[A Case of Advanced Gastric Cancer Who Experienced Multiple Immune-Related Adverse Events with Nivolumab and SOX Therapy].

A 59-year-old woman who has HER2-negative advanced gastric cancer with peritoneal dissemination was treated with nivolumab plus SOX therapy as primary treatment, and hemorrhagic cystitis occurred on the 28th day after the 6 courses. On the 21st day after the 7 courses, right knee arthralgia appeared, and on the 26th day, she was admitted to the hospital due to a fever of 39℃ and anorexia. After admission, frequent diarrhea occurred and new symptoms of neck pain and left knee arthralgia appeared. Abdominal CT showed increased fatty tissue density around the sigmoid colon, and wall thickening and contrast enhancement of the mucosal surface of the bladder. Lower gastrointestinal endoscopy revealed the diffuse redness and erosions in some areas, and lymphocytic infiltration in the epithelium of the crypts was seen in biopsy from the erosions. The hemorrhagic cystitis was aseptic pyuria. Therefore, we suspected that the series of symptoms were immune-related adverse events(irAE)and started prednisolone 50 mg(1 mg/kg/day), which quickly relieved the diarrhea, cystitis and arthralgia. As a result, the patient was diagnosed as having irAE. We report a case of advanced gastric cancer who experienced multiple irAE with nivolumab plus SOX therapy, with some discussion of the literature.

[A Case of Resection of Primary Hepatic Neuroendocrine Tumor].

Neuroendocrine tumors(NET)often occur in the digestive tract, pancreas, and lungs. Primary hepatic neuroendocrine tumor(PHNET)is extremely rare and has a high malignancy and poor prognosis. Diagnosis is extremely difficult only by imaging findings, and in majority of the cases, definitive diagnosis is produced by an excisional biopsy. We report a case of PHNET diagnosed by preoperative liver tumor biopsy and underwent surgical resection. A 60's man was admitted with the main complaint of weight loss. Image examination(abdominal echo, CT, MRI)revealed continuous tumors of 6 cm and 5 cm in the liver S4 to S8 area, respectively, and a tumor of <1 cm in the S5 and S7 areas. When liver biopsy was performed, immunostaining revealed that it was chromogranin A-positive. Therefore, it was diagnosed as NET. No other lesions were observed in PET-CT, and the patient was diagnosed with PHNET. Extended left hepatectomy and partial S5/S7 liver resections were performed. The pathological diagnosis was NET and Ki-67 index was 7%, which was equivalent to NET G2 in the WHO classification.

[A Case of Simultaneous Laparoscopic Surgery for Intrahepatic Cholangiocarcinoma and Sigmoid Colon Cancer].

The patient was an 83-year-old woman. CT scan showed a 20 mm mass in the surgical anatomy of the medial segment (S4)of the liver, but the patient refused to undergo surgery and continued periodic clinical follow-up. After 1 year and 3 months of initial examination, a CT scan showed an enlargement of 36 mm. Therefore, surgical treatment was adopted. Preoperative lower gastrointestinal endoscopy revealed a type 1 tumor of the sigmoid colon quarter circumference 30 mm from the anal verge, and the biopsy led to a diagnosis of adenocarcinoma equivalent to tub 1. The hepatic mass showed heterogeneous contrast effect centered on the arterial phase margins and prolonged contrast effect in the equilibrium phase. Since the liver tumor was a single S4 mass with a 36 mm diameter, laparoscopic sigmoidectomy and laparoscopic partial hepatic resection were performed subsequently. Pathology results showed that the sigmoid colon tumor and hepatic S4 mass were predominantly well-differentiated and moderately-differentiated adenocarcinomas, respectively. Immunohistochemical results were cytokeratin 7 antibody-positive and cytokeratin 20 antibody-negative, leading to a definitive diagnosis of intrahepatic cholangiocarcinoma. The patient's postoperative course was well and was discharged from the hospital on postoperative day 12. After 1 year postoperatively, the patient remains recurrence-free.

[A Case on the Long‒Term Effect of Imatinib on GIST of Unknown Primary Origin with Multiple Liver Metastases, Peritoneal Dissemination, and Bone Metastasis].

A 61‒year‒old woman observed that she had a lower limb edema approximately 1 month ago and began to feel a general malaise. The symptom was caused by multiple liver metastases, and the primary lesion was suspected to be an ovarian cancer. Peritoneal disseminations throughout the abdominal cavity were found in the exploratory laparotomy. No obvious primary lesion could be found in the searchable gastrointestinal tract. The patient was diagnosed with a gastrointestinal stromal tumor(GIST)based on the biopsy results of the peritoneal dissemination. Treatment with imatinib mesylate(imatinib) was initiated 13 days after surgery. The severe lower extremity edema disappeared within 2 months. Computed tomography (CT)scan showed a reduction of the multiple liver metastases and peritoneal dissemination, and the appearance and increase of calcifications in the tumor and cystic degeneration inside the liver metastasis. The abnormal accumulation observed by bone scintigraphy also disappeared. Imatinib has a long‒term effect on GIST of unknown primary origin with multiple liver metastases, peritoneal dissemination, and bone metastasis. Five years after the initiation of the treatment, the patient is still alive, and new lesions have not developed.

Timing of resumption of immune checkpoint inhibitor therapy after successful control of immune-related adverse events in seven advanced non-small cell lung cancer patients.

Among advanced non-small cell lung cancer (NSCLC) patients in whom grade 2/3 immune-related adverse events (irAEs) that had developed during the initial immune checkpoint inhibitor (ICI) therapy had been successfully controlled, we experienced three patients in whom ICI therapy was resumed at the diagnosis of progressive disease (PD group, n = 3) and four patients in whom it was resumed immediately after successful control of irAEs (non-PD group, n = 4). The tumor response rate, disease control rate to the resumed ICI and progression-free survival from the resumption of ICI therapy were 0%, 0% and 2 months in the PD group and 25%, 75% and 4.8 months in the non-PD group. In advanced NSCLC patients in whom resumption of discontinued ICI therapy was planned, the ICI therapy should be resumed immediately after successful control of irAEs, rather than at the diagnosis of PD.

Chemotherapy should be performed in epidermal growth factor receptor mutation-positive lung adenocarcinoma patients who had progressive disease to the first epidermal growth factor receptor-tyrosine kinase inhibitor.

After the failure of first-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, some non-small cell lung cancer patients desire to receive switching with another EGFR-TKI (TKI-switching), although cytotoxic chemotherapy has been recommended as second-line therapy. It is unclear who should not receive TKI-switching in these patients. We retrospectively evaluated overall survival (OS) from the initiation of first EGFR-TKI (first-TKI) therapy in advanced lung adenocarcinoma patients with active EGFR mutations (deletion of exon 19 or L858R in exon 21) who received TKI-switching according to the best response of the first-TKI. There was no difference in the OS between patients receiving TKI-switching (n = 35) and patients receiving additional chemotherapy between the first-TKI and second-TKI therapy (n =10) (P = 0.614). Among patients receiving TKI-switching, the OS in cases with progressive disease to the first-TKI (n = 9) was shorter than that in cases with disease control to the first-TKI (n = 26) (12.7 months vs. 49.4 months, P < 0.001). Five of the nine progressive disease cases who received TKI-switching missed an opportunity to receive chemotherapy. Their OS tended to be shorter than that in patients who received chemotherapy during the whole period of anticancer therapy (12.2 months vs. 20.3 months, P = 0.060). The multivariate analysis showed that disease control to the first-TKI therapy (P = 0.005) or the presence of chemotherapy (P = 0.087) decreased the risk of mortality. Chemotherapy should be performed in patients with progressive disease to the first-TKI.

[A Case of Thyroid and Endotracheal Metastasis from Rectal Cancer].

A 75-year-old woman previously underwent low anterior resection for rectal cancer(pT3N0M1a[PUL1], Stage Ⅳa)in October 2012. We administered 7 courses of mFOLFOX6 plus bevacizumab(BV)followed by oral UFT/LV for 6 months. In November 2014, we performed partial lung resection for relapsing metastatic lung tumor. In April 2017, we performed right lower lobectomy for recurrence at the site of partial resection. In October 2018, since serum CEA was gradually elevated, FDG-PET was performed for metastasis. FDG-PET indicated FDG accumulation in the left neck and the trachea. Enhanced CT revealed the thyroid tumor, an enlarged cervical lymph node and a small nodule in the trachea. Needle aspiration cytology of the thyroid tumor and the lymph node showed Class Ⅴ(adenocarcinoma). Bronchoscopy indicated a polypoid tumor Class Ⅴ(adenocarcinoma). After 18 courses of FOLFIRI plus BV, all metastases were reduced significantly. We conclude that FOLFIRI plus BV seems to be effective for patients with thyroid and endotracheal metastasis from rectal cancer.

Significance of neoadjuvant therapy for borderline resectable pancreatic cancer: a multicenter retrospective study.

PURPOSE: Neoadjuvant therapy (NAT) is increasingly used to improve the prognosis of patients with borderline resectable pancreatic cancer (BRPC) albeit with little evidence of its advantage over upfront surgical resection. We analyzed the prognostic impact of NAT on patients with BRPC in a multicenter retrospective study. METHODS: Medical data of 165 consecutive patients who underwent treatment for BRPC between January 2010 and December 2014 were collected from ten institutions. We defined BRPC according to the National Comprehensive Cancer Network guidelines, and subclassified patients according to venous invasion alone (BR-PV) and arterial invasion (BR-A). RESULTS: The rates of NAT administration and resection were 35% and 79%, respectively. There were no significant differences in resection rates and prognoses between patients in the BR-PV and BR-A subgroups. NAT did not have a significant impact on prognosis according to intention-to-treat analysis. However, in patients who underwent surgical resection, NAT was independently associated with longer overall survival (OS). The median OS of patients who underwent resection after NAT (53.7 months) was significantly longer than that of patients who underwent upfront (17.8 months) or no resection (14.9 months). The rates of superior mesenteric or portal vein invasion, lymphatic invasion, venous invasion, and lymph node metastasis were significantly lower in patients who underwent resection after NAT than in those who underwent upfront resection despite similar baseline clinical profiles. CONCLUSIONS: Resection after NAT in patients with BRPC is associated with longer OS and lower rates of both invasion to the surrounding tissues and lymph node metastasis.

[A Case of Metaplastic Squamous Cell Carcinoma of the Breast Successfully Treated with S-1].

Metaplastic squamous cell carcinoma(MSCC)of the breast is very unusual and is histologically characterized by rapid progression. Conventionalchemotherapy for ductalcarcinoma of the breast is ineffective against MSCC. Here, we report a case of MSCC of the breast successfully treated with S-1. A 57-year-old woman was admitted to our hospital because of a left breast tumor. A tumor approximately 10 cm in diameter was palpable in the lower-outer quadrant(D region)of the left breast. Core needle biopsy indicated estrogen receptor(ER)-negative, progesterone receptor(PR)-negative, and human epidermalgrowth factor receptor 2(HER2)-negative MSCC of the breast. Computed tomography(CT)showed left axillary lymph node metastases but did not indicate distant metastasis. A diagnosis of T4N3cM0, Stage ⅢC, MSCC of the left breast was made. Each treatment course consisted of the administration of S-1(120mg/body/day)for 4weeks, followed by 2 drugfree weeks. After the second course, significant tumor and lymph node reduction was observed. We concluded that S-1 chemotherapy seems to be effective for patients with MSCC of the breast.

[Questionnaire Survey on Adjuvant Chemotherapy for Colorectal Cancer in Yamaguchi Prefecture].

A questionnaire survey on postoperative chemotherapy for colorectal cancer was conducted in 22 hospitals in Yamaguchi Prefecture. Adjuvant chemotherapy was performed in<95% of Stage Ⅲ cancer, and oxaliplatin(OX)combination therapy was selected depending on the risk of recurrence. However, the proportion of OX combination therapy was lower than that in other prefectures, which was 24% in Stage Ⅲa, 44% in Ⅲb, and 76% in Ⅲc. In addition, among the OX combination therapy regimens(FOLFOX or CAPOX), the proportion of FOLFOX administration was higher in Yamaguchi Prefecture than in other prefectures. In Stage Ⅱ, most hospitals set up high-risk factors for recurrence and underwent adjuvant chemotherapy. FU-based monotherapy was selected in 80% of hospitals. A few hospitals decided the requirement of OX combination therapy based on age alone. In Yamaguchi Prefecture, the indication of postoperative adjuvant chemotherapy for colorectal cancer was almost standard; however, the rate of administering OX combination therapy was low.

Metastatic ability and the epithelial-mesenchymal transition in induced cancer stem-like hepatoma cells.

Cancer stem cells (CSCs) are thought to play important roles in cancer malignancy. Previously, we successfully induced sphere cancer stem-like cells (CSLCs) from several cell lines and observed the property of chemoresistance. In the present study, we examined the metastatic potential of these induced CSLCs. Sphere cancer stem-like cells were induced from a human hepatoma cell line (SK-HEP-1) in a unique medium containing neural survival factor-1. Splenic injection of cells into immune-deficient mice was used to assess hematogenous liver metastasis. Transcriptomic strand-specific RNA-sequencing analysis, quantitative real-time PCR, and flow cytometry were carried out to examine the expression of epithelial-mesenchymal transition (EMT)-related genes. Splenic injection of CSLCs resulted in a significantly increased frequency of liver metastasis compared to parental cancer cells (P < .05). In CSLCs, a mesenchymal marker, Vimentin, and EMT-promoting transcription factors, Snail and Twist1, were upregulated compared to parental cells. Correspondingly, significant enrichment of the molecular signature of the EMT in CSLCs relative to parental cancer cells was shown (q < 0.01) by RNA-sequencing analysis. This analysis also revealed differential expression of CD44 isoforms between CSLCs and parental cancer cells. Increasing CD44 isoforms containing an extra exon were observed, and the standard CD44 isoform decreased in CSLCs compared to parental cells. Interestingly, another CD44 variant isoform encoding a short cytoplasmic tail was also upregulated in CSLCs (11.7-fold). Our induced CSLCs possess an increased liver metastatic potential in which promotion of the EMT and upregulation of CD44 variant isoforms, especially short-tail, were observed.

Low invasiveness of thoracoscopic esophagectomy in the prone position for esophageal cancer: a propensity score-matched comparison of operative approaches between thoracoscopic and open esophagectomy.

BACKGROUND: In this study, cytokine levels, outcome, and survival rates after esophagectomy for esophageal cancer were retrospectively investigated in a propensity score-matched comparison of operative approaches between the thoracoscopic esophagectomy (TE) in the prone position and open esophagectomy (OE). PATIENTS AND METHODS: Between 2005 and 2014, TE was performed on a group of 85 patients, which was compared with a group of 104 OE cases. Eventually, 65 paired cases were matched using propensity score matching. RESULTS: Although the TE group underwent a significantly longer operation time than the OE group (P < 0.001), the TE group exhibited less blood loss (P < 0.001) and had a shorter postoperative hospital stay (P = 0.038) than the OE group. The serum interleukin-6 levels on ICU admission (P < 0.001) and on POD 1 (P < 0.001) were significantly lower in the TE group. The interleukin-10 levels on ICU admission (P < 0.001), POD 1 (P = 0.016), and POD 3 (P < 0.001) were also significantly lower in the TE group. Pulmonary complication was significantly lower in the TE group (P = 0.043). The 5-year PFS rates in the TE and OE groups were 70.6 and 58.7% (P = 0.328), respectively, and OS rates were 64.9 and 50.2% (P = 0.101), respectively. CONCLUSION: TE compared to OE is a less invasive procedure with lower surgical stress and less pulmonary complication for the treatment of esophageal squamous cell carcinoma.

Outcomes of surgery for hepatocellular carcinoma with tumor thrombus in the inferior vena cava or right atrium.

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is extremely poor. We reviewed the recent surgical treatments and outcomes of this form of advanced HCC. TT is classified into three types according to its anatomic location relative to the heart: the inferior hepatic type (type I), where the TT is in the IVC below the diaphragm; the superior hepatic type (type II), where the TT is in the IVC above the diaphragm, but still outside the RA; and the intracardiac type (type III), where the TT is above the diaphragm and has entered the RA. Type I can be treated relatively easily by standard radical hepatectomy. For type II, the intrathoracic IVC is approached via the abdominal cavity and an incision in the diaphragm with total hepatic vascular exclusion (THVE). For type III, hepatectomy plus thrombectomy is generally performed under cardiopulmonary bypass. If the TT is only just inside the RA, THVE can be performed by mobilizing the liver caudally. The median overall survival of HCC patients with TT in the IVC or RA, who undergo curative resection, is 19.0-30.8 months. As postoperative recurrence is likely to develop, even after curative surgery, effective postoperative adjuvant chemotherapy is required.

[A Case of Chest Wall Metastasis after Surgery for Lower Bile Duct Carcinoma].

A 76-year-old woman with lower bile duct carcinoma underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD)after percutaneous transhepatic biliary drainages(PTBD). Nine months after the operation, chest computed tomography revealed a mass in the subcutis of the right chest wall, which was a different lesion from that in the PTBD site. The aspiration biopsy cytology and needle biopsy indicated no malignant findings. However, the mass was growing and was suspected to be a metastasis of bile duct cancer. We resected the mass, including portions of the sixth and seventh ribs. The pathological diagnosis was metastasis of bile duct carcinoma. The postoperative course was uneventful. Now, 2 years have passed since the resection of the primary lesion and 9 months since the resection of the chest wall metastasis. Thus far, no manifestations of recurrence have been observed, and the patient has been in a favorable condition. We report this case with a literature review.

[A Case of Advanced Breast Cancer with Improvement in the Quality of Life by Local Treatment Using Mohs Paste and Systemic Pharmacotherapy].

Locally advanced breast cancer with skin invasion often causes malodor, bleeding, and massive exudates, which degrades patients' quality of life(QOL). A 61-year-old woman presented with locally advanced breast cancer with malodor and massive exudates, which had carcinomatous pleurisy causing dyspnea. We administered endocrine therapy and chemotherapy and used Mohs paste for local therapy. The exposed part of the tumor was fixed using Mohs paste. After continuing to apply Vaseline over the fixed part, the lesion spontaneously detached without surgical removal and completely epithelized, and malodor and exudates disappeared. Cancerous pleurisy also improved, and dyspnea disappeared. Local treatment using Mohs paste and systemic pharmacotherapy dramatically improved her QOL.

[Three Cases of Obstructive Left-Sided Colon Cancer Resected by Laparoscopic Surgery].

We report 3 cases of obstructive left-sided colon cancer that could be treated with laparoscopic resection.Case 1: A 25- year-old man was given a diagnosis of colonic obstruction due to transverse colon cancer.Twenty -four days after decompression by a nasointestinal tube, we performed a laparoscopic partial colectomy.Case 2: A 75-year-old woman was given a diagnosis of colonic obstruction due to sigmoid colon.Forty -nine days after decompression by a laparoscopic transverse colostomy, we performed a laparoscopic sigmoidectomy.Case 3: A 48-year-old man was given a diagnosis of colonic obstruction due to sigmoid colon cancer.Twenty -two days after decompression by colonic stent, we performed a laparoscopic sigmoidectomy.In these 3 cases, decompression was sufficient when resecting the primary lesions, and the operations could be completed laparoscopically.Elective radical surgery was possible by resolution of oncologic emergency state.

Cetuximab strongly enhances immune cell infiltration into liver metastatic sites in colorectal cancer.

Cetuximab has activity against colorectal cancers. Recent studies demonstrated that cetuximab induces antibody-dependent cell-mediated cytotoxicity via immune cells, and a new immune-related mechanism of inducing immunogenic cell death. This study aimed to evaluate the immune responses induced by cetuximab in tumor microenvironments at liver metastasis sites of metastatic colorectal cancer patients. We assessed immune cell infiltration in the liver metastatic sites of 53 colorectal cancer patients. These patients were divided into three groups according to the treatment before operation: chemotherapy with cetuximab, chemotherapy without cetuximab, and no chemotherapy. The inflammatory cells in the liver metastatic sites were assessed by hematoxylin-eosin staining, focusing on the invasive margin. The overall inflammatory reaction and number of lymphoid cells were assessed with a four-point scoring system. We then assessed immune cell infiltration (CD3, CD8 and CD56) in 15 liver metastatic sites. Hematoxylin-eosin staining demonstrated more inflammatory cells in the chemotherapy with cetuximab group than in the other groups (P < 0.001). Of note, inflammatory cells were found in intratumoral areas, and the destruction of cancer cell foci was observed in the chemotherapy with cetuximab group. Moreover, a higher infiltration of CD3+ (P = 0.003), CD8+ (P = 0.003) and CD56+ (P = 0.001) cells was observed in the chemotherapy with cetuximab group than in the other groups. These results suggest that cetuximab might have an immune-enhancing effect. As such, the immune-related mechanism of action of cetuximab may enhance the efficacy of combination therapy, such as chemotherapy and immunotherapy using therapeutic peptides.

miR-125b-1 and miR-378a are predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer.

Many clinical trials of peptide vaccines have been conducted. However, these vaccines have provided clinical benefits in only a small fraction of patients. The purpose of the present study was to explore microRNAs (miRNAs) as novel predictive biomarkers for the efficacy of vaccine treatment against colorectal cancer. First, we carried out microarray analysis of pretreatment cancer tissues in a phase I study, in which peptide vaccines alone were given. Candidate miRNAs were selected by comparison of the better prognosis group with the poorer prognosis group. Next, we conducted microarray analysis of cancer tissues in a phase II study, in which peptide vaccines combined with chemotherapy were given. Candidate miRNAs were further selected by a similar comparison of prognosis. Subsequently, we carried out reverse-transcription PCR analysis of phase II cases, separating cancer tissues into cancer cells and stromal tissue using laser capture microdissection. Treatment effect in relation to overall survival (OS) and miRNA expression was analyzed. Three miRNA predictors were negatively associated with OS: miR-125b-1 in cancer cells (P = 0.040), and miR-378a in both cancer cells (P = 0.009) and stromal cells (P < 0.001). Multivariate analysis showed that expression of miR-378a in stromal cells was the best among the three predictors (HR, 2.730; 95% CI, 1.027-7.585; P = 0.044). In conclusion, miR-125b-1 and miR-378a expression might be considered as novel biomarkers to predict the efficacy of vaccine treatment against colorectal cancer.

Novel Indications for Surgical Resection of Metachronous Lung Metastases From Pancreatic Cancer After Curative Resection.

Few reports exist regarding surgical resection of metachronous lung metastases (MLM) from pancreatic ductal adenocarcinoma (PDA) after curative resection. To elucidate the indications for surgical resection of MLM and long-term survival, we analyzed Japanese case reports of MLM from PDA. Between 1983 and 2014, 17 Japanese case reports concerning surgical resection of MLM from PDA were published. We determined long-term survival in 16 patients (considering the published data of 15 patients and 1 of our own) by using a questionnaire survey and analyzing the relationships between background factors and long-term survival. In 16 patients with long-term survival, 4 patients were still alive without recurrence. The remaining 12 patients died of disease after recurrence. The median survival after the initial lobectomy was 37 months and the 3- and 5-year survival for all patients after lobectomy was 50% and 41%, respectively. Fourteen patients had a disease-free interval after initial resection of the primary pancreatic tumor of >20 months. These patients had a longer median survival period after lobectomy (46 vs. 25.5 mo, P=0.19). Seven patients had MLM of <16 mm. These patients had a statistically longer overall survival after lobectomy (83 vs. 16 mo, P=0.04). Three of 4 patients with primary stage I tumors were still alive without recurrence. We found that the conventional criteria for surgical resection of MLM from PDA (first disease-free interval of >20 mo with no other metastatic lesions) were appropriate. In addition, it is possible that MLM of <16 mm or primary stage I tumors are novel criteria.

Surgical treatment for advanced hepatocellular carcinoma with portal vein tumor thrombus.

The Barcelona Clinic Liver Cancer staging system recommends a tyrosine kinase inhibitor (sorafenib) as standard therapy in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). Sorafenib has been shown to prolong median overall survival (OS) by approximately 3 months in advanced HCC patients with PVTT (8.1 vs. 4.9 months). However, its clinical effectiveness is still controversial and standard treatment with sorafenib is not established in Japan. Surgical resection is considered a potentially curative treatment and provides an acceptable outcome for carefully selected patients. The surgical mortality rate in patients with PVTT who receive surgical resection ranges from 0% to 10%. The median survival time and 1-year OS rate in HCC patients with PVTT who undergo surgical resection have been found to range from 8 to 22 months and 21.7% to 69.6%, respectively. But improvement in therapeutic outcome is difficult with surgical treatment alone. Combination treatment in conjunction with such methods as transarterial chemoembolization, hepatic artery infusion chemotherapy, and radiotherapy has been found to improve the prognosis (median survival time, 11.5-37 months; 1-year OS rate, 46.8-100%). Yet, many problems remain, such as surgical indications and surgical techniques. After resolving these points, a multidisciplinary strategy based on surgical treatment should be established for advanced HCC with PVTT.