ABSTRACT
BACKGROUND: The effect of cetuximab plus mFOLFOX on downsizing of the tumors for curative resection has yet to be assessed for patients with advanced colorectal liver metastases (CRLMs). This study aimed to assess the oncologic benefit of cetuximab plus mFOLFOX for wild-type KRAS patients with advanced CRLMs. METHODS: In this multicenter phase 2 trial, patients with technically unresectable tumor and/or five or more CRLMs harboring wild-type KRAS were treated with mFOLFOX plus cetuximab. The patients were assessed for resectability after 4 treatments, and then every 2 months up to 12 treatments. Patients with resectable disease were offered surgery after a waiting period of 1 month. The primary end point of the study was the R0 resection rate. The secondary end points were safety, progression-free survival (PFS), and overall survival (OS). The study is registered with the University Hospital Medical Information Network-Clinical Trials Registry Clinical Trials Registry (no. C000007923). RESULTS: Between 2012 and 2015, 50 patients from 13 centers were enrolled in this trial. Two patients were excluded because they had not received induction therapy. The 48 patients had a complete response rate of 0% and a partial response rate of 64.6%. For 26 R0 resections (54.2%) and 5 R1 resections (10.4%), no mortality occurred. During a median follow-up period of 31 months, the median OS for all the patients was calculated to be 41 months (95% confidence interval, 28-not reached). The 3-year OS rate was 59%. CONCLUSION: For patients with advanced CRLMs harboring wild-type KRAS, cetuximab administered in combination with mFOLFOX yields high response rates, leading to significantly high R0 resection rates and favorable prognoses.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Liver Neoplasms , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cetuximab/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/surgery , Combined Modality Therapy , Cytoreduction Surgical Procedures , Fluorouracil/administration & dosage , Humans , Induction Chemotherapy , Leucovorin/administration & dosage , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Organoplatinum Compounds/administration & dosageABSTRACT
Undifferentiated pleomorphic sarcoma (UPS) is a soft tissue sarcoma, occurring most commonly on the lower extremities. We herein report a rare case of primary UPS adjacent to the ascending colon and in the right iliopsoas muscle. Computed tomography of the abdomen revealed large masses, and the patient experienced a high-grade fever, leukocytosis, elevated serum C-reactive protein level, and hematopoietic activation on 18F-fluorodeoxyglucose-positron emission tomography. This inflammatory reaction was caused by granulocyte colony-stimulating factor secreted by tumor cells. Surgical resection was performed, and the inflammatory reaction disappeared immediately. The patient received adjuvant chemotherapy and survived one year after the operation without evidence of recurrence.
Subject(s)
Colon, Ascending/diagnostic imaging , Granulocyte Colony-Stimulating Factor/metabolism , Liposarcoma/diagnosis , Psoas Muscles/diagnostic imaging , Humans , Liposarcoma/metabolism , Male , Middle Aged , Positron-Emission Tomography , Thigh , Tomography, X-Ray ComputedABSTRACT
BACKGROUND: In biliary tract cancer treatment, a precise preoperative evaluation of the patient's liver function is essential to avoid post-hepatectomy liver failure (PHLF) and mortality. The present study aimed to evaluate the role of the Albumin-Indocyanine Green Evaluation (ALICE) grading system in predicting PHLF in biliary tract cancer patients. METHODS: Data from 166 patients who underwent hepatectomy for biliary tract cancer between 2000 and 2016 were retrospectively analyzed. Univariate and multivariate analyses were performed to identify the risk factors for PHLF. RESULTS: Among the 166 patients, major hepatectomy was performed in 101 (61%) and bile duct resection was performed in 99 (60%) patients. Thirteen (8%) patients developed PHLF. Furthermore, PHLF, major complications, and mortality were significantly higher in patients with high ALICE grades (≥2b) than in those with low ALICE grades (<2b) (PHLF, 42 vs. 18%, p = 0.002; major complications, 35 vs. 19%, p = 0.036; mortality, 9.3 vs. 0%, p = 0.001). In multivariate analysis, high ALICE grade (p = 0.016) and blood loss ≥1,500 mL (p = 0.009) were identified as independent risk factors for PHLF. CONCLUSIONS: The ALICE grading system effectively stratified the risks for PHLF for biliary tract cancer.
Subject(s)
Biliary Tract Neoplasms/surgery , Coloring Agents/pharmacokinetics , Hepatectomy/adverse effects , Indocyanine Green/pharmacokinetics , Liver Failure/etiology , Serum Albumin/metabolism , Aged , Blood Loss, Surgical , Female , Hepatobiliary Elimination , Humans , Liver Function Tests/methods , Male , Metabolic Clearance Rate , Middle Aged , Postoperative Complications/etiology , Predictive Value of Tests , Preoperative Period , Retrospective Studies , Survival RateABSTRACT
PURPOSE: Splenic infarction may occur if the splenic branches are injured or ligated accidentally during gastrectomy. We used three-dimensional computed tomography (3D-CT) imaging to distinguish the vascular anatomy of the splenic hilum in individual patients, focusing on the splenic polar branches and the gastric branches. METHODS: The subjects of this study were 104 patients who underwent computed tomography (CT) with intravenous contrast before gastrectomy. SYNAPSE 3D® (Fujifilm Medical, Tokyo, Japan) was used to generate the 3D-CT images. The total spleen volume and the area supplied by the superior polar artery (SPA) in each patient were estimated using the "liver analysis" function. RESULTS: The SPA without the gastric branch (supplying only the spleen), the SPA with the gastric branch (supplying both the stomach and the spleen), and the posterior gastric artery (supplying only the stomach) were present in 14, 45, and 18% of the patients, respectively. The SPA supplied 12% of the total spleen volume on average; however, it supplied over 30% in two patients. CONCLUSION: We identified the vascular anatomy around the splenic hilum in over 100 patients. Based on our findings, we recommend preservation of the SPA when it is supplying a large area of the spleen. Preoperative 3D-CT analysis provides useful information to optimize safe gastrectomy.
Subject(s)
Gastrectomy , Imaging, Three-Dimensional , Spleen/blood supply , Splenic Artery/anatomy & histology , Splenic Artery/diagnostic imaging , Splenic Vein/anatomy & histology , Splenic Vein/diagnostic imaging , Stomach Neoplasms/surgery , Tomography, X-Ray Computed , Adult , Aged , Aged, 80 and over , Female , Humans , Intraoperative Complications/prevention & control , Male , Middle Aged , Organ Sparing Treatments , Splenic Infarction/prevention & controlABSTRACT
BACKGROUND: The role of adjuvant chemotherapy has not yet been established for patients with resected biliary tract cancer. S-1 has been shown to exert activity against advanced biliary tract cancer. Therefore, we evaluated the feasibility of adjuvant chemotherapy with S-1 in patients with resected biliary tract cancer. METHODS: Patients with complete macroscopic resection of intrahepatic/extrahepatic bile duct, gall bladder, or ampullary cancer were eligible. S-1 was administered orally twice daily for 4 weeks every 6 weeks, up to 4 cycles. The treatment was continued up to 24 weeks or until recurrence/appearance of unacceptable toxicity. The primary endpoint was the treatment completion rate, which was defined as the percentage of patients who received a relative dose intensity of ≥ 75%. This trial was registered as UMIN000004051. RESULTS: Thirty-three patients were enrolled between June 2010 and March 2011. The relative dose intensity was ≥ 75% in 27 patients representing a treatment completion rate of 81.8%. The most common grade 3/4 adverse event was neutropenia (18%). Grade 2 nausea or diarrhea was observed in 12%. The 3-year relapse-free survival rate was 39.4%. The 3-year survival rate was 54.5%. CONCLUSION: Adjuvant chemotherapy with S-1 is feasible treatment in patients with resected biliary tract cancer. It is necessary to conduct a phase III study to confirm the efficacy of adjuvant therapy of S-1 in patients with resected BTC.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Biliary Tract Neoplasms/drug therapy , Carcinoma, Papillary/drug therapy , Carcinoma, Signet Ring Cell/drug therapy , Neoplasm Recurrence, Local/diagnosis , Oxonic Acid/therapeutic use , Tegafur/therapeutic use , Adult , Aged , Biliary Tract Neoplasms/pathology , Biliary Tract Neoplasms/surgery , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Carcinoma, Signet Ring Cell/pathology , Carcinoma, Signet Ring Cell/surgery , Chemotherapy, Adjuvant , Drug Combinations , Feasibility Studies , Female , Humans , Male , Middle Aged , Neutropenia/chemically induced , Postoperative Period , Prognosis , Survival Rate , Young AdultABSTRACT
We experienced 3 impressive colorectal cancer patients who developed peritoneal recurrences and underwent surgery several times and survived for more than 5 years. Case No. 1 was of a 44-year-old woman who underwent right hemicolectomy for her stage II A ascending colon cancer. She developed left ovarian metastasis, which was resected 3 years later. Five years later, she developed a pelvic peritoneal recurrence, which was resected successfully. Thirteen years later, she is doing well. Case No. 2 was of a 61-year-old man who underwent transverse colectomy for his stage II B colon cancer. He developed ileus 2 years 9 months later due to peritoneal recurrence, which was removed successfully. He underwent another resection for peritoneal metastasis 2 years 6 months later. He was administered 15 courses of FOLFOX6. He has remained cancer-free since 2009. Case No. 3 was of a 62-year-old man who underwent sigmoidectomy for his stage II A colon cancer. One year 8 months later, he underwent resection for a painful abdominal wall metastasis. Eight months later, he developed another abdominal wall recurrence, which was resected successfully. He underwent thoracoscopic resection 4 times for lung metastases and was given 16 courses of FOLFOX6. In 2009, he developed pelvic peritoneal nodules, which were resected. He later needed lymphadenectomy twice. He has remained cancer-free for the last 5 years and 6 months. Curative resection must be performed for a patient with peritoneal recurrence of colorectal cancer when surgery is indicated.
Subject(s)
Colonic Neoplasms/pathology , Peritoneal Neoplasms/secondary , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colectomy , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery , Female , Humans , Male , Middle Aged , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial. METHODS: Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m2 weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles). HRQOL was assessed using the EuroQol-5D-3L (EQ-5D) questionnaire at baseline, months three and six, and every 6 months thereafter. HRQOL end-points included change in EQ-5D index from baseline, responses to five items in the EQ-5D, and quality-adjusted life months up to 24 months. RESULTS: Of randomised 385 patients, 354 patients were included in HRQOL analysis. Mean change in the EQ-5D index was similar in the S-1 and gemcitabine groups within 6 months from treatment initiation (difference, 0.024; P = 0.112), whereas corresponding mean from 12 to 24 months was better in the S-1 group than in the gemcitabine group (difference, 0.071; P < 0.001). Problems in mobility and pain/discomfort were also less frequent in the S-1 group than in the gemcitabine group in that period. Quality-adjusted life months were longer in the S-1 group than in the gemcitabine group (P < 0.001). CONCLUSION: Adjuvant chemotherapy with S-1 does not improve HRQOL within 6 months from treatment initiation but does improve HRQOL thereafter and quality-adjusted life months. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000000655 at UMIN CTR.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pancreatic Neoplasms/drug therapy , Quality of Life , Aged , Chemotherapy, Adjuvant , Combined Modality Therapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Drug Combinations , Female , Follow-Up Studies , Humans , Male , Oxonic Acid/administration & dosage , Pancreatectomy , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/surgery , Prognosis , Survival Rate , Tegafur/administration & dosage , GemcitabineABSTRACT
Few cases of recurrent colorectal carcinomas were treated non-surgically and cured. Here, we report 3 such cases. Case No. 1 was of a 66-year-old woman, who underwent ISR for very low rectal cancer. Her disease Stage was tub2, T2N0M0. Two years and 6 months later, she developed intrapelvic recurrence involving sacral bones(S1-S3). Radiotherapy of 50 Gy followed by mFOLFOX6 with bevacizumab was administered for a year. She has been cancer-free for 6 years. Case No. 2 was of a 47-year-old man who underwent preoperative CRT of 40 Gy with 5-FU plus Leucovorin, and LAR was performed for very low rectal cancer. The disease Stage was tub2, T3N2M0. One year later, he was diagnosed with recurrent aortic lymph node metastasis. After 7 months of mFOLFOX6 with bevacizumab, he developed an anastomotic fistula. His chemotherapy was discontinued; he was cancer-free for 6 years. Case No. 3 was of a 56-year-old man who underwent TPE for low rectal cancer. The disease Stage was muc, T4b(urinary bladder)N0M1a(perianal skin). One year and 6 months later, he developed ileus and was diagnosed with intrapelvic recurrence. He underwent intestinal bypass operation, and CRT of 46 Gy with capecitabine was administered. He attained CR quickly, and was cancer-free for 5 years. Collecting similar cases to analyze the key to successful treatment is important.
Subject(s)
Rectal Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Male , Middle Aged , Rectal Neoplasms/drug therapy , Treatment OutcomeABSTRACT
INTRODUCTION: We investigated the impact of mutations in KRAS exons 3-4 and NRAS exons 2-3 in addition to KRAS exon 2, so-called all-RAS mutations, in patients with colorectal liver metastasis (CLM) undergoing hepatic resection. METHODS: We analyzed 421 samples from CLM patients for their all-RAS mutation status to compare the overall survival rate (OS), recurrence-free survival rate (RFS), and the pattern of recurrence between the patients with and without RAS mutations. RESULTS: RAS mutations were detected in 191 (43.8%). Thirty-two rare mutations (12.2%) were detected in 262 patients with KRAS exon 2 wild-type. After excluding 79 patients who received anti-EGFR antibody therapy, 168 were classified as all-RAS wild-type, and 174 as RAS mutant-type. A multivariate analysis of factors associated with OS and RFS identified the RAS status as an independent factor (OS; hazard ratio [HR] = 1.672, P = 0.0031, RFS; HR = 1.703, P = 0.0024). Recurrence with lung metastasis was observed significantly more frequent in patients with RAS mutations than in patients with RAS wild-type (P = 0.0005). CONCLUSIONS: Approximately half of CLM patients may have a RAS mutation. CLM patients with RAS mutations had a significantly worse survival rate in comparison to patients with RAS wild-type, regardless of the administration of anti-EGFR antibody therapy.
Subject(s)
Colorectal Neoplasms/genetics , GTP Phosphohydrolases/genetics , Liver Neoplasms/genetics , Liver Neoplasms/surgery , Membrane Proteins/genetics , Mutation , Proto-Oncogene Proteins p21(ras)/genetics , Aged , Colorectal Neoplasms/pathology , Female , Genes, ras , Humans , Liver Neoplasms/secondary , MaleABSTRACT
Microsatellite instability (MSI) is an important biomarker for screening for Lynch syndrome, and also of response to immune checkpoint inhibitors. The aim of this study is to create a predictive model to determine which elderly patients with colorectal cancer (CRC) should undergo MSI and/or immunohistochemistry testing on the basis of clinicopathological data. We analyzed a test cohort of CRC patients aged ≥50 years (n = 2219) by multivariate logistic regression analyses to identify predictors of high-frequency MSI (MSI-H). The created prediction model was validated in an external cohort (n = 992). The frequency of MSI-H was 5.5% among CRC patients aged ≥ 50 years. The following five predictors of MSI-H were identified in the test cohort: female (1 point), mucinous component (2 points), tumor size ≥ 60 mm (2 points), location in proximal colon (3 points), and BRAF mutation (6 points). The area under curve (AUC) in the receiver-operating characteristic (ROC) analysis of this prediction model was 0.832 (95% confidence interval: 0.790-0.874). The sensitivity and specificity were 74.4% and 77.7%, respectively, for a cut-off score of 4 points. The receiver-operating characteristic curve of the validation cohort also showed an AUC of 0.856 (95% CI: 0.806-0.905). This prediction model is useful to select elderly CRC patients who should undergo MSI testing, and who may benefit from treatment with 5-FU-based adjuvant chemotherapy and cancer immunotherapy.
Subject(s)
Colorectal Neoplasms/genetics , Microsatellite Instability , Models, Biological , Aged , Colorectal Neoplasms/pathology , DNA Methylation , Female , Humans , Male , Middle Aged , MutL Protein Homolog 1/genetics , Mutation , Promoter Regions, Genetic , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Reproducibility of Results , Tumor BurdenABSTRACT
BACKGROUND: For recurrent biliary tract cancer, chemotherapy is the standard treatment. However, the efficacy of surgery is unknown. Here, the prognostic benefit of surgery for recurrent biliary tract cancer was investigated. METHODS: Data of 206 patients who underwent surgery for biliary tract cancer between 2005 and 2015 were retrospectively analyzed. Of these, 107 recurrent patients were divided into two groups, surgery (n = 14) and non-surgery (n = 93) groups. In the latter group, 45 patients received chemotherapy and 48 received best supportive care. RESULTS: Of the total 121 sites of recurrence, the liver was the most common (n = 41), followed by locoregional recurrence (n = 32) and lymph nodes (n = 18). Surgery was performed in the 14 patients with recurrence, comprising nine patients with intrahepatic cholangiocarcinoma, three with perihilar cholangiocarcinoma, one with distal cholangiocarcinoma and one with gallbladder carcinoma. Survival after recurrence was significantly better after surgery than after chemotherapy or best supportive care (38% vs. 5.3% vs. 0% at 3 years and 19% vs. 5.3% vs. 0% at 5 years; P < 0.0001). Multivariate analysis identified the residual status of the primary tumor (hazard ratio = 1.58, 95% confidence interval = 1.00-2.44; P = 0.047), time to recurrence ≥1 year (hazard ratio = 0.62, 95% confidence interval = 0.39-0.97; P = 0.037) and surgery for recurrence (hazard ratio = 0.32, 95% confidence interval = 0.14-0.62; P < 0.001) as independent prognostic factors. CONCLUSIONS: Surgery for recurrent biliary tract cancer may prolong survival in patients with time to recurrence ≥1 year.
Subject(s)
Biliary Tract Neoplasms/surgery , Aged , Aged, 80 and over , Biliary Tract Neoplasms/mortality , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Prospective Studies , Retrospective Studies , Survival AnalysisABSTRACT
Genetic testing is needed for the treatment of colorectal cancer (CRC), especially molecular-targeted therapy. The effects of anti-EGFR therapy and prognosis are affected by the presence of KRAS mutations. However, whether primary CRC or metastatic tissues are appropriate in the analysis is still unclear. In the present study, we assessed the concordance of KRAS/BRAF mutation status and microsatellite instability (MSI) in primary CRC and corresponding metastases. This study enrolled 457 patients with surgically resected primary and corresponding metastatic CRC (499 synchronous metastases and 57 metachronous metastases) and seven local recurrences, and KRAS/BRAF mutation and MSI status were analysed for these tumours. The concordance rates of KRAS mutation, BRAF mutation, wild-type, MSI-H and MSS between primary CRC and corresponding metastases were 93.9% (214/228), 100% (30/30), 99.3% (304/306), 87.5% (21/24) and 100% (137/137), respectively. These high concordance rates were not different between synchronous and metachronous metastases. In conclusion, a high concordance of KRAS/BRAF mutation status and MSI status was observed between primary CRC and corresponding metastases in this study. Either primary CRC or metastatic tissues can be used for testing KRAS/BRAF mutation status and MSI status.
Subject(s)
Colorectal Neoplasms/genetics , Microsatellite Instability , Mutation/genetics , Neoplasms, Multiple Primary/genetics , Neoplasms, Second Primary/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Biomarkers, Tumor/genetics , Case-Control Studies , Colorectal Neoplasms/pathology , Follow-Up Studies , Humans , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Lymphatic Metastasis , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/secondary , Neoplasm Staging , Neoplasms, Multiple Primary/secondary , Neoplasms, Second Primary/secondary , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/secondary , PrognosisABSTRACT
BACKGROUND: A recent clinical trial on the immune check-point inhibitor pembrolizumab demonstrated that microsatellite instability (MSI) is a good biomarker for response to this inhibitor. However, clinicopathological features of advanced colorectal cancer (CRC) with high-frequency MSI (MSI-H) are unclear. PATIENTS AND METHODS: A total of 2,439 surgically resected CRC tissues were analyzed for MSI status, and mutational status of V-Ki-Ras2 Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B (BRAF). Stage IV cases were selected, and clinical and molecular features were evaluated. RESULTS: There was no significant survival difference observed between MSI-H CRC and microsatellite-stable (MSS) CRC in patients with stage IV disease (3.92 vs. 2.50 years; p=0.766). However, hematogenous and lymphogenous metastasis-dominant CRC with MSI-H demonstrated poor prognosis, whereas peritoneal metastasis-dominant CRC with MSI-H demonstrated good prognosis, (1.33 vs. 5.2 years; p=0.006). CONCLUSION: Prognosis of stage IV CRC with MSI-H depended on the metastatic pattern. These findings provide useful information for the adaptation of CRC immunotherapy.
Subject(s)
Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Microsatellite Instability , Adult , Aged , Female , GTP Phosphohydrolases/genetics , Humans , Liver Neoplasms/genetics , Liver Neoplasms/secondary , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Lymphatic Metastasis , Male , Membrane Proteins/genetics , Middle Aged , MutL Protein Homolog 1/genetics , Mutation , Neoplasm Staging , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/secondary , Prognosis , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
We herein report 2 cases of laparoscopic total gastrectomy(LTG)in patient with multiple gastric neuroendocrine tumor (NET)related to multiple endocrine neoplasia type 1(MEN1). Case 1: A 66-year-old female was diagnosed with multiple gastric NET. There was no finding of any other tumor, and parathyroid function was normal. She underwent LTG. Case 2: A 58-year-old female was diagnosed with multiple gastric NET. The patient had a previous history of surgery for pituitary gland tumor. There was no finding of any other tumor, and parathyroid function was normal. She underwent LTG. In our cases, we could perform complete resection of gastric NET by laparoscopic surgery. Multiple gastric NET is a good indication of laparoscopic gastrectomy.
Subject(s)
Multiple Endocrine Neoplasia Type 1/surgery , Neuroendocrine Tumors/surgery , Stomach Neoplasms/surgery , Aged , Female , Gastrectomy , Humans , Laparoscopy , Middle Aged , Treatment OutcomeABSTRACT
Patients with advanced hepatocellular carcinoma (HCC) showing portal vein tumor thrombosis (PVTT) have an extremely poor prognosis. According to treatment guidelines, the only option for HCC patients with PVTT is sorafenib chemotherapy. However, in Asia, various treatments have been attempted and possible prolongation of overall survival has been repeatedly reported. We herein report the first case of a patient with an initially unresectable advanced HCC with PVTT who underwent curative hepatectomy after sorafenib and transcatheter arterial chemoembolization (TACE) showing complete histological response. Two months after induction with sorafenib, a significant decrease in serum alpha-fetoprotein level was observed and computed tomography imaging showed a significant decrease in tumor size. Because of remaining PVTT, TACE and curative resection were performed. The combination of sorafenib and TACE may be an effective treatment for HCC patients with PVTT.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/therapy , Chemoembolization, Therapeutic , Liver Neoplasms/therapy , Niacinamide/analogs & derivatives , Phenylurea Compounds/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Aged , Angiography, Digital Subtraction , Carcinoma, Hepatocellular/complications , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Hepatectomy , Humans , Liver Neoplasms/complications , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Male , Niacinamide/therapeutic use , Phlebography/methods , Portal Vein/diagnostic imaging , Sorafenib , Time Factors , Tomography, X-Ray Computed , Treatment Outcome , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/etiology , Venous Thrombosis/therapyABSTRACT
AIM: To clarify the clinical factors associated with liver regeneration after major hepatectomy and the hypertrophic rate after portal vein embolization (PVE). METHODS: A total of 63 patients who underwent major hepatectomy and 13 patients who underwent PVE in a tertiary care hospital between January 2012 and August 2015 were included in the analysis. We calculated the remnant liver volume following hepatectomy using contrast-enhanced computed tomography (CT) performed before and approximately 3-6 mo after hepatectomy. Furthermore, we calculated the liver volume using CT performed 2-4 wk after PVE. Preoperative patient characteristics and laboratory data were analyzed to identify factors affecting postoperative liver regeneration or hypertrophy rate following PVE. RESULTS: The remnant liver volume/total liver volume ratio negatively correlated with the liver regeneration rate after hepatectomy (ρ = -0.850, P < 0.001). The regeneration rate was significantly lower in patients with an indocyanine green retention rate at 15 min (ICG-R15) of ≥ 20% in the right hepatectomy group but not in the left hepatectomy group. The hypertrophic rate after PVE positively correlated with the regeneration rate after hepatectomy (ρ = 0.648, P = 0.017). In addition, the hypertrophic rate after PVE was significantly lower in patients with an ICG-R15 ≥ 20% and a serum total bilirubin ≥ 1.5 mg/dL. CONCLUSION: The regeneration rate after major hepatectomy correlated with hypertrophic rate after PVE. Both of them were attenuated in the presence of impaired liver function.
ABSTRACT
We aimed to evaluate the feasibility of pancreaticoduodenectomy (PD) in elderly patients. We retrospectively analyzed data from 206 patients who underwent PD between 2008 and 2015. The patients were divided into two groups: patients aged < 70 years (n = 117) and those aged ≥ 70 years (n = 89). To update the outcome of PD in elderly patients, we performed a systematic review of published work. The preoperative patient characteristics were similar between the two groups except for hypertension, which was significantly more frequent in the older group (25% vs. 52%; p < 0.001). There was no difference in the mortality (0% vs. 1%; p = 0.43) or morbidity (26% vs. 20%; p = 0.41) rates between the two groups. The overall survival rate in patients with pancreatic cancer between the two groups did not differ (p = 0.40). Twenty-one studies, including our own, were identified in the published work. The overall median morbidity and mortality rates of the elderly patients were 41.5% (range, 20-78%) and 5.8% (range, 0-10.5%), respectively. PD is feasible in elderly patients with acceptable morbidity and mortality rates.
Subject(s)
Pancreaticoduodenectomy/mortality , Postoperative Complications/epidemiology , Adult , Age Factors , Aged , Female , Humans , Male , Middle Aged , Nutrition Assessment , Postoperative Complications/mortality , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: Most patients with hepatocellular carcinoma (HCC) have underlying liver disease, therefore, precise preoperative evaluation of the patient's liver function is essential for surgical decision making. METHODS: We developed a grading system incorporating only two variables, namely, the serum albumin level and the indocyanine green retention rate at 15 minutes (ICG R15), to assess the preoperative liver function, based on the overall survival of 1868 patients with HCC who underwent liver resection. We then tested the model in a European cohort (n = 70) and analyzed the predictive power for the postoperative short-term outcome. RESULTS: The Albumin-Indocyanine Green Evaluation (ALICE) grading system was developed in a randomly assigned training cohort: linear predictor = 0.663 × log10ICG R15 (%)-0.0718 × albumin (g/L) (cut-off value: -2.20 and -1.39). This new grading system showed a predictive power for the overall survival similar to the Child-Pugh grading system in the validation cohort. Determination of the ALICE grade in Child-Pugh A patients allowed further stratification of the postoperative prognosis. This result was reproducible in the European cohort. Determination of the ALICE grade allowed better prediction of the risk of postoperative liver failure and mortality (ascites: grade 1, 2.1%; grade 2, 6.5%; grade 3, 16.0%; mortality: grade 1, 0%; grade 2, 1.3%; grade 3, 5.3%) than the previously reported model based on the presence/absence of portal hypertension. CONCLUSIONS: This new grading system is a simple method for prediction of the postoperative long-term and short-term outcomes.
Subject(s)
Carcinoma, Hepatocellular/diagnosis , Hepatectomy , Indocyanine Green/pharmacokinetics , Liver Neoplasms/diagnosis , Serum Albumin/metabolism , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/physiopathology , Carcinoma, Hepatocellular/surgery , Female , Humans , Liver/metabolism , Liver/physiopathology , Liver/surgery , Liver Function Tests , Liver Neoplasms/mortality , Liver Neoplasms/physiopathology , Liver Neoplasms/surgery , Male , Middle Aged , Neoplasm Grading , Preoperative Period , Prognosis , Prospective Studies , Survival Analysis , Treatment FailureABSTRACT
BACKGROUND: Although adjuvant chemotherapy with gemcitabine is standard care for resected pancreatic cancer, S-1 has shown non-inferiority to gemcitabine for advanced disease. We aimed to investigate the non-inferiority of S-1 to gemcitabine as adjuvant chemotherapy for pancreatic cancer in terms of overall survival. METHODS: We did a randomised, open-label, multicentre, non-inferiority phase 3 trial undertaken at 33 hospitals in Japan. Patients who had histologically proven invasive ductal carcinoma of the pancreas, pathologically documented stage I-III, and no local residual or microscopic residual tumour, and were aged 20 years or older were eligible. Patients with resected pancreatic cancer were randomly assigned (in a 1:1 ratio) to receive gemcitabine (1000 mg/m(2), intravenously administered on days 1, 8, and 15, every 4 weeks [one cycle], for up to six cycles) or S-1 (40 mg, 50 mg, or 60 mg according to body-surface area, orally administered twice a day for 28 days followed by a 14 day rest, every 6 weeks [one cycle], for up to four cycles) at the data centre by a modified minimisation method, balancing residual tumour status, nodal status, and institutions. The primary outcome was overall survival in the two treatment groups, assessed in the per-protocol population, excluding ineligible patients and those not receiving the allocated treatment. The protocol prespecified that the superiority of S-1 with respect to overall survival was also to be assessed in the per-protocol population by a log-rank test, if the non-inferiority of S-1 was verified. We estimated overall and relapse-free survival using the Kaplan-Meier methods, and assessed non-inferiority of S-1 to gemcitabine using the Cox proportional hazard model. The expected hazard ratio (HR) for mortality was 0.87 with a non-inferiority margin of 1.25 (power 80%; one-sided type I error 2.5%). This trial is registered at UMIN CTR (UMIN000000655). FINDINGS: 385 patients were randomly assigned to treatment between April 11, 2007, and June 29, 2010 (193 to the gemcitabine group and 192 to the S-1 group). Of these, three were exlcuded because of ineligibility and five did not receive chemotherapy. The per-protocol population therefore consisted of 190 patients in the gemcitabine group and 187 patients in the S-1 group. On Sept 15, 2012, following the recommendation from the independent data and safety monitoring committee, this study was discontinued because the prespecified criteria for early discontinuation were met at the interim analysis for efficacy, when all the protocol treatments had been finished. Analysis with the follow-up data on Jan 15, 2016, showed HR of mortality was 0.57 (95% CI 0.44-0.72, pnon-inferiority<0.0001, p<0.0001 for superiority), associated with 5-year overall survival of 24.4% (18.6-30.8) in the gemcitabine group and 44.1% (36.9-51.1) in the S-1 group. Grade 3 or 4 leucopenia, neutropenia, aspartate aminotransferase, and alanine aminotransferase were observed more frequently in the gemcitabine group, whereas stomatitis and diarrhoea were more frequently experienced in the S-1 group. INTERPRETATION: Adjuvant chemotherapy with S-1 can be a new standard care for resected pancreatic cancer in Japanese patients. These results should be assessed in non-Asian patients. FUNDING: Pharma Valley Center, Shizuoka Industrial Foundation, Taiho Pharmaceutical.