Preoperatively diagnosed intraductal oncocytic papillary neoplasm of the pancreas with prominent invasion: a case report.

Previously considered as one of the less-invasive subtypes of intraductal papillary mucinous neoplasm, intraductal oncocytic papillary neoplasm (IOPN) has recently been acknowledged as a new entity of pancreatic tumor. We herein present a case of preoperatively diagnosable IOPN invasion in the stomach and colon. A 78-year-old woman was referred to our hospital for evaluation of anorexia and gastroesophageal reflux. Upper gastrointestinal endoscopy revealed a gastric subepithelial lesion with ulcerated mucosa that required hemostasis. Computed tomography revealed a 96-mm-diameter solid tumor with a well-defined border and centrally positioned necrotic area, extending from the stomach to the transverse colon and pancreatic tail. Because it was suspected to be a pancreatic solid tumor with direct stomach invasion, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) was performed, which led to a preoperative diagnosis of IOPN. Moreover, laparoscopic pancreatosplenectomy, proximal gastrectomy, and transverse colectomy were performed. Analysis of the surgical specimen revealed that the tumor was IOPN and had invaded the stomach and transverse colon. Lymph node metastasis was also confirmed. These findings indicate that IOPN can manifest as an invasive tumor, and EUS-FNB may be equally helpful for assessing the invaded area of a cystic lesion as it is for a solid lesion.

High predictive ability of apparent diffusion coefficient value for wall-invasion pattern of advanced gallbladder carcinoma.

PURPOSE: The wall-invasion pattern classification of advanced gallbladder carcinoma (GBC) has been reported. However, its association with clinical findings remains unclear. We aimed to clarify relationships between clinicopathological characteristics, prognosis, and apparent diffusion coefficient (ADC) values of advanced GBC based on the wall-invasion pattern. METHODS: We reviewed the data of 37 patients who had undergone advanced GBC cholecystectomy at our institution between 2009 and 2021. Clinicopathological findings, prognosis, and ADC values were retrospectively analyzed. RESULTS: Based on the wall-invasion pattern, patients were classified into infiltrative growth (IG) type (n = 22) and destructive growth (DG) type (n = 15). In the DG-type, the incidence of venous invasion (P = 0.027), neural invasion (P = 0.008), and lymph node metastasis (P = 0.047) was significantly higher than in the IG-type, and recurrent-free survival (RFS) was significantly shorter (P = 0.015); the median RFS was 11.4 months (95% confidence interval, 6.3-16.5 months) in the DG-type and not reached in the IG-type. The ADC value in the DG-type was significantly lower than in the IG-type (median, 1.19 × 10-3 mm2/s vs. 1.86 × 10-3 mm2/s, P < 0.001). The area under the receiver operating characteristic curve for the ADC values to differentiate wall-invasion patterns was 0.95 (95% confidence interval, 0.87-1.00). The optimal cutoff ADC value was 1.45 × 10-3 mm2/s (sensitivity, 92.9%; specificity, 90.9%). CONCLUSIONS: The wall-invasion pattern of advanced GBC is associated with its aggressiveness and prognosis, and can be predicted by ADC values with high accuracy.

Standardized Methods Using EUS-guided Fine-needle Biopsy and a Minimal Medium Creates Three Pancreatic Cancer Organoids.

BACKGROUND/AIM: Recently, endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been conducted for diagnosing pancreatic ductal adenocarcinoma (PDAC), after which obtained samples were used in organoid cultures. However, no standardized method for PDAC organoid cultures exists. Therefore, to standardize or simplify sample collection and culture methods for PDAC organoids, we performed a floating culture using non-minced specimens obtained by EUS-FNB in a minimal medium, lacking growth factors or inhibitors for pancreatic organoids. PATIENTS AND METHODS: A total of 38 patients with clinically diagnosed PDAC were enrolled in the study. First, EUS-FNB was conducted using a 22- or 25-gauge biopsy needle. Then, a surplus of samples was collected for organoid formation after rapid on-site cytological evaluations of sample adequacy. Subsequently, the established organoids were compared with clinical data and pathological diagnosis, following periodic observations and evaluations for morphology. RESULTS: PDAC organoids were successfully created in 24 of the 38 cases (63.2%), including four cases with pathologically inconclusive EUS-FNB results. Afterward, PDAC organoid morphology was classified into ductal, dormant, and adhesive small cluster (ASC) types. Although the ductal and ASC types were seen separately, they were also seen together in other cases, which we named "mixed type". CONCLUSION: We propose a feasible and straightforward method for establishing organoids, especially for diagnosing PDAC, particularly when the result of EUS-FNB is pathologically inconclusive. Furthermore, PDAC organoids are morphologically classified into three types reported for the first time.

Gallbladder Intramucosal Carcinoma Arising in a Cholesterol Polyp: A Case Report.

Cholesterol polyp is the most common benign disease of gallbladder polyps, and is considered not to be the origin of malignancy. Herein, we report a rare case of a well-differentiated adenocarcinoma arising in a gallbladder cholesterol polyp. A pedunculated mulberry-like gallbladder polyp diagnosed with a cholesterol polyp preoperatively consisted of two distinct components macroscopically: a yellow-whitish lobulated lesion and a brownish irregular lesion. Microscopically, the former revealed to be a cholesterol polyp, but the latter demonstrated a well-differentiated adenocarcinoma. Even if imaging findings suggest a gallbladder cholesterol polyp, it is important to keep in mind that carcinoma can coexist like our case.

Eosinophilic Granuloma of the Liver Mimicking Metastatic Liver Tumor.

We herein report a case of coagulation necrosis with granulation and eosinophilic infiltration of the liver. A 37-year-old woman was diagnosed with a new mass lesion in the liver 1 month after breast cancer surgery and admitted for a further examination. Because the tumor occurred immediately after surgery, it was considered essential to determine whether or not it was a metastatic liver tumor from breast cancer. A percutaneous liver tumor biopsy revealed eosinophilic granuloma of the liver, which is considered to have a high possibility of visceral larva migrans with suspected gnathostomiasis infection. A detailed medical history and histological diagnosis are important for making a differential diagnosis.

Recognition and pathological features of periampullary region adenocarcinoma with an indeterminable origin.

Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer.

A deep learning model to detect pancreatic ductal adenocarcinoma on endoscopic ultrasound-guided fine-needle biopsy.

Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.

Gastroesophageal Varices and Hyperplastic Nodules of the Liver in a Patient with Anorexia Nervosa.

We report a case of anorexia nervosa (AN) with gastroesophageal varices (GEV) in a 36-year-old woman. The patient presented to our hospital with progressive bloating due to severe ascites. She had no history of alcohol intake. Esophagogastroduodenoscopy and enhanced computed tomography revealed GEV and multiple hepatic nodules, respectively. The histological examination of a liver biopsy specimen revealed similar features to nonalcoholic fatty liver disease and showed hyperplastic nodules that were suspected to be related to the uneven distribution of portal blood flow in the liver. In conclusion, patients with long-term AN should undergo abdominal imaging to detect signs of portal hypertension.

Mucinous cystic neoplasm of the liver communicated with intrahepatic duct exhibiting peculiar chronological change in MR imaging appearances: a case report.

A 70-year-old woman has been followed up for chronic hepatitis C and hepatocellular carcinoma which had been successfully controlled by several sessions of radiofrequency ablation. A small cystic lesion in segment IV associated with adjacent intrahepatic duct dilatation was firstly noted 4 years before on MR imaging, which showed gradual increase in size and significant interval change in the MRI signal intensity of the cystic content on the follow-up examinations. The mass finally reached 4 cm in its largest dimension, associated with slightly enhancing thickened wall, suggesting its neoplastic nature. The mass was surgically resected and a final diagnosis of mucinous cystic neoplasm (MCN) of the liver was made. MCN is usually considered to have no communication with intrahepatic duct, but in this particular case, the communication with the biliary duct was suggested from its early stage of the lesion, which would be the cause of peculiar chronological change in MR appearance.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells showing intraductal growth and intratumoral hemorrhage: MRI features.

We report a case of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells ocalized within the main pancreatic duct (MPD). A 61-year-old woman was referred to our hospital for evaluation of dilatation of the MPD that was detected on screening sonogram. Preoperative MR imaging revealed a small hypervascular tumor within the dilated MPD, showing high signal on R2* map and signal reduction on in-phase as compared to out-of-phase. R2* hyperintensity and in-phase signal reduction may be a characteristic feature of undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, which indicates intratumoral hemorrhage even if they are small.

Aggressive venous invasion in the area of carcinoma correlates with liver metastasis as an index of metastasis for invasive ductal carcinoma of the pancreas.

BACKGROUND: Invasive ductal carcinoma of the pancreas (IDCP) predominantly causes death through liver metastasis (LM) and peritoneal dissemination with local recurrence. However, whether its venous invasion is from the enlarged carcinoma accompanied by tumor growth, or from a distinct carcinoma group, for which venous invasion is facilitated by proximity to the origin, is unclear. We analyzed the correlation between LM and venous invasion in patients with small IDCP tumors. METHODS: Of 388 patients who were diagnosed with IDCP, 20 (5.2%) had tumors with diameters <2 cm. The follow-up period of the 20 patients with smaller tumors was 1-24 years. RESULTS: The small-tumor group (n = 20) included 11 men and 9 women, aged 51-80 years. Five died of liver metastasis (LM group, n = 5) and 15 patients (non-LM group, n = 15) were either alive without recurrence (n = 11) or died of peritonitis carcinomatosa following local recurrence, subarachnoid hemorrhage, primary lung cancer, or old age (n = 1 for each cause of death). The LM and non-LM groups did not significantly differ in numbers of venous invasion by the carcinoma in IDCP and non-IDCP area of the pancreas. However, median numbers of invaded veins in the area of IDCP and percentage of invaded vein/total number of vein in IDCP area were significantly higher in the LM group. CONCLUSION: Among patients with small IDCP tumors, the LM group showed more aggressive venous invasion by IDPC. Patients in whom ≥60% of veins were invaded by IDCP should be prepared for LM.

Hepatectomy for Liver Metastases of Colorectal Cancer After Adoptive Chemoimmunotherapy Using Activated αß T-cells.

BACKGROUND/AIM: Various types of chemoimmunotherapies for malignant tumors have been reported. However, there are few reports on hepatectomy after chemoimmunotherapy. We evaluated the safety and efficacy of hepatectomy for patients with stage IV colorectal liver metastases (CLM) after chemoimmunotherapy using activated αß T-cells. PATIENTS AND METHODS: From June 2012 to December 2016, five patients who underwent hepatectomy after receiving capecitabine and oxaliplatin (XELOX) plus bevacizumab and ex vivo-expanded αß T-lymphocytes as first-line chemoimmunotherapy were included. RESULTS: The median age of the five patients (two men, three women) was 61.4 (range=56-75) years. The surgical procedure was partial hepatectomy in two, laparoscopic partial hepatectomy in two, and one case of partial hepatectomy with subsegmentectomy. There was no postoperative complication of Clavien-Dindo grade 3A or higher. One patient had multiple lung metastases. CONCLUSION: Hepatectomy after chemoimmunotherapy using activated αß T-cells for CLM can be performed safely.

A case of porphyria cutanea tarda of the liver exhibiting multifocal macrovesicular steatosis in the background of microvesicular steatosis, probably caused by uneven iron accumulation.

A 61-year-old man with chronic hepatitis B and a history of alcohol overconsumption was admitted to our hospital for the scrutiny of multiple echogenic liver nodules. CT and hepatobiliary phase of gadoxetate-enhanced MR imaging revealed no nodular lesions. Quantitative fat fraction images and R2* map of MR imaging suggested homogeneous steatosis and uneven iron deposition in the liver, namely moderately and severely elevated R2* values at the nodules and surrounding background liver, respectively. Biopsy specimens showed macrovesicular fatty liver and less iron deposition at the echogenic nodules, and microvesicular fatty change and more prominent iron deposition at the surrounding liver tissue. The patient's urinary uroporphyrin level was elevated, and the final diagnosis of porphyria cutanea tarda was made. In patients with history of excessive alcohol intake or viral hepatitis, echogenic nodules on ultrasonography along with radiological evidence of absence of space occupying lesions, and presence of excessive intrahepatic fat and iron, might suggest a possible diagnosis of porphyria cutanea tarda.

Influence of microscopically positive resection margins on long-term (>5-year) survival after resection of pancreatic ductal adenocarcinoma.

CONTEXT: The impact of R1 resection on outcomes in patients with pancreatic ductal adenocarcinoma (PDAC) is unclear, with most studies assessing survival for up to 5 years. OBJECTIVE: The aim of this study was to evaluate the prognostic influence of R1 and R0 resection on >5-year survival in patients with PDAC. MATERIAL AND METHODS: Of the 271 patients with PDAC who underwent pancreatic resection over a 26-year period, 33 had survived for ≥5 years. R1 status was defined as the presence of tumor tissue ≤1 mm from a circumferential margin surface. Patients were followed-up for 61 to 288 months. RESULTS: Of the 33 long-term survivors, 19 and 14 underwent R0 and R1 resection, respectively. The percentage of male patients was significantly higher in the R1 than in the R0 group. The R0 group tended to show a weaker relationship between R status and stage than the R1 group. Multivariate analysis showed that R status was an independent prognostic marker (P=0.0071), and Kaplan-Meier curves showed that >5-year survivors in the R1 group had significantly poorer prognoses (P=0.002). CONCLUSIONS: Patients who have survived >5 years following R1 resection for PDAC can experience tumor recurrence in the resected area.

Two rare metachronous metastases of hepatocellular carcinoma after liver transplantation.

A 59-year-old male with hepatocellular carcinoma (HCC) due to liver cirrhosis caused by the hepatitis C virus underwent cadaveric whole liver transplantation. Two years later, he had a metastatic HCC in the superior mediastinum. Over the following postoperative year, he underwent transcatheter arterial chemoembolization (TACE) for 4 tumors in the implanted liver. In the third post-TACE month, he was emergently hospitalized due to intracerebral hematoma with a tumor invading the bone in the medial frontal segment. He underwent emergency intracranial tumorectomy and hemorrhage removal. The histopathologic diagnosis was metastatic HCC. He regained consciousness as well as the ability to speak and to feed himself, resulting in an improved quality of life. The incidence of HCC recurrence after liver transplantation is observed in approximately 8% to 11% of selected cases, with frequent relapses observed in the implanted liver, bones, adrenal glands, and lungs. Mediastinal and intracranial metastases from HCC post-liver transplantation are very rare.

MK-1 expression in gastric carcinoma with liver metastasis.

OBJECTIVE: The prognosis for gastric carcinoma patients with liver metastasis is very poor. This retrospective study investigated the prognostic significance of MK-1 expression in gastric carcinoma patients with liver metastasis. METHODS: Immunohistochemical staining using monoclonal antibody FU-MK-1 against MK-1 antigen was performed on paraffin-embedded tissues from 64 gastric carcinoma patients with liver metastasis. We attempted to determine the presence of any relationship between pathological prognostic factors and the expression of MK-1 in 64 gastric carcinoma patients with liver metastasis. RESULTS: MK-1 expression was found in 43 (67%) of 64 tumor samples. MK-1 expression was significantly higher in the intestinal type (73%) than in the diffuse type carcinoma (33%, P = 0.049). Multivariate analysis showed that MK-1 expression and lymph node metastasis were significant factors for overall survival. The difference between overall survival rates with positive or negative MK-1 expression was statistically significant as shown by Kaplan-Meier survival analysis (P < 0.0001; log-rank). In addition, the difference between cumulative disease-free survival rates with positive or negative MK-1 expression in gastric carcinoma patients with metachronous liver metastasis was statistically significant as well, as shown by Kaplan-Meier survival analysis (P = 0.0006; log-rank). CONCLUSIONS: The prognostic significance of MK-1 expression as a biological tumor marker was demonstrated in a series of gastric carcinoma patients with liver metastasis. MK-1 positivity may be a reliable marker for predicting and taking measures to control liver metastasis after curative gastrectomy for gastric carcinoma.

Early colorectal carcinomas: CD10 expression, mucin phenotype and submucosal invasion.

We analyzed 170 tumors (polypoid, 98; non-polypoid, 72) of early colorectal carcinoma with or without submucosal invasions (Tis and T1 of TNM classification) from 161 patients to evaluate correlations between clinicopathological factors and immunohistochemical expressions of CD10, MUC2, and MUC5AC. The coexistence of adenomatous components was significantly less common in non-polypoid carcinomas (4.2%) than in polypoid carcinomas (66.3%) (P < 0.0001). Non-polypoid carcinomas were smaller in size and tended to infiltrate into the submucosa with higher incidence of lymphatic and venous permeations. CD10 was more frequently expressed in non-polypoid carcinomas (70.8%) than in polypoid carcinomas (51.0%) (P= 0.01). Total carcinomas with high grade atypia showed higher incidence of CD10 expression (60.6%) than those with low grade atypia (28.9%) (P < 0.0001). Carcinomas with low grade atypia exhibited a higher incidence of MUC2 and MUC5AC expression (91.1% and 57.8%, respectively), when compared with carcinomas with high grade atypia (41.6% and 20.0%, respectively) (both, P < 0.0001). In submucosal invasive carcinomas with residual intramucosal carcinoma component (IMCC), CD10 expression in IMCC and submucosal invasive carcinoma component (SMCC) simultaneously exhibited identical positive or negative results, regardless of the polypoid or non-polypoid growth pattern. The CD10 expression may occur in the early stage of carcinogenesis within the mucosa, and these neoplasms may retain CD10 in SMCC, possibly resulting in more advanced stages of stromal invasion and distant metastases. In conclusion, our data suggest that the CD10 expression and mucin phenotypes may be potentially useful markers for estimating biological properties of early colorectal carcinomas.

CT differentiation of solid serous cystadenoma vs endocrine tumor of the pancreas.

AIM: To differentiate between solid serous cystadenoma (SSCA) and endocrine tumor (ET) of the pancreas using dynamic CT findings. MATERIALS AND METHODS: Between 2001 and 2008, there were 3 SSCA and 15 ET surgically resected in our institute, for whom preoperative multidetector-row CT were available. Various CT features were retrospectively evaluated by two radiologists in consensus for the differentiation between the two entities. Delay time for early and delayed phase images were 40 and 180 or 240s, respectively. For qualitative assessment, density of the tumors relative to the surrounding parenchyma was evaluated, along with other characteristic features. In patients for whom digital data were available, CT values of the tumors were measured, and quantitative assessment was also performed. Relative and absolute washout rate (RWR and AWR, respectively) were also calculated. RESULTS: Mean sizes of the two groups were similar. Tumors were seen as low density area more frequently in SSCA than in ET on unenhanced CT (3/3 vs 1/14), and also on the delayed phase image (2/3 vs 0/14) (p<0.05). Fibrous capsule was observed more frequently in SSCA (2/3) than in ET (0/14). CT value of the tumor on unenhanced CT was significantly lower, and RWR was higher in SSCA than in ET (p<0.05, Mann-Whitney's U test). The difference in delayed phase CT density and AWR did not reach statistically significant level. CONCLUSION: Unenhanced and enhanced CT findings may be of value in differentiation between SSCA and ET.