[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.

[Primary Small Intestinal Cancer-A Clinicopathological Study of Seven Cases].

The clinicopathological features of primarysmall intestinal cancer were assessed retrospectively. Seven patients underwent resection of small bowel cancer in our hospital between June 2011 and January 2019. The mean age of the patients was 62.9 years, and the male to female ratio was 4:3. Five patients were symptomatic, and the correct preoperative diagnosis rate was 28.6%. The average tumor diameter was 5.3 cm, and the median resected intestine length was 25 cm. Histopathological examination revealed that there were 2 patients with poorlydifferentiated tumors and 3 patients with pStage ⅡA, 3 with pStage ⅡB, and 1 with pStage ⅢA disease. Recurrence after surgeryoccurred in 4 patients, including local recurrence in 2 patients and lymph node recurrence in 1 patient. Median survival was 24.5 months. The resected intestinal length was longer and the mesenteric arterydissection was more extensive in survivors than in dead patients. In contrast, the dead patients were older than the survivors and had undifferentiated tumor, ly2/ly3, lymph node metastasis, and recurrence. Moreover, recur- rence occurred in 4 patients who had lymph node metastasis, and/or undifferentiated tumor type, and/or ly2/ly3. An adequate intestinal excision margin along with mesenteric lymph node dissection might be required to improve the survival of patients with primaryintestinal cancer.

[A Patient with Multiple Colorectal Liver Metastases for Whom Partial Splenic Embolization Contributed Extremely to Maintain Multidisciplinary Treatment].

After approximately 2.5 years of chemotherapy at the referred hospital, a 69-year-old man with double colon cancer and unresectable liver metastases(H3)sought consultation. A total of 8 liver metastases were deemed resectable; however, the disease was progressive. He received 2 courses of mFOLFOX6 plus Bmab before hepatectomy. Seven weeks after starting chemotherapy, Grade 4 thrombocytopenia occurred, which required platelet transfusion. Ten weeks after, curative parenchymal- preserving hepatectomy was performed under platelet transfusion. Hematologic examination including bone marrow aspiration showed no significant abnormalities, including normal megakaryocyte formation. Therefore, the patient was diagnosed with thrombocytopenia due to sinusoidal obstruction syndrome associated with past chemotherapy including oxaliplatin. Partial splenic embolization(PSE)was performed 8 weeks after the first hepatectomy. The infarcted splenic ratio was 79.5%, and the infarcted splenic volume was 444.3 mL. Curative resection of the primary colorectal cancer and the 2nd hepatectomy for the newly developed recurrent liver lesions was successfully performed at 2 weeks and 19 weeks after PSE, respectively. Platelet transfusion was never required in the perioperative period of the 2 operations performed after the PSE. Forty-five months after the initial treatment, the patient is alive with no recurrent tumors and normal tumor marker levels.

[A Case of Locally Advanced Rectal Cancer with a Pathological Complete Response to Preoperative Chemoradiotherapy].

A 61-year-old woman presented with the chief complaint of melena. She was diagnosed with rectal cancer via colonoscopy. Computed tomography (CT) revealed a rectal cancer with wall thickening, accompanied by several regional lymph node metastases with no distant metastasis. The tumor stage was cT3, cN2a, cM0 according to the TNM Classification of Malignant Tumors (7th Edition, UICC). Preoperative chemoradiotherapy (CRT) (UFT 400 mg/day tegafur-uracil and 75 mg/day Leucovorin; 1.8 Gy in 25 fractions, total 45 Gy) was administered. Eight weeks after CRT, laparoscopy-assisted low anterior resection was performed. A pathological examination revealed that both the primary site and regional lymph nodes had no residual cancer cells, and a diagnosis of pathological complete response was made. The patient has been disease-free for 4 years since the operation. We report a case of rectal cancer that was successfully treated via preoperative CRT. This case may aid the development of a standard therapy for advanced rectal cancer.

[A case report of primary adenocarcinoma of the small intestine with peritoneal dissemination treated with multidisciplinary therapy].

A 55-year-old woman consulted our hospital complaining of abdominal distention and vomiting. She was diagnosed with a malignant tumor in the small intestine and an ovarian tumor with an upper gastro-intestinal series based on a computerized tomography(CT)examination. Intra-operative findings showed that the primary tumor was located in the proximal jejunum, 10 cm on the anal side from Treitz's ligament. There were no liver metastases, but the tumor had spread into the peritoneal cavity(light ovary). The jejunum and light ovary were therefore resected. Pathological diagnosis of the resected specimen revealed adenocarcinoma with lymph node metastases(T4N1M1, UICC StageIV). The patient received systemic chemotherapy with oral S-1. A recurrent lesion on the right ovary was detected 6 months after surgery. The patient subsequently underwent resection of the right ovary. For lung metastases and recurrent peritoneal dissemination, combination chemotherapy with XELOX or FOLFIRI, along with capecitabine plus bevacizumab, and cetuximab, was administered. The patient died 33 months after the first surgery. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed at an advanced stage because there are very few characteristic symptoms. This case may be an important case for the development of a standard chemotherapy regimen for advanced and recurrent adenocarcinoma of the small intestine.

[A case of imatinib-resistant gastrointestinal stromal tumor treated with low-dose sunitinib].

The patient was an 82-year-old man who had undergone resection of a gastrointestinal stromal tumor(GIST)of the small intestine in January 2000, when he was 69 years old. As peritoneal recurrences were diagnosed in June 2002, we performed peritoneal tumorectomy twice, and the perirectal tumor was controlled with imatinib for over 7 years. Resistance to imatinib was diagnosed in March 2011, and treatment was switched to sunitinib. Administration of sunitinib was started at 50mg/day for 28 days followed by treatment withdrawal for 14 days; however, the dose needed to be reduced twice and then discontinued owing to the occurrence of side effects and pemphigoid. During discontinuation of sunitinib, the tumor increased in size and cancer pain appeared; therefore, sunitinib was re-administered at a very low-dose of 12.5mg every alternate day. Low dose sunitinib was effective; the perirectal tumor was reduced and cancer pain disappeared.

Conversion Surgery for Hepatocellular Carcinoma Following Molecular Therapy.

Novel molecular therapies using targeted drugs and immune checkpoint inhibitors for advanced hepatocellular carcinoma have been evolving. Sorafenib and lenvatinib have been commonly used as first-line therapy, followed by recent atezolizumab plus bevacizumab. The median survival time has gradually improved to over 1.5 years. The complete radiological response does not always mean a complete pathological response and a permanent cure of disease. To resolve this, conversion surgery has developed. Lenvatinib is the most suitable drug due to its high response rate. A recent large cohort study using lenvatinib had a conversion rate of 8.4% and an estimated disease-specific survival time of >80% at three years. Conversion to curative resection was an independent predictive factor for better disease-specific survival compared with lenvatinib monotherapy. In conclusion, conversion surgery following molecular therapy is a promising treatment strategy for prolonging long-term outcomes. We should discuss promising drugs and the timing for conversion surgery.

Successful Treatment of Intrahepatic Cholangiocarcinoma With Liver/Lung Metastasis and Peritoneal Dissemination After Liver Resection.

BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (ICC) is increasing in incidence and has a poor prognosis. CASE REPORT: A 79-year-old woman with two liver tumors was referred to our institution. The tumors demonstrated irregular margins and continuous peripheral enhancement. She had a good liver function and an elevated CA19-9 level. Extended left hepatectomy, and partial hepatectomy was performed. The patient was diagnosed with poorly differentiated ICC. Two lung metastases, one liver metastasis, and localized intraperitoneal dissemination occurred 19, 24, and 32 months after the initial hepatectomy. The lung metastases were treated with computed tomography-guided radiofrequency ablation approximately after one year of observation. The liver metastasis was resected immediately. The peritoneal dissemination was removed entirely after effective 3-month chemotherapy using gemcitabine and S-1. The patient is alive with no tumor 44 months after the first surgery. CONCLUSION: Multidisciplinary treatment considering a metastatic site and tumor malignancy might be effective for patients with ICC who have multiple recurrences.

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.

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.

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.

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.

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.

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.

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.

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.

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.