[Analysis of Hepatectomy for Extreme Elderly Patients with Hepatocellular Carcinoma].

Although the first-line treatment for hepatocellular carcinoma(HCC)is hepatectomy, extreme elderly(80 years or older) patients often tend to have a variety of underlying diseases and decreased cardiopulmonary function, which means that surgery involves a high risk. In this case, we examined the safety and efficacy of hepatectomy performed in an extreme elderly patient with HCC. Of the patients with HCC that underwent initial hepatectomy at Kobe University Hospital(n=348)between 2009 and 2015, 23 patients aged 80 years or older at the time of surgery(Group 1, n=23)and those younger than 80 years at the time(Group 2, n=325)were compared, based on parameters related to safety and prognosis. We did not identify differences between the 2 groups with respect to blood loss and operating time. Intraoperative blood transfusion was more common in Group 1. There was no significant difference between the 2 groups with respect to complications of Grade Ⅲ or higher. The median survival of Group 2 patients following hepatectomy(42 months)was better than that of Group 1 patients(34 months), but there was no significant difference between the 2 groups(p=0.429). Furthermore, when the same parameters were compared after adjusting for and matching propensity scores, there were no significant differences in complications, hospitalization periods, and prognosis between the 2 groups. Through proper assessment of oncologic factors and patient risk factors, hepatectomy can be performed safely and effectively even for extreme elderly patients with HCC. If there is no other disease regulating the prognosis, we can expect to achieve similar prognosis in non-extreme elderly patients. Hence, treatments should not be limited solely based on a patient being extremely elderly; rather, proactive treatments should be considered.

[A Case of Multiple Lung Metastases after Liver Resection for Multiple Hepatocellular Carcinomas with Remarkable Effects of Regorafenib].

The patient was a 63-year-old man with hepatitis C. He discontinued combination therapy containing interferon and ribavirin because of the development of skin symptoms. A screening examination showed multiple early-stage hepatocellular carcinomas. He refused treatment and was followed up as an outpatient. During follow-up, his PIVKA-Ⅱ level remarkably elevated to 59,994mAU/mL. Computed tomography(CT)showed an enlarged tumor with portal invasion(vp2)in segment 8 and intrahepaticmetastasis. We performed right and partial hepatectomy. Three months later, CT showed multiple lung metastases. We initiated the daily administration of 800 mg of sorafenib. However, 6 months after hepatectomy, the lung metastases increased in size and number. We considered the therapeutic effect as progressive disease(PD)according to the RECIST criteria. We then initiated administering 120 mg of regorafenib daily as second-line therapy. In a course of the treatment containing sorafenib and regorafenib, the dose was reduced due to hand-foot skin reactions. 8.5 months after hepatectomy, the lung metastases significantly decreased in size. One year after hepatectomy, almost complete response(CR) was obtained, and no intrahepatic recurrence was found.

New macroscopic classification and back-flow thrombectomy for advanced hepatocellular carcinoma with portal vein tumor thrombus invading the contralateral second portal branch.

PURPOSE: Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. METHODS: Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. RESULTS: The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. CONCLUSIONS: BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

Preoperative neutrophil-to-lymphocyte ratio as a predictor of survival after reductive surgery plus percutaneous isolated hepatic perfusion for hepatocellular carcinoma: a retrospective analysis.

PURPOSE: We assessed the predictive value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients who underwent a two-stage treatment combining reductive surgery and percutaneous isolated hepatic perfusion for multiple hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). METHODS: Forty-two patients underwent the two-stage treatment between January 2000 and December 2014 at Kobe University Hospital (Hyogo, Japan). The NLR was calculated from lymphocyte and neutrophil counts in the preoperative routine blood test. Clinical data and overall survival were compared statistically and multivariate analysis was done to identify prognostic factors. RESULTS: The median survival of patients with a preoperative NLR > 2.3 was 14.9 months (n = 13), whereas that of patients with a preoperative NLR ≤ 2.3 was 26.1 months (n = 29; P = 0.022). A preoperative NLR > 2.3 was an independent prognostic factor in patients with multiple HCC with PVTT [hazard ratio (HR) 2.329; 95 % confidence interval (CI) 1.058-5.667; P = 0.036]. CONCLUSION: Based on the results of this study, an elevated preoperative NLR is an independent predictive risk factor for patients undergoing two-stage treatment for multiple HCC with PVTT.

[Multidisciplinary Therapy for Hepatocellular Carcinoma with Peritoneal Dissemination].

We report a case of bilobar multiple hepatocellular carcinoma(HCC)with peritoneal dissemination successfullytreated by dual treatment with reductive surgeryplus percutaneous isolated hepatic perfusion(PIHP). A 73-year-old man had sudden abdominal pain and was diagnosed bilobar multiple HCC through some examinations. The abdominal CT scan demonstrated onlya peritoneal dissemination under the liver. We performed partial hepatectomyof the lateral segment and the Spiegel lobe, and resected a peritoneal dissemination. Subsequently, we underwent PIHP twice. The tumor marker was normalized, and CT images demonstrated complete response according to the RECIST. Dual treatment is considered to be a unique therapeutic modalityfor severe advanced HCC.

[A Case of Pancreatic Cancer with Multiple Lymph Node Swelling Caused by Sarcoidosis].

A 69-year-old woman who was identified the tumor of the pancreas tail by CT scan for postoperative inspection of breast cancer. Pancreas tail cancer with para-aortic lymph node metastases was diagnosed by close inspection. She consulted a different hospital to receive their second opinion. She was diagnosed of sarcoidosis from points with lymphadenopathy in hilar region and para-aorta for 3 years and uveitis. The patient was referred to our institution for treatment. We performed distal pancreatectomy in March, 2014. No.16 lymph nodes were cancer-negative, but lymph nodes around the pancreas were cancer positive. Abdominal CT, 9 months after surgery, showed lymph node swelling. We recommended a definitive diagnosis by EUS-FNA, but she refused the inspection. She was checked by CT scan regularly afterwards and is alive without recurrence 39 months after the operation. Diagnosis for lymph node metastases is difficult for a malignant tumor when the sarcoidosis coexisted.

[A Surgical Resected Case of VIPoma with Para-Aortic Lymph Node Involvement].

A 72-year-old woman had severe watery diarrhea and weight loss. Computed tomography demonstrated a 55mm tumor in pancreatic tail with enlargement of para-aortic lymph nodes. There was no apparent liver metastasis. Endoscopic ultrasound demonstrated a well-circumscribed heterogenous tumor, which was diagnosed neuroendocrine tumor by endoscopic ultrasound-guided fine needle aspiration biopsy. For suspected VIPoma with para-aortic lymph node involvement, distal pancreatectomy and para-aortic lymphadenectomy was performed. The tumor was diagnosed as VIPoma by immunohistochemistry. The diarrhea improved after surgery. No evidence of recurrence was detected after a follow-up of 11 months.

[A Case of Pancreatic Metastasis of Osteosarcoma Resected Using Laparoscopic Spleen Preserving Distal Pancreatectomy].

A 44-year-old woman underwent surgical resection and received preoperative and postoperative chemotherapy for conventional osteosarcoma in the right fibular head. Three years later, follow-up PET-CT revealed accumulation ofFDG in the tail ofthe pancreas. Contrast-enhanced computed tomography showed a 13mm well-circumscribed hypovascular tumor. EUS showed a heterogeneous solid tumor, which was diagnosed as metastasis ofosteosarcoma to the pancreas. Laparoscopic spleen preserving distal pancreatectomy(LAP-SPDP)was performed. Pathologically, the tumor was diagnosed as metastasis ofconventional osteosarcoma to the pancreas. Cells from pancreas islet tissue were detected in the tumor, suggesting invasion ofthe tumor into the pancreatic body and surrounding adipose tissue. Although postoperative chemotherapy was administered, lung metastasis was detected 1.1 years after surgery. Laparoscopic partial resection of the lung metastasis was performed, and the patient is still alive. Metastasis ofosteosarcoma to the pancreas is rare, and there is no report oflaparoscopic approach as a treatment. Herein, we report a case with several references.

[Resection of Initially Unresectable Gallbladder Cancer with Multiple Liver Metastases after Chemotherapy with Gemcitabine plus Cisplatin].

A 61-year-old woman was referred to our hospital for surgery for gallstones. She was diagnosed as having gallbladder cancer after a detailed radiologic examination. At the first laparotomy, gallbladder cancer with bulky invasion to the liver and multiple liver metastases were observed. Gemcitabine plus cisplatin (GC) administration was chosen. After 7 administration of GC, we changed GC to gemcitabine alone due to blood toxicity. After 7 months of chemotherapy, although CT findings showed regression of the liver invasion and the liver metastases, the serum CA19-9 level gradually increased. Because there were no obvious distant metastases on detailed radiologic examination, we performed surgery for the primary lesion after obtaining informed consent. Pathological examination demonstrated fibrosis without viable cancer cells in the metastatic liver tumor. Gemcitabine was administered as post-operative adjuvant chemotherapy. Twelve months after surgery, there was no sign of recurrence.

[A Case of Invasive Intraductal Papillary Mucinous Carcinoma, Penetrating the Stomach, Colon, and Jejunum].

A 69-year-old woman was admitted to a nearby clinic complaining of abdominal pain. Abdominal CT showed a 10 cm diameter huge cystic lesion in the body and tail of the pancreas. The patient was referred to our institution for treatment. Endoscopic ultrasonography (EUS) revealed a cystic mass with a solid lesion. Endoscopic retrograde pancreatography(ERP) demonstrated mucous at the opening of the papilla of Vater and dilatation of the pancreatic duct with a solid nodule. Contrast radiography revealed a fistula from the tumor to the jejunum. A biopsy specimen from the lesion showed adenocarcinoma. Intraoperative findings showed a tumor occupying the pancreas body and tail with suspected invasion to the stomach, jejunum, and transverse colon. We performed distal pancreatectomy with partial resection of stomach, jejunum, and colon. Pathological findings showed an invasive type of IPMC, with invasion to the subserosal layer of the stomach and colon and the mucous layer of the jejunum. While IPMC is recognized as a slow growing malignancy, some cases of invasive carcinoma with fistulation into adjacent organs have been reported. To our knowledge, a case of IPMC penetrating to 3 adjacent organs is rare.

[Successful Multimodal Treatment for Aggressive Extrahepatic Metastatic Hepatocellular Carcinoma - A Case Report].

A 38-year-old man underwent right hepatectomy for a huge hepatocellular carcinoma(HCC)in the right hepatic lobe. Four months later, recurrent and metastatic disease were observed in the remnant liver and right lung, respectively. We performed a hepatectomy for the recurrent lesion because transcatheter arterial chemoembolization (TACE) was not effective. After surgery, we initiated sorafenib treatment for the lung metastases. One year later, the lung metastases worsened and metastases were observed in the mediastinal lymph nodes, and both metastatic lesions were resected. Seven months later, para-aortic lymph nodal metastasis was observed and dissected. Three months later, metastasis to the supraclavicular lymph node was observed. We performed particle radiation therapy and a complete response was achieved. One year later, metastases in both lungs were observed and resected. Despite continued sorafenib administration throughout the clinical course, a metastasis to the left adrenal gland was observed. This lesion was extirpated because no other recurrent lesions were detected. At 4 years and 6 months after the first operation, no other recurrences have occurred. Currently, sorafenib is the initial drug of choice for HCC with extrahepatic metastases. It is possible to improve the prognosis of patients with HCC and extrahepatic metastases by applying surgical treatment during the course of sorafenib administration.

[A case of resection of a metastatic liver tumor that recurred after particle beam therapy].

Recently, the indications for particle beam therapy have been expanded to include metastatic liver tumors. However, its adverse effects on the treated liver are unclear, and the possibility of local recurrence after treatment should not be ignored. A 65-year-old man with advanced rectal carcinoma underwent low anterior resection. Resectable metastatic liver tumors were detected after adjuvant chemotherapy; however, he opted to undergo particle beam therapy. Nine months after treatment, a local recurrence was detected around the treated area, and central bisegmentectomy of the liver was performed as a salvage operation. The operation was technically complicated owing to severe adhesions and inflammatory changes in the liver parenchyma around the treated area. Pathological examination revealed advanced liver fibrosis at the treated area, in contrast with normal parenchyma in the untreated area. Although the procedure requires advanced surgical techniques, salvage surgery is a feasible option for recurrent liver tumors after particle beam therapy.

[Long-term survival in a patient receiving multidisciplinary therapy for hepatocellular carcinoma with left iliac bone metastasis].

The patient was a 79-year-old man diagnosed with a single 9.3-cm hepatocellular carcinoma (HCC) in the medial segment of the liver, and left iliac bone metastasis. Initially, the patient was treated with a hepatic arterial infusion of low-dose FP (cisplatin/5-fluorouracil) at another hospital. Here, the patient received particle therapy for the left iliac bone metastasis at a total dose of 52.8 Gy in 4 fractions. Subsequently, he underwent medial segmentectomy of the liver to treat the primary HCC. Eleven months later, the first intrahepatic recurrence occurred, and the tumor was treated with percutaneous radiofrequency ablation (RFA). A second intrahepatic recurrence was detected 39 months later, which was also treated with percutaneous RFA. The patient remains well, with no evidence of tumor recurrence.

[Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy].

Here, we report a case of Hassab's operation for left-sided portal hypertension after pancreatoduodenectomy. A 69-year old man underwent pancreatoduodenectomy for pancreatic cancer in 2006 in which the splenic vein was ligated near the portal vein and then divided. The patient suffered repeated episodes of anemia between 2010 and 2013. However, we could not identify the bleeding site at that time. In 2011, local recurrence was detected. Disease progression occurred despite chemotherapy treatment, which was then discontinued. The left-sided portal hypertension gradually progressed, and the collateral vessels became dilated. In 2014, he was examined in our department for gastrointestinal bleeding. An upper gastrointestinal endoscopy revealed bleeding from gastric varices. Gastrointestinal bleeding ceased after endoscopic injection sclerotherapy ( EIS) was performed; however, the bleeding recurred. Balloon retrograde transvenous occlusion (BRTO) could not be performed because blood flow was not detected within the gastro-renal shunt. An emergency surgery was performed. Surgical splenectomy and devascularization (Hassab's operation) were performed. After surgery, the gastric body varices and gastrointestinal anastomosis disappeared and the bleeding did not occur. He is currently receiving outpatient treatment.

[Analysis of the safety and efficacy of percutaneous isolated hepatic perfusion after particle therapy for advanced hepatocellular carcinoma].

Here, we report the efficacy of dual treatment with hepatic resection and percutaneous isolated hepatic perfusion (PIHP) for advanced hepatocellular carcinoma( HCC). Recently, we introduced treatment with combined particle therapy and PIHP for unresectable HCC in cases of insufficient liver function. The purpose of this study was to evaluate the safety and efficacy of PIHP for local control in the liver after particle therapy. From 2006 to 2013, 6 patients underwent particle therapy for the main lesion and subsequent PIHP for remnant liver lesions. Their mean age was 64 years, and the mean size of the main lesion was 6.2 cm (range, 2.0-10.8 cm). All patients had liver cirrhosis. After particle therapy, PIHP was performed by hepatic arterial infusion of 100 mg/m2 of doxorubicin and 30 mg/m2 of mitomycin C. With regard to side effects, neutropenia occurred in all patients but no serious hepatobiliary injury was observed. The response rate for PIHP was 50% (partial response: 3 and stable disease: 3). The mean overall survival time was 26.9 months after particle therapy. In conclusion, even after particle therapy, PIHP is a safe treatment and is associated with a good local control rate for remnant HCCs. Further accumulation of data is needed to evaluate the efficacy of this treatment strategy in terms of prognosis.

[The role of preoperative percutaneous isolated hepatic perfusion and hepatectomy in multidisciplinary treatment].

We report a case of multiple bilobar hepatocellular carcinoma( HCC) that was successfully treated with a multidisciplinary treatment including preoperative percutaneous isolated hepatic perfusion and hepatectomy. The patient was a 61- year-old man who was detected as having HCC mainly in segment 4 and 8 of the liver and multiple bilobar intrahepatic metastasis during follow-up evaluation for chronic hepatitis B. Curative resection was difficult because the patient had insufficient liver function and because of the location of the tumor. Hence, we performed preoperative percutaneous isolated hepatic perfusion (PIHP) to control the multiple HCC. Seven weeks after the PIHP, the tumor size had reduced, and therefore we performed an extended left hepatic lobectomy. In addition to these treatment modalities, we performed transcatheter arterial chemoembolization (TACE) 3 times owing to recurrent HCC in the right liver lobe. Considering that HCC in segment 8 can be treated with TACE, we performed partial hepatectomy. As of the last follow-up visit, the patient was alive without disease recurrence. Thus, preoperative PIHP may improve the resectability rate in patients with multiple bilobar HCC for which curative resection is difficult to perform.

[A case of duodenal carcinoid tumor accompanied by liver metastasis and lymph node metastases in a patient with von Recklinghausen disease].

We report a case of duodenal carcinoid tumor accompanied by liver metastasis and lymph node metastases in a patient with von Recklinghausen disease. A 48-year-old woman with von Recklinghausen disease was referred to our hospital because of a submucosal tumor at the ampulla of Vater detected by upper gastrointestinal endoscopy. The lesion was diagnosed as a carcinoid tumor based on the pathology of the biopsy specimen. At operation, although there were liver metastasis on the surface of S3 the liver and regional lymph node metastases, we selected pancreatoduodenectomy with lymph node dissection and enucleation of the liver metastasis. The postoperative course was good and the woman was discharged on postoperative day 33. No recurrence has been seen at 24 months since surgery.

Novel assessment of hepatic iron distribution by synchrotron radiation X-ray fluorescence microscopy.

Excess iron deposition in the liver is known to be hepatotoxic and may exacerbate liver injury. However, little is known about iron distribution in the lobule because of the lack of a highly sensitive detection method. The aim of this study is to determine iron distribution in the lobule of human liver by means of synchrotron radiation X-ray fluorescence (SRXRF) microscopy. Mapping of the trace elements was done with use of SRXRF microscopy and compared with the results of staining by Berlin blue and oxidative stress markers. Iron deposits were distributed predominantly in periportal hepatocytes in the normal liver in a decreasing gradient from the periportal area to the perivenous area. This distribution was consistent with the formation of oxidative stress markers, suggesting that hepatocytes in the periportal area may be predominantly primed by iron-induced free radical damage even in normal liver. On the other hand, iron deposits in the periportal area were more intense than those in the centrilobular area in both the liver with chronic hepatitis C and the cirrhotic liver. In conclusion, elemental mapping by SRXRF microscopy was a highly sensitive method for the detection and mapping of elements such as iron and copper in liver sections.