BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.Howev...BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.展开更多
BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated a...BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.展开更多
Hepatocellular carcinoma(HCC)is most commonly found in the context of liver cirrhosis and,in rare cases,in a healthy liver.Its prevalence has risen in recent years,particularly in Western nations,due to the increasing...Hepatocellular carcinoma(HCC)is most commonly found in the context of liver cirrhosis and,in rare cases,in a healthy liver.Its prevalence has risen in recent years,particularly in Western nations,due to the increasing frequency of nonalcoholic fatty liver disease.Advanced HCC has a poor prognosis.For many years,the only proven therapy for unresectable HCC(uHCC)was sorafenib,a tyrosine kinase inhibitor.Recently,the synergistic effect of an immune checkpoint inhibitor,atezolizumab,and bevacizumab outperformed sorafenib alone in terms of survival,making it the recommended first-line therapy.Other multikinase inhibitors,lenvatinib and regorafenib,were also recommended as first and second-line drugs,respectively.Intermediate-stage HCC patients with retained liver function,particularly uHCC without extrahepatic metastasis,may benefit from trans-arterial chemoembolization.The current problem in uHCC is selecting a patient for the best treatment while considering the preexisting liver condition and liver function.Indeed,all study patients had a Child-Pugh class A,and the best therapy for other individuals is unknown.Additionally,in the absence of a medical contraindication,atezolizumab could be combined with bevacizumab for uHCC systemic therapy.Several studies are now underway to evaluate immune checkpoint inhibitors in combination with anti-angiogenic drugs,and the first findings are encouraging.The paradigm of uHCC therapy is changing dramatically,and many obstacles remain for optimum patient management in the near future.The purpose of this commentary review was to give an insight into current systemic treatment options for patients with uHCC who are not candidates for surgery to cure the disease.展开更多
BACKGROUND Modified albumin-bilirubin(mALBI)grade has been established as a survival determinant in hepatocellular carcinoma(HCC)patients who receive locoregional and targeted therapies.AIM To investigate whether mALB...BACKGROUND Modified albumin-bilirubin(mALBI)grade has been established as a survival determinant in hepatocellular carcinoma(HCC)patients who receive locoregional and targeted therapies.AIM To investigate whether mALBI could predict survival in unresectable HCC(uHCC)patients who were treated with atezolizumab plus bevacizumab(AB).METHODS A single-center,retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023.An association between mALBI and patient survival was determined using Cox proportional hazards analysis.RESULTS Of the 83 patients,67 patients(80.7%)were male with the mean age of 60.6 years.Among them,22 patients(26.5%)were classified as Barcelona Clinic Liver Cancer B,and 61 patients(73.5%)were classified as Barcelona Clinic Liver Cancer C.Cirrhosis was present in 76 patients(91.6%),with 58 patients classified as Child-Turcotte-Pugh(CTP)A and 18 as CTP B.The median overall survival(OS)and progression-free survival were 13.0 mo[95%confidence interval(CI):5.2-20.8]and 9.0 mo(95%CI:5.0-13.0),respectively.The patients were divided into two groups based on mALBI grades:42 patients(50.6%)in the mALBI 1+2a group;and 41 patients(49.4%)in the mALBI 2b+3 group.During the median follow-up period of 7.0 mo,the mALBI 1+2a group exhibited significantly better survival compared to the mALBI 2b+3 group,with a median OS that was not reached vs 3.0 mo(95%CI:0.1-6.0,P<0.001).In a subgroup of patients with CTP A,the mALBI 1+2a group also showed significantly longer survival compared to the mALBI 2b+3 group,with a median OS that was not reached vs 6.0 mo(95%CI:3.4-8.6,P<0.001).In the multivariate analysis,both CTP class and mALBI grade were independently associated with survival,with adjusted hazard ratios(95%CI)of 2.63(1.19-5.78,P=0.020)and 3.90(1.71-8.90,P=0.001),respectively.CONCLUSION mALBI grades can determine survival of uHCC patients receiving AB treatment,particularly those who have mildly impaired liver function.This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.展开更多
Hepatocellular carcinoma(HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification syste...Hepatocellular carcinoma(HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization(TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidatesfor systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies(TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.展开更多
A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis(CRLM),which involved the right hepatic vein(RHV)and the inferior vena cava(IVC),was referred to our hospital.The metastatic...A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis(CRLM),which involved the right hepatic vein(RHV)and the inferior vena cava(IVC),was referred to our hospital.The metastatic lesion was diagnosed as initially unresectable because of its invasion into the confluence of the RHV and IVC.After she had undergone laparoscopic sigmoidectomy for the original tumor,she consequently had 3 courses of modified 5-fluorouracil,leucovorin,and oxaliplatin(m FOLFOX6)plus cetuximab.Computed tomography revealed a partial response,and the confluence of the RHV and IVC got free from cancer invasion.After 3 additional courses of m FOLFOX6 plus cetuximab,preoperative percutaneous transhepatic portal vein embolization(PTPE)was performed to secure the future remnant liver volume.Finally,a right hemihepatectomy was performed.The postoperative course was uneventful.The patient was discharged from the hospital on postoperative day 13.She had neither local recurrence nor distant metastasis 18 mo after the last surgical intervention.This multidisciplinary strategy,consisting of conversion chemotherapy using FOLFOX plus cetuximab and PTPE,could contribute in facilitating curative hepatic resection for initially unresectable CRLM.展开更多
AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 mal...AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body and tail of 9 patients, was found to be unresectable during operation. Diagnosis of pancreatic cancer was made through intraoperative biopsy. Patients were treated with FRA combined with 125 iodine seed implantation. In brief, a RFA needle was placed, which was confirmed by intraoperative ultrasound to decrease the potential injury of surrounding vital structures, a 125 iodine seed was implanted near the blood vessels and around the tumor border followed by bypass palliative procedure (cholangio-jejunostomy and/or gastrojejunostomy) in 29 patients.RESULTS: The serum CA 19-9 level was decreased from 512 ± 86 U/mL before operation to 176 ± 64 U/mL, 108 ± 42 U/mL and 114 ± 48 U/mL, respectively, 1, 3 and 6 mo after operation (P < 0.05). The pain score on day 7 after operation, 1 and 3 mo after combined therapy was decreased from 5.86 ± 1.92 before operation to 2.65 ± 1.04, 1.65 ± 0.88 and 2.03 ± 1.16, respectively, after operation (P < 0.05). The rate of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) in 32 patients was 21.8% (7/32), 56.3% (18/32), 15.6% (5/32) and 6.3% (2/32), respectively, 6 mo after operation, with a median overall survival time of 17. 5 mo. The median survival time of patients at stage Ⅲ was longer than that of those at stage Ⅳ (19 mo vs 10 mo, P = 0.0026). The median survival time of patients who received and did not receive chemotherapy after operation was 20 mo and 16 mo, respectively (P = 0.0176). Of the 32 patients, 3 (10.6%) experienced postoperative complications including transient biliary leaks in 2 patients and acute pancreatitis in 1 patient. All the patients recovered well after conservative support treatment. CONCLUSION: Intraoperative RFA combined with 125 iodine seed implantation is a feasible and safe procedure for unresectable pancreatic cancer with acceptable minor complications, and can prolong the survival time of patients, especially those at stage Ⅲ.展开更多
AIM:To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer.METHODS:A total of 186 consecutive patients with unresectable biliary tract cancer,wh...AIM:To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer.METHODS:A total of 186 consecutive patients with unresectable biliary tract cancer,who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan,were retrospectively analyzed.These patients were divided into three groups based on the year beginning chemotherapy:Group A(2000-2003),Group B(2004-2006),and Group C(2007-2009).The data were fixed at the end of December 2011.Overall survival and time-to-progression were analyzed and compared chronologically.RESULTS:No patient characteristics were significantly different among the three groups.The gallbladder was involved in about half of the patients in each group,and metastatic biliary tract cancer was present in three quarters of the enrollees.In Group A,5-fluorouracilbased chemotherapies were primarily selected as firstline chemotherapy,and only 24% were treated with second-line chemotherapy.In Group B,gemcitabine or S-1 monotherapy was mainly introduced as firstline chemotherapy,and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy.In Group C,the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy,and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy.The median timeto-progressions were 4.4 mo,3.5 mo and 5.9 mo in Groups A,B and C,respectively(4.4 mo vs 3.5 mo vs 5.9 mo,P < 0.01).The median overall survivals were 7.1,7.3,and 11.7 mo in Groups A,B and C(7.1 mo vs 7.3 mo vs 11.7 mo,P = 0.03).Induction rates of all three drugs(gemcitabine,platinum analogs,and fluoropyrimidine) in Groups A,B and C were 4%,2% and 27%(4% vs 2% vs 27%,P < 0.01).CONCLUSION:The prognosis of unresectable biliary tract cancer has improved recently.Using three effective drugs(gemcitabine,platinum analogs,and fluoropyrimidine) may improve the prognosis of this cancer.展开更多
AIM To review the conversion therapy for initially unre-sectable hepatocellular carcinoma(HCC) patients and the suitable timing for subsequent salvage surgery. METHODS A Pub Med search was undertaken from 1987 to 2017...AIM To review the conversion therapy for initially unre-sectable hepatocellular carcinoma(HCC) patients and the suitable timing for subsequent salvage surgery. METHODS A Pub Med search was undertaken from 1987 to 2017 to identify articles using the keywords including "unresectable" "hepatocellular carcinoma", "hepate-ctomy", "conversion therapy", "resection", "salvage surgery" and "downstaging". Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction. RESULTS Liver volume measurements [future liver remnant(FLR)/total liver volume or residual liver volume/bodyweight ratio] and function tests(scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing com-plications, morbidity or mortality. The requirementsfor performing salvage surgery after transcatheter arterial chemoembolization were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis, and the lack of extrahepatic metastasis. Patients with a standardized FLR(sF LR) > 20% were good candidates for surgery after portal vein embolization, while other predictive parameters like growth rate, kinetic growth rate were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy or yttrium-90 microsphere radioembolization. The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehen-sively evaluated. CONCLUSION Conversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subse-quent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.展开更多
AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for p...AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs.展开更多
Celiac plexus neurolysis (CPN) has become a minimally invasive approach for the management of patients with unresectable pancreatic cancer and abdominal pain unresponsive to medical treatment. CPN has been shown to ha...Celiac plexus neurolysis (CPN) has become a minimally invasive approach for the management of patients with unresectable pancreatic cancer and abdominal pain unresponsive to medical treatment. CPN has been shown to have long-lasting improvement in abdominal pain and decreased narcotic usage in 70% to 90% of patients. Therefore, the aim of this paper was to report our experience with CPN in the treatment of two cases of advanced pancreatic cancer, with satisfying results in controlling pain. The use of CT scan-guided CPN should be considered and performed relatively early in the course of disease to offer optimal pain relief and increase the patient’s quality of life.展开更多
This study aimed to investigate the dose-volume effects of γ-ray stereotactic body radiotherapy (SBRT) on clinical outcomes of patients with huge-size (≥10 cm) unresectable hepatocellular carcinoma (HCC). A total of...This study aimed to investigate the dose-volume effects of γ-ray stereotactic body radiotherapy (SBRT) on clinical outcomes of patients with huge-size (≥10 cm) unresectable hepatocellular carcinoma (HCC). A total of 59 patients with huge-size unresectable HCC were treated with SBRT following TACE between May 2006 and Dec. 2009. The analyzed parameters included fractional dose, marginal dose, maximal dose, and mean dose that the target received, as well as percentages of tumor volume encompassed by 60% (P<sub>60</sub>), 70% (P<sub>70</sub>), and 80% (P<sub>80</sub>) of isodose curves in entire tumor. The clinical outcomes included objective response rate (ORR), disease-free survival (DFS), overall survival (OS), and adverse event (AE). During median follow-up of 18.4 months, 81.4% of ORR (8.5% CR and 72.9% PR) was achieved, higher than 28.9% of ORR recently reported for TACE alone. 1- and 3-year DFS rates were 31.1% and 2.6% with median DFS of 8.7 months;1-, 3-, and 5-year OS rates were 46.5%, 13.7%, and 2.9%, with median OS of 11.8 months. P<sub>70</sub> was the only factor significantly correlating to DFS (P = 0.009) and OS (P = 0.01). Neither severe radiation-related liver disease nor > grade 3 AE was observed. In conclusion, SBRT was a safe and effective option for treatment of huge-size unresectable HCC. P<sub>70</sub> represented a parameter for predicting DFS and OS, and high dose-volume (e.g., P<sub>70</sub>) might be required to achieve improved clinical outcomes of patients with this type of HCC.展开更多
AIM:To evaluate the use of the Roux loop on the postoperative course in patients submitted for gastroenteroanastomosis(GE).METHODS:Non-jaundiced patients(n=41)operated on in the Department of General and Transplant Su...AIM:To evaluate the use of the Roux loop on the postoperative course in patients submitted for gastroenteroanastomosis(GE).METHODS:Non-jaundiced patients(n=41)operated on in the Department of General and Transplant Surgery in Lodz,between January 2010 and December 2011 were enrolled.The tumor was considered unresectable when liver metastases or major vascular involvement were confirmed.Patients were randomized to receive Roux(n=21)or conventional GE(n=20)on a prophylactic basis.RESULTS:The mean time to nasogastric tube withdrawal in Roux GE group was shorter(1.4±0.75 vs2.8±1.1,P<0.001).Time to starting oral liquids,soft diet and regular diet were decreased(2.3±0.86 vs 3.45±1.19;P<0.001;3.3±0.73 vs 4.4±1.23,P<0.001and 4.5±0.76 vs 5.6±1.42,P=0.002;respectively).The Roux GE group had a lower use of prokinetics(10mg thrice daily for 2.2±1.8 d vs 3.7±2.6 d,P=0.044;total 62±49 mg vs 111±79 mg,P=0.025).The mean hospitalization time following Roux GE was shorter(7.7 d vs 9.6 d,P=0.006).Delayed gastric emptying(DGE)was confirmed in 20%after conventional GE but in none of the patients following Roux GE.CONCLUSION:Roux gastrojejunostomy during open abdomen exploration in patients with unresectable pancreatic cancer is easy to perform,decreases the incidence of DGE and lowers hospitalization time.展开更多
AIM:To evaluate the differences in the treatment outcomes between the unresectable and recurrent biliary tract cancer patients who received chemotherapy.METHODS:Patients who were treated with gemcitabine and S-1 combi...AIM:To evaluate the differences in the treatment outcomes between the unresectable and recurrent biliary tract cancer patients who received chemotherapy.METHODS:Patients who were treated with gemcitabine and S-1 combination therapy in the previous prospective studies were divided into groups of unresectable and recurrent cases.The tumor response,time-toprogression,overall survival,toxicity,and dose intensity were compared between these two groups.RESULTS:Response rate of the recurrent group was higher than that of the unresectable group(40.0%vs25.5%;P=0.34).Median time-to-progression of the recurrent and unresectable groups were 8.7 mo(95%CI),1.2 mo,not reached)and 5.7 mo(95%CI:4.0-7.0 mo),respectively(P=0.14).Median overall survival of the recurrent and the unresectable groups were 16.1 mo(95%CI:2.0 mo-not reached)and 9.6 mo(95%CI:7.1-11.7 mo),respectively(P=0.10).Dose intensities were significantly lower in the recurrent groups(gemcitabine:recurrent group 83.5%vs unresectable group 96.8%;P<0.01,S-1:Recurrent group 75.9%vs unresectable group 91.8%;P<0.01).Neutropenia occurred more frequently in recurrent group(recurrent group 90%vs unresectable group 55%;P=0.04).CONCLUSION:Not only the efficacy but also the toxicity and dose intensity were significantly different between unresectable and recurrent biliary tract cancer.展开更多
Despite the fact that gastric cancer is decreasing in incidence in the United States,it remains one of the most commonly diagnosed and most fatal cancers worldwide.In localised disease,surgery remains the cornerstone ...Despite the fact that gastric cancer is decreasing in incidence in the United States,it remains one of the most commonly diagnosed and most fatal cancers worldwide.In localised disease,surgery remains the cornerstone of treatment.Nevertheless,the low overall survival rates at 5 years due to locoregional and distant recurrences has led to a large debate regarding the role of radiation therapy and chemotherapy in addition to curative resection.Recent data have shown that,even with improved surgical techniques,locoregional failure rates in these patients ranged between 57% and 88%.Failures were noted in the gastric bed,regional nodes,gastric remnant,anastomosis and duodenal stump,all of which can be encompassed in a regional radiation f ield,indicating the need of further locoregional treatment.In this article,a comprehensive literature review of the reliable medical databases of PubMed and Cochrane is made and we present all available information on the role of radiation therapy in the preoperative and postoperative setting of gastric cancer.Data reported show that in locally advanced gastric cancer the addition of radiation therapy post surgery has signif icantly improved diseasefree survival as well as overall survival.Moreover,in unresectable gastric cancer,the combination of radiation therapy with chemotherapy has significantly improvedmean and overall survival rates.The role of radiation therapy in patients with resectable gastric cancer is being further evaluated in ongoing phase Ⅲ trials.展开更多
Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tu...Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy(PBT), at a total dose of 60 Gy(relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC(maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.展开更多
AIM To investigate the efficacy and safety of isolated hepatic perfusion(IHP) in the management of unresectable liver malignancies.METHODS Studies were identified manually and on-line by using Pub Med and EMBASE datab...AIM To investigate the efficacy and safety of isolated hepatic perfusion(IHP) in the management of unresectable liver malignancies.METHODS Studies were identified manually and on-line by using Pub Med and EMBASE database.We formulate the eligibility criteria according to the PICOS elements,and accessed the quality of studies using the MINORS instrument.Data from all included studies were carefully investigated.We calculated the pooled response rate and incidences of mortality reported from all eligible studies by using the Meta-Analyst software,and we computed a pooled relative risk(RR) and 95%CI by using the Comprehensive Meta-Analysis software.Heterogeneity was quantified evaluated using I^2 statistic.RESULTS Eight studies,including 502 patients,were selected.Of these,six studies performed IHP,while the other two studies performed percutaneous IHP.The results showed that the pooled response rate was 60.8%(95%CI:53.1%-68%),I^2 = 37.1%.The median overall survival was 20 mo(range:12.1 to 25 mo) following IHP or PIHP.The pooled mortality rate was 5.4%(95%CI:2.5%-11.2%),I^2 = 37.5%.Prognostic factors predict the response to IHP or survival,and were reported in six studies.Meta-analysis demonstrated that Gender was not associated with overall survival(RR = 0.877,95%CI:0.564-1.365);however,carcino-embryonic antigen ≤ 30 ng/mL was associated with a significant improvement in survival outcomes with colorectal cancer patients(RR = 2.082,95%CI:1.371-3.163),and there was no significant heterogeneity.CONCLUSION The present systemic review and meta-analysis suggest that IHP and PIHP are potentially efficient and safe techniques for unresectable liver primary and secondary malignancies.展开更多
BACKGROUND Definitive chemoradiotherapy(dCRT)using cisplatin plus 5fluorouracil(CF)with radiation is considered the standard treatment for unresectable locally advanced T4 esophageal squamous cell carcinoma(ESCC).Rece...BACKGROUND Definitive chemoradiotherapy(dCRT)using cisplatin plus 5fluorouracil(CF)with radiation is considered the standard treatment for unresectable locally advanced T4 esophageal squamous cell carcinoma(ESCC).Recently,induction chemotherapy has received attention as an effective treatment strategy.CASE SUMMARY We report a successful case of a 59-year-old female with unresectable locally advanced T4 ESCC treated by two additional courses of chemotherapy with CF after induction chemotherapy with docetaxel,cisplatin and fluorouracil(DCF)followed by dCRT.Initial esophagogastroduodenoscopy(EGD)detected a type 2 advanced lesion located on the middle part of the esophagus,with stenosis.Computed tomography detected the primary tumor with suspected invasion of the left bronchus and 90°of direct contact with the aorta,and upper mediastinal lymph node metastasis.Pathological findings from biopsy revealed squamous cell carcinoma.We initially performed induction chemotherapy using three courses of DCF,but the lesion was still evaluated unresectable after DCF chemotherapy.Therefore,we subsequently performed dCRT treatment(CF and radiation).After dCRT,prominent reduction of the primary tumor was recognized but a residual tumor with ulceration was detected by EGD.Since the patient had some surgical risk,we performed two additional courses of CF and achieved a clinically complete response.After 14 mo from last administration of CF chemotherapy,recurrence has not been detected by computed tomography and EGD,and biopsy from the scar formation has revealed no cancer cells.CONCLUSION We report successful case with tumor remnants even after DCF and subsequent dCRT,for whom a complete response was finally achieved with two additional courses of CF chemotherapy.Additional CF chemotherapy could be one radical treatment option for residual ESCC after treatment with induction DCF followed by dCRT to avoid salvage surgery,especially for high-risk patients.展开更多
Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for th...Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.展开更多
基金Supported by Natural Science Foundation of Guangdong Province,No.2020A1515011539.
文摘BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.
文摘BACKGROUND The efficacy and safety of transarterial chemoembolization(TACE)combined with lenvatinib plus programmed cell death protein-1(PD-1)for unresectable hepato-cellular carcinoma(HCC)have rarely been evaluated and it is unknown which factors are related to efficacy.AIM To evaluate the efficacy and independent predictive factors of TACE combined with lenvatinib plus PD-1 inhibitors for unresectable HCC.METHODS This study retrospectively enrolled patients with unresectable HCC who received TACE/lenvatinib/PD-1 treatment between March 2019 and April 2022.Overall survival(OS)and progression-free survival(PFS)were determined.The objective response rate(ORR)and disease control rate(DCR)were evaluated in accordance with the modified Response Evaluation Criteria in Solid Tumors.Additionally,the prognostic factors affecting the clinical outcome were assessed.RESULTS One hundred and two patients were enrolled with a median follow-up duration of 12.63 months.The median OS was 26.43 months(95%CI:17.00-35.87),and the median PFS was 10.07 months(95%CI:8.50-11.65).The ORR and DCR were 61.76%and 81.37%,respectively.The patients with Barcelona Clinic Liver Cancer Classification(BCLC)B stage,early neutrophil-to-lymphocyte ratio(NLR)response(decrease),or early alpha-fetoprotein(AFP)response(decrease>20%)had superior OS and PFS than their counterparts.CONCLUSION This study showed that TACE/lenvatinib/PD-1 treatment was well tolerated with encouraging efficacy in patients with unresectable HCC.The patients with BCLC B-stage disease with early NLR response(decrease)and early AFP response(decrease>20%)may achieve better clinical outcomes with this triple therapy.
文摘Hepatocellular carcinoma(HCC)is most commonly found in the context of liver cirrhosis and,in rare cases,in a healthy liver.Its prevalence has risen in recent years,particularly in Western nations,due to the increasing frequency of nonalcoholic fatty liver disease.Advanced HCC has a poor prognosis.For many years,the only proven therapy for unresectable HCC(uHCC)was sorafenib,a tyrosine kinase inhibitor.Recently,the synergistic effect of an immune checkpoint inhibitor,atezolizumab,and bevacizumab outperformed sorafenib alone in terms of survival,making it the recommended first-line therapy.Other multikinase inhibitors,lenvatinib and regorafenib,were also recommended as first and second-line drugs,respectively.Intermediate-stage HCC patients with retained liver function,particularly uHCC without extrahepatic metastasis,may benefit from trans-arterial chemoembolization.The current problem in uHCC is selecting a patient for the best treatment while considering the preexisting liver condition and liver function.Indeed,all study patients had a Child-Pugh class A,and the best therapy for other individuals is unknown.Additionally,in the absence of a medical contraindication,atezolizumab could be combined with bevacizumab for uHCC systemic therapy.Several studies are now underway to evaluate immune checkpoint inhibitors in combination with anti-angiogenic drugs,and the first findings are encouraging.The paradigm of uHCC therapy is changing dramatically,and many obstacles remain for optimum patient management in the near future.The purpose of this commentary review was to give an insight into current systemic treatment options for patients with uHCC who are not candidates for surgery to cure the disease.
文摘BACKGROUND Modified albumin-bilirubin(mALBI)grade has been established as a survival determinant in hepatocellular carcinoma(HCC)patients who receive locoregional and targeted therapies.AIM To investigate whether mALBI could predict survival in unresectable HCC(uHCC)patients who were treated with atezolizumab plus bevacizumab(AB).METHODS A single-center,retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023.An association between mALBI and patient survival was determined using Cox proportional hazards analysis.RESULTS Of the 83 patients,67 patients(80.7%)were male with the mean age of 60.6 years.Among them,22 patients(26.5%)were classified as Barcelona Clinic Liver Cancer B,and 61 patients(73.5%)were classified as Barcelona Clinic Liver Cancer C.Cirrhosis was present in 76 patients(91.6%),with 58 patients classified as Child-Turcotte-Pugh(CTP)A and 18 as CTP B.The median overall survival(OS)and progression-free survival were 13.0 mo[95%confidence interval(CI):5.2-20.8]and 9.0 mo(95%CI:5.0-13.0),respectively.The patients were divided into two groups based on mALBI grades:42 patients(50.6%)in the mALBI 1+2a group;and 41 patients(49.4%)in the mALBI 2b+3 group.During the median follow-up period of 7.0 mo,the mALBI 1+2a group exhibited significantly better survival compared to the mALBI 2b+3 group,with a median OS that was not reached vs 3.0 mo(95%CI:0.1-6.0,P<0.001).In a subgroup of patients with CTP A,the mALBI 1+2a group also showed significantly longer survival compared to the mALBI 2b+3 group,with a median OS that was not reached vs 6.0 mo(95%CI:3.4-8.6,P<0.001).In the multivariate analysis,both CTP class and mALBI grade were independently associated with survival,with adjusted hazard ratios(95%CI)of 2.63(1.19-5.78,P=0.020)and 3.90(1.71-8.90,P=0.001),respectively.CONCLUSION mALBI grades can determine survival of uHCC patients receiving AB treatment,particularly those who have mildly impaired liver function.This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.
文摘Hepatocellular carcinoma(HCC) is the sixth most common cancer and third leading cause of cancer-related death in the world. The Barcelona clinic liver cancer classification is the current standard classification system for the clinical management of patients with HCC and suggests that patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization(TACE). Interventional treatments such as TACE, balloon-occluded TACE, drug-eluting bead embolization, radioembolization, and combined therapies including TACE and radiofrequency ablation, continue to evolve, resulting in improved patient prognosis. However, patients with advanced-stage HCC typically receive only chemotherapy with sorafenib, a multi-kinase inhibitor, or palliative and conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidatesfor systemic therapy. However, these patients require therapy that is more effective than sorafenib or conservative treatment. Several researchers try to perform more effective therapies, such as combined therapies(TACE with radiotherapy and sorafenib with TACE), modified TACE for HCC with arterioportal or arteriohepatic vein shunts, TACE based on hepatic hemodynamics, and isolated hepatic perfusion. This review summarizes the published data and data on important ongoing studies concerning interventional treatments for unresectable HCC and discusses the technical improvements in these interventions, particularly for advanced-stage HCC.
文摘A 72-year-old woman with a sigmoid colon cancer and a synchronous colorectal liver metastasis(CRLM),which involved the right hepatic vein(RHV)and the inferior vena cava(IVC),was referred to our hospital.The metastatic lesion was diagnosed as initially unresectable because of its invasion into the confluence of the RHV and IVC.After she had undergone laparoscopic sigmoidectomy for the original tumor,she consequently had 3 courses of modified 5-fluorouracil,leucovorin,and oxaliplatin(m FOLFOX6)plus cetuximab.Computed tomography revealed a partial response,and the confluence of the RHV and IVC got free from cancer invasion.After 3 additional courses of m FOLFOX6 plus cetuximab,preoperative percutaneous transhepatic portal vein embolization(PTPE)was performed to secure the future remnant liver volume.Finally,a right hemihepatectomy was performed.The postoperative course was uneventful.The patient was discharged from the hospital on postoperative day 13.She had neither local recurrence nor distant metastasis 18 mo after the last surgical intervention.This multidisciplinary strategy,consisting of conversion chemotherapy using FOLFOX plus cetuximab and PTPE,could contribute in facilitating curative hepatic resection for initially unresectable CRLM.
文摘AIM: To evaluate the feasibility, efficacy and safety of intraoperative radiofrequency ablation (RFA) combined with 125 iodine seed implantation for unresectable pancreatic cancer. METHODS: Thirty-two patients (21 males and 11 females) at the age of 68 years (range 48-90 years) with unresectable locally advanced pancreatic cancer admitted to our hospital from January 2006 to May 2008 were enrolled in this study. The tumor, 4-12 cm in diameter, located in pancreatic head of 23 patients and in pancreatic body and tail of 9 patients, was found to be unresectable during operation. Diagnosis of pancreatic cancer was made through intraoperative biopsy. Patients were treated with FRA combined with 125 iodine seed implantation. In brief, a RFA needle was placed, which was confirmed by intraoperative ultrasound to decrease the potential injury of surrounding vital structures, a 125 iodine seed was implanted near the blood vessels and around the tumor border followed by bypass palliative procedure (cholangio-jejunostomy and/or gastrojejunostomy) in 29 patients.RESULTS: The serum CA 19-9 level was decreased from 512 ± 86 U/mL before operation to 176 ± 64 U/mL, 108 ± 42 U/mL and 114 ± 48 U/mL, respectively, 1, 3 and 6 mo after operation (P < 0.05). The pain score on day 7 after operation, 1 and 3 mo after combined therapy was decreased from 5.86 ± 1.92 before operation to 2.65 ± 1.04, 1.65 ± 0.88 and 2.03 ± 1.16, respectively, after operation (P < 0.05). The rate of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) in 32 patients was 21.8% (7/32), 56.3% (18/32), 15.6% (5/32) and 6.3% (2/32), respectively, 6 mo after operation, with a median overall survival time of 17. 5 mo. The median survival time of patients at stage Ⅲ was longer than that of those at stage Ⅳ (19 mo vs 10 mo, P = 0.0026). The median survival time of patients who received and did not receive chemotherapy after operation was 20 mo and 16 mo, respectively (P = 0.0176). Of the 32 patients, 3 (10.6%) experienced postoperative complications including transient biliary leaks in 2 patients and acute pancreatitis in 1 patient. All the patients recovered well after conservative support treatment. CONCLUSION: Intraoperative RFA combined with 125 iodine seed implantation is a feasible and safe procedure for unresectable pancreatic cancer with acceptable minor complications, and can prolong the survival time of patients, especially those at stage Ⅲ.
文摘AIM:To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer.METHODS:A total of 186 consecutive patients with unresectable biliary tract cancer,who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan,were retrospectively analyzed.These patients were divided into three groups based on the year beginning chemotherapy:Group A(2000-2003),Group B(2004-2006),and Group C(2007-2009).The data were fixed at the end of December 2011.Overall survival and time-to-progression were analyzed and compared chronologically.RESULTS:No patient characteristics were significantly different among the three groups.The gallbladder was involved in about half of the patients in each group,and metastatic biliary tract cancer was present in three quarters of the enrollees.In Group A,5-fluorouracilbased chemotherapies were primarily selected as firstline chemotherapy,and only 24% were treated with second-line chemotherapy.In Group B,gemcitabine or S-1 monotherapy was mainly introduced as firstline chemotherapy,and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy.In Group C,the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy,and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy.The median timeto-progressions were 4.4 mo,3.5 mo and 5.9 mo in Groups A,B and C,respectively(4.4 mo vs 3.5 mo vs 5.9 mo,P < 0.01).The median overall survivals were 7.1,7.3,and 11.7 mo in Groups A,B and C(7.1 mo vs 7.3 mo vs 11.7 mo,P = 0.03).Induction rates of all three drugs(gemcitabine,platinum analogs,and fluoropyrimidine) in Groups A,B and C were 4%,2% and 27%(4% vs 2% vs 27%,P < 0.01).CONCLUSION:The prognosis of unresectable biliary tract cancer has improved recently.Using three effective drugs(gemcitabine,platinum analogs,and fluoropyrimidine) may improve the prognosis of this cancer.
文摘AIM To review the conversion therapy for initially unre-sectable hepatocellular carcinoma(HCC) patients and the suitable timing for subsequent salvage surgery. METHODS A Pub Med search was undertaken from 1987 to 2017 to identify articles using the keywords including "unresectable" "hepatocellular carcinoma", "hepate-ctomy", "conversion therapy", "resection", "salvage surgery" and "downstaging". Additional studies were investigated through a manual search of the references from the articles. The exclusion criteria were duplicates, case reports, case series, videos, contents unrelated to the topic, comments, and editorial essays. The main and widely used conversion therapies and the suitable timing for subsequent salvage surgery were discussed in detail. Two members of our group independently performed the literature search and data extraction. RESULTS Liver volume measurements [future liver remnant(FLR)/total liver volume or residual liver volume/bodyweight ratio] and function tests(scoring systems and liver stiffness) were often performed in order to justify whether patients were suitable candidates for surgery. Successful conversion therapy was usually defined as downstaging the tumor, increasing FLR and providing subsequent salvage surgery, without increasing com-plications, morbidity or mortality. The requirementsfor performing salvage surgery after transcatheter arterial chemoembolization were the achievement of a partial remission in radiology, the disappearance of the portal vein thrombosis, and the lack of extrahepatic metastasis. Patients with a standardized FLR(sF LR) > 20% were good candidates for surgery after portal vein embolization, while other predictive parameters like growth rate, kinetic growth rate were treated as an effective supplementary. There was probably not enough evidence to provide a standard operation time after associating liver partition and portal vein ligation for staged hepatectomy or yttrium-90 microsphere radioembolization. The indications of any combinations of conversion therapies and the subsequent salvage surgery time still need to be carefully and comprehen-sively evaluated. CONCLUSION Conversion therapy is recommended for the treatment of initially unresectable HCC, and the suitable subse-quent salvage surgery time should be reappraised and is closely related to its previous therapeutic effect.
基金Supported by Grants from Novartis Pharmaceuticals Corporation,One Health Plaza,East Hanover,NJ 07936-1080,United States
文摘AIM:To evaluate systemic treatment choices in unresectable metastatic well-differentiated pancreatic neuroendocrine tumors(PNETs)and provide consensus treatment recommendations.METHODS:Systemic treatment options for pancreatic neuroendocrine tumors have expanded in recent years to include somatostatin analogs,angiogenesis inhibitors,inhibitors of mammalian target of rapamycinand cytotoxic agents.At this time,there is little data to guide treatment selection and sequence.We therefore assembled a panel of expert physicians to evaluate systemic treatment choices and provide consensus treatment recommendations.Treatment appropriateness ratings were collected using the RAND/UCLA modified Delphi process.After studying the literature,a multidisciplinary panel of 10 physicians assessed the appropriateness of various medical treatment scenarios on a 1-9 scale.Ratings were done both before and after an extended discussion of the evidence.Quantitative measurements of agreement were made and consensus statements developed from the second round ratings.RESULTS:Specialties represented were medical and surgical oncology,interventional radiology,and gastroenterology.Panelists had practiced for a mean of15.5 years(range:6-33).Among 202 rated scenarios,disagreement decreased from 13.2%(26 scenarios)before the face-to-face discussion of evidence to 1%(2)after.In the final ratings,46.5%(94 scenarios)were rated inappropriate,21.8%(44)were uncertain,and30.7%(62)were appropriate.Consensus statements from the scenarios included:(1)it is appropriate to use somatostatin analogs as first line therapy in patients with hormonally functional tumors and may be appropriate in patients who are asymptomatic;(2)it is appropriate to use everolimus,sunitinib,or cytotoxic chemotherapy therapy as first line therapy in patients with symptomatic or progressive tumors;and(3)beyond first line,these same agents can be used.In patients with uncontrolled secretory symptoms,octreotide LAR doses can be titrated up to 60 mg every4 wk or up to 40 mg every 3 or 4 wk.CONCLUSION:Using the Delphi process allowed physician experts to systematically obtain a consensus on the appropriateness of a variety of medical therapies in patients with PNETs.
文摘Celiac plexus neurolysis (CPN) has become a minimally invasive approach for the management of patients with unresectable pancreatic cancer and abdominal pain unresponsive to medical treatment. CPN has been shown to have long-lasting improvement in abdominal pain and decreased narcotic usage in 70% to 90% of patients. Therefore, the aim of this paper was to report our experience with CPN in the treatment of two cases of advanced pancreatic cancer, with satisfying results in controlling pain. The use of CT scan-guided CPN should be considered and performed relatively early in the course of disease to offer optimal pain relief and increase the patient’s quality of life.
文摘This study aimed to investigate the dose-volume effects of γ-ray stereotactic body radiotherapy (SBRT) on clinical outcomes of patients with huge-size (≥10 cm) unresectable hepatocellular carcinoma (HCC). A total of 59 patients with huge-size unresectable HCC were treated with SBRT following TACE between May 2006 and Dec. 2009. The analyzed parameters included fractional dose, marginal dose, maximal dose, and mean dose that the target received, as well as percentages of tumor volume encompassed by 60% (P<sub>60</sub>), 70% (P<sub>70</sub>), and 80% (P<sub>80</sub>) of isodose curves in entire tumor. The clinical outcomes included objective response rate (ORR), disease-free survival (DFS), overall survival (OS), and adverse event (AE). During median follow-up of 18.4 months, 81.4% of ORR (8.5% CR and 72.9% PR) was achieved, higher than 28.9% of ORR recently reported for TACE alone. 1- and 3-year DFS rates were 31.1% and 2.6% with median DFS of 8.7 months;1-, 3-, and 5-year OS rates were 46.5%, 13.7%, and 2.9%, with median OS of 11.8 months. P<sub>70</sub> was the only factor significantly correlating to DFS (P = 0.009) and OS (P = 0.01). Neither severe radiation-related liver disease nor > grade 3 AE was observed. In conclusion, SBRT was a safe and effective option for treatment of huge-size unresectable HCC. P<sub>70</sub> represented a parameter for predicting DFS and OS, and high dose-volume (e.g., P<sub>70</sub>) might be required to achieve improved clinical outcomes of patients with this type of HCC.
文摘AIM:To evaluate the use of the Roux loop on the postoperative course in patients submitted for gastroenteroanastomosis(GE).METHODS:Non-jaundiced patients(n=41)operated on in the Department of General and Transplant Surgery in Lodz,between January 2010 and December 2011 were enrolled.The tumor was considered unresectable when liver metastases or major vascular involvement were confirmed.Patients were randomized to receive Roux(n=21)or conventional GE(n=20)on a prophylactic basis.RESULTS:The mean time to nasogastric tube withdrawal in Roux GE group was shorter(1.4±0.75 vs2.8±1.1,P<0.001).Time to starting oral liquids,soft diet and regular diet were decreased(2.3±0.86 vs 3.45±1.19;P<0.001;3.3±0.73 vs 4.4±1.23,P<0.001and 4.5±0.76 vs 5.6±1.42,P=0.002;respectively).The Roux GE group had a lower use of prokinetics(10mg thrice daily for 2.2±1.8 d vs 3.7±2.6 d,P=0.044;total 62±49 mg vs 111±79 mg,P=0.025).The mean hospitalization time following Roux GE was shorter(7.7 d vs 9.6 d,P=0.006).Delayed gastric emptying(DGE)was confirmed in 20%after conventional GE but in none of the patients following Roux GE.CONCLUSION:Roux gastrojejunostomy during open abdomen exploration in patients with unresectable pancreatic cancer is easy to perform,decreases the incidence of DGE and lowers hospitalization time.
文摘AIM:To evaluate the differences in the treatment outcomes between the unresectable and recurrent biliary tract cancer patients who received chemotherapy.METHODS:Patients who were treated with gemcitabine and S-1 combination therapy in the previous prospective studies were divided into groups of unresectable and recurrent cases.The tumor response,time-toprogression,overall survival,toxicity,and dose intensity were compared between these two groups.RESULTS:Response rate of the recurrent group was higher than that of the unresectable group(40.0%vs25.5%;P=0.34).Median time-to-progression of the recurrent and unresectable groups were 8.7 mo(95%CI),1.2 mo,not reached)and 5.7 mo(95%CI:4.0-7.0 mo),respectively(P=0.14).Median overall survival of the recurrent and the unresectable groups were 16.1 mo(95%CI:2.0 mo-not reached)and 9.6 mo(95%CI:7.1-11.7 mo),respectively(P=0.10).Dose intensities were significantly lower in the recurrent groups(gemcitabine:recurrent group 83.5%vs unresectable group 96.8%;P<0.01,S-1:Recurrent group 75.9%vs unresectable group 91.8%;P<0.01).Neutropenia occurred more frequently in recurrent group(recurrent group 90%vs unresectable group 55%;P=0.04).CONCLUSION:Not only the efficacy but also the toxicity and dose intensity were significantly different between unresectable and recurrent biliary tract cancer.
文摘Despite the fact that gastric cancer is decreasing in incidence in the United States,it remains one of the most commonly diagnosed and most fatal cancers worldwide.In localised disease,surgery remains the cornerstone of treatment.Nevertheless,the low overall survival rates at 5 years due to locoregional and distant recurrences has led to a large debate regarding the role of radiation therapy and chemotherapy in addition to curative resection.Recent data have shown that,even with improved surgical techniques,locoregional failure rates in these patients ranged between 57% and 88%.Failures were noted in the gastric bed,regional nodes,gastric remnant,anastomosis and duodenal stump,all of which can be encompassed in a regional radiation f ield,indicating the need of further locoregional treatment.In this article,a comprehensive literature review of the reliable medical databases of PubMed and Cochrane is made and we present all available information on the role of radiation therapy in the preoperative and postoperative setting of gastric cancer.Data reported show that in locally advanced gastric cancer the addition of radiation therapy post surgery has signif icantly improved diseasefree survival as well as overall survival.Moreover,in unresectable gastric cancer,the combination of radiation therapy with chemotherapy has significantly improvedmean and overall survival rates.The role of radiation therapy in patients with resectable gastric cancer is being further evaluated in ongoing phase Ⅲ trials.
基金Supported by Rinecker Proton Therapy Center(RPTC),Munich,Germany
文摘Presented here is the clinical course of a 63-yearold patient with a central, large and unresectable hepatocellular carcinoma(HCC) with liver metastases and tumor invasion of the portal and hepatic veins. After the tumor had been diagnosed, the patient was immediately treated with proton beam therapy(PBT), at a total dose of 60 Gy(relative biological effectiveness) in 20 fractions administered within 4 wk. To manage the respiratory movements, at the Rinecker Proton Therapy Center, apneic oxygenation was given daily, under general anesthesia. The patient tolerated both the PBT and general anesthesia very well, and did now show any signs of acute or late toxicity. The treatment was followed by constant reductions in the tumor marker alpha-fetoprotein and the cholestatic parameters gamma-glutamyltransferase and alkaline phosphatase. The patient commenced an adjuvant treatment with sorafenib, given at 6-wk intervals, after the PBT. Follow-up with regular magnetic resonance imaging has continued for 40 mo so far, demonstrating remarkable shrinkage of the HCC(maximal diameter dropping from approximately 13 cm to 2 cm). To date, the patient remains free of tumor recurrence. PBT served as a safe and effective treatment method for an unresectable HCC with vascular invasion.
文摘AIM To investigate the efficacy and safety of isolated hepatic perfusion(IHP) in the management of unresectable liver malignancies.METHODS Studies were identified manually and on-line by using Pub Med and EMBASE database.We formulate the eligibility criteria according to the PICOS elements,and accessed the quality of studies using the MINORS instrument.Data from all included studies were carefully investigated.We calculated the pooled response rate and incidences of mortality reported from all eligible studies by using the Meta-Analyst software,and we computed a pooled relative risk(RR) and 95%CI by using the Comprehensive Meta-Analysis software.Heterogeneity was quantified evaluated using I^2 statistic.RESULTS Eight studies,including 502 patients,were selected.Of these,six studies performed IHP,while the other two studies performed percutaneous IHP.The results showed that the pooled response rate was 60.8%(95%CI:53.1%-68%),I^2 = 37.1%.The median overall survival was 20 mo(range:12.1 to 25 mo) following IHP or PIHP.The pooled mortality rate was 5.4%(95%CI:2.5%-11.2%),I^2 = 37.5%.Prognostic factors predict the response to IHP or survival,and were reported in six studies.Meta-analysis demonstrated that Gender was not associated with overall survival(RR = 0.877,95%CI:0.564-1.365);however,carcino-embryonic antigen ≤ 30 ng/mL was associated with a significant improvement in survival outcomes with colorectal cancer patients(RR = 2.082,95%CI:1.371-3.163),and there was no significant heterogeneity.CONCLUSION The present systemic review and meta-analysis suggest that IHP and PIHP are potentially efficient and safe techniques for unresectable liver primary and secondary malignancies.
文摘BACKGROUND Definitive chemoradiotherapy(dCRT)using cisplatin plus 5fluorouracil(CF)with radiation is considered the standard treatment for unresectable locally advanced T4 esophageal squamous cell carcinoma(ESCC).Recently,induction chemotherapy has received attention as an effective treatment strategy.CASE SUMMARY We report a successful case of a 59-year-old female with unresectable locally advanced T4 ESCC treated by two additional courses of chemotherapy with CF after induction chemotherapy with docetaxel,cisplatin and fluorouracil(DCF)followed by dCRT.Initial esophagogastroduodenoscopy(EGD)detected a type 2 advanced lesion located on the middle part of the esophagus,with stenosis.Computed tomography detected the primary tumor with suspected invasion of the left bronchus and 90°of direct contact with the aorta,and upper mediastinal lymph node metastasis.Pathological findings from biopsy revealed squamous cell carcinoma.We initially performed induction chemotherapy using three courses of DCF,but the lesion was still evaluated unresectable after DCF chemotherapy.Therefore,we subsequently performed dCRT treatment(CF and radiation).After dCRT,prominent reduction of the primary tumor was recognized but a residual tumor with ulceration was detected by EGD.Since the patient had some surgical risk,we performed two additional courses of CF and achieved a clinically complete response.After 14 mo from last administration of CF chemotherapy,recurrence has not been detected by computed tomography and EGD,and biopsy from the scar formation has revealed no cancer cells.CONCLUSION We report successful case with tumor remnants even after DCF and subsequent dCRT,for whom a complete response was finally achieved with two additional courses of CF chemotherapy.Additional CF chemotherapy could be one radical treatment option for residual ESCC after treatment with induction DCF followed by dCRT to avoid salvage surgery,especially for high-risk patients.
文摘Background: The regional chronomodulated hepatic arterial infusion chemotherapy (HAIC) is an effective regimen for the treatment of patients with unresectable liver metastases from colorectal cancer, especially for the conversion into resectability. Aim: To demonstrate that chronomodulated HAI triplet chemotherapy according to OPTILIV protocol is well tolerated and displayed high antitumor activity in this heavily-pretreated patient. Case Presentation: A 54 years old patient from Russia was treated for a tumor in the ascending colon presented with 13 hepatic metastases ranging from 0.3 to 2.7 cm in diameter. He underwent a laparoscopic right hemicolectomy, 12 cycles of FOLFIRINOX combined to bevacizumab for the last 5 cycles, resulting in a partial response according to CT scan. It was decided to perform a two-stage hepatectomy at Paul Brousse hospital: left partial hepatectomy allowed the excision of 9 lesions. Radio frequency ablation was performed in 2 nodular lesions. Afterwards, the patient received 5 cycles of chronomodulated triplet chemotherapy into the hepatic artery, according to the OPTILIV protocol design, yet without cetuximab, because of the KRAS mutation in the liver metastases, with a partial re-sponse. The patient could then undergo the second stage of the planned right hepatectomy, which turned out to be an R0 resection followed by receiving three courses of chronomodulated HAIC. Disease progression was documented after 3 months. Chronomodulated FOLFIRI chemotherapy was re-started intravenously, in combination with Aflibercept and it was associated with further disease progression. The genetic analysis of our patient’s cancer revealed a high level of MSI. The patient was included in the Phase 2 CheckMate-142 trial and received nivolumab 3 mg/kg every 2 weeks within 3 months. Treatment was discontinued due to ineffectiveness. Then the patient underwent radiotherapy geared towards reduction of pain. Afterwards, the patient died from the disease progression 2 years after the beginning of treatment. Conclusion: In this article, the authors report a clinical case with chronomodulated HAIC as rescue therapy in a heavily pretreated patient with metastatic colorectal cancer, allowing to achieve an objective response despite prior progression on FOLFIRINOX (the same triplet chemo by IV route). This strategy permitted to overcome drug resistance and to perform further complete resection of the liver me-tastases with prolonged patient survival. Thus, chronomodulated HAI is useful in patients with liver metastases from colorectal cancer and de-serves to be further assessed prospectively in clinical trials chemotherapy.
