT, the CA19-9 levels were normal in 57% of the patients, and 92% underwent resection. Multivariate analysis showed that radiological partial response (hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.26-0.99; p = 0.047); a normal CA19-9 level after NAT (HR, 0.30; 95% CI, 0.22-0.66; p = 0.006); and tumor resection (HR, 0.29; 95% CI, 0.13-0.67; p = 0.005) were independent predictors of better survival. The median CA19-9 level and the rate of normal CA19-9 levels before and after NAT were 256 (interquartile range (IQR), 23-1197) U/mL and 33%, and 27 (IQR, 7-176) U/mL and 57%, respectively. CONCLUSION: A normal CA19-9 level after NAT was an independent predictor of better survival in patients with BRPC. A longer NAT duration might contribute to improved prognosis of patients with elevated CA19-9 levels.

A Multicenter, Randomized, Controlled Trial Comparing Reinforced Staplers with Bare Staplers During Distal Pancreatectomy (HiSCO-07 Trial).

BACKGROUND: Although distal pancreatectomy (DP) using a reinforced stapler is expected to reduce PF, no multicenter RCT has been performed. To investigate whether reinforced staplers reduce the incidence of clinically relevant pancreatic fistula (PF) after DP compared with staplers without reinforcement. METHODS: Between July 2016 and December 2017, patients scheduled for DP were enrolled in a multicenter, randomized, controlled trial (RCT) at nine hospitals in Hiroshima Japan. Patients were randomized either to reinforced stapler or bare stapler. The primary endpoint was incidence of clinically relevant PF. This RCT was registered with UMIN Clinical Trial Registry (UMIN000022341). RESULTS: A total of 122 patients were assigned to reinforced stapler (n = 61) or bare stapler (n = 61), and 119 patients (61 reinforced stapler and 59 bare stapler) were analyzed. There was no significant difference in the incidence of clinically relevant PF between the reinforced stapler and bare stapler groups (16.3% vs. 27.1%, p = 0.15). Furthermore, the rates of major complication (16.3% vs. 18.6%, p = 0.74), postpancreatectomy hemorrhage (0% vs. 3.4%, p = 0.08), and median postoperative in-hospital days (19 days vs. 20 days, p = 0.78) did not differ between the two groups. Within a subset of 82 patients in whom the thickness of pancreatic transection line was less than 14 mm, a significant difference was found in the incidence of clinically relevant PF (4.5% vs. 21.0% in the reinforced stapler vs. bare stapler groups, respectively, p = 0.01). CONCLUSIONS: Reinforced stapler for pancreatic transection during DP does not reduce the incidence of clinically relevant PF compared to stapler without reinforcement.

Cytoplasmic Hu-Antigen R (HuR) Expression is Associated with Poor Survival in Patients with Surgically Resected Cholangiocarcinoma Treated with Adjuvant Gemcitabine-Based Chemotherapy.

BACKGROUND: Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). OBJECTIVE: The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. METHODS: Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. RESULTS: High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. CONCLUSIONS: High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.

The high stromal SPARC expression is independently associated with poor survival of patients with resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine in combination with S-1 or adjuvant gemcitabine alone.

BACKGROUND: Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival, its efficacy varies among individuals. Identification of biomarkers that can predict the efficacy of adjuvant chemotherapy for PDAC is essential. OBJECTIVES: To investigate the predictive value of secreted protein acidic and rich in cysteine (SPARC) expression in patients with PDAC treated with adjuvant gemcitabine in combination with S-1 (adjuvant GS) or adjuvant gemcitabine alone (adjuvant G alone). METHODS: Stromal SPARC and cytoplasmic SPARC were examined immunohistochemically in 211 PDAC patients treated with adjuvant GS or G alone after resection. The association of SPARC expression with clinicopathological factors, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: In multivariate analysis, borderline resectable with arterial contact (BR-A) (P = .002), higher preoperative CA 19-9 level (≥91 U/ml) (P = .005), moderately or poorly (P = .003), presence of lymph node metastasis (P = .012) and high stromal SPARC expression (P = .013) were independent predictors of poor DFS. Moreover, BR-A (P = .003), higher preoperative CA 19-9 level (≥91 U/ml) (P = .007) and high stromal SPARC expression (P < .001) were identified as independent predictors of poor OS. In contrast, cytoplasmic SPARC expression did not affect DFS and OS. CONCLUSIONS: High stromal SPARC expression was an independent predictor of poor DFS and OS in patients treated with adjuvant GS or G alone. Stromal SPARC expression could be a relevant biomarker for prediction of prognosis in PDAC patients after resection treated with adjuvant GS or G alone.