Splenic sarcoid reaction mimicking metastases in patients after uterine cancer surgery: a report of two cases.

BACKGROUND: Tumor-associated sarcoid reactions have been observed with various tumors; however, they have not been reported with uterine cancer. We present two cases of splenic sarcoid reactions that mimicked metastases a few years after uterine cancer surgery. CASE PRESENTATION: Case 1 involved a 67-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent open total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Three years after the initial surgery, computed tomography (CT) and positron emission tomography CT showed multiple splenic masses with increasing numbers and sizes. Splenic metastases were diagnosed, and laparoscopic splenectomy was performed. The histopathological analysis revealed sarcoid reactions in the spleen. Case 2 involved a 47-year-old female patient diagnosed with endometrial cancer (pT1aN0M0, pStage Ia, grade 1). The patient underwent laparoscopic total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymphadenectomy. Two years after the initial surgery, multiple splenic masses were observed. We performed laparoscopic splenectomy for the splenic metastases. Granuloma formations were identified in the splenic specimen and perisplenic lymph nodes that were removed simultaneously, resulting in a final diagnosis of sarcoid reaction. A review of the lymph nodes at the time of the previous uterine surgery revealed granuloma formation. Other than the presence of splenic masses, no findings suggestive of recurrence were observed in these cases. Uterine cancer and sarcoid reactions progressed without recurrence after splenectomy. CONCLUSIONS: To the best of our knowledge, this is the first report of the late development of splenic sarcoid reactions after uterine cancer surgery. Sarcoid reactions and metastases are difficult to diagnose based on preoperative imaging results. However, reviewing the specimen at the time of the initial resection, the number of lesions, and the clinical findings (other than imaging findings) may aid in the determination of the correct diagnosis.

Prognostic Value of Peritoneal Lavage Cytology in Potentially Resectable Pancreatic Cancer Stratified by Cytologic Status.

BACKGROUND/AIM: Patients with pancreatic ductal adenocarcinoma (PDAC) with positive peritoneal lavage cytology (CY) reportedly have poor prognoses. However, the value of diagnosis of suspicious for malignancy on CY is unknown. This study aimed to elucidate the prognostic impact of CY by focusing on CY subgroups. PATIENTS AND METHODS: Data were collected from 231 resectable PDAC patients who underwent curative-intent resection. Patients were divided into three CY-based groups: negative (CY0), suspicious for malignancy (CY-S), and positive (CY1). Clinicopathological characteristics and prognostic factors were analyzed. RESULTS: CY1 and CY-S were diagnosed in 7.8% and 3.9% of the patients, respectively. The CY1 group had significantly larger tumors and higher frequencies of distal tumors, anterior pancreatic tissue invasion, retropancreatic tissue invasion, and R1 resection than the CY0 group. Patient characteristics did not differ between the CY0 and CY-S groups. The CY1 group exhibited worse survival than the CY0 and CY-S groups (median survival time: 18.8 vs. 39.6 months, p=0.0021 and vs. 62.2 months, p=0.018). Multivariate analysis for survival indicated that a tumor size >2 cm, preoperative CA19-9 value >100 U/ml, CY1, lymph node metastasis, R1 resection, and lack of adjuvant chemotherapy were associated with poor prognosis. Both the CY1 and CY-S groups had higher frequencies of peritoneal recurrence than the CY0 group (50% vs. 11.8%, p<0.001 and 44.4% vs. 11.8%, p=0.019). CONCLUSION: The prognosis of the CY1 group was poor. Although CY-S was associated with a higher frequency of peritoneal recurrence than CY0, the long-term outcomes of patients with surgical treatment were acceptable.

Transduodenal ampullectomy for early ampullary cancer: Clinical management, histopathological findings and long-term outcomes at a single center.

BACKGROUND: Transduodenal ampullectomy has been attempted in ampullary tumors, including early ampullary cancer. However, the indication and extent of transduodenal ampullectomy with curative intent remain controversial. Herein, we address the perioperative and long-term outcomes of patients with early ampullary cancer who underwent transduodenal ampullectomy at a single center. METHODS: We retrospectively enrolled 10 early ampullary cancer patients who underwent transduodenal ampullectomy and 11 early ampullary cancer patients who underwent subtotal stomach-preserving pancreatoduodenectomy at Saitama Cancer Center between October 2008 and May 2021. Among this cohort, we analyzed the perioperative outcomes and long-term outcomes. RESULTS: In terms of the perioperative outcomes between the transduodenal ampullectomy and subtotal stomach-preserving pancreatoduodenectomy groups, the transduodenal ampullectomy group exhibited a shorter operating time (244 minutes vs 390 minutes, P = .003), less intraoperative blood loss (67.5 grams vs 774 grams, P = .006) and shorter length of postoperative hospital stay (15 days vs 33 days). With respect to the postoperative nutrition status, the transduodenal ampullectomy group exhibited less postoperative weight loss (0.67% vs 8.95%, P = .021), a better Controlling Nutritional Status score (1.0 vs 2.1, P = .011) and a better Prognostic Nutritional Index score (42.9 vs 40.9, P = .018). The 5-year survival in the adenoma with high-grade dysplasia and T1 ampullary cancer which invaded the mucosal layer groups was 100%, whereas the median survival time in the T1 ampullary cancer which invaded the sphincter of Oddi group was 20.7 months (P = .0028). CONCLUSION: Transduodenal ampullectomy is assumed to be a feasible and effective surgical procedure for the treatment of selected patients with early ampullary cancer, including patients with adenoma with high-grade dysplasia or T1 ampullary cancer which invaded the mucosal layer ampullary cancer.

[A Rare Case of Cronkhite-Canada Syndrome Associated with Gastric Cancer and Gastric Outlet Obstruction].

Cronkhite-Canada syndrome(CCS)is a rare non-inherited disease characterized by gastrointestinal polyposis and ectodermal abnormalities. We report a rare case of CCS associated with gastric cancer and gastric outlet obstruction with a review of the literature. A 75-year-old man was admitted because of frequent vomiting and hypoproteinemia. He was diagnosed with CCS due to typical clinical and laboratory findings including alopecia, nail atrophy, hypoproteinemia, and typical gastrointestinal polyposis. Upper endoscopic examination also pointed out a large gastric cancer mainly located in the antrum and the reversible pyloric obstruction caused by the gastric tumor. Biopsy of the tumor revealed tubular adenocarcinoma. Computed tomography demonstrated the dilated duodenum caused by packing of the gastric tumor. 1.5 months after prednisolone therapy, he underwent total gastrectomy with complete resection of the dilated duodenal bulb. Histological examination revealed gastric cancer(pap>tub1)classified into Stage ⅢC. Postoperative course was uneventful and he moved to another hospital. To our knowledge, including the present case, there were 20 reported cases of CCS associated with gastric cancer from Japan(1979-2022). Also, 7 cases of CCS associated with gastric outlet obstruction was reported.

Three-dimensional simulation of the pancreatic parenchyma, pancreatic duct and vascular arrangement in pancreatic surgery using a deep learning algorithm.

Three-dimensional surgical simulation, already in use for hepatic surgery, can be used in pancreatic surgery. However, some problems still need to be overcome to achieve more precise pancreatic surgical simulation. The present study evaluates the performance of SYNAPSE VINCENT® (version 6.6, Fujifilm Medical Co., Ltd., Tokyo, Japan) in the semiautomated surgical simulation of the pancreatic parenchyma, pancreatic ducts, and peripancreatic vessels using an artificial intelligence (AI) engine designed with deep learning algorithms. One-hundred pancreatic cancer patients and a control group of 100 nonpancreatic cancer patients were enrolled. The evaluation methods for visualizing the extraction were compared using the Dice coefficient (DC). In the pancreatic cancer patients, tumor size, position, and stagewise correlations with the pancreatic parenchymal DC were analyzed. The relationship between the pancreatic duct diameter and the DC, and between the manually and AI-measured diameters of the pancreatic duct were analyzed. In the pancreatic cancer/control groups, the pancreatic parenchymal DC and pancreatic duct extraction were 0.83/0.86 and 0.84/0.77. The DC of the arteries (portal veins/veins) and associated sensitivity and specificity were 0.89/0.88 (0.89/0.88), 0.85/0.83 (0.85/0.82), and 0.82/0.81 (0.84/0.81), respectively. No correlations were observed between pancreatic parenchymal DC and tumor size, position, or stage. No correlation was observed between the pancreatic duct diameter and the DC. A positive correlation (r = 0.61, p<0.001) was observed between the manually and AI-measured diameters of the pancreatic duct. Extraction of the pancreatic parenchyma, pancreatic duct, and surrounding vessels with the SYNAPSE VINCENT® AI engine assumed to be useful as surgical simulation.

Conversion surgery for initially unresectable advanced biliary tract cancer treated with gemcitabine plus cisplatin combination chemotherapy: a case report and literature review.

Recently, the number of reports describing patients with initially unresectable biliary tract cancer (BTC) who underwent resection in the form of conversion surgery is increasing. Gemcitabine plus cisplatin (GC) combination therapy has been reported to significantly prolong the median survival time from 8.1 to 11.7 months compared with conventional gemcitabine therapy in patients with unresectable BTC. We report the case of a patient with unresectable BTC who underwent conversion surgery with a partial response to GC combination therapy. A 78-year-old woman was diagnosed with unresectable BTC with invasion of the right hepatic artery by lymph node metastasis and liver metastases. The patient received GC combination therapy. After 6 cycles of chemotherapy, the patient achieved a partial response. The radiological findings revealed a marked shrinkage in the primary lesion and the disappearance of lymph node and liver metastases. Therefore, the patient underwent conversion surgery, including biliary tract resection and regional lymph node dissection. For postoperative follow-up, the patient was monitored without receiving adjuvant chemotherapy. The patient had not exhibited recurrence during the 12-month follow-up period. We report the case of a patient with unresectable BTC who underwent conversion surgery with a partial response to GC combination therapy.

An International Retrospective Observational Study of Liver Functional Deterioration after Repeat Liver Resection for Patients with Hepatocellular Carcinoma.

Whether albumin and bilirubin levels, platelet counts, ALBI, and ALPlat scores could be useful for the assessment of permanent liver functional deterioration after repeat liver resection was examined, and the deterioration after laparoscopic procedure was evaluated. For 657 patients with liver resection of segment or less in whom results of plasma albumin and bilirubin levels and platelet counts before and 3 months after surgery could be retrieved, liver functional indicators were compared before and after surgery. There were 268 patients who underwent open repeat after previous open liver resection, and 224 patients who underwent laparoscopic repeat after laparoscopic liver resection. The background factors, liver functional indicators before and after surgery and their changes were compared between both groups. Plasma levels of albumin (p = 0.006) and total bilirubin (p = 0.01) were decreased, and ALBI score (p = 0.001) indicated worse liver function after surgery. Laparoscopic group had poorer preoperative performance status and liver function. Changes of liver functional values before and after surgery and overall survivals were similar between laparoscopic and open groups. Plasma levels of albumin and bilirubin and ALBI score could be the indicators for permanent liver functional deterioration after liver resection. Laparoscopic group with poorer conditions showed the similar deterioration of liver function and overall survivals to open group.

Strategy of Pancreatectomies for Pancreatic Ductal Adenocarcinoma in Patients with a History of Gastrectomy.

Recently, the incidence of pancreatectomy for patients with a history of upper abdominal surgery has been increasing. The clinical courses of 307 patients who underwent the pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) were retrospectively reviewed to clarify the impact of a history of gastrectomy in patients undergoing a pancreatectomy for PDAC. Among 307 patients, 28 (9.1%) had a history of gastrectomy, while 279 did not. We compared the difference in clinical course and prognostic outcomes between the groups. In patients with a history of gastrectomy, the 5-year survival rate was 17.6%, which was relatively poorer than that of patients without it (33.4%, P = 0.1329). A multivariate analysis of factors associated with the overall survival rate identified the low preoperative body mass index [BMI < 20.3 kg/m2, hazard ratio (HR) 1.646, P = 0.0190] and adjuvant chemotherapy (not-completed, HR 1.652, P = 0.0170) as independent prognostic factors. In patients with a history of gastrectomy, there were significantly more patients with poor prognostic factors, including a low preoperative BMI (P = 0.0009) and low completion rate of adjuvant chemotherapy (P = 0.0294) as compared with those without a history of gastrectomy. A low preoperative BMI significantly reduced the completion rate of adjuvant chemotherapy (P = 0.0186), which may lead to poor prognostic outcomes. In conclusion, perioperative nutritional management is important to reduce postoperative BMI loss and obtain a better prognosis after a pancreatectomy for PDAC in patients with a history of gastrectomy.

Optimal Region of Lymph Node Dissection in Distal Pancreatectomy for Left-Sided Pancreatic Cancer Based on Tumor Location.

BACKGROUND: The optimal lymph node (LN) dissection for left-sided pancreatic cancer based on tumor location has remained unknown. In particular, the efficacy of LN dissection around the common hepatic artery and the celiac axis for distal tumors has not been established. This study was designed to elucidate the frequency and prognostic impact of LN metastasis, focusing on tumor location. METHODS: Data from 110 patients with invasive pancreatic cancer who underwent distal pancreatectomy between 2007 and 2020 were collected. We used a quantitative value-the distance between the left side of the portal vein and the right side of tumor (DPT)-to define the tumor location. LN stations were divided into two groups: peripancreatic lymph nodes (PLN) and non-PLN. We then analyzed the frequency of LN metastasis based on the tumor location and prognostic factors. RESULTS: Non-PLN metastasis was observed in 7.3% of patients. Non-PLN metastasis was found only in patients with a DPT < 20 mm. Patients with non-PLN metastasis exhibited a significantly worse prognosis than those with only-PLN metastasis (median survival time: 20.3 vs. 42.5 months, p = 0.048). Multivariate analysis for survival indicated that tumor size > 4 cm (hazard ratio [HR]: 2.23, p = 0.012) and metastasis in the non-PLN region (HR: 3.02, p = 0.015), and inability to undergo adjuvant chemotherapy (HR: 2.81, p = 0.0018) were also associated with poor prognosis. CONCLUSIONS: Dissection of the non-PLN region can be avoided in selected patients with DPT ≥ 20 mm.

Colloid carcinoma derived from intraductal papillary mucinous neoplasm of the pancreatic head with calcification: A case report and literature review.

BACKGROUND: Colloid carcinoma derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreatic head with prominent calcification is exceedingly rare. Only a few studies about this entity have been reported in the literature. Therefore, its biological behavior, appropriate treatment modalities, and overall patient prognosis remain largely unclear. In this report, we present a case of a resected colloid carcinoma derived from IPMN with prominent calcification. In addition, we review the relevant literature and discuss the clinical management of colloid carcinoma derived from IPMN with prominent calcification, including the histopathological features. CASE PRESENTATION: A 75-year-old man presented with a pancreatic tumor measuring 58 mm on the head of the pancreas that was incidentally detected by abdominal ultrasonography. Abdominal computed tomography and endosonography revealed a multilobular cystic lesion with a 17 mm mural nodule in the pancreatic head. Furthermore, prominent calcification was observed on part of the cyst wall. Magnetic resonance cholangiopancreatography showed a multilobular cyst in the branch duct lacking communication between the cystic lesion and the main pancreatic duct. Thus, the lesion was diagnosed as intraductal papillary mucinous carcinoma (IPMC) with a preoperative classification of T1N0M0 stage IA according to the 8th Union for International Cancer Control (UICC) guidelines, and the patient underwent conventional pancreatoduodenectomy. The resected specimen was microscopically found to contain colloid carcinoma, probably derived from IPMN. In addition, marked calcification was confirmed in the partition wall of the cystic mass. The postoperative course was uneventful, and no evidence of recurrence or metastasis was observed after 10 months of follow-up. CONCLUSIONS: We consider that colloid carcinoma derived from IPMN should be differentially diagnosed as a pancreatic multilobular cystic lesion with prominent calcification that shows no sign of systemic chronic pancreatitis.

Multicenter Propensity Score-Based Study of Laparoscopic Repeat Liver Resection for Hepatocellular Carcinoma: A Subgroup Analysis of Cases with Tumors Far from Major Vessels.

Less morbidity is considered among the advantages of laparoscopic liver resection (LLR) for HCC patients. However, our previous international, multi-institutional, propensity score-based study of emerging laparoscopic repeat liver resection (LRLR) failed to prove this advantage. We hypothesize that these results may be since the study included complex LRLR cases performed during the procedure's developing stage. To examine it, subgroup analysis based on propensity score were performed, defining the proximity of the tumors to major vessels as the indicator of complex cases. Among 1582 LRLR cases from 42 international high-volume liver surgery centers, 620 cases without the proximity to major vessels (more than 1 cm far from both first-second branches of Glissonian pedicles and major hepatic veins) were selected for this subgroup analysis. A propensity score matching (PSM) analysis was performed based on their patient characteristics, preoperative liver function, tumor characteristics and surgical procedures. One hundred and fifteen of each patient groups of LRLR and open repeat liver resection (ORLR) were earned, and the outcomes were compared. Backgrounds were well-balanced between LRLR and ORLR groups after matching. With comparable operation time and long-term outcome, less blood loss (283.3±823.0 vs. 603.5±664.9 mL, p = 0.001) and less morbidity (8.7 vs. 18.3 %, p = 0.034) were shown in LRLR group than ORLR. Even in its worldwide developing stage, LRLR for HCC patients could be beneficial in blood loss and morbidity for the patients with less complexity in surgery.

Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells.

BACKGROUND: RRM1 is functionally associated with DNA replication and DNA damage repair. However, the biological activity of RRM1 in pancreatic cancer remains undetermined. METHODS: To determine relationships between RRM1 expression and the prognosis of pancreatic cancer, and to explore RRM1 function in cancer biology, we investigated RRM1 expression levels in 121 pancreatic cancer patients by immunohistochemical staining and performed in vitro experiments to analyze the functional consequences of RRM1 expression. RESULTS: Patients with high RRM1 expression had significantly poorer clinical outcomes (overall survival; p = 0.006, disease-free survival; p = 0.0491). In particular, high RRM1 expression was also associated with poorer overall survival on adjuvant chemotherapy (p = 0.008). We found that RRM1 expression was increased 24 hours after exposure to gemcitabine and could be suppressed by histone acetyltransferase inhibition. RRM1 activation in response to gemcitabine exposure was induced mainly in the cytoplasm and cytoplasmic RRM1 activation was related to cancer cell viability. In contrast, cancer cells lacking cytoplasmic RRM1 activation were confirmed to show severe DNA damage. RRM1 inhibition with specific siRNA or hydroxyurea enhanced the cytotoxic effects of gemcitabine for pancreatic cancer cells. CONCLUSIONS: Cytoplasmic RRM1 activation is involved in biological processes related to drug resistance in response to gemcitabine exposure and could be a potential target for pancreatic cancer treatment.

C646 inhibits G2/M cell cycle-related proteins and potentiates anti-tumor effects in pancreatic cancer.

The activity of histone acetyltransferases (HATs) plays a central role in an epigenetic modification in cooperation with HDACs (histone deacetyl transferases). It is likely that malfunction of this enzymatic machinery controlling epigenetic modification is relevant to carcinogenesis and tumor progression. However, in pancreatic cancer, the clinical relevance of HAT activity and histone acetylation has remained unclear. We identified that H3 acetylation was expressed in all pancreatic cancer patients, indicating that H3 acetylation may be essential in pancreatic cancer cells. We also found that the HAT inhibitor C646 augmented anti-tumor effects in vitro by inhibiting cell proliferation and cell cycle progression concomitantly with suppression of acetylated H3K9 and H3K27 expression. C646 or p300 and CBP (CREB-binding protein)-specific siRNA treatment inhibited the transcription of the G2/M cell cycle regulatory proteins cyclin B1 and CDK1 (cyclin-dependent kinase 1). C646 treatment also inhibited tumor growth in vivo in a xenograft mouse model. C646 could be an effective therapeutic agent for pancreatic cancer. The epigenetic status of pancreatic cancers based on their level of histone H3 acetylation may influence patient survival. Epigenetic stratification according to H3K27 acetylation could be useful for predicting disease prognosis as well as the therapeutic efficacy of C646 in pancreatic cancer.

The interplay of KRAS mutational status with tumor laterality in non-metastatic colorectal cancer: An international, multi-institutional study in patients with known KRAS, BRAF, and MSI status.

BACKGROUND: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. METHODS: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary centers in Europe and Japan. The prognostic relevance of KRAS status in patients with right-sided (RS), left-sided (LS), and rectal cancers was assessed. RESULTS: Of the 1093 eligible patients, 378 had right-sided tumors and 715 had left-sided tumors. Among patients with RS tumors, the 5-year overall (OS) and recurrence-free survival (RFS) for patients with KRASmut versus wild-type tumors was not shown to differ significantly (82.2% vs. 83.2% and 72.1% vs. 76.7%, respectively, all p > .05). Among those with LS tumors, KRAS mutation was associated with shorter 5-year OS and RFS on both the univariable (OS: 79.4% vs. 86.1%, p = .004; RFS: 68.8% vs. 77.3%, p = .005) and multivariable analysis (OS: HR: 1.52, p = .019; RFS: HR: 1.32, p = .05). CONCLUSIONS: KRAS mutation status was independently prognostic among patients with LS tumors, but this association failed to reach statistical significance in RS and rectal tumors. These findings confirm reports in metastatic CRC and underline the possible biologic importance of tumor location.

Downregulated Pancreatic Beta Cell Genes Indicate Poor Prognosis in Patients With Pancreatic Neuroendocrine Neoplasms.

OBJECTIVE: To predict metachronous liver metastasis after pancreatectomy for pancreatic neuroendocrine neoplasms (Pan-NENs). SUMMARY OF BACKGROUND DATA: Liver metastasis determines the prognosis of patients with Pan-NENs, but no index exists in the WHO 2017 classification for this prediction. METHODS: Between April 2014 and March 2018, resected primary tumors from 20 patients with or without simultaneous liver metastasis were examined using genome-wide gene expression analysis. For validation analysis, resected primary tumors from 62 patients without simultaneous liver metastasis were examined for PAX6 expression. RESULTS: Gene expression profiling revealed pancreatic beta cell genes (NES, -2.0; P < 0.001) as the most downregulated set in patients with simultaneous liver metastasis. In the test study, PAX6 was the most valuable index for liver metastasis (log FC, -3.683; P = 0.0096). Multivariate analysis identified PAX6 expression (hazard ratio, 0.2; P = 0.03) as an independent risk factor for metachronous liver metastasis-free survival (mLM-FS). The 5-year mLM-FS of patients with high versus low PAX6 expression was significantly better (95% vs 66%, respectively; P < 0.0001). The 5-year overall survival rate of was also better than in those with high versus low PAX6 expression (100% vs 87%, respectively). Patients with low PAX 6 expression were significantly younger and leaner, had a higher Ki-67 index (P = 0.01, 0.007, 0.008, respectively), and showed a higher mitotic rate than patients with high PAX6 expression. CONCLUSIONS: Downregulated pancreatic beta cell genes involving PAX6 in primary tumors may predict mLM and poor overall survival after primary tumor resection in Pan-NEN patients.

Loss of ARID1A induces a stemness gene ALDH1A1 expression with histone acetylation in the malignant subtype of cholangiocarcinoma.

Genomic analyses have recently discovered the malignant subtype of human intrahepatic cholangiocarcinoma (ICC) characterized by frequent mutations of chromatin remodeling gene ARID1A; however, the biological and molecular functions still remain obscure. We here examined the clinical and biological significances of ARID1A deficiency in human ICC. Immunohistochemical analysis demonstrated that the loss of ARID1A was an independent prognostic factor for overall survival of ICC patients (P = 0.023). We established ARID1A-knockout (KO) cells by using the CRISPR/Cas9 system from two human cholangiocarcinoma cell lines. ARID1A-KO cells exhibited significantly enhanced migration, invasion, and sphere formation activity. Microarray analysis revealed that ALDH1A1, a stemness gene, was the most significantly elevated genes in ARID1A-KO cells. In addition, ALDH enzymatic activity as a hallmark of cancer stem cells was markedly high in the KO cells. ARID1A and histone deacetylase 1 were directly recruited to the ALDH1A1 promoter region in cholangiocarcinoma cells with undetectable ALDH1A1 expression by chromatin immunoprecipitation assay. The histone H3K27 acetylation level at the ALDH1A1 promoter region was increased in cells when ARID1A was disrupted (P < 0.01). Clinically, inverse correlation between ARID1A and ALDH1A1 expression was also identified in primary ICC (P = 0.018), and ARID1A-negative and ALDH1A1-positve ICCs showed worse prognosis than only ARID1A-negative cases (P = 0.002). In conclusion, ARID1A may function as a tumor suppressor in ICC through transcriptional downregulation of ALDH1A1 expression with decreasing histone H3K27 acetylation. Our studies provide the basis for the development of new epigenetic approaches to ARID1A-negative ICC. Immunohistochemical loss of ARID1A is an independent prognostic factor in intrahepatic cholangiocarcinoma patients. ARID1A recruits HDAC1 to the promoter region of ALDH1A1, a stemness gene, and epigenetically suppresses ALDH1A1 expression with decreasing histone H3K27 acetylation in cholangiocarcinoma cells.

Combination of weekly streptozocin and oral S-1 treatment for patients of unresectable or metastatic pancreatic neuroendocrine neoplasms.

BACKGROUND: Streptozocin (STZ) administration with or without other cytotoxic drugs remains a crucial chemotherapy for patients with advanced pancreatic neuroendocrine neoplasms (Pan-NENs). However, the therapeutic effects of combination treatment with weekly STZ and oral S-1 therapy (STS1) remain unknown. Therefore, the aim of this study was to evaluate the safety and clinical feasibility of STS1. METHODS: Twenty of 243 Pan-NEN patients were included in this retrospective study, all of whom had received STS1 for unresectable or distant metastatic diseases from November 2015 to January 2019. The maximum tumor shrinkage rate, time course of the tumor shrinkage rate, prognosis (progression-free survival and overall survival), and adverse events were evaluated. RESULTS: The median age of the patients was 61.5 years and the median tumor size was 35 mm. The number of NET-G1, NET-G2, NET-G3, and NEC-G3 patients was 3, 13, 3, and 1, respectively. The median Ki-67 index and mitoses were 10.2% and 2/10 high-power fields, respectively. The overall objective response rate and disease control rate were 30% and 90%, respectively. The median maximum tumor reduction rate was 19%. The Ki-67 index and tumor size did not influence the tumor shrinkage rate. Progression-free survival after STS1 treatment was 19 months with no significant difference between NET-G1/G2 and NET-G3/NEC-G3 patients (p = 0.4). There was one case each of grade 3/4 toxicity, including general fatigue, hyperglycemia, and renal dysfunction. No serious myelosuppressive events are manifested. CONCLUSIONS: STS1 treatment is an effective and safe therapeutic option for patients with advanced Pan-NEN.

Reticular pattern around superior mesenteric artery in computed tomography imaging predicting poor prognosis of pancreatic head cancer.

BACKGROUND: Some patients with pancreatic ductal adenocarcinoma (PDAC) demonstrate a reticular pattern around the superior mesenteric artery (SMA) in computed tomography scans. This study aimed to clarify the clinical significance of the reticular pattern in pancreatic head cancer. METHODS: A total of 91 patients with pancreatic head cancer, who underwent upfront pancreaticoduodenectomy between 2004 and 2017, were included. Patients without reticular pattern (Non-group, n = 39); with reticular pattern around SMA (Ret-group, n = 39); and with soft tissue contact (Soft-group, n = 13) were compared. RESULTS: Median overall survival (OS) of patients in the Ret-group was significantly worse than that in the Non-group (21.3 vs. 57.0 months; P < 0.001) and equivalent to that in the Soft-group. In the multivariate analysis, reticular pattern and high CA19-9 levels were identified as independent predictors of OS. Microscopically, only fibrotic thickenings were identified corresponding to the reticular pattern areas, and no difference in the frequency of early local recurrence was noted between the Non and Ret-groups. Lymphovascular invasion was significantly different between the two groups; furthermore, early distant recurrence was more frequent in the Ret-group. CONCLUSIONS: The reticular pattern around SMA is an important prognostic factor related to frequent distant recurrence in patients with pancreatic cancer.