Clinical Utility of the Combined Use of CA19-9 and DUPAN-2 in Pancreatic Adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) patients with normal carbohydrate antigen (CA) 19-9 levels can have early-stage cancer or advanced cancer without elevation of CA19-9 level; estimating their malignant potential is difficult. This study investigated the clinical utility of the combined use of preoperative CA 19-9 and Duke pancreatic monoclonal antigen type 2 (DUPAN-2) levels in patients with PDAC. METHODS: Patients who underwent curative-intent surgery for PDAC between November 2005 and December 2021 were investigated. Eligible patients were classified into four groups based on these two markers. Among patients with normal CA19-9 levels, those with normal and high DUPAN-2 levels were classified into normal/normal (N/N) and normal/high (N/H) groups, respectively. Among patients with high CA19-9 levels, those with normal and high DUPAN-2 levels were classified into high/normal (H/N) and high/high (H/H) groups, respectively. Survival rates were compared between the groups. RESULTS: Among 521 patients, the N/N, N/H, H/N, and H/H groups accounted for 25.0%, 10.6%, 35.1%, and 29.4% of patients, respectively. The proportions of resectable PDAC in the N/N and H/N groups (71.5% and 66.7%) were significantly higher than those in the N/H and H/H groups (49.1% and 54.9%) (P < 0.01). The 5-year survival rates in the N/N, N/H, H/N, and H/H groups were 66.0%, 31.1%, 34.9%, and 29.7%, respectively; the rate in the N/N group was significantly better than those in the other three groups (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). CONCLUSIONS: Only patients with normal CA19-9 and DUPNA-2 values should be diagnosed with early-stage PDAC.

Prognostic impact of peritoneal washing cytology in patients with biliary tract cancer.

PURPOSE: To elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC). METHODS: Clinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis. RESULTS: Among the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19-9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively). CONCLUSION: Patients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.

Prognostic impact of pre- and postoperative tumor markers in patients with intrahepatic cholangiocarcinoma.

PURPOSE: The present study assessed the impact of pre- and postoperative tumor markers on the survival of patients with intrahepatic cholangiocarcinoma. METHODS: Medical records of 73 patients with intrahepatic cholangiocarcinoma were reviewed retrospectively. The pre- and postoperative carcinoembryonic antigen and carbohydrate antigen 19-9 levels were assessed. Patient characteristics, clinicopathological factors, and prognostic factors were analyzed. RESULTS: The median recurrence-free survival and overall survival were 30.0 and 90.9 months, respectively. A multivariate survival analysis revealed that elevated postoperative carbohydrate antigen 19-9 (p = 0.023) was the only independent poor prognostic factor. The median overall survival of patients with normal and elevated postoperative carbohydrate antigen 19-9 levels was 101.4 and 15.7 months (p < 0.001), respectively. Multivariate logistic regression identified elevated preoperative carbohydrate antigen 19-9 as an independent preoperative risk factor for elevated postoperative carbohydrate antigen 19-9. The optimal cutoff value of preoperative carbohydrate antigen 19-9 for predicting elevated postoperative carbohydrate antigen 19-9 was 40 U/mL, with a sensitivity and specificity of 92% and 87%, respectively (area under curve = 0.915). CONCLUSIONS: Elevated postoperative carbohydrate antigen 19-9 was an independent poor prognostic factor. Preoperative predictors, such as elevated preoperative carbohydrate antigen 19-9, may indicate the need for neoadjuvant therapies to improve the survival.

Increased plasma miR-370-3p expression in poor-outcome patients with pancreatic ductal adenocarcinoma.

OBJECTIVE: To determine whether circulating microRNAs (miRNAs) can be used as prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients with PDAC (N = 120) who underwent surgical resection at Hiroshima University Hospital between November 2006 and January 2020 were enrolled in this study and grouped based on their overall survival (OS) into two groups: favorable prognosis group (F group; OS ≥ 18 months) and unfavorable prognosis group (U group; OS < 18 months). Blood plasma samples were collected prior to surgery. To identify candidate prognostic miRNAs, next-generation sequencing (NGS) analysis was used to evaluate the expression levels of miRNAs in seven of the plasma samples. Using quantitative real-time PCR (qRT-PCR), the expression levels of the selected miRNAs were determined in the remaining 113 patient plasma samples, and the relationship between miRNA expression and survival was statistically evaluated. RESULTS: NGS analysis and qRT-PCR revealed significantly upregulated plasma miR-370-3p expression in the U group compared to that in the F group (p = 0.028 and p = 0.005, respectively). Moreover, miR-370-3p expression and lymph node metastasis showed a statistically significant association (p = 0.028). In a multivariate analysis of OS and recurrence-free survival (RFS), the upregulation of miR-370-3p expression in plasma was identified as an independent risk factor for poor OS (HR2.13, p = 0.004) and RFS (HR1.84, p = 0.015). CONCLUSIONS: Plasma miR-370-3p expression upregulation correlates with poor prognosis in patients with PDAC.

Surgical resection for liver recurrence after curative resection of pancreatic ductal adenocarcinoma.

PURPOSE: This study aimed to evaluate the clinical significance of surgical resection for liver recurrence in patients with curatively resected pancreatic ductal adenocarcinoma. METHODS: The medical records of patients with a liver recurrence after undergoing curative pancreatectomy for pancreatic ductal adenocarcinoma were retrospectively reviewed. Clinicopathological and prognostic factors were analyzed, as was the clinical impact of surgical resection for liver recurrence. RESULTS: Overall, 502 patients underwent curative pancreatic ductal adenocarcinoma resection. Of the 311 patients with recurrence after curative pancreatectomy, 71 (23%) had an initial recurrence in the liver, with 35 having solitary recurrence (11%). Patients with solitary, two or three, or more than four recurrences had median overall survival times of 28.5, 18.0, and 12.2 months, respectively (p < 0.001). Surgical indications for liver recurrence in our institution included solitary tumor, good disease control under chemotherapy after recurrence for > 6 months, and sufficient remnant liver function. Ten patients who met our institutional policy inclusion criteria underwent liver resection. Among 35 patients with initially solitary liver recurrence, those who underwent liver resection outlived those who did not (57.6 months vs. 20.1 months, p < 0.001). In multivariate analysis of overall survival, solitary liver recurrence and liver resection were independent favorable prognostic factors in patients with initial liver recurrence. CONCLUSION: In selected patients with solitary liver recurrence after curatively resected pancreatic ductal adenocarcinoma, liver resection may be a treatment option.

Prognostic impact of lung recurrence in patients with biliary tract cancer.

PURPOSE: This study aimed to evaluate the prognostic impact of the initial recurrence site following resection for biliary tract carcinoma (BTC), focusing on lung recurrence. METHODS: The clinical data of patients with recurrent BTC who underwent curative intent surgery between March 2009 and December 2021 were retrospectively analyzed. The prognosis of patients with recurrent BTC was investigated in each recurrence site. Eligible patients were classified into two groups according to lung or non-lung recurrence. Clinicopathological factors, survival after recurrence, and overall survival were compared between the two groups. Independent factors associated with survival after recurrence were investigated using multivariate analysis. RESULTS: Of 119 patients, the initial recurrence site was local in 26 (21.8%) patients, liver in 19 (16.8%), peritoneum in 14 (11.8%), lymph node in 12 (10.1%), lung in 11 (9.2%), multiple organs in 32 (26.9%), and others in 5 (4.2%). The survival period after recurrence in patients with lung recurrence was significantly longer than those in patients with other six recurrence patterns. The median survival after recurrence was 34.3 and 9.3 months in lung recurrence and non-lung recurrence groups, respectively (p < 0.0001); that after initial surgery was 50.8 and 26.4 months, respectively (p = 0.0383). Multivariate analysis revealed that lung recurrence and normal albumin level at recurrence were independently associated with survival after recurrence (Hazard Ratio (HR), 0.291; p = 0.0128; HR, 0.476; p = 0.00126, respectively). CONCLUSIONS: Survival period after recurrence was significantly longer in patients with lung recurrence.

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.

Difficulty of adjuvant chemotherapy administration in patients with biliary tract cancer.

PURPOSE: This study aimed to elucidate the difficulty of adjuvant chemotherapy administration in patients with biliary tract carcinoma (BTC). METHODS: Clinical data of patients with BTC who underwent curative-intent surgery were retrospectively analyzed. The eligible patients were stratified into two groups according to the presence or absence of adjuvant chemotherapy administration (adjuvant and non-adjuvant groups), and the clinicopathological features were compared between the two groups. The ratios of adjuvant chemotherapy administration were investigated in each surgical procedure. Independent factors associated with no administration of adjuvant chemotherapy were analyzed using multivariate analyses. RESULTS: Among 168 eligible patients, 141 (83.9%) received adjuvant chemotherapy (adjuvant group), while 27 (16.1%) did not (non-adjuvant group). The most common surgical procedure was pancreaticoduodenectomy in the adjuvant group, and it was hepatectomy with extrahepatic bile duct resection (BDR) in the non-adjuvant group, respectively. The rate of no adjuvant chemotherapy was significantly higher in patients who underwent hepatectomy with BDR than in those who underwent other surgeries (p < 0.001). The most common cause of no adjuvant chemotherapy was bile leak in 12 patients, which occurred after hepatectomy with BDR in ten patients. Multivariate analyses revealed that hepatectomy with BDR and preoperative anemia were independently associated with no adjuvant chemotherapy (p < 0.001 and p < 0.001, respectively). CONCLUSIONS: Hepatectomy with BDR and subsequent refractory bile leak can be the obstacle to adjuvant chemotherapy administration in patients with BTC.

Prognostic factor in patient with recurrent pancreatic adenocarcinoma.

PURPOSE: To elucidate prognostic factors for post-recurrence survival in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Patients who underwent curative-intent surgery for PDAC between January 2014 and May 2020 were identified. Among them, patients who had postoperative recurrences and received chemotherapy were retrospectively investigated. Independent prognostic factors for survival after recurrence were investigated using multivariate analyses. Eligible patients were divided into two groups according to the presence or absence of the identified prognostic factors, and survival times after recurrence were compared. RESULTS: Eighty-four patients with recurrent PDAC were included. Multivariate analysis showed that red blood cell (RBC) transfusion (HR, 2.80; p = 0.0051), low albumin level (HR, 1.84; p = 0.0402), and high carbohydrate antigen 19-9 (CA19-9) level at recurrence (HR, 2.11; p = 0.0258) were significant predictors of shorter survival after recurrence. The median survival times after recurrence in the transfusion and non-transfusion groups were 5.5 vs. 18.1 months (p < 0.0001), respectively; those in the low and normal albumin groups were 10.1 vs. 18.7 months (p = 0.0049), and those in the high and normal CA19-9 groups were 11.5 vs. 22.6 months (p = 0.0023), respectively. CONCLUSIONS: RBC transfusion, low albumin, and high CA19-9 levels at recurrence negatively affected survival after recurrence in patients with PDAC.

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.