TRIM27-USP7 complex promotes tumour progression via STAT3 activation in human hepatocellular carcinoma.

BACKGROUND & AIMS: TRIM27 is stabilized by binding to USP7 and mediates tumour progression in several cancers; however, the roles of TRIM27-USP7 complex on STAT3 activation in HCC are unknown. METHODS: Regulations and functions of TRIM27 for activating STAT3 in HCC were assessed using 207 HCC samples or HCC cells. RESULTS: TRIM27 expression was increased in some cases of HCC. High TRIM27 expression was an independent predictor for poor prognosis in HCC after surgery. It was correlated with the expression of EpCAM, vimentin, MMP-9, and activation of STAT3 in HCC. TRIM27 expression was correlated with USP7 expression, and HCC with high TRIM27 expression together with high USP7 expression showed enhanced STAT3 activation, resulting in poorer prognosis. p-JAK1 expression was correlated with STAT3 activation in HCC with high TRIM27 expression. In vitro, USP7 knockdown decreased TRIM27 expression, suggesting that USP7 was essential for TRIM27 stabilization. Knocking down of TRIM27 or USP7 suppressed STAT3 activation and overexpression of TRIM27 accelerated STAT3 activation; therefore, the formation of TRIM27-USP7 complex was needed for STAT3 activation, which led to aggressive tumour proliferation and invasion by enhancing EMT and CSC-like property. Binding of JAK1 to TRIM27-USP7 complex was confirmed in vitro. Deletion of TRIM27-USP7 complex by USP7 inhibitor significantly inhibited tumour cell invasion by suppressing STAT3 activation. CONCLUSIONS: TRIM27 is stabilized by binding to USP7 and is related to aggressive tumour progression in HCC via STAT3 activation, resulting in poor prognosis after operation. Therefore, TRIM27-USP7 complex is a useful prognostic predictor and a promising therapeutic target for HCC.

Prosaposin, tumor-secreted protein, promotes pancreatic cancer progression by decreasing tumor-infiltrating lymphocytes.

Glycoproteins produced by tumor cells are involved in cancer progression, metastasis, and the immune response, and serve as possible therapeutic targets. Considering the dismal outcomes of pancreatic ductal adenocarcinoma (PDAC) due to its unique tumor microenvironment, which is characterized by low antitumor T-cell infiltration, we hypothesized that tumor-derived glycoproteins may serve as regulating the tumor microenvironment. We used glycoproteomics with tandem mass tag labeling to investigate the culture media of three human PDAC cell lines, and attempted to identify the key secreted proteins from PDAC cells. Among the identified glycoproteins, prosaposin (PSAP) was investigated for its functional contribution to PDAC progression. PSAP is highly expressed in various PDAC cell lines; however, knockdown of intrinsic PSAP expression did not affect the proliferation and migration capacities. Based on the immunohistochemistry of resected human PDAC tissues, high PSAP expression was associated with poor prognosis in patients with PDAC. Notably, tumors with high PSAP expression showed significantly lower CD8+ T-cell infiltration than those with low PSAP expression. Furthermore, PSAP stimulation decreased the proportion of CD8+ T cells in peripheral blood monocytes. Finally, in an orthotopic transplantation model, the number of CD8+ T cells in the PSAP shRNA groups was significantly increased, resulting in a decreased tumor volume compared with that in the control shRNA group. PSAP suppresses CD8+ T-cell infiltration, leading to the promotion of PDAC progression. However, further studies are warranted to determine whether this study contributes to the development of a novel immunomodulating therapy for PDAC.

Preoperative Diagnosis of Lymph Node Metastasis of Perihilar Cholangiocarcinoma Using Diffusion-Weighted Magnetic Resonance Imaging.

INTRODUCTION: Although the prognosis of patients with resected perihilar cholangiocarcinoma (PHC) with histological lymph node metastasis (LNM) is poor, preoperative prediction of LNM is difficult. This study aimed to evaluate the diagnostic performance of diffusion-weighted magnetic resonance imaging (DWI) for LNM of PHC. METHOD: Consecutive patients who underwent surgical resection of PHC between January 2012 and May 2020 were retrospectively reviewed. The lymph node (LN) area (mm2) and apparent diffusion coefficient (ADC) value ( × 10-3 mm2/s) of pericholedochal LNs were measured by DWI. The characteristics of the patients and the LNs were evaluated according to the histological presence or absence of regional LNM. Univariate and multivariate analyses were performed to identify the predictors of LNM of PHC. RESULTS: Of the 93 eligible patients, 49 (53%) were LNM positive and 44 (47%) were LNM negative. Although the characteristics of the patients were similar between the two groups, the mean ADC value was significantly lower in the LNM positive group than in the LNM negative group. On multivariate analysis, mean ADC value ≤1.80 × 10-3 mm2/s was independently associated with LNM of PHC (risk ratio: 12.5, 95% confidence interval: 3.05-51.4; p = 0.0004). The sensitivity, specificity and accuracy of mean ADC values ≤ 1.80 × 10-3 mm2/s for predicting LNM of PHC were 94%, 55% and 75%, respectively. CONCLUSIONS: DWI might be useful for the preoperative diagnosis of LNM of PHC.

Impact of resection margin status on survival after operation for pancreatic head cancer with extrapancreatic nerve plexus invasion.

BACKGROUND: Extrapancreatic nerve plexus (PL) invasion of pancreatic ductal adenocarcinoma (PDAC) is an important factor for determining resectability and surgical method. We sought to clarify the characteristics of PDAC with PL invasion and clinical impact of the resection margin status on prognosis for PDAC with PL invasion. METHODS: A total of 242 patients with pancreatic head cancer who underwent pancreatectomy were evaluated. Clinicopathological data and patient survival were analyzed. RESULTS: Pathological PL invasion was observed in 68 patients (28.1%). Patients with PL invasion had significantly shorter disease-free survival (DFS) and showed trends toward worse overall survival (OS) than those without PL invasion. While multivariate analysis revealed that PL invasion was not an independent prognostic factor, PL invasion was associated with extensive venous invasion and a high percentage of lymph node metastases, both of which were independent factors affecting DFS and OS. Among patients with PL invasion, there was no significant difference in DFS and OS between the R0 and R1 resection groups. CONCLUSIONS: PL invasion is a common pathological feature of aggressive PDAC with high propensity for invasiveness and metastatic potential. The microscopic resection margin status may not affect the survival of pancreatic head cancer patients with PL invasion.

Fat signal fraction assessed with MRI predicts hepatic recurrence following hepatic resection for colorectal liver metastases.

PURPOSE: The effect of hepatic steatosis on the development of colorectal liver metastases (CRLM) remains unknown. This study evaluated the usefulness of fat signal fraction assessed with magnetic resonance imaging (MRI) and the effect of hepatic steatosis on hepatic recurrences following initial hepatectomy for CRLM. METHODS: Between January 2013 and December 2019, 64 patients underwent initial hepatectomy for CRLM. The medical records of these patients were reviewed to evaluate the recurrence and survival outcomes. RESULTS: The fat signal fraction was positively correlated with the nonalcoholic fatty liver disease activity score and liver-spleen ratio. Recurrence following the initial hepatectomy was observed in 48/64 patients, and hepatic recurrence was observed in 30/64 patients. The fat signal fraction was significantly higher in patients with hepatic recurrence after initial hepatectomy. The hepatic recurrence rate was 69.2% in patients with fat signal fraction ≥ 0.0258, which was significantly higher than that in patients with fat signal fraction < 0.0258. Hepatic recurrence-free survival rate was significantly higher in patients with fat signal fraction < 0.0258 than in those with fat signal fraction ≥ 0.0258. Multivariate analyses revealed that fat signal fraction ≥ 0.0258 was an independent risk factor for hepatic recurrence. CONCLUSION: The fat signal fraction assessed with MRI was significantly associated with hepatic recurrence following initial hepatectomy for CRLM.

[A Case of Hepatocellular Carcinoma with Erythrocytosis].

Hepatocellular carcinoma is associated with a relatively high rate of paraneoplastic syndrome, but the frequency of erythrocytosis is low. We report a case of hepatocellular carcinoma with preoperative erythrocytosis and hypererythropoietinemia. The case is a 50-year-old man who has been cured by interferon treatment for hepatitis C 20 years ago(SVR). He visited our hospital with the complaint of right hypochondrial pain, and was diagnosed with hepatocellular carcinoma, which occupied S8/5/7 of the liver, and showed erythrocytosis and high erythropoietin(Epo)as tumor-related symptoms. A right hepatic lobectomy was performed, and the patient was discharged 13 days after the operation. The red blood cell count and Epo were normalized immediately after the operation. One year and 2 months after the operation, multiple lung metastases recurred, and chemotherapy is currently underway. Hepatocellular carcinoma with erythrocytosis and hypererythropoietinemia has been reported to have a poor prognosis, and multimodal treatment and strict surveillance are considered necessary.

Differential effects of KRAS mutational status on long-term survival according to the timing of colorectal liver metastases.

BACKGROUND: The relationship between KRAS mutational status and timing of colorectal liver metastasis (CRLM) remains unclear. This study evaluated the relationship between KRAS mutational status and long-term survival in patients with synchronous CRLM. METHODS: Of the 255 patients who underwent initial hepatic resection for CRLM between January 2001 and December 2018, the KRAS mutational status was examined in 101 patients. Medical records of these patients were reviewed to evaluate recurrence and survival outcomes. RESULTS: KRAS mutant status was identified in 38 patients (37.6%). The overall survival (OS) was significantly better in patients with wild-type KRAS than in those with mutant KRAS status. In patients with synchronous metastases, the OS of patients with wild-type KRAS was significantly better than those with mutant KRAS. Multivariate analyses indicated shorter OS to be independently associated with positive primary lymph node, and large tumor size and R1 resection in patients with metachronous metastasis, whereas to be independently associated with mutant KRAS status in patients with synchronous metastasis. Furthermore, in the subgroup of patients with synchronous metastases, the repeat resection rate for hepatic recurrence was significantly high in those with wild type KRAS than in those with mutant KRAS. CONCLUSION: KRAS mutation is an independent prognostic factor in patients with synchronous CRLM, but not in patients with metachronous CRLM.

LGR5 induces ß-catenin activation and augments tumour progression by activating STAT3 in human intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: LGR5 enhances Wnt-ß-catenin signalling; however, involvement of LGR5 or Wnt-ß-catenin signalling in ICC progression has not been reported. METHODS: Functions and regulations of LGR5-mediated ß-catenin activation in ICC progression were evaluated using surgical specimens collected from 61 ICC patients or 2 ICC cell lines. RESULTS: LGR5 expression was increased in some cases of ICC. It was positively correlated with ß-catenin activation, OLFM4 expression and STAT3 activation, and negatively correlated with GRIM19 expression in ICC, thereby enhancing cancer stem cell (CSC)-like property and EMT. High LGR5 expression was an independent factor for poor prognosis in ICC after operation. In vitro, Wnt inhibition by IWP-2 suppressed ß-catenin activation, OLFM4 expression and STAT3 activation. IWP-2 treatment decreased expression of EpCAM, CD133, vimentin and increased E-cadherin expression. The rate of mesenchymal cells was decreased and cell invasiveness was suppressed after IWP-2 treatment, suggesting that Wnt-ß-catenin signalling enhanced CSC-like property and EMT by activating STAT3. In addition, LGR5 knockdown inhibited ß-catenin activation, resulting in suppression of ß-catenin-induced STAT3 activation through inhibition of OLFM4-GRIM19 cascade. As these results, LGR5 knockdown suppressed CSC-like property and EMT. Therefore, LGR5 was a key regulator for ß-catenin activation, and ß-catenin was unable to be activated without LGR5. CONCLUSIONS: LGR5 is essential for ß-catenin activation induced by Wnt signalling. Activated ß-catenin further activates STAT3 and enhances CSC-like property and EMT, leading to aggressive tumour progression and poor prognosis in patients with ICC. Therefore, LGR5 is an excellent prognostic predictor and a promising therapeutic target for ICC.

Sphingosine-1-phosphate Receptor-1 Promotes Vascular Invasion and EMT in Hepatocellular Carcinoma.

BACKGROUND: It remains unknown whether epithelial-mesenchymal transition (EMT)-mediated vascular invasion and cancer stemness are associated with sphingosine-1-phosphate receptor-1 (S1PR1) expression in human hepatocellular carcinoma (HCC). The aim of this study was to investigate the correlation between S1PR1 expression and prognosis of patients with primary HCC and to define the potential of S1PR as a therapeutic target. MATERIALS AND METHODS: We investigated 108 patients who underwent primary surgical resection for HCC treatment. Expression of S1PR1 and EMT markers was analyzed to predict prognosis of patients with HCC. Furthermore, three-dimensional organotypic culture, anoikis assay, and cell invasion were performed to validate the association of S1PR1 with EMT and cancer stemness. RESULTS: Among patients with HCC, the high S1PR1 expression group had significantly shorter overall survival than the low expression group. Moreover, high S1PR1 expression was significantly associated with shorter recurrence-free survival, increased risk of portal and hepatic vein invasion, and intrahepatic metastasis. Multivariate analyses revealed that S1PR1 overexpression was an independent prognostic factor in patients with HCC. S1PR1 overexpression positively correlated with vimentin and MMP-9 expression and negatively correlated with E-cadherin. In addition, S1PR1 overexpression induced EMT and enhanced tumor invasion and cancer stemness. CONCLUSIONS: S1PR1 overexpression, via EMT-induced vascular invasion and increased cancer stem cell properties, establishes a metastatic niche, enhances the capacity of hematogenous metastasis, and associates with poor outcomes in patients with HCC. Hence, S1PR1 may serve as a therapeutic target for patients with HCC with vascular invasion.

Phosphorylated mTOR expression as a predictor of survival after liver resection for colorectal liver metastases.

BACKGROUND: Phosphorylated mammalian target of rapamycin (p-mTOR) plays a crucial role in the process of cancer progression. Common gene mutations of colorectal cancer lead to the activation of the PI3k/Akt/mTOR pathway. In this study, we determined whether p-mTOR expression in colorectal liver metastases is a predictive marker of prognosis following liver resection. METHODS: Eighty-one patients with colorectal liver metastases who had undergone curative resection were evaluated using immunohistochemistry of p-mTOR. Data regarding clinicopathological features and patient survival were analyzed. RESULTS: The p-mTOR expression in colorectal liver metastases was detected in 55 (67.9%) patients. Patients whose metastases had high p-mTOR expression showed a significantly lower overall survival rate after resection as compared to patients with low p-mTOR expression (p = 0.016), while there was no significant difference in the disease-free survival between the two groups. Repeat resection for recurrence was performed more frequently in patients with p-mTOR positive than others (p = 0.024). Multivariate analysis showed that p-mTOR expression was an independent prognostic factor of overall survival after liver resection (p = 0.019). CONCLUSIONS: mTOR was frequently activated in colorectal liver metastases, and the p-mTOR expression was a biological marker for predicting the overall survival of patients with colorectal liver metastases following liver resection.

Simultaneous brain and lung metastases of pancreatic ductal adenocarcinoma after curative pancreatectomy: a case report and literature review.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) rarely metastasizes to the brain; therefore, the features of brain metastasis of PDAC are still unknown. We encountered simultaneous metastases to the brain and lung in a PDAC patient after curative surgery. Case presentation A 68-year-old man with PDAC in the tail of the pancreas underwent distal pancreato-splenectomy. He received gemcitabine as adjuvant chemotherapy for 6 months. Two months later, brain and lung metastases occurred simultaneously. Considering the systemic condition, the patient received gamma knife treatment and an Ommaya reservoir was inserted for drainage. The patient's condition gradually worsened and he received the best supportive care. To the best of our knowledge, only 28 cases in which brain metastases of PDAC were identified at the time of ante-mortem have been reported to date, including the present case. Notably, the percentage of simultaneous brain and lung metastases was higher (32%) in a series of reviewed cohorts. Thus, lung metastasis might be one of the risk factors for the development of brain metastasis in patients with PDAC. As a systemic disease, it can be inferred that neoplastic cells will develop brain metastasis via hematogenous dissemination beyond the blood-brain barrier, even if local recurrence is controlled. In our case, immunohistochemical staining showed that the neoplastic cells were positive for carbonic anhydrase 9 (CAIX), mucin core protein 1 (MUC1), and MUC5AC in the resected primary PDAC. CONCLUSION: We describe a case of simultaneous brain and lung metastases of PDAC after curative pancreatectomy, review previous literature, and discuss the clinical features of brain metastasis of PDAC.

Recurrence patterns and their effects on clinical outcomes after R1 resection of colorectal liver metastases: a propensity score-matched analysis.

PURPOSE: The prognostic significance of the surgical margin status remains controversial for patients who undergo hepatectomy for colorectal liver metastases. This study evaluated the influence of R1 resection on recurrence patterns and prognosis in these patients. METHODS: Between January 2001 and December 2016, 232 consecutive Japanese patients underwent initial hepatic resection for colorectal liver metastases. Their medical records were reviewed to evaluate recurrence and survival outcomes. RESULTS: Relative to patients with R0 resection, patients with R1 resection had significantly poorer recurrence-free survival (RFS) and overall survival (OS). However, after propensity score matching, there were no significant differences in RFS and OS associated with the margin status. Nevertheless, R1 resection was associated with a significantly higher incidence of intrahepatic recurrence and early recurrence, while R0 resection was associated with a significantly higher re-resection rate for hepatic recurrence. Only eight of 55 patients with R1 resection developed recurrence at the R1 resection margin, whereas 36 patients developed recurrence at other sites/organs. CONCLUSION: Among patients with similar characteristics, R1 resection does not affect long-term outcomes. This suggests that R1 resection itself is not a cause of a poor prognosis, but rather a potent indicator of aggressive tumor biology.

High expression of Krüppel-like factor 5 is associated with poor prognosis in patients with colorectal cancer.

Krüppel-like factor 5 (KLF5) plays an oncogenic role and has diverse functions in cancer cells. However, correlation between KLF5 and clinical outcome has not been determined in patients with colorectal cancer and colorectal liver metastasis. Herein, we analyzed 65 patients with colorectal cancer who developed colorectal liver metastasis. Clinical effects were assessed through immunohistochemical analysis of primary colorectal cancer lesions and metastatic liver lesions. High expression of KLF5 in these tissues correlated with the presence of vascular invasion, elevated serum carbohydrate antigen 19-9 levels, large diameters of metastatic liver tumors, and poor prognosis following surgery. Multivariate analyses revealed that high expression of KLF5 was an independent prognostic factor. Increased expression of KLF5 in both colorectal cancer primaries and colorectal liver metastasis was significantly associated with shorter overall survival time and time to surgical failure. Krüppel-like factor 5 expression positively correlated with Ki-67 and c-Myc expression in colorectal cancer tissues. In vitro experiments with colon cancer cell lines showed that siRNA knockdown of KLF5 inhibited cell proliferation. Western blot analyses revealed that knockdown of KLF5 expression reduced cyclin D1 and c-Myc expression. It also impaired the stem cell-like properties of cancer cells in tumorsphere formation assays. Furthermore, anoikis assay indicated that KLF5 contributed to anoikis resistance. High KLF5 expression is associated with poor prognosis in patients with colorectal cancer and liver metastasis by promoting cell proliferation and cancer stem cell-like properties.

The Expression of Yes-Associated Protein (YAP) Maintains Putative Cancer Stemness and Is Associated with Poor Prognosis in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is resistant to most chemotherapeutic agents. Yes-associated protein (YAP) is related to tumor progression; however, its role in ICC remains unknown. We investigated the mechanism underlying YAP-mediated cancer progression by focusing on the property of cancer stem cells (CSCs) in ICC. Immunohistochemistry results revealed the positive YAP expression in 37 of 52 resected ICC cases. Those with positive YAP expression showed poor prognosis in Kaplan-Meier analysis (P = 0.023). YAP expression was associated with vimentin and the putative CSC marker, hepatic oval cell marker 6 (OV-6). The knockdown of YAP expression using specific siRNAs in ICC cells decreased octamer-binding transcription factor 4 (OCT4) expression in Western blot analyses and OV-6 and CD133 expression in flow cytometry analysis. Verteporfin, a YAP inhibitor, decreased N-cadherin and OCT4 expression in Western blot analyses. In vitro sphere formation and anoikis resistance assays revealed the impairment in CSC property and anoikis resistance in response to the decrease in YAP expression. Verteporfin treatment activated the protein kinase B/mechanistic target of rapamycin signaling pathway and dramatically impaired IL-6-stimulated STAT3 phosphorylation in ICC cells. The combination of verteporfin and rapamycin, an inhibitor of mechanistic target of rapamycin phosphorylation, inhibited cell proliferation and tumor growth. In conclusion, verteporfin regulates multiple signaling pathways and, in combination with rapamycin, might be a promising therapeutic strategy for ICC treatment.

Long-term outcomes and significance of preoperative lymphocyte-to-monocyte ratio as a prognostic indicator in patients with invasive pancreatic neoplasms after repeat pancreatectomy.

BACKGROUND: Invasive pancreatic neoplasms have a high propensity for recurrence even after curative resection. Recently, patients who underwent pancreatectomy have an opportunity of undergoing secondary pancreatic resection, so-called "repeat pancreatectomy" to achieve curative operation and prolong their survival. We evaluated the long-term clinical outcomes and identified the prognostic factors, including systemic inflammation markers and the lymphocyte-to-monocyte ratio (LMR) of patients who underwent repeat pancreatectomy for invasive pancreatic tumors. METHODS: Twenty-eight consecutive patients with invasive pancreatic neoplasms (22 pancreatic ductal adenocarcinomas, 2 pancreatic acinar cell carcinomas, and 4 invasive intra-papillary mucinous carcinomas) with isolated local recurrence only in the remnant pancreas were analyzed retrospectively. To identify factors for the selection of optimal patients who should undergo repeat pancreatectomy, perioperative clinical parameters were analyzed by Cox proportional regression models. RESULTS: Of 28 patients, 12 patients experienced recurrence within 3 years after repeat pancreatectomy. Kaplan-Meier analysis showed that the median cancer-specific overall survival time of patients with invasive pancreatic neoplasms was 61 months, showing favorable outcomes. High preoperative LMR (LMR ≥ 3.3) (p = 0.022), no portal vein resection (p = 0.021), no arterial resection (p = 0.037), and pathological lymph node negative (p = 0.0057) were identified as favorable prognostic parameters on univariate analysis, and LMR ≥ 3.3 (p = 0.0005), and pathological lymph node negative (p = 0.018) on multivariate analysis. CONCLUSIONS: Preoperative LMR is potentially a good indicator for selecting suitable patients to undergo repeat pancreatectomy in patients with isolated local recurrence of invasive pancreatic neoplasms.

Comparing prognostic factors of Glut-1 expression and maximum standardized uptake value by FDG-PET in patients with resectable pancreatic cancer.

BACKGROUND: This study aimed to assess the prognostic values of preoperative maximum standardized uptake value (SUVmax) of primary pancreatic tumors and Glut-1 expression in patients with resectable pancreatic ductal adenocarcinoma (R-PDAC), and to investigate whether Glut-1 expression is more effective than SUVmax in predicting survival in patients with R-PDAC. METHODS: We investigated 101 R-PDAC patients who underwent pancreatectomy for pancreatic cancer treatment. SUVmax analyzed through 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and Glut-1 expression, were assessed for predicting the prognosis of patients with R-PDAC. RESULTS: In patients with R-PDAC, the high SUVmax group (≥4.25) had significantly shorter overall survival (OS) and disease-free survival (DFS) than the low SUVmax group (＜4.25). Surprisingly, Glut-1 expression was not significantly correlated with SUVmax. Moreover, the high Glut-1 expression group, which was related to higher levels of CA 19-9, had significantly shorter OS and DFS than the low Glut-1 expression group. Furthermore, among the high SUVmax group, OS and DFS were significantly shorter in the high Glut-1 expression group. Multivariate analyses revealed that Glut-1 overexpression was an independent prognostic factor in patients with R-PDAC. Glut-1 knockdown also induced cell cycle arrest in PDAC cells in vitro. CONCLUSIONS: The study determined that Glut-1 overexpression is a more powerful prognostic factor than SUVmax for predicting OS and higher risk of recurrence in R-PDAC patients. Glut-1 overexpression is also more likely to be associated with malignant activity in PDAC patients.

Needle tract seeding recurrence of pancreatic cancer in the gastric wall with paragastric lymph node metastasis after endoscopic ultrasound-guided fine needle aspiration followed by pancreatectomy: a case report and literature review.

BACKGROUND: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has high accuracy and a low complication rate; therefore, it has been widely used as a useful tool for diagnosis of and to determine treatment strategies for pancreatic tumors. Recently, reports of the recurrence of needle tract seeding after EUS-FNA are emerging. CASE PRESENTATION: An 83-year-old woman was referred to our hospital to undergo further examination of her pancreatic tumor. Multidetector computed tomography (MDCT) revealed a 25-mm-diameter mass in the pancreatic body. She underwent EUS-FNA (transgastric, 22-G needle, 2 passes) and was subsequently diagnosed with adenocarcinoma. Distal pancreatosplenectomy followed by adjuvant chemotherapy with S-1 for 6 months was performed. The level of carbohydrate antigen 19-9 gradually increased 22 months after surgery, and MDCT, which was performed 3 months later, revealed a 23-mm low-density mass in the stomach and paragastric lymph node swelling. Gastroendoscopy revealed a submucosal tumor, and endoscopic ultrasound revealed a hypoechoic mass in the submucosa of the gastric wall. Partial gastrectomy with lymph node resection was performed. The pathological findings showed adenocarcinoma extending from the subserosa to the submucosa and lymph node metastasis, consistent with a tumor recurrence from the resected pancreatic tumor. She received adjuvant chemotherapy with S-1; recurrence was not observed for 5 months, at the time of this writing. CONCLUSION: It is important to pay careful attention to the development of needle tract seeding in patients with pancreatic cancer diagnosed by EUS-FNA. This is the first case of needle tract seeding with lymph node metastasis, highlighting the need for caution and providing novel insight in the postoperative follow-up of patients with pancreatic body/tail cancer.

Outcome of interventional radiology for delayed postoperative hemorrhage in hepatobiliary and pancreatic surgery.

BACKGROUND AND AIM: Postoperative hemorrhage is a rare but potentially lethal complication of hepatobiliary and pancreatic surgeries. This study aimed to retrospectively evaluate the clinical outcome of patients with delayed postoperative hemorrhage and compare the results according to the surgical procedure. METHODS: Overall, 4220 patients underwent surgery for hepatobiliary and pancreatic diseases. Delayed postoperative hemorrhage (observed more than 24 h postoperatively) occurred in 62 patients. Of these, 61 underwent interventional radiology to achieve hemostasis. Patients' clinical data were analyzed retrospectively. The chi-squared or Fisher's exact test was used in data analysis. RESULTS: A total of 62 patients (1.5%) developed delayed postoperative hemorrhage; 61 (1.4%) of them underwent interventional radiology to achieve hemostasis. Median duration from surgery to interventional radiology was 19 days (range: 5-252 days). Sentinel bleeding was detected in 31 patients; Clinical success was achieved in 54 patients (88.5%) by interventional radiology. Overall mortality rate was 26.2%. Causes of 16 in-hospital deaths were uncontrollable hemorrhage (n = 4) and worsening of general condition after hemostasis (n = 12). Mortality rates were 50.0% (11/22) and 12.8% (5/39) after hepatobiliary surgery and pancreatic resection, respectively. Mortality rate was significantly higher after hepatobiliary surgery than after pancreatic surgery (P = 0.002). CONCLUSIONS: Interventional radiology can be successfully performed to achieve hemostasis for delayed hemorrhage after hepatobiliary and pancreatic surgeries. Because successful interventional radiology does not necessarily lead to survival, particularly after hepatobiliary surgery, meticulous attention to prevent surgical complications and intensive treatments before and after interventional radiology are required to improve outcomes.

Splenic enlargement induced by preoperative chemotherapy is a useful indicator for predicting liver regeneration after resection for colorectal liver metastases.

BACKGROUND: Conversion chemotherapy may downsize unresectable colorectal liver metastases (CRLMs), but may cause liver injury and splenic enlargement. The effect of preoperative chemotherapy on liver regeneration after liver resection remains undetermined. The aim of this study was to examine whether splenic enlargement induced by preoperative chemotherapy is an indicator to identify high-risk patients for impaired liver regeneration and liver dysfunction after resection. METHODS: We retrospectively reviewed 118 Japanese patients with CRLMs. Fifty-one patients had conversion chemotherapy. The other 67 patients underwent up-front liver resection. We clarified effects of conversion chemotherapy on splenic volume, liver function, and postoperative liver regeneration. Perioperative outcome was also analyzed. RESULTS: A ratio of the splenic volume before and after chemotherapy (SP index) in the oxaliplatin-based chemotherapy group was significantly greater than other chemotherapy groups after 9 or more chemotherapy cycles. Patients whose SP index was 1.2 or more had significantly higher indocyanine green retention rate at 15 min (ICG-R15) than patients without chemotherapy. Analyses of covariance showed liver regeneration rate after resection was decreased in patients whose SP index was 1.2 or more. The incidence of postoperative liver dysfunction in patients whose SP index was 1.2 or more was significantly greater than patients without chemotherapy. Multivariate analysis showed SP index was a significant predictive factor of impaired liver regeneration. CONCLUSIONS: Splenic enlargement induced by preoperative chemotherapy was a useful indicator for impaired liver regeneration after resection and a decision-making tool of treatment strategy for unresectable CRLMs.

[A Case of Long-Term Survival in a Patient with Recurrence of Peritoneal Dissemination after Resection of Pancreatic Tail Cancer].

A 60-year-old man underwent distal pancreatectomy with splenectomy and combined resection partially of the stomach, jejunum, and left renal vein. We administered S-1 adjuvant chemotherapy for 1 year. After its completion, the patient showed no evidence of recurrence. However, his carbohydrate antigen(CA)19-9 level was elevated for 1 year and 8 months postoperatively. We administered gemcitabine chemotherapy. He was admitted for bowel obstruction 3 years and 10 months postoperatively. Conservative treatment with an ileus tube did not improve the bowel obstruction. Therefore, we performed the surgery. Intraoperative findings revealed peritoneal nodules invading the small intestine. We performed a small bowel bypass. Pathological examination revealed the peritoneal nodule of pancreatic cancer. Although we administered FOLFIRINOX chemotherapy postoperatively, his CA19-9 level remained elevated for 4 years and 8 months after the first surgery. Therefore, chemotherapy was changed to gemcitabine and nab-paclitaxel. Six years and 11 months after the first surgery and 5 years and 3 months after the diagnosis of peritoneal dissemination, he survives with recurrence. Herein, there were 2 contributors to long-term survival; the patient not only showed positive responses to each chemotherapy regimen but could also continue chemotherapy without developing significant adverse effects.