Highly Advanced Colorectal Liver Metastases Successfully Treated With Fluorouracil Plus Leucovorin Monotherapy and Microwave Ablation.

BACKGROUND: Fluorouracil plus leucovorin (5-FU/LV) is a less toxic but mild chemotherapy. CASE REPORT: A 63-year-old male patient with rectal cancer and multiple colorectal liver metastases (CRLM, total volume of 1,826 ml) was hospitalized. He had several poor prognostic factors, including elevated levels of tumor markers, with carcinoembryonic antigen and carbohydrate antigen 19-9 levels of 17,119 ng/ml and 7,617 U/ml, respectively. Additionally, the patient had a low body mass index, poor performance status, and a history of apparent weight loss. After capecitabine and oxaliplatin for four cycles, 5-FU/LV has been lasting for nine months. Interestingly, tumor marker levels returned close to normal limits, and the total CRLM volume decreased to 154 ml without any enhancements. The patient's general condition clearly improved after a year of chemotherapy. CONCLUSION: Chemotherapy with 5-FU/LV and percutaneous microwave ablation is beneficial to achieve tumor control in patients with highly advanced liver-only CRLM and poor general condition.

Far-advanced Colorectal Liver Metastases Successfully Managed With Modified ALPPS and Radiofrequency Ablation in Combination With Chemotherapy.

BACKGROUND: Large numbers of synchronous colorectal liver metastases are associated with poor prognosis. CASE REPORT: A 47-year-old male patient with rectal cancer and unresectable colorectal liver metastases (over 15 cm in diameter and over 30 metastases) was treated with a multidisciplinary treatment including systemic chemotherapy with mFOLFOX6/panitumumab and surgical therapies (colostomy, modified associating liver partition and portal vein ligation for staged hepatectomy together with radiofrequency ablation). For solitary recurrent colorectal liver metastases, percutaneous radiofrequency ablation with chemoembolization and open radiofrequency ablation in combination with the same systemic chemotherapy was performed. Since the diagnosis 3 years ago, he has been leading a good quality of life, free of any tumor or treatment. CONCLUSION: For patients with far-advanced but liver-only colorectal liver metastases, surgical therapy, systemic chemotherapy, and interventional treatment can be important for achieving good prognosis.

A Case Report of Metachronous Multiple Adenosquamous Carcinoma of the Colon Over-expressing PD-L1 and a Literature Review.

BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer in both men and women, and one of the more widely recognized preventable cancers. Adenosquamous carcinoma (ASC) of the colon/rectum is an uncommon disease that consists of both glandular and squamous components, and the most common site of ACS is the right and transverse colon. CASE REPORT: Here, we present the case of a 78-year-old woman, who complained of abdominal pain. Colonoscopy revealed a circumscribed tumor in the ascending colon, and no specific lesion was detected in the other areas of the colon or rectum. ASC (pT3N0M0) was diagnosed from right hemicolectomy specimens. Three months after the first surgery, the serum levels of tumor markers had gradually increased, and a new tumor was subsequently detected in the sigmoid colon 2 months later. The sigmoid lesion was surgically resected and diagnosed as ASC (pT3N3M0). Strong PD-L1 expression was also found in the squamous component. CONCLUSION: To our knowledge, this is the first report of a recurrent sigmoid colon ASC that likely originated from the ascending colon, and PD-L1/PD-1 signaling was likely involved in the immune escape mechanism.

Intrahepatic Cholangiocarcinoma Coexisting With Multiple Bile Duct Adenoma Treated as Liver Metastasis from a Pancreatic Neuroendocrine Tumor.

BACKGROUND: Bile duct adenomas (BDA) may be precursor lesions of small duct-type, including mass-forming type intrahepatic cholangiocarcinoma (ICC). CASE REPORT: A 68-year-old woman was transferred to our facility for the treatment of a liver tumor, possibly metastasized from a pancreatic neuroendocrine tumor. Finally, two liver tumors were resected and histopathologically diagnosed as "BDA" and "ICC with a BDA-like component". In the BDA-like component, the MUC6 positive rate was notably lower and the Ki-67 positive rate was higher than the other BDAs and ICC component, respectively. The doubling time of the tumor volume in BDA was very long but was shortened (1,510 and 719 days). Distinct enlargement of the tumor and appearance of enhancement through diagnostic imaging was useful in diagnosing the transformation from a BDA to an ICC. CONCLUSION: An "adenoma-carcinoma sequence" may exist in the transformation process from a BDA to an ICC.

Laparoscopic Surgery for a Patient With Multiple Liver Metastases of Unknown Origin Concomitant With Gallbladder Tumor.

BACKGROUND: The liver is the digestive organ where metastatic adenocarcinoma of unknown primary site is most often observed. CASE REPORT: A 74-year-old man was diagnosed with a growing gallbladder tumor and multiple liver tumors limited to the left lateral sector. Liver tumors were suggested to be primary or secondary adenocarcinoma with no relation to the gallbladder tumor. Also for diagnostic purposes, laparoscopic full-thickness resection of the gallbladder, laparoscopic lateral sectionectomy and lymph node sampling were performed. The final histopathological diagnosis was hyperplastic polyp of the gallbladder and metastatic poorly differentiated adenocarcinoma of the liver. Liver tumors were suspected to originate from the stomach, duodenum, or small intestine; however, the primary sites could not be identified. The patient has been closely followed up without any chemotherapy 3 months after surgery. CONCLUSION: Laparoscopic surgery can be strongly recommended for patients with multiple liver tumors of unknown origin concomitant with a gallbladder tumor.

Hepatic Inflammatory Pseudotumor Mimicking Malignant Tumor With Rare Onset of Intra-abdominal Hemorrhage.

BACKGROUND: Hepatic inflammatory pseudotumor (HIPT) is an uncommon benign tumor-like mass that mimics malignant tumors. CASE REPORT: A 73-year-old man was admitted with severe epigastric pain and high fever. He had received choledocojejunostomy. Enhanced computed tomography showed a 76 mm, heterogeneous, gradual enhanced low-density mass in the caudate lobe and hyperdense fluid was detected around the mass. Based on the diagnosis of hemorrhage from a hypervascular malignant liver tumor, chemoembolization was conducted. Antibiotics (Meropenem) were administered for 2 weeks, and methylprednisolone (125 mg) was administered twice as a premedication for chemoembolization. After the 2nd chemoembolization, rapid tumor shrinkage was observed and the inflammatory changes gradually disappeared. The tumor was finally diagnosed as fibrohistiocytic type HIPT with an ultrasound-guided percutaneous tumor biopsy. The diameter of the liver tumor decreased to 15 mm and intra-abdominal hemorrhage disappeared in 3 months. CONCLUSION: Development of HIPT can be associated with intra-abdominal hemorrhage.

Huge hepatocellular carcinoma with extrahepatic collateral arteries successfully treated by multidisciplinary treatment including laparoscopic devascularization: a case report.

Multidisciplinary treatment is recommended for the management of patients with advanced hepatocellular carcinoma (HCC). Some operative decollateralization of extrahepatic feeding arteries with laparotomy have been introduced for HCC. We herein newly develop laparoscopic devascularization (LDEV) to continue transarterial chemoembolization (TACE) for HCC with extrahepatic collateral arteries. A 74-year-old man with multiple huge HCC (4 tumors, 18 cm in diameter) and poor liver function (non-alcoholic steatohepatitis, Child-Pugh score 7) was treated with 6 times of chemoembolization in combination with LDEV, 3 times of ablation therapies, and lenvatinib therapy. His tumor markers were triple positive (AFP, 12,906.5 ng/ml; PIVKA-II, 491,743 mAU/ml; AFP-L3, 91.8%) before treatments; however, they all returned to normal limits. Complete response was achieved according to the modified RECIST criteria. Unfortunately, he died 6 months after the final treatment with no recurrence of HCC due to the postoperative complication of primary lung cancer. LDEV is a useful tool to continue effective TACE, and multidisciplinary treatment including chemoembolization and LDEV can cure advanced HCC patients with extrahepatic collaterals and impaired liver function.

Cholangiolocarcinoma With Multiple Recurrences Successfully Treated With Repeated Liver Resection and Radiofrequency Ablation.

BACKGROUND/AIM: The prognosis of cholangiolocarcinoma, a rare malignant liver tumor derived from hepatic progenitor or stem cells, is considered relatively good; however, it frequently recurs. We herein present the diagnosis, histological findings, and treatment of cholangiolocarcinoma. CASE REPORT: A 65-year-old woman with a large liver tumor (70 mm in diameter) was referred. Hepatocellular carcinoma was suspected based on strong early enhancement and delayed washout by enhanced computed tomography. The patient underwent curative left tri-sectionectomy. Histologically, she was diagnosed with pure cholangiolocarcinoma in a slightly fibrous liver. Three metachronous recurrent lesions (all ≤10 mm in diameter) were found between fifteen and twenty months after the initial hepatectomy. One lesion and the remaining two lesions were treated with hepatectomy and radiofrequency ablation, respectively. Two years after the initial diagnosis, she was doing well without recurrence. CONCLUSION: Repeated hepatectomy and radiofrequency ablation might be useful for small intrahepatic recurrences of cholangiolocarcinoma.

Hepatocellular Carcinoma With Extensive Cancer-associated Thrombosis Successfully Treated With Liver Resection and Direct Oral Anticoagulant: A Case Report.

AIM: To assess the utility of the perioperative use of direct oral anticoagulants for patients with hepatocellular carcinoma (HCC) with cancer-associated thrombosis. CASE REPORT: An 83-year-old woman was admitted with a solitary HCC (10-cm diameter), as well as with multiple sites of venous thromboembolism and macroscopic portal vein tumor thrombosis. She had appropriate liver function without viral hepatitis, triple-positive tumor markers, and secondary polycythemia. Edoxaban at 30 mg was initiated 10 days before surgery to remove HCC. Complete remission of the pulmonary embolism and stability of the deep vein thrombosis and massive superior mesenteric vein thrombosis were recognized preoperatively. An extended left hepatectomy was successfully performed. To avoid hemorrhage complications, we used intravenous administration of nafamostat mesylate for 2 days, thereafter we restarted edoxaban. Superior mesenteric vein thrombosis resolved 5 months after surgery. CONCLUSION: Perioperative oral administration of edoxaban was useful in multidisciplinary treatment for a patient with advanced HCC with cancer-associated thrombosis.

Complete Removal of Adrenal Metastasis in Hepatocellular Carcinoma Using Indocyanine Green Fluorescent Imaging.

AIM: Our aim was to confirm the utility of Indocyanine green (ICG) fluorescence imaging for intraoperative detection of adrenal hepatocellular carcinoma (HCC) metastasis. CASE REPORT: An 83-year-old man with a right adrenal HCC metastasis was admitted after complete remission of primary HCC and a metachronous left adrenal metastasis. He was treated with ICG fluorescence-guided limited resection to preserve adrenal function. ICG was administered intravenously at a dose of 0.5 mg/kg, 6 days before the operation. After removal of the entire suspicious metastatic HCC, ICG fluorescence imaging clearly demonstrated two illuminated lesions. The lesions were separately resected using an energy device. Finally, there were no ICG fluorescent lesions which meant residual tumor. Histopathological examination confirmed adrenal metastasis of moderately differentiated HCC in the initial specimen and the additional resected specimens. Three months after the operation, adrenal function was well preserved without recurrence of HCC. CONCLUSION: ICG fluorescence imaging is essential for complete resection of adrenal HCC metastasis.

Hepatic Xanthogranuloma that Originated from a Liver Cyst and Mimicked a Malignant Tumor.

BACKGROUND/AIM: Hepatic xanthogranuloma is a very rale disease and formation process is unknown. CASE REPORT: A 69-year-old woman previously diagnosed as simple liver cyst. Two years before, a 36-mm liver cyst was found in segment 5, while one year later, the hemorrhagic cyst was 40 mm in diameter and a thin septum had formed. The most recent T1-weighted magnetic resonance imaging (MRI) showed a regular 21-mm hepatic mass with a hyperintense 11-mm center and a hypointense periphery. Peripheral enhancement was seen on gadolinium enhanced MRI. Hepatobiliary cystadenoma or cystadenocarcinoma was suspected because of wall thickness and slight enhancement. Microscopic examination following laparoscopic partial liver resection revealed fibroblasts, dense collagen fibers, and a double layer of hemosiderin-laden as well as foamy macrophages attached to the fibrous capsule. CONCLUSION: The patient was diagnosed with a hepatic xanthogranuloma that originated from a hemorrhagic liver cyst. Intracystic hemorrhage may be one of the reasons for hepatic xanthogranuloma formation.

A hepatic sclerosed hemangioma with drastic changes in contrast-enhanced ultrasonography.

Hepatic sclerosed hemangioma is a rare benign liver tumor that originated from hepatic cavernous hemangioma; however, the process of its formation has been unclear. We herein present the patient of a histologically proven hepatic sclerosed hemangioma that showed drastic changes in diagnostic images in a short period. A 56-year-old man was referred to our hospital for the treatment of suspicious hepatocellular carcinoma with hepatitis C, approximately 2 cm in diameter in liver segment 8. Initially, the tumor manifested as early entire enhancement with mildly delayed washout in contrast-enhanced ultrasonography; however, it manifested as continuous peripheral enhancement with the central non-enhanced area after 1 month in various diagnostic images. He completely quit drinking and smoking 1 month preoperatively. No special symptoms and signs were found to suggest tumor ischemia. Anatomical resection of segment 8 was completed. Histological examination confirmed the final diagnosis of common type hepatic sclerosed hemangioma, derived from atypically enhancing cavernous hemangioma. No signs of impaired blood flow were observed in both diagnostic images and histological examination. Sclerosing changes in hepatic cavernous hemangioma may be completed in a relatively short time with no apparent reason.

[A Case of Long-Term Survival after Chemotherapy and Ablation Therapy Using Various Approaches for Multiple Colon Cancer Liver Metastases].

A 58-year-old man with unresectable sigmoid colon cancer and multiple liver metastases(H2, more than 30)received chemotherapy for 2 years. Subsequently, the patient was diagnosed with stenosis of the primary lesion and 5 bilobar, metastatic tumors. Simultaneous resection was unsuitable because of the performance status and comorbidities of the patient. The first surgery consisted of laparoscopic-assisted sigmoidectomy, laparoscopic microwave coagulation therapy(MCT), and percutaneous radiofrequency ablation(RFA). Percutaneous RFA was additionally performed after 2 months. Since 2 liver metastases(S3 and S8)were inadequately treated, 3 courses of P-mab plus FOLFIRI were administered. Finally, laparoscopic- assisted RFA was performed. Subsequently, serum CEA reduced from 288.3 ng/mL to the normal level. We used fusion imaging US, sonazoid US, laparoscopic convex probe, and ICG fluorescence imaging for ablation therapy. Chemotherapy and ablation therapy using various approaches can control unresectable multiple liver metastases and prolong survival by more than 3 years.

Evaluation of Significant Coronary Artery Disease Based on CT Fractional Flow Reserve and Plaque Characteristics Using Random Forest Analysis in Machine Learning.

RATIONALE AND OBJECTIVES: Fractional flow reserve (FFR) is an established technique for detecting lesion-specific ischemia but is invasive. Our objective was to investigate the effects of combined assessment of coronary CT angiography (CCTA) imaging features and CT-FFR on detecting lesion-specific ischemia by comparing with invasive FFR. MATERIALS AND METHODS: Forty-seven patients who had 60 coronary vessels with 30%-90% stenosis were included. Six anatomic CCTA descriptors (Agatston score, stenosis severity, mean plaque CT attenuation value, noncalcified and calcified plaque volumes, remodeling index) and a functional descriptor (CT-FFR) were measured. Random forest was used to identify which descriptors were useful to identify ischemia-related lesion. Receiver-operating characteristic (ROC) curves were calculated for 2 models: i.e. Model-1 for anatomical CT descriptors and Model-2 for anatomical CT descriptors plus CT-FFR. RESULTS: Stenosis severity (40.8 ± 15.7% vs 57.6 ± 14.1%), noncalcified plaque volume (190 ± 100 vs 254.8 ± 133.3), and remodeling index (1.04 ± 0.12 vs 1.11 ± 0.13) were significantly higher in ischemia-related lesions than nonischemia-related lesions. CT-FFR was 0.84 ± 0.14 and 0.71 ± 0.14, respectively, for ischemia-related and nonischemia-related lesions, and the difference was significant. The area under the ROC curve was 0.738 and 0.835 in Model-1 and Model-2, respectively. Reclassification of ischemic lesion risk was significantly improved after adding CT-FFR: net reclassification improvement was 0.297 and integrated discrimination improvement was 0.254. CONCLUSION: Combined assessment of anatomical CCTA features and functional CT-FFR was helpful for detecting lesion-specific ischemia.

Partial Splenic Embolization for Lenvatinib Therapy-associated Thrombocytopenia Among Patients With Hepatocellular Carcinoma.

BACKGROUND: Lenvatinib, a newly developed oral multi-tyrosine kinase inhibitor, has amazing potential in the multidisciplinary treatment of advanced or metastatic hepatocellular carcinoma. Thrombocytopenia is a serious adverse event that causes drug dose reduction or withdrawal. Partial splenic embolization is currently being used as a non-surgical treatment for thrombocytopenia caused by various pharmacotherapies. CASE REPORT: Partial splenic embolization was performed for three patients with hepatocellular carcinoma receiving lenvatinib therapy with/without transarterial chemoembolization. Partial splenic embolization was advantageous for various situations, including the induction of lenvatinib for patients with thrombocytopenia, application of lenvatinib after multiple transarterial chemoembolization using cisplatin and radiotherapy, and re-administration of lenvatinib after lenvatinib therapy-induced thrombocytopenia. In all cases, lenvatinib therapy was completed without need for cessation due to thrombocytopenia. CONCLUSION: We strongly recommend the new concept of combining partial splenic embolization and lenvatinib therapy for hepatocellular carcinoma.

Conversion Hepatectomy for Huge Hepatocellular Carcinoma With Arterioportal Shunt After Chemoembolization and Lenvatinib Therapy.

Large tumor size and arterioportal shunt are poor prognostic factors for hepatocellular carcinoma. Lenvatinib is a novel and potent multi-tyrosine kinase inhibitor developed in Japan. A 66-year-old woman with hepatocellular carcinoma and untreated hepatitis C was referred to our hospital. She was judged as unresectable and was treated with four sessions of transarterial chemoembolization; however, the therapeutic effect was unsatisfactory because of major arterioportal shunt. Lenvatinib was sequentially administered for 4 months. Thereafter, we observed tumor shrinkage, complete disappearance of arterioportal shunt, and obvious improvement in liver function. A curative conversion hepatectomy was successfully accomplished. The extremely high levels of tumor markers almost normalized; the pretreatment levels were 1,008,021 ng/ml for alpha-fetoprotein. At 1 year after the primary treatment, the patient has not experienced recurrence. To our knowledge, this is the first case of a patient with initially unresectable hepatocellular carcinoma with arterioportal shunt who underwent conversion hepatectomy after multidisciplinary treatment, including lenvatinib.

Five-year Recurrence-free Survival After Surgery Followed by Oral Chemotherapy for Gastric Cancer With Portal Vein Tumor Thrombosis.

Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.

Machine Learning to Differentiate T2-Weighted Hyperintense Uterine Leiomyomas from Uterine Sarcomas by Utilizing Multiparametric Magnetic Resonance Quantitative Imaging Features.

RATIONALE AND OBJECTIVE: Uterine leiomyomas with high signal intensity on T2-weighted imaging (T2WI) can be difficult to distinguish from sarcomas. This study assessed the feasibility of using machine learning to differentiate uterine sarcomas from leiomyomas with high signal intensity on T2WI on multiparametric magnetic resonance imaging. MATERIALS AND METHODS: This retrospective study included 80 patients (50 with benign leiomyoma and 30 with uterine sarcoma) who underwent pelvic 3 T magnetic resonance imaging examination for the evaluation of uterine myometrial smooth muscle masses with high signal intensity on T2WI. We used six machine learning techniques to develop prediction models based on 12 texture parameters on T1WI and T2WI, apparent diffusion coefficient maps, and contrast-enhanced T1WI, as well as tumor size and age. We calculated the areas under the curve (AUCs) using receiver-operating characteristic analysis for each model by 10-fold cross-validation and compared these to those for two board-certified radiologists. RESULTS: The eXtreme Gradient Boosting model gave the highest AUC (0.93), followed by the random forest, support vector machine, multilayer perceptron, k-nearest neighbors, and logistic regression models. Age was the most important factor for differentiation (leiomyoma 44.9 ± 11.1 years; sarcoma 58.9 ± 14.7 years; p < 0.001). The AUC for the eXtreme Gradient Boosting was significantly higher than those for both radiologists (0.93 vs 0.80 and 0.68, p = 0.03 and p < 0.001, respectively). CONCLUSION: Machine learning outperformed experienced radiologists in the differentiation of uterine sarcomas from leiomyomas with high signal intensity on T2WI.