Liquid biopsy of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy: Comparison with liquid biopsy of plasma in pancreatic cancer.

OBJECTIVES: Pancreatic cancer (PC) has a poor prognosis and limited treatment options. Liquid biopsy, which analyzes circulating tumor DNA (ctDNA) in blood, holds promise for precision medicine; however, low ctDNA detection rates pose challenges. This study aimed to investigate the utility of wash samples obtained via endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a liquid biopsy for PC. METHODS: A total of 166 samples (42 formalin-fixed paraffin-embedded [FFPE] tissues, 80 wash samples, and 44 plasma samples) were collected from 48 patients with PC for genomic analysis. DNA was extracted and quantified, and 60 significantly mutated genes were sequenced. The genomic profiles of FFPE tissues, wash samples, and plasma samples were compared. Finally, the ability to detect druggable mutations in 80 wash samples and 44 plasma samples was investigated. RESULTS: The amount of DNA was significantly lower in plasma samples than in wash samples. Genomic analysis revealed a higher detection rate of oncogenic mutations in FFPE tissues (98%) and wash samples (96%) than in plasma samples (18%) and a comparable detection rate in FFPE tissues and wash samples. Tumor-derived oncogenic mutations were detected more frequently in wash samples than in plasma samples. Furthermore, the oncogenic mutations detection rate remained high in wash samples at all PC stages but low in plasma samples even at advanced PC stages. Using wash samples was more sensitive than plasma samples for identifying oncogenic and druggable mutations. CONCLUSIONS: The wash sample obtained via EUS-FNB is an ideal specimen for use as a liquid biopsy for PC.

Development of a molecular barcode detection system for pancreaticobiliary malignancies and comparison with next-generation sequencing.

BACKGROUND: Obtaining sufficient tumor tissue for genomic profiling is challenging in pancreaticobiliary cancer (PBCA). We determined the utility of molecular barcoding (MB) of liquid biopsies (bile, duodenal fluid, and plasma) for highly sensitive genomic diagnosis and detection of druggable mutations for PBCA. METHODS: Two in-house panels of 60 genes (non-MB panel) and 21 genes using MB (MB panel) were used for the genomic analysis of 112 DNA samples from 20 PBCA patients. We measured the yield of DNA and compared the genomic profiles of liquid samples obtained using the non-MB panel and the MB panel. The utility of the panels in detecting druggable mutations was investigated. RESULTS: A significantly greater amount of DNA was obtained from bile supernatants and precipitates compared to tumor samples (P < 0.001 and P = 0.001, respectively). The number of mutations per patient was significantly higher using the MB panel than using the non-MB panel (2.8 vs. 1.3, P = 0.002). Tumor-derived mutations were detected more frequently using the MB panel than the non-MB panel (P = 0.023). Five drug-matched mutations were detected in liquid samples. CONCLUSIONS: Liquid biopsy with MB may have utility in providing genomic information for the prognosis of patients with PBCA.

Comparison of genomic profiling of circulating tumor DNA in pancreaticobiliary malignancies in plasma and bile.

BACKGROUND: Obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling has limitations. Liquid biopsies using plasma do not provide sufficient sensitivity. Thus, this study aimed to determine the effectiveness of liquid biopsy between bile and plasma for identifying oncogenic and drug-matched mutations. METHODS: This study created a panel of 60 significantly mutated genes specific to pancreaticobiliary cancer (PBCA) and used it for genomic analysis of 212 deoxyribonucleic acid (DNA) samples (87 bile supernatant, 87 bile precipitate, and 38 plasma) from 87 patients with PBCA. The quantity of extracted DNA from bile and plasma was compared, as were genomic profiles of 38 pairs of bile and plasma from 38 patients with PBCA. Finally, we investigated 87 bile and 38 plasma for the ability to detect druggable mutations. RESULTS: The amount of DNA was significantly lower in plasma than in bile (p < .001). Oncogenic mutations were identified in 21 of 38 (55%) patients in bile and nine (24%) in plasma samples (p = .005). Bile was significantly more sensitive than plasma in identifying druggable mutations (p = .032). The authors detected 23 drug-matched mutations in combined bile and plasma, including five ERBB2, four ATM, three BRAF, three BRCA2, three NF1, two PIK3CA, one BRCA1, one IDH1, and one PALB2. CONCLUSIONS: Liquid biopsy using bile may be useful in searching for therapeutic agents, and using the obtained genomic information may improve the prognoses of patients with PBCA. PLAIN LANGUAGE SUMMARY: Genomic profiling of formalin-fixed paraffin-embedded tissues may provide actionable targets for molecular and immuno-oncological treatment. However, most pancreaticobiliary malignancies are unresectable and formalin-fixed paraffin-embedded tissues cannot be obtained. Although comprehensive genomic profiling tests using plasma have been used in recent years, the utility of those using bile is not clear. Our study revealed that bile identified more drug-matched mutations than plasma in advanced pancreaticobiliary cancer patients. Bile may help widen the patient population benefiting from targeted drugs.

Genomic profiling amplifies the utility of endoscopic ultrasound-guided fine needle biopsy by identifying clinically applicable druggable mutations in pancreatic cancer.

BACKGROUND: Genomic profiling of tumors is available, but whether the small fragment obtained via endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is sufficient for these examinations is unknown. Here we investigated whether EUS-FNB specimens are suitable for genomic profiling to identify oncogenic and drug-matched mutations. METHODS: We constructed a pancreatobiliary cancer panel for targeted panel sequencing that covered 60 significantly mutated genes and compared the results with those of whole-exome sequencing (WES). In total, 20 and 53 formalin-fixed paraffin-embedded tissues obtained via surgery and EUS-FNB were analyzed, respectively. First, we examined the DNA quality and genomic profiles of 20 paired samples from 20 malignant lesions obtained via surgery and EUS-FNB. We then tested 33 samples obtained via EUS-FNB from 24 malignant and 9 benign lesions for the discrimination of malignancy. Finally, we explored drug-matched mutations from EUS-FNB specimens. RESULTS: Although the DNA quantity obtained via surgery was higher than that obtained via EUS-FNB (P = 0.017), the DNA quality and mean depth were equivalent (P = 0.441 and P = 0.251). Panel sequencing of EUS-FNB specimens identified more oncogenic mutations than WES (90 % vs. 50 %). Furthermore, the number of oncogenic mutations did not differ between EUS-FNB and surgically resected specimens. Genomic profiling of EUS-FNB specimens enabled the discrimination of malignancy with 98 % accuracy. Of 44 malignant lesions, drug-matched alterations were identified in 14 % (6/44) of malignant lesions. CONCLUSION: EUS-FNB specimens can be widely utilized for diagnostic purposes, discrimination of malignancy, and detection of drug-matched mutations for the treatment of pancreatic cancer.

Detection of actionable mutations in cytological specimens obtained by endoscopic ultrasound-guided fine needle aspiration with rapid onsite evaluation in pancreatic cancer.

BACKGROUND: It is not clear whether archived cytological specimens (ACSs) obtained with endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with rapid onsite evaluation (ROSE) can be used for genomic profiling of tumors. We used ACSs to perform genomic analysis of specimens to identify oncogenic and druggable mutations. METHODS: A panel of 60 significantly mutated genes specific to pancreatobiliary cancer was created and used for genomic analysis of 113 specimens of 44 formalin-fixed paraffin-embedded (FFPE) tissues and 69 ACSs obtained by EUS-FNA with ROSE were included. The quantity and quality of DNA extracted from FFPE tissues and ACSs were compared. We also compared DNA from spray and touch ACSs. Next, genomic profiles were compared. We also evaluated detection of target gene mutations in each specimen. RESULTS: The amount of DNA in FFPE tissues was greater than in ACSs (P = 0.014), but the quality of DNA was comparable (P = 0.378). There was no quantitative or qualitative difference between spray and touch ACSs (P = 0.154 and P = 0.734, respectively). Oncogenic mutations were shared at 82 % in FFPE tissues and ACSs and 82 % in spray and touch ACSs. The sensitivity of genomic analysis in ACSs was 97 % (67 of 69), which was comparable to that of cytology (62 of 69, 90 %; P = 0.165), and was significantly higher than that of histology (32/44, 73 %; P < 0.001). Drug-matched mutations were identified in five of the 44 lesions (11 %). CONCLUSION: Genomic analysis of ACSs is useful in the prognosis of pancreatic cancer because detection of driver mutations is similar to detection in FFPE tissues.

Detection of actionable mutations in archived cytological bile specimens.

BACKGROUND/PURPOSE: There are limitations in obtaining sufficient pancreaticobiliary tumor tissue for genomic profiling of tumors. Herein, we investigated whether archived cytological specimen (ACS) is suitable for genomic profiling to identify oncogenic and drug-matched mutations. METHODS: We constructed a pancreaticobiliary cancer panel for targeted sequencing covering 60 significantly mutated genes (280 220 bp). Eighty DNA samples (19 formalin-fixed paraffin-embedded [FFPE] tissues and 61 ACS) from 44 patients with pancreaticobiliary disease were analyzed. We compared genomic profiles of 19 FFPE and 29 ACS from 19 patients with malignancies (Validation Cohort). We tested 32 ACS from 25 patients (15 malignant and 10 benign) for the ability to discriminate between malignant and benign disorders (Testing Cohort). We explored whether actionable and drug-matched mutations (Validation and Testing Cohorts) could be identified from ACS. RESULTS: Oncogenic mutations observed in ACS were identical to those identified in FFPE specimens (76% consistency). Genomic profiling using only ACS discriminated between malignant and benign disorders with 93% accuracy, 91% sensitivity, and 100% specificity. Actionable and drug-matched mutations were identified in 74% and 32% of ACS, respectively, and in 79% and 21% in FFPE samples, respectively. CONCLUSION: Archived cytological specimen may be used to discriminate malignancy and to detect drug-matched mutations in patients with advanced pancreaticobiliary cancer.

Cytoglobin-expressing cells in the splenic cords contribute to splenic fibrosis in cirrhotic patients.

BACKGROUND AND AIM: Among several noninvasive evaluation methods of portal hypertension (PH), the measurement of spleen stiffness is a reliable method for predicting esophageal variceal bleeding; however, the underlying mechanisms for increased stiffness remain unclear. We attempted to elucidate the pathological changes to the spleen and the underlying mechanisms in patients with PH. METHODS: Histological examination was performed using splenic tissues from 42 patients with PH who underwent laparoscopic splenectomy, and the results were compared with those from patients without PH. RESULTS: In addition to splenic sinus congestion, diffuse fibrosis was detected in the splenic cords in the red pulp of patients with PH. The degree of the fibrosis was well correlated with severity in thrombocytopenia and splenomegaly. Cells expressing α-smooth muscle actin dramatically increased in the splenic cord. Cytoglobin (Cygb) expression was detected in human splenic cords as reported in animal reticular cells, and fluorescent double immunostaining revealed that these cells expressed α-smooth muscle actin in patients with PH, suggesting transformation of Cygb-expressing cells to myofibroblastic cells. Expression levels of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 2, nitrotyrosine, and transforming growth factor-ß were markedly upregulated in the red pulp of patients with PH, implying a significant role of oxidative stress in the mechanism for splenic fibrosis. CONCLUSION: Splenic fibrosis progresses along with advancement of PH. Cygb-expressing cells in the splenic cord possibly participate in this process through mechanisms including oxidative stress.

A case with hepatic portal vein gas who required delayed elective surgery.

INTRODUCTION: Hepatic portal venous gas (HPVG) is believed to be an indication for emergent surgery because it is associated with high mortality rate. However, the recent increase in the use of modern abdominal computed tomography (CT) has resulted in the detection of HPVG in more benign conditions. Therefore, the decision-making process whether we chose emergent surgery or conservative treatment without surgery is important for the patients with HPVG. CASE PRESENTATION: An 84-year-old male was referred to our hospital due to the sudden onset of abdominal pain and massive hepatic portal vein gas on emergent CT. The Acute Physiology and Chronic Health Evaluation (APACHE) II Score was calculated as 17; slightly elevated comparing with the other cases who were successfully treated without surgery. Although the PHVG was remained at follow up CT on the next day after the onset, the symptoms were improved. We selected conservative treatment without emergent surgery and he discharged on 9th day after the onset. However, he was suffered from right lower abdominal pain and vomiting and admitted our hospital on 23th day. He developed ischemic intestinal stenosis and underwent a surgery of partial resection of ileum. CONCLUSIONS: The clinical finding of this case showing subtle differences from cases who were successfully treated without surgery. We hope this report will help physician's decision-making process for HPVG.

Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). METHODS: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis. The LHL15 index (uptake ratio of the liver to that of the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium-labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 × [1 - (resected liver weight - tumor volume)/whole liver volume without tumor]. RESULTS: A total of 163 patients were classified as having no PHLF, whereas 17, 37, and 1 patient had PHLF grade A, B, and C, respectively. There were significant differences in indocyanine green R15, serum albumin, prothrombin time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a cut-off value of 0.755. CONCLUSIONS: Remnant LHL15 was an independent risk factor for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should be carefully monitored for PHLF.

ICG Clearance Test and 99mTc-GSA SPECT/CT Fusion Images.

Preoperative estimation of future remnant liver function is critical for major hepatic surgery to avoid postoperative morbidity and mortality. Among several liver function tests, the indocyanine green (ICG) clearance test is still the most popular dynamic method. The usefulness of ICG clearance test parameters, such as ICGR15, KICG, or PDRICG, has been reported by many investigators. The transcutaneous non-invasive pulse dye densitometry system has made the ICG clearance test more convenient and attractive, even in Western countries. The concept of future remnant KICG (rem KICG), which combines the functional aspect and the volumetric factor of the future remnant liver, seems ideal for determining the maximum extent of major hepatic resection that will not cause postoperative liver failure. For damaged livers with functional heterogeneity among the hepatic segments, fusion images combining technetium-99m-diethylenetriaminepentaacetic acid-galactosyl human serum albumin single photon emission computed tomography (99mTc-GSA SPECT) and X-ray CT are helpful to precisely estimate the functional reserve of the future remnant liver. Another technique for image-based liver function estimation, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid(Gd-EOB)-enhanced magnetic resonance imaging, may be an ideal candidate for the preoperative determination of future remnant liver function. Using these methods effectively, morbidity and mortality after major hepatic resection could be reduced.

Bronchobiliary fistula caused after hepatectomy for hepatocellular carcinoma: a case report.

BACKGROUND: A bronchobiliary fistula, an intercommunication between the biliary tract and bronchial trees, is an extremely rare complication after hepatectomy. CASE PRESENTATION: A 70-year-old male underwent partial resection of the liver for recurrent hepatocellular carcinoma under a thoracoabdominal approach. The immediate postoperative clinical course was uneventful, but the patient was febrile and laboratory examinations revealed leukocytosis on the 15th postoperative day. An intraabdominal abscess was suspected based on the computed tomography findings, and percutaneous drainage was performed. Bile was drained, and fluoroscopy using a contrast medium from the drainage tube revealed a communication between the cavity and the common hepatic duct. Two weeks after drainage, bilioptysis was seen. Fistulography demonstrated the presence of the bronchus in the right lower lobe of the lung via the subphrenic space. Therefore, the patient was diagnosed to have a bronchobiliary fistula. Fistulography revealed closure of the communication with the bronchus about a month after drainage. However, the bile leakage and bilioptysis did not stop even after endoscopic nasogastric biliary drainage, and ethanol injection therapy were performed. Eventually, residual right bisectionectomy without resection of the fistulous tract and involved lung was performed to remedy the intractable bile leakage. The clinical course after the reoperation was good without bile leakage, bilioptysis, or pulmonary disorders, and the patient was discharged 40 days after reoperation. CONCLUSIONS: We experienced a rare case of bronchobiliary fistula that occurred after hepatectomy for hepatocellular carcinoma. Careful attention should be paid to prevent bile leakage during hepatectomy, since bile leakage has the potential to cause a bronchobiliary fistula.

Successful laparoscopic extirpation of peritoneal dissemination after hepatectomy for ruptured hepatocellular carcinoma.

Clinically, peritoneal dissemination of hepatocellular carcinoma (HCC) rarely occurs. We herein report a case that had a good outcome following laparoscopic extirpation of peritoneal dissemination after hepatectomy for ruptured HCC. A 66-year-old man underwent central bisectionectomy 12 days after emergency transcatheter arterial embolization for a ruptured HCC. Thereafter, pulmonary resection was performed twice for lung metastasis. About 8 months after the second pulmonary resection, a mass lesion was detected at the left subphrenic space on CT and (18) F-fluorodeoxyglucose PET scans. We made a diagnosis of peritoneal dissemination of HCC, and laparoscopic extirpation was performed. The patient is now doing well without any signs of recurrence 2 years after the last operation. Laparoscopic surgical resection for peritoneal dissemination that develops after hepatectomy for HCC may have a beneficial effect as a less-invasive approach and may improve the prognosis in select patients.

Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

BACKGROUND & AIMS: Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. METHODS: C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. RESULTS: TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of ß-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. CONCLUSIONS: The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy.

Development of hepatocellular carcinoma in cardiac congestive liver fibrosis: report of a case.

We report an extremely rare case of the development of hepatocellular carcinoma (HCC) in cardiac congestive liver fibrosis. A 62-year-old female presented to our hospital with a complaint of right upper quadrant pain. The patient had undergone cardiac surgery for pulmonary valve insufficiency, pulmonary stenosis and atrial septal defect when she was fifteen years of age. During the subsequent 47 years, she had occasionally suffered from various symptoms associated with right-sided heart failure due to pulmonary stenosis. Computed tomography revealed a liver tumor measuring 63 mm in diameter in segment 5 and other liver tumors in segments 5 (18 mm), 8 (17 mm) and 4 (12 mm), which were diagnosed as HCCs. There was no evidence of stenosis in any hepatic veins or inferior vena cava, and no infectious hepatitis or alcoholic liver damage. Anterior sectionectomy and partial resection of segment 4 was performed, and histological examination showed that these tumors were HCC accompanied by congestive liver fibrosis. Nine months later, multiple recurrent HCCs were detected in segment 6, and transcatheter arterial chemoembolization was employed thereafter. The patient died 40 months after surgery due to advanced recurrence.

Anatomic liver resection of right paramedian sector: ventral and dorsal resection.

The purpose of anatomic resection of the liver is to systemically eliminate malignant tumors that spread via the portal vein. Moreover, it results in reducing bleeding and bile leakage from the cut surface of the liver because Glisson's pedicle resection leads to parenchyma transection. Anatomical resection includes hemi-hepatectomy, sectionectomy, and segmentectomy. Recently, it has been noticed that this concept is not always appropriate for the liver resection including the right paramedian sector. It can be divided vertically into the ventral and the dorsal area according to the ramification of the third order of the portal veins. In the present study, we focused on the right paramedian sector and described techniques of surgical procedures of hepatectomy including resection of the ventral or dorsal areas.

Outcomes of hepatic resection for large hepatocellular carcinoma: special reference to postoperative recurrence.

Safety and efficacy of hepatic resection for large hepatocellular carcinomas (HCCs 10 cm or greater in diameter) remain controversial. Surgical results of patients with HCCs 10 cm or greater (n = 24) who underwent hepatic resection over an 11-year period were compared with those of patients with HCCs less than 10 cm (n = 291). There was no significant difference in mortality between the two groups (P > 0.99). Overall 5-year survival rate was 44.6 per cent among patients with HCCs 10 cm or greater and 70.5 per cent among those with HCCs less than 10 cm (P = 0.010); however, there was no significant difference in disease-free survival rate between the two groups (P = 0.16). Incidence of synchronous intra- and extrahepatic recurrence was higher in patients with HCCs 10 cm or greater than in those with HCCs less than 10 cm (P = 0.0012). Macrovascular invasion alone was an independent risk factor for poor prognosis (hazard ratio [HR],: 11.1) and recurrence (HR, 6.02) after hepatic resection for HCCs 10 cm or greater, which was correlated with synchronous intra- and extrahepatic recurrence. Hepatic resection for large HCCs is safe and efficacious. However, incidence of synchronous intra- and extrahepatic recurrence is high, especially in patients with macrovascular invasion.

Granulocyte colony-stimulating factor-producing cholangiocellular carcinoma.

A 61-year-old female was admitted to our hospital with epigastric pain and fever. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the left hepatic lobe and swelling of lymph nodes. (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, the patient was diagnosed with a granulocyte colony-stimulating factor (G-CSF)-producing tumor (G-CSF, 213 pg/mL). We performed left trisegmentectomy of the liver, bile duct resection, and lymph node dissection. Histologically, the tumor was a poorly differentiated adenocarcinoma with some lymph nodes metastasis. Immunohistochemical staining of the tumor cells was positive for G-CSF. Therefore, the tumor was diagnosed as G-CSF-producing cholangiocellular carcinoma. The inflammatory reactions and serum G-CSF level transiently improved immediately after surgery. However, 1 month later, the leukocyte count and serum G-CSF level increased again, and recurrence was observed in the remnant liver. The patient died 3 months after the operation. G-CSF-producing cholangiocellular carcinoma is rare. This tumor progresses rapidly, and surgical treatment for advanced condition should be carefully selected.

Primary adenocarcinoma of the minor duodenal papilla with mass-forming chronic pancreatitis: report of a case.

A 70-year-old male was treated for gastric ulcers. Follow-up upper gastrointestinal endoscopy revealed an irregular, elevated tumor in the second portion of the duodenum. Upon pathological inspection of a biopsy specimen, a diagnosis of adenocarcinoma was made, and the patient was admitted to our hospital. Computed tomography showed an irregular mass in the pancreatic head and dilatation of the main pancreatic duct and bile duct. Pancreatic head carcinoma with infiltration of the duodenum was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. A histopathological examination of the resected specimen showed moderately differentiated adenocarcinoma in the minor duodenal papilla and chronic pancreatitis in the pancreatic head. Therefore, primary adenocarcinoma of the minor duodenal papilla with mass-forming chronic pancreatitis was diagnosed. Currently, the patient is alive without recurrence 17 months after the surgery. Primary adenocarcinoma of the minor duodenal papilla is extremely rare. We herein report this case, and also provide a review of the literature.

Hemodynamic analysis and treatment of an enlarging extrahepatic portal aneurysm: report of a case.

Aneurysms in the portal venous system are relatively rare. We report the case of an extrahepatic portal venous aneurysm, detected incidentally by ultrasonography. The patient, a 75-year-old woman, was initially observed over 18 months, during which time, the aneurysm grew from 36 mm × 32 mm to 51 mm × 37 mm in size, without symptoms. Hemodynamic analysis employing computational flow dynamics technique showed obvious turbulence in the aneurysm, and the wall shear stress (WSS) against that part of the aneurysmal wall was greater than in other sites. To prevent complications such as spontaneous rupture and portal vein thrombosis, the aneurysm was resected, with reconstruction of the portal trunk. While careful follow-up is sufficient for most portal venous aneurysms, its enlargement could indicate possible spontaneous rupture. The increased WSS against part of the aneurysmal wall most likely accounts for the aneurysm enlargement in this case.

Granulocyte-colony stimulating factor-producing gallbladder carcinoma.

Abstract A 78-year-old man was admitted to our hospital with right upper abdominal pain and fever. His general condition was poor. The laboratory data showed severe inflammatory reactions. Computed tomography revealed an irregular tumor in the gallbladder. (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) showed high uptake by the tumor, with diffuse uptake in the spine. Based on the elevated leukocyte count and FDG-PET findings, a granulocyte-colony stimulating factor (G-CSF)-producing tumor was diagnosed (G-CSF 120 pg/mL). We performed cholecystectomy with central bisegmentectomy of the liver, lymph node dissection and right hemicolectomy. Histologically, the tumor was an adenosquamous cell carcinoma of the gallbladder. Immunohistochemical staining of the tumor cells was positive for G-CSF. Postoperatively, the general condition of the patient was improved. The fever subsided, the leukocyte count and serum G-CSF level normalized, and FDG-PET showed no uptake in the spine postoperatively. The patient showed no signs of recurrence at 27 months after undergoing surgery. FDG-PET is a useful method for diagnosing G-CSF-producing gallbladder carcinoma. Aggressive curative resection for G-CSF-producing gallbladder carcinoma may improve patients' general condition and prognosis.