Clonal analysis of metachronous double biliary tract cancers.

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and ß-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled. Among the 12 metachronous tumors, six exhibited anterograde growth in the lower portion and six exhibited retrograde growth in the upper portion of the biliary tree. Surgical resection of metachronous BTCs resulted in recurrence-free survival in seven, local recurrence in five, and death in two patients. Nine achieved 5-year overall survival after primary surgery. Molecular analyses revealed that recurrently altered genes were: TP53, SMAD4, CDKN2A, ELF3, ARID1A, GNAS, NF1, STK11, RNF43, KMT2D and ERBB3. Each of these was altered in at least three cases. A comparison of the molecular features between 12 paired primary and metachronous BTCs indicated that 10 (83%) metachronous tumors developed in clonal association with corresponding primary tumors either successionally or phylogenically. The remaining two (17%) developed distinctly. The successional tumors consisted of direct or evolved primary tumor clones that spread along the bile duct. The phylogenic tumors consisted of genetically unstable clones and conferred a poor prognosis. Metachronous tumors distinct from their primaries harbored fewer mutations than successional and phylogenic tumors. In conclusion, over 80% of metachronous BTCs that develop following primary BTC resection are probably molecularly associated with their primaries in either a successional or a phylogenetic manner. Comparison between the molecular features of a metachronous tumor and those of a preceding tumor may provide effective therapeutic clues for the treatment of metachronous BTC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

GATA6 and CK5 Stratify the Survival of Patients With Pancreatic Cancer Undergoing Neoadjuvant Chemotherapy.

Relevant protein expression of GATA6, CK5, vimentin, and mucins using immunohistochemistry was assessed for predicting the prognosis of and chemotherapy efficacy in patients with pancreatic cancers (PCs). The protein expression was examined in 159 PCs resected after neoadjuvant chemotherapy (NAC-PCs) and compared with that of 120 matched biopsy specimens taken before NAC. KRAS mutations were assessed by digital PCR. NAC-PCs were classified by GATA6 expression initially and CK5 expression subsequently into 4 types: classical-type (n = 22) with GATA6-high (≥50%)/CK5-low (<10%) PCs; hybrid-type (n = 45) with GATA6-high/CK5-high (≥10%) PCs; basal-like-type (n = 53) with GATA6-low (<50%)/CK5-high (≥30%) PCs; and null-type (n = 39) with GATA6-low/CK5-low (<30%) PCs, which resulted in clear stratification of patient prognosis. The classical-type was associated with the most favorable prognosis, whereas the null-type was associated with the worst prognosis (multivariate hazard ratio: 3.56; 95% CI, 1.63-7.77; P = .0015). The hybrid and basal-like types correlated with in-between levels of prognosis. The risk of hepatic recurrence was lower in the classical-type than in null (multivariate odds ratio [mOR]: 0.18; 95% CI, 0.04-0.96; P = .0449) and basal-like (mOR: 0.24; 95% CI, 0.05-1.16; P =.0750) types. By contrast, the risk of locoregional recurrence was higher in the classical-type than in the basal-like-type (mOR: 5.03; 95% CI, 1.20-21.1; P = .0272). The hybrid-type was subclassified into transition and coexpression patterns with different gastric mucin expression levels. High levels of vimentin (≥10%, n = 30) in pre-NAC-PC tissues was associated with poor prognosis (P = .0256). Phenotypic transitions between pre-NAC and post-NAC-PCs were common (73/120; 61%). PCs with NAC regression grades 2 and 3 showed a transition to poorer prognostic phenotypes (P = .0497). KRAS mutations were not associated with these phenotypes. In conclusion, GATA6 and CK5 immunohistochemical expression phenotypes may stratify the survival of patients with NAC-PCs and reflect post-NAC phenotypic transitions associated with poor prognosis. Prompt evaluation of immunohistochemical phenotypes may contribute to designing a precision therapeutic strategy for patients with PCs.

Reduced expression of phosphorylated ataxia-telangiectasia mutated gene is related to poor prognosis and gemcitabine chemoresistance in pancreatic cancer.

BACKGROUND: Loss of expression of the gene ataxia-telangiectasia mutated (ATM), occurring in patients with multiple primary malignancies, including pancreatic cancer, is associated with poor prognosis. In this study, we investigated the detailed molecular mechanism through which ATM expression affects the prognosis of patients with pancreatic cancer. METHODS: The levels of expression of ATM and phosphorylated ATM in patients with pancreatic cancer who had undergone surgical resection were analyzed using immunohistochemistry staining. RNA sequencing was performed on ATM-knockdown pancreatic-cancer cells to elucidate the mechanism underlying the invlovement of ATM in pancreatic cancer. RESULTS: Immunohistochemical analysis showed that 15.3% and 27.8% of clinical samples had low levels of ATM and phosphorylated ATM, respectively. Low expression of phosphorylated ATM substantially reduced overall and disease-free survival in patients with pancreatic cancer. In the pancreatic cancer cell lines with ATM low expression, resistance to gemcitabine was demonstrated. The RNA sequence demonstrated that ATM knockdown induced the expression of MET and NTN1. In ATM knockdown cells, it was also revealed that the protein expression levels of HIF-1α and antiapoptotic BCL-2/BAD were upregulated. CONCLUSIONS: These findings demonstrate that loss of ATM expression increases tumor development, suppresses apoptosis, and reduces gemcitabine sensitivity. Additionally, loss of phosphorylated ATM is associated with a poor prognosis in patients with pancreatic cancer. Thus, phosphorylated ATM could be a possible target for pancreatic cancer treatment as well as a molecular marker to track patient prognosis.

Clinical impact of multimodal treatment including chemoradiotherapy, conversion surgery and postoperative chemotherapy for borderline resectable and unresectable locally advanced pancreatic cancer without disease progression after gemcitabine plus nab-paclitaxel.

BACKGROUND: The purpose of this study was to investigate treatment outcomes of chemoradiotherapy (CRT) using S-1 with or without conversion surgery after gemcitabine plus nab-paclitaxel (GnP) for borderline resectable (BR) and unresectable locally advanced (UR-LA) pancreatic cancer. METHODS: From 2016 to 2020, patients without disease progression after GnP for BR or UR-LA pancreatic cancer underwent CRT with S-1. If distant metastasis was not detected after CRT, conversion surgery and oral administration of S-1 as postoperative adjuvant chemotherapy for at least 6 months was performed. RESULTS: Forty patients were included in the present study. The median number of cycles of GnP was 6. Surgery was performed after CRT in 25 patients. The median progression-free survival (PFS) and overall survival (OS) periods from the start of radiotherapy were 24.6 and 27.4 months, respectively. The OS periods from the start of radiotherapy in patients who underwent conversion surgery and those who did not undergo conversion surgery were 41.3 and 16.8 months, respectively. The PFS periods from the start of radiotherapy in patients who underwent surgery and those who did not undergo surgery were 28.3 and 8.6 months, respectively. Patients who were able to receive S-1 after conversion surgery for more than 6 months had better OS than those who were not (p = 0.039), although there was no significant difference of PFS (p = 0.365). CONCLUSIONS: In BR/UR-LA pancreatic cancer without disease progression after GnP, multimodal treatment including CRT, conversion surgery and the scheduled postoperative chemotherapy may be effective.

Negative prognostic impact of sarcopenia before and after neoadjuvant chemotherapy for pancreatic cancer.

OBJECTIVES: To elucidate the prognostic impact of sarcopenia before and after neoadjuvant chemotherapy (NAC) for pancreatic cancer (PC). METHODS: We retrospectively studied 75 consecutive PC patients who underwent neoadjuvant gemcitabine plus S-1 combination therapy followed by pancreatectomy between 2008 and 2016. According to the skeletal muscle volume index (SMI), the patients were divided into the muscle attenuation group (MAG) and normal group (NG) before or after NAC. Prognostic factors for overall survival (OS) were analyzed by Cox proportional hazards models. RESULTS: The MAG showed significantly poorer OS than the NG before and after NAC. Pre-NAC, median OS was 20.0 months in the MAG versus 49.0 months in the NG (p = 0.006). Post-NAC, median OS was 21.3 months in the MAG versus 48.8 months in the NG (p = 0.014). Multivariate analysis, excluding muscle attenuation after NAC because of confounding factors and lower hazard ratio (2.08, 95% confidence interval: 1.14-3.78, p = 0.016) than that before NAC (2.14, 1.23-3.70, p = 0.007) by univariate analysis, revealed the following independent prognostic factors: muscle attenuation pre-NAC (2.25, 1.26-4.05, p = 0.007); borderline resectability (1.96, 1.04-3.69, p = 0.038); operative blood loss (2.60, 1.38-4.88, p = 0.003); and distant metastasis (3.31, 1.40-7.82, p = 0.006). CONCLUSIONS: Sarcopenia before and after NAC for PC is suggested to be a poor prognostic factor, with a stronger impact before than after NAC.

Chronic Glucocorticoid Use is a Potential Risk Factor for Delayed Pancreatic Fistula after Laparoscopic Distal Pancreatectomy: A Retrospective Analysis.

Pancreatic fistula is a potentially morbid complication after distal pancreatectomy. Chronic glucocorticoid use is one of the risk factors for pancreatic fistula in pancreaticoduodenectomy, though it has not been reported in distal pancreatectomy. We explored whether chronic glucocorticoid use can be a risk factor for pancreatic fistula in distal pancreatectomy. We reviewed 408 consecutive patients who underwent elective distal pancreatectomy from 2011 to 2021. We evaluated two kinds of pancreatic fistula (postoperative pancreatic fistula and delayed pancreatic fistula). We defined delayed pancreatic fistula as a patient who was re-admitted for pancreatic fistula after the first discharge from the hospital. Preoperative characteristics and postoperative outcomes were analyzed. Two hundred sixty-seven patients underwent open distal pancreatectomy, while 141 patients had laparoscopic distal pancreatectomy. A comparison of patient with and without chronic glucocorticoid use showed that only patients with chronic glucocorticoid use developed delayed pancreatic fistula (0% vs. 16.7%; p < 0.001). In addition, delayed pancreatic fistula occurred in only laparoscopic distal pancreatectomy patients with chronic glucocorticoid use (0% vs. 25.0%; p < 0.001). Although sample size is small, it is reasonable to presume that chronic glucocorticoid use is a potential risk factor for delayed pancreatic fistula in laparoscopic distal pancreatectomy.

[A Case of an Elderly Patient Who Underwent Conversion Resection for Pancreatic Cancer with Positive Peritoneal Cytology].

We report a case of an elderly patient, 82 years-old, with initially-unresectable pancreatic head cancer, who successfully underwent complete resection of the primary lesion after systemic chemotherapy for 6 months. The patient had a history of pancreatic body-tail resection for intraductal papillary mucinous carcinoma in 2005. In 2020, a routine examination revealed an increased CA19-9 value of 1,958 U/mL and showed a pancreatic head tumor of 35 mm on CT images. Finally, the tumor was pathologically diagnosed as pancreatic cancer by a biopsied sample. Although CT images showed no distant metastasis, peritoneal lavage cytology was indicated as positivity(H0P0CY1)in the staging laparoscopy. We implanted a peritoneal port and introduced systemic chemotherapy of gemcitabine and nab-paclitaxel combination therapy. This treatment for 6 months induced tumor shrinkage to 30 mm on the CT image, normalized CA19-9 value to 22.6 U/mL, and negative cytology in the collected lavage fluid from the peritoneal port. The patient's general condition was maintained even after the chemotherapy and the lavage cytology was pathologically diagnosed as negative(H0P0CY0)in the repeated staging laparoscopy, therefore we decided to perform pancreaticoduodenectomy as a conversion surgery. The patient was discharged on the 21st postoperative day with an uneventful course and underwent adjuvant chemotherapy of S-1 for 6 months. No recurrence was found in 8 months after the surgery. In such a case of the selected elderly patient with a maintained general condition, it is feasible to undergo multimodal treatments including conversion surgery for an initially-unresectable pancreatic cancer with positive peritoneal cytology.

Impact of Tumor-Derived DNA Testing in Peritoneal Lavage of Pancreatic Cancer Patients with and Without Occult Intra-Abdominal Metastases.

BACKGROUND: The fractional abundance of tumor-derived DNA in body fluids depends on the metastatic sites and the degree of expansion. We aimed to assess the clinical significance of tumor-derived DNA testing in the peritoneal lavage of patients with pancreatic cancer. METHODS: The prevalence and abundance of tumor-derived DNA was assessed in 204 subjects with ascites by peritoneal lavage (AS) and the evaluable paired plasma (PL) from 149 pancreatic cancer patients undergoing abdominal exploration. Genetic profiles were evaluated by next-generation sequencing, and prognostic impact was assessed using Cox proportional hazard models. RESULTS: Of 204 subjects, AS samples from patients with peritoneal dissemination (PER+) and positive cytology (CY+) showed significantly higher prevalence and abundance of tumor-derived DNA than those with negative counterparts. Tumor-derived DNA prevalence and abundance in AS were more likely to be higher than in paired PL in a subgroup of patients with PER+ and CY+, respectively. Next-generation sequencing revealed concordant or discrepant mutational patterns between the AS and PL samples. Multivariate analysis showed that both tumor-derived DNA in AS (hazard ratio [HR] 3.940, p = 0.009) and PL (HR 2.936, p = 0.026) were independently associated with poor survival in treatment-naïve patients. In patients who underwent resection, tumor-derived DNA positivity in the AS was more predictive of early recurrence than in PL. CONCLUSIONS: Tumor-derived DNA in AS can serve as characterizing the genetic profiles of tumor cells attributable to the development of PER+ and predicting the minimal residual disease and early recurrence in patients with pancreatic cancer.

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

BACKGROUND: and purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: Of 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified. RESULTS: ZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025). CONCLUSIONS: The current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.

Laparoscopic and robot-assisted surgery for adult congenital biliary dilatation achieves favorable short-term outcomes without increasing the risk of late complications.

PURPOSE: Minimally invasive surgery (MIS) is the optimal treatment for congenital biliary dilatation (CBD), but few studies on adults have been reported. We compared the postoperative outcomes of MIS with those of open surgery (OS) in adult patients with CBD. METHODS: The subjects of this retrospective study were 36 adult patients who underwent surgery for CBD. We compared the postoperative outcomes of 20 patients who underwent laparoscopic (n = 15) or robotic (n = 5) surgery with those of 16 patients who underwent OS. RESULTS: MIS was associated with a significantly higher rate of type I (p < 0.001), significantly less blood loss (p < 0.001), a significantly lower rate of internal stents (p = 0.048), significantly longer operation times (p = 0.009), and a significantly shorter postoperative hospital stay (p = 0.007) than OS. The postoperative outcomes of MIS for type I CBD were similar to those of the whole cohort. There were no significant differences in late complications between the groups. The robotic procedure had a significantly shorter operative time than laparoscopic surgery for hepaticojejunostomy (HJ; p = 0.029). CONCLUSIONS: MIS achieved favorable short-term outcomes without compromising mid-term outcomes compared to OS and is appropriate for adult patients with CBD. Robotic HJ may be more ideal than its laparoscopic counterpart.

The value of reputation capital during the COVID-19 crisis: Evidence from Japan.

This study investigates the value of reputation capital with regard to the stock market crash in the early stages of the COVID-19 pandemic. At that time, when stock prices fell precipitously, firms with a positive reputation for the usefulness of products/services seen from within their business network showed stock returns five to seven percentage points higher than firms with a low reputation score. This suggests a positive reputation among stakeholders can serve as insurance against shocks in times of crisis. Notably, results suggest firms that can build public trust owing to the usefulness of the product/service are more resilient from crash caused by real economic damage, as occurred with the COVID-19-related crash.

[A Case of Resected Pancreatic Adenosquamous Carcinoma with Early Hepatic Metastatic Recurrence].

A 73-year-old man was presented with epigastric pain and indicated high CA19-9 levels, and computed tomography detected a tumor in the uncinate process of the pancreas infiltrated duodenum and superior mesenteric artery. The patient was diagnosed with borderline resectable pancreatic carcinoma and received neoadjuvant chemotherapy with gemcitabine and S-1. During neoadjuvant chemotherapy, the patient also received radiotherapy to control duodenal bleeding. After neoadjuvant chemotherapy, stable disease(SD)was proven on the Response Evaluation Criteria in Solid Tumors(RECIST), and subtotal stomach-preserving pancreaticoduodenectomy was performed. The pathological findings showed pancreatic adenosquamous carcinoma. After 7 days postoperatively, hepatic metastasis was detected, and after 78 days postoperatively, the patient died.

MicroRNA-593-3p Expression in Peritoneal Lavage Fluid as a Prognostic Marker for Pancreatic Cancer Patients Undergoing Staging Laparoscopy.

BACKGROUND: Some presumed resectable pancreatic cancer patients harbor radiographically occult metastases that are incidentally identified at the time of abdominal exploration. This study aims to identify novel diagnostic or predictive microRNA (miRNA) markers for subclinical peritoneal dissemination in patients with pancreatic cancer undergoing abdominal exploration. METHODS: Peritoneal lavage fluid samples were harvested from 74 patients with pancreatic cancer at the time of staging laparoscopy. Microarray analysis was performed using peritoneal lavage fluids with positive and negative cytology. Candidate microRNA expression was quantified and validated by droplet-digital PCR assays. RESULTS: In the miRNA array analysis, miR-593-3p showed significant upregulation in peritoneal lavage fluids with positive cytology. Of the 74 patients validated, peritoneal lavage fluids with positive cytology had significantly higher expression of miR-593-3p than those with negative cytology (P < 0.001). Even in cases with no peritoneal dissemination and negative cytology, multivariate analysis revealed that elevated miR-593-3p expression was significantly correlated with worse overall survival than those with low expression (hazard ratio: 3.474, P = 0.042). Of the 48 patients who underwent pancreatectomy, multivariate analysis also demonstrated that higher expression of miR-593-3p in peritoneal lavage was the only significant poor prognostic marker influencing both overall survival (hazard ratio: 23.38, P = 0.005) and recurrence-free survival (hazard ratio: 5.700, P = 0.002). CONCLUSIONS: Elevated miR-593-3p expression in peritoneal lavage suggests the presence of subclinical micrometastasis even in cases with localized pancreatic cancer, and miR-593-3p could be a useful prognostic predictor for pancreatic cancer patients undergoing staging laparoscopy.

Preceding Systemic Chemotherapy for Patients with Pancreatic Ductal Adenocarcinoma with Positive Peritoneal Cytology Provides Survival Benefit Compared with Up-Front Surgery.

BACKGROUND: The significance of surgical resection in pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal cytology (PPC) is controversial. This study aimed to evaluate whether preceding chemotherapy could be beneficial for patients with PDAC with PPC. METHODS: Between 2017 and 2019, 34 consecutive PDAC patients diagnosed with PPC without distant metastasis were retrospectively reviewed. Twenty-three patients did not receive neoadjuvant treatment (NAT) and 11 received NAT. All patients received systemic chemotherapy after PPC was confirmed, and they underwent surgical resection if PPC turned negative. The treatment course, ratio of conversion surgery (CS), and prognosis were evaluated. Moreover, the prognosis of PPC patients who underwent up-front surgery without NAT between 2003 and 2016 was analyzed as a comparative cohort. RESULTS: The median survival time (MST) of the patients without NAT was 31.4 months. CS was performed in 52.2% of the patients. Patients who underwent CS had better prognoses than those who did not undergo CS (p = 0.005). The CS rate was significantly higher in resectable PDAC (78.5%) than in borderline/unresectable PDAC (11.1%) (p = 0.002). The prognosis of patients with resectable PDAC was improved with preceding chemotherapy compared with up-front surgery (MST 13.0 months; p = 0.016). After NAT, the CS rate was low (27.3%), and the MST was only 14.1 months. CONCLUSIONS: As an initial treatment for PDAC patients with PPC, chemotherapy may lead to a favorable prognosis. Especially, resectable PDAC is associated with a greater chance of improved prognosis. Future studies are required to ascertain whether up-front surgery or preceding chemotherapy should be performed for these patients.

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

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

Prognostic value of an inflammation-based nutritional score for patients with initially unresectable pancreatic adenocarcinoma undergoing conversion surgery following chemo-/radiotherapy.

PURPOSE: To clarify the prognostic value of the preoperative nutrition status of patients undergoing conversion surgery (CS) for initially unresectable pancreatic adenocarcinoma (UR-PA). METHODS: The subjects of this retrospective study were 41 consecutive patients with initially UR-PA treated with chemo-/radiotherapy and subsequent CS between 2007 and 2014, at Tohoku University Hospital. The preoperative Glasgow Prognostic Score (GPS) was 0, conveying normal nutrition, in 25 patients (N group) and 1-2, conveying malnutrition, in 16 patients (M group). The clinicopathological factors influencing overall survival were defined by uni- and multivariate analyses. RESULTS: The M group had a significantly worse prognosis than the N group (median overall survival (mOS) 9.6 vs 40.7 months, p = 0.001). Multivariate analysis identified a GPS of 1-2 as an independent predictor of worse prognosis [hazard ratio (HR)3.437, p = 0.032], followed by CA19-9 elevation before CS (HR4.089, p = 0.012) and pathological lymph node metastases (HR2.314, p = 0.046). Patients who maintained a favorable nutritional status (GPS 0) during preoperative treatment had a significantly better prognosis, whereas those whose nutritional status deteriorated (elevated to GPS 1-2) had poorer survival (mOS 40.7 vs. 9.7 months, p = 0.003) CONCLUSION: Preoperative malnutrition status (GPS 1-2) is considered an independent predictor of a worse prognosis for patients undergoing CS for initially UR-PA.

Liver resections in patients with prior bilioenteric anastomosis are predisposed to develop organ/space surgical site infections and biliary leakage: results from a propensity score matching analysis.

PURPOSE: The aims of this study were to compare the perioperative outcomes after hepatectomy with prior bilioenteric anastomosis to those without prior anastomosis, and to elucidate the mechanisms and preventative measures of its characteristic complications. METHODS: The demographic data and perioperative outcomes of 525 hepatectomies performed between January 2007 and December 2018, including 40 hepatectomies with prior bilioenteric anastomosis, were retrospectively analyzed. RESULTS: A propensity score matching analysis demonstrated that hepatectomies with prior bilioenteric anastomosis were associated with a higher frequency of major complications (p = 0.015), surgical site infection (p = 0.005), organ/space surgical site infection (p = 0.003), and bile leakage (p = 0.007) compared to those without. A multivariate analysis also elucidated that prior bilioenteric anastomosis was one of the independent risk factors of organ/space surgical site infection. In the patients with prior bilioenteric anastomosis, bile leakage was associated with organ/space surgical site infection at a significantly higher rate than those without prior bilioenteric anastomosis (p < 0.001). CONCLUSIONS: Prior bilioenteric anastomosis is a strong risk factor for organ/space surgical site infections, which might be induced by bile leakage. To prevent infectious complications after hepatectomy with prior bilioenteric anastomosis, meticulous liver transection to reduce bile leakage rate is thus considered to be mandatory.

Staging laparoscopy is mandatory for the treatment of pancreatic cancer to avoid missing radiologically negative metastases.

PURPOSE: Staging laparoscopy is considered useful for determining treatment plans for advanced pancreatic cancer. However, the indications for staging laparoscopy are not clear. This study aimed to evaluate the safety of staging laparoscopy and its usefulness for detecting distant metastases in patients with pancreatic cancer. METHODS: A total of 146 patients with pancreatic cancer who underwent staging laparoscopy between 2013 and 2019 were analyzed. Staging laparoscopy was performed in all pancreatic cancer patients in whom surgery was considered possible. RESULTS: In this cohort, 42 patients (29%) were diagnosed with malignant cells on peritoneal lavage cytology, 9 (6%) had peritoneal dissemination, and 11 (8%) had liver metastases. A total of 48 (33%) had radiologically negative metastases. On a multivariate analysis, body and tail cancer [odds ratio (OR) 5.00, 95% confidence interval (CI) 2.15-11.6, p < 0.001], high CA19-9 level [OR 4.04, 95% CI 1.74-9.38, p = 0.001], and a resectability status of unresectable (OR 2.31, 95% CI 1.03-5.20, p = 0.04) were independent risk factors for radiologically negative metastases. CONCLUSIONS: Staging laparoscopy can be safely performed and is useful for the diagnosis of radiologically negative metastases. Staging laparoscopy should be routinely performed for the accurate diagnosis of pancreatic cancer patients before pancreatectomy and/or local treatment, such as radiotherapy.

Increased neutrophil-lymphocyte ratio predicts recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

BACKGROUND: The prognostic values of inflammation-based markers in well-differentiated pancreatic neuroendocrine neoplasms, diagnosed according to the new 2017 World Health Organization classification, have remained unclear. Therefore, we assessed the ability to predict the recurrence of such markers after curative resection in patients with these neoplasms. METHODS: Circulating/systemic neutrophil-lymphocyte, monocyte-lymphocyte, platelet-lymphocyte, and platelet-white cell ratios were evaluated in 120 patients who underwent curative resection for well-differentiated pancreatic neuroendocrine neoplasms without synchronous distant metastasis between 2001 and 2018. Recurrence-free-survival and overall survival were compared using Kaplan-Meier analysis and log-rank tests. Univariate or multivariate analyses, using a Cox proportional hazards model, were used to calculate hazard ratios with 95% confidence intervals. RESULTS: Univariate analysis demonstrated that preoperative neutrophil-lymphocyte ratio, tumor size, European Neuroendocrine Tumor Society TMN classification, 2017 World Health Organization classification, and venous invasion were associated with recurrence. The optimal preoperative neutrophil-lymphocyte ratio cut-off value was 2.62, based on receiver operating characteristic curve analysis. In multivariate analysis, a higher preoperative neutrophil-lymphocyte ratio (HR = 3.49 95% CI 1.05-11.7; P = 0.042) and 2017 World Health Organization classification (HR = 8.81, 95% CI 1.46-168.2; P = 0.015) were independent recurrence predictors. CONCLUSIONS: The circulating/systemic neutrophil-lymphocyte ratio is a useful and convenient preoperative prognostic marker of recurrence in patients with well-differentiated pancreatic neuroendocrine neoplasm based on the 2017 World Health Organization classification.

Entropy Based Student's t-Process Dynamical Model.

Volatility, which represents the magnitude of fluctuating asset prices or returns, is used in the problems of finance to design optimal asset allocations and to calculate the price of derivatives. Since volatility is unobservable, it is identified and estimated by latent variable models known as volatility fluctuation models. Almost all conventional volatility fluctuation models are linear time-series models and thus are difficult to capture nonlinear and/or non-Gaussian properties of volatility dynamics. In this study, we propose an entropy based Student's t-process Dynamical model (ETPDM) as a volatility fluctuation model combined with both nonlinear dynamics and non-Gaussian noise. The ETPDM estimates its latent variables and intrinsic parameters by a robust particle filtering based on a generalized H-theorem for a relative entropy. To test the performance of the ETPDM, we implement numerical experiments for financial time-series and confirm the robustness for a small number of particles by comparing with the conventional particle filtering.