•There have been few studies of the long-term outcomes of surgically resected intraductal papillary neoplasm of the bile duct (IPNB).•Mucus might be produced even after the R0 resection of IPNB, and ...frequent cholangitis or jaundice might be occurred.•The biliary tract of the remnant liver after curative resection should be managed carefully for a long time after surgical resection.
Few studies have reported the long-term outcomes of surgical resected intraductal papillary neoplasm of the bile duct (IPNB). Here, we describe the long-term observation and treatment of a case of widespread IPNB.
A 57-year-old male was referred to our hospital due to jaundice and dilation of the intrahepatic bile duct. Computed tomography showed dilation and irregularities of the right intrahepatic and extrahepatic bile ducts together with a 3cm nodule in the common hepatic duct. Peroral cholangioscopy revealed mucinous discharge from the ampulla of Vater, which resulted in a diagnosis of IPNB. A biopsy of the nodule and the bile duct revealed papillary adenoma in all of them. Right hepatectomy, caudate lobectomy, extrahepatic bile duct resection, and left hepaticojejunostomy were performed. The nodule was histologically diagnosed as papillary carcinoma in situ, and R0 resection was performed. However, mucus production from the papillary adenoma in the B3 and B4 was observed. We carefully managed the patient's biliary tract by inserting a biliary drainage tube into the segment 2, and he has survived for more than 7 years since the initial treatment.
Mucus might be produced after the surgical resection of IPNB even if s surgical margin was benign. Five-year survival rate of benign IPNB was reported from 85% to 100%. That might be caused by difference of the postoperative management of the biliary tract.
Careful management of the biliary tract should be performed after surgical resection of IPNB.
CD155 is expressed in many types of human cells and has diverse functions. We herein evaluated the clinical importance of CD155 in pancreatic cancer.
We investigated CD155 expression in 134 patients ...with pancreatic cancer, and evaluated the correlations of CD155 with prognosis, tumor immunity and angiogenesis. Furthermore, CD155 functions were examined.
CD155 expression was abundant in pancreatic cancer tissues. Patients with high CD155 expression had poorer postoperative prognosis than those with low expression. Multivariate analysis indicated that CD155 expression had a significant independent prognostic value. Tumor CD155 expression inversely correlated with the presence of tumor-infiltrating lymphocytes. Furthermore, it significantly positively correlated with vascular endothelial growth factor expression and intra tumoral microvessel density. In addition, silencing of CD155 inhibited proliferation, and induced cell-cycle arrest at G2/M phase in pancreatic cancer cells.
CD155 may play a critical role through both immunological and non-immuno logical mechanisms in pancreatic cancer and may be a therapeutic target for this intractable malignancy.
Hyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. ...This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data.BACKGROUNDHyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data.The study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity.METHODSThe study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity.Overall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time MST: 35.0 vs. 47.9 months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6 months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4+ (p = 0.015) and CD8+ (p = 0.017) T cells and a lower CD8+/Foxp3+ ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression.RESULTSOverall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time MST: 35.0 vs. 47.9 months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6 months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4+ (p = 0.015) and CD8+ (p = 0.017) T cells and a lower CD8+/Foxp3+ ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression.The patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors.CONCLUSIONSThe patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors.
Although patient-risk stratification is important for selecting individualized treatment for pancreatic ductal adenocarcinoma (PDAC), predicting the oncologic outcomes after surgery remains a ...challenge. In this study, we identified a nectin family gene panel (NFGP) that can accurately stratify oncologic outcomes in patients with PDAC.
Comprehensive analysis of the expression of 9 nectin family genes identified the NFGP, which was assessed for predictive performance in 2 independent public cohorts (The Cancer Genome Atlas TCGA n = 176; International Cancer Genome Consortium ICGC n = 89). It was subsequently trained and validated for the in-house training cohort without neo-adjuvant therapy (NAT, n = 213) and the validation cohort with NAT (n = 307).
Using the Cox regression model, NFGP derived from 9 nectin family genes accurately stratified overall survival (OS) in TCGA (p = 0.038) and ICGC (p = 0.005). We subsequently optimized NFGP, which robustly discriminated postoperative prognosis, OS (p = 0.014) and relapse-free survival (RFS p = 0.006) in the training cohort. The NFGP was successfully validated in an independent validation cohort (OS: p < 0.001; RFS: p = 0.004). Multivariate analysis demonstrated the NFGP was an independent prognostic factor for OS and RFS in the training (p = 0.028 and 0.008, respectively) and validation (p < 0.001 and 0.013, respectively) cohorts. The subcohort analyses showed that the predictive performance of NFGP is applicable to the patients' subcohort according to resectability or adjuvant therapy status. Additionally, a combination model of NFGP score and CA19-9 level emerged with improved accuracy for predicting prognosis.
This study established the predictive significance of NFGP for oncologic outcomes after surgery in PDAC. Our data demonstrate its clinical impact as a potent biomarker for optimal patient selection for individualized treatment strategies.
The management of malignant ascites is critical for treating patients with advanced pancreatic cancer. The purpose of this study was to assess the safety of cell-free and concentrated ascites ...reinfusion therapy (CART) and its impact on the prognosis of patients with advanced pancreatic cancer who have massive malignant ascites.
This study analyzed 47 procedures in 29 patients who underwent CART for ascites caused by pancreatic cancer between 2015 and 2022. Among them, 7 patients who received chemotherapy following CART were classified as the chemotherapy group, while 22 patients without chemotherapy after CART were classified as the palliative care group.
Among the 47 procedures, adverse events (AEs) were observed in 9 procedures (19%). Grade 2 adverse events were observed only in one procedure, manifested as fever. There were no grade 3 or 4 AEs, nor were there any treatment-related deaths. The median survival time was 4.0 months in the chemotherapy group and 0.7 months in the palliative care group (p=0.004). The albumin level in the chemotherapy group was significantly higher than that in the palliative care group.
CART is feasible and might be the optimal option to enable prolonged use of chemotherapy to improve the prognosis for late-stage pancreatic cancer patients.
Central pancreatectomy (CP) is accepted as a function-preserving procedure for benign tumors. However, the indication of CP for pancreatic cancers is limited. This multicenter study aimed to clarify ...the indications of CP for clinical T1 pancreatic body cancer.
This multicenter study analyzed patients who underwent CP or distal pancreatectomy (DP) for clinical T1 pancreatic body cancer between 2013 and 2020 at three high-volume centers.
A total of 50 patients were enrolled: nine patients, who underwent CP, were classified into the CP group, while 38 patients, who underwent DP, served as controls. Three patients converted CP to DP during operation were excluded. Five patients in the CP group and 15 patients in the control group underwent preoperative treatment. The 5-year survival rate was 100% in the CP group, and 42% (p = .040) in the control group. Recurrence was found in three patients in the CP group. Importantly, insulin was not required after surgery in patients in the CP group.
The clinical outcomes of CP were comparable to or even better than that of conventional pancreatectomy. Our collaborative study suggests that CP may be an acceptable therapeutic option for selected patients with clinical T1 pancreatic body cancer.
Purpose
This study investigated the role of sarcopenia in the long-term outcomes of patients with early-stage intrahepatic recurrent hepatocellular carcinoma (HCC).
Methods
The study included 136 ...patients with intrahepatic recurrent Barcelona Clinic Liver Cancer (BCLC) stage 0/A HCC following liver resection diagnosed between 2006 and 2020 and underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial chemoembolization (TACE). Sarcopenia was defined based on the skeletal muscle index using computed tomography at the time of recurrence, and its association with long-term outcomes was evaluated. Tumor-infiltrating lymphocytes (CD4 + , CD8 + , and CD45RO + T cells) were assayed using immunohistochemistry on specimens obtained from repeat hepatectomies, and their association with sarcopenia was evaluated.
Results
The overall survival (OS) and recurrence-free survival (RFS) rates after initial recurrence of patients with sarcopenia were significantly lower than those without sarcopenia (
p
< 0.001 and
p
< 0.001, respectively). Multivariate analysis identified sarcopenia as an independent prognostic factor for RFS (
p
< 0.001). In patients without sarcopenia, surgery resulted in better RFS than RFA or TACE. Contrastingly, in patients with sarcopenia, the RFS was extremely poor regardless of the treatment type: surgery, RFA, or TACE (median RFS, 11.7, 12.7, and 10.1 months). Significantly low levels of tumor-infiltrating CD4 + , CD8 + , and CD45RO + lymphocytes were observed in patients with sarcopenia (
p
= 0.001,
p
= 0.001, and
p
= 0.001, respectively).
Conclusions
This study suggests that patients with sarcopenia have poor RFS regardless of the treatment type for early-stage intrahepatic recurrent HCC. Impaired host immunity might be one of the underlying mechanisms.
Background
The influence of prolonged intermittent Pringle maneuver (IPM) on post-hepatectomy liver failure (PHLF) remains unclear. We evaluated the impact of the prolonged IPM on PHLF in patients ...undergoing open and laparoscopic hepatectomy.
Methods
We retrospectively included 546 patients who underwent hepatectomy using IPM. The patients were divided into open (n = 294) and laparoscopic (n = 252) groups. Odds ratios for PHLF occurrence were estimated in each group according to cumulative Pringle time (CPT). The cut-off value was set at CPT of 120 min. Risk factors for PHLF were evaluated in the open and laparoscopic groups. Additionally, we analyzed the post-operative outcomes in the open and laparoscopic groups with CPT ≥ 120 min and performed propensity score matching analysis based on PFLF-associated factors.
Results
In the open group, the risk of PHLF increased as CPT increased, particularly after 120 min. However, in the laparoscopic group, PHLF did not occur at less than 60 min, and the risk of PHLF was not significantly different at more than 60 min. Multivariate analysis identified CPT ≥ 120 min as an independent risk factor for PHLF in the open group (
p
< 0.001), but not in the laparoscopic group. Propensity score matching analysis showed that the PHLF rate was significantly lower in the laparoscopic group with CPT ≥ 120 min (
p
= 0.027). The post-operative transaminase levels were significantly lower in the laparoscopic group with CPT ≥ 120 min.
Conclusions
Laparoscopic hepatectomy may cause less PHLF with prolonged IPM compared with open hepatectomy.
This study aimed to evaluate the significance of multiple tumor markers (TMs) measurements in determining the indications for conversion surgery (CS) in the management of unresectable locally ...advanced pancreatic cancer (UR-LAPC).
A total of 103 patients with UR-LAPC, treated between 2008 and June 2021, were enrolled in this study. Three TMs, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and Duke pancreatic monoclonal antigen type 2 (DUPAN-2), were measured.
Twenty-five patients (24%) underwent CS. The median preoperative treatment period was 9.5 months. The median survival time (MST) from the initial treatment for patients with CS was significantly longer than that for patients without surgery (34.6 vs. 18.9 months, P < 0.001). The number of elevated TMs before CS was one in five patients and two in five patients, while 15 patients had normal levels of all three TMs. Notably, the MST from the initial treatment for patients with all three preoperative normal TMs levels was favorable for 70.5 months. In contrast, patients with one or two preoperatively elevated TMs levels had a significantly worse prognosis (25.4 and 21.0 months, respectively, P < 0.001). Furthermore, the relapse-free survival of patients with three preoperative normal TMs levels was significantly longer than those with one or two elevated TMs levels (21.9 vs. 11.3 or 3.0 months, respectively, P < 0.001). Non-normal values of all TMs before CS were identified as independent poor prognostic factors.
Simultaneous measurement and assessment of the three TMs levels may help determine the surgical indications for UR-LAPC after systemic anticancer treatment.
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