1.Introduction Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver.HCC is the sixth most frequently diagnosed cancer and the third leading cause of cancer-relatedmortality worldwide.[1]Part...1.Introduction Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver.HCC is the sixth most frequently diagnosed cancer and the third leading cause of cancer-relatedmortality worldwide.[1]Partial hepatectomy is recommended for patients with early stage HCC.[2]A large proportion of patients with HCC inChina are diagnosed in the intermediate to advanced HCC stages,rendering them ineligible for hepatectomy due to aspects such as liver dysfunction,insufficient residual liver volume,or surgical technique.展开更多
Treatment of locally advanced unresectable pancreatic cancer remains a major clinical challenge due to pronounced heterogeneity and resistance to standard regimens.Increasing evidence highlights the critical role of t...Treatment of locally advanced unresectable pancreatic cancer remains a major clinical challenge due to pronounced heterogeneity and resistance to standard regimens.Increasing evidence highlights the critical role of the tumor microenvironment(TME)in shaping therapeutic response and driving drug resistance.In this minireview,we summarize recent advances in TME phenotyping and its potential to guide precision therapy.A four-dimensional framework integrating stromal,immune,genomic,and metabolic features has been proposed to better characterize TME heterogeneity.Preclinical and clinical studies indicate that strategies targeting the stroma,modulating immunity,or exploiting genomic vulnerabilities such as homologous recombination deficiency may enhance the efficacy of chemotherapy,immunotherapy,and targeted agents.Dynamic biomarkers,including circulating tumor DNA and carbohydrate antigen 19-9,also show promise for real-time therapy adaptation,although their clinical application remains limited.By synthesizing current evidence,we emphasize the importance of individualized treatment strategies that account for TME complexity.While encouraging,the translation of multiomics phenotyping and biomarker monitoring into routine clinical practice requires standardization,prospective validation,and integration of novel technologies.Future research should focus on establishing reproducible TME-guided models to enable dynamic and personalized therapy for patients with unresectable pancreatic cancer.展开更多
BACKGROUND Palliative care for unresectable pancreatic cancer(PC)focuses mainly on the symptoms of the disease,including abdominal pain,obstructive jaundice,and malnutrition.Biliary stent placement using endoscopic re...BACKGROUND Palliative care for unresectable pancreatic cancer(PC)focuses mainly on the symptoms of the disease,including abdominal pain,obstructive jaundice,and malnutrition.Biliary stent placement using endoscopic retrograde cholangiopan-creatography(ERCP)to relieve biliary obstruction has become an internationally recognized treatment.Although a few studies have evaluated the efficacy of endoscopic pancreatic duct stenting in advanced PC,no consensus exists on the use of endoscopic treatment to relieve pain and improve nutritional status.METHODS Patients with unresectable PC were recruited.The participants were randomized into two groups:The double-stent group underwent ERCP with a fully-covered self-expandable metallic biliary stent(FCSEMS)and a pancreatic duct stent,while the single-stent group underwent ERCP with an FCSEMS only.Abdominal pain,nutritional status,and incidence of adverse events were compared between the two groups using the SPSS software.RESULTS Seventy-eight patients with unresectable PC were included in the analysis(40 and 38 in the double-and single-stent groups,respectively).The median pain scores of patients in the double-stent group were lower than those in the single-stent group at 1(0 vs 2.5,P=0.002),2(0 vs 3,P<0.001),3(0 vs 4,P<0.001),and 6 months(0 vs 4,P<0.001)after ERCP.Total serum protein levels in patients in the double-stent group were higher than those in the single-stent group(66.6±8.4 g/L vs 60.4±4.0 g/L,P=0.046)6 months postoperatively.The body mass index(BMI)of patients in both groups decreased at six months.However,the BMI in the single-stent group was higher than that in the double-stent group(P<0.001).CONCLUSION Early pancreatic duct stenting reduces abdominal pain and improves nutritional status in patients with unre-sectable PC without reducing the technical success rate or increasing the incidence of adverse events.展开更多
BACKGROUND The treatment of gastric cancer remains highly challenging,particularly in cases of unresectable locally advanced or metastatic disease.Although chemotherapy and immunotherapy have shown some efficacy in su...BACKGROUND The treatment of gastric cancer remains highly challenging,particularly in cases of unresectable locally advanced or metastatic disease.Although chemotherapy and immunotherapy have shown some efficacy in such patients,significant limitations persist in extending survival and enhancing safety.To address these challenges,we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1(PD-1)inhibitor with chemotherapy,and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity,with the metastasis being notably large in size.The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry.Considering the patient's status,the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel(nab-paclitaxel),S-1,and oxaliplatin as a quadruple drug conversion therapy.After 4 cycles of conversion therapy,the patient's epigastric pain was significantly alleviated,his stool color normalized,the volume of the primary tumor and lymph node metastases was markedly reduced,and the tumor marker levels decreased to within the normal range.The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection,and postoperative pathological biopsy revealed a pathological complete response and R0 resection,after which the patient recovered to an excellent physical status.CONCLUSION To the best of our knowledge,this is the first reported case of unresectable locally advanced gastric adenocar-cinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen.This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.展开更多
The Zhang et al’s study addresses an important clinical question of timing and role of salvage surgery post-downstaging procedures in patients with advanced hepatocellular carcinoma wherein different modalities like ...The Zhang et al’s study addresses an important clinical question of timing and role of salvage surgery post-downstaging procedures in patients with advanced hepatocellular carcinoma wherein different modalities like trans arterial chemoembolization,tyrosine kinase inhibitors,and anti-programmed cell death 1 antibodies have been used as downstaging procedure.Although proper selection of patients is a pre-requisite for salvage related liver failure.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
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
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 retrospectively evaluate the prognosis of patients with hepatocellular carcinoma （HCC） with or without a history of therapy for HCC following transcatheter arterial embolization （TAE）. METHODS： One hundr...AIM： To retrospectively evaluate the prognosis of patients with hepatocellular carcinoma （HCC） with or without a history of therapy for HCC following transcatheter arterial embolization （TAE）. METHODS： One hundred and twenty-one patients with HCC treated with TAE from 1992 to 2004 in our hospital were enrolled in this study. Eighty-four patients had a history of treatment for HCC, while 37 did not. At the time of entry, patients with extra-hepatic metastasis, portal vein tumor thrombosis, or Child-Pugh class C were excluded. TAE was repeated when recurrence of HCC was diagnosed by elevated tumor markers, or ultrasonography or dynamic computed tomography findings. RESULTS： Tumor size was larger and the number of tumors was fewer in patients without past treatment （P〈0.01）. However, there were no differences in tumor node metastasis （TNM） stage or survival rate between the 2 groups. A bilobular tumor and high level of α-fetoprotein （AFP） （〉100 ng/mL） were factors related to a poor prognosis in patients with a history of HCC. CONCLUSION： The prognosis following TAE is similar between HCC patients with and without past treatment. Early diagnosis of HCC or recurrent HCC and obtaining good local control against HCC before entry to a repeated TAE course can improve prognosis.展开更多
Objective：To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma （HCC）.Methods：Patients with unresectable advanced HCC received cryoabla...Objective：To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma （HCC）.Methods：Patients with unresectable advanced HCC received cryoablation and sorafenib at a dose of 400 mg twice daily in 4-week cycles on the same day of the cryoablation.Tumor response,median overall survival and the median time to radiological progression were calculated and the toxicity was evaluated.Results：Seventy-eight patients with unresectable HCC were involved in this study.The median age was 52 years （range,22-81 years）.The Eastern Cooperative Oncology Group （ECOG） performance status scores were 0 （39.7%）,1 （55.1%）,and 2 （5.1%）.Nine （11.5%） patients were at Barcelona clinic liver cancer （BCLC） stage A,twenty-four （30.8%） patients were at stage B and 45 （57.7%） patients were at stage C.Five （6.4%） achieved partial responses,and 34 （43.6%） achieved stable disease.The median time to progression （TTP） for all enrolled patients was 6.6 months and the median overall survival （OS） was 12.2 months.Conclusion：Cryoablation combined with sorafenib demonstrates good efficacy and acceptable tolerability in treating unresectable advanced HCC patients.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 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
AIM: To assess optimum endoscopic biliary drainage (EBD) in cases with unresectable pancreatic cancer in the era of gemcitabine (GEM). METHODS: Thirty patients with unresectable pancreatic cancer, who presented with j...AIM: To assess optimum endoscopic biliary drainage (EBD) in cases with unresectable pancreatic cancer in the era of gemcitabine (GEM). METHODS: Thirty patients with unresectable pancreatic cancer, who presented with jaundice and underwent chemotherapy using GEM after EBD were included in this study (GEM group). Fifteen cases with the same clinical manifestation and stage of pancreatic cancer treated with EBD alone were also included as controls. A covered metallic stent (CMS) or a plastic stent (PS) was used for EBD. The mean survival time (MST) in each group, risk factors of survival time, type of stent used and associated survival time, occlusion rate of stent, patency period of stent, and risk factors of stent occlusion were evaluated. RESULTS: MST in the GEM group was longer than that in the control (9.9 mo vs 6.2 mo). In the GEM group, the survival time was not different between those who underwent metallic stenting and those who underwent plastic stenting. Stent occlusion occurred in 60% of the PS group and 7% of the CMS group. The median stent patency in the PS-GEM group and the CMS-GEM group was 5 mo and 7.5 mo, respectively. Use of a PS was the only risk factor of stent occlusion. CONCLUSION: A CMS is recommended in cases presenting with jaundice due to unresectable pancreatic cancer, since the use of a CMS makes it possible to continue chemotherapy using GEM without repetition of stent replacement.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
Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of ...Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.展开更多
Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidiscipl...Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidisciplinary approach,particularly with new treatment modalities,has provided a new hope for unresectable HCC.This paper reports 477 patients with surgically verified unresectable HCC treated by different modalities, sequential resection was done in 55 patients(11.5%)due to marked shrinkage of the tumor.Patients treated with hepatic artery ligation(HAL),cannulation with infusion (HAI)and plus intraarterial targeting therapy(131I-antiHCC Ferritin IgG,131I-antiHCC monoclonal antibody,or 131I-Lipiodol)has higher sequential resection rate(33. 0%,31/94)when compared with other combination treatment(HAL+HAI,HAL+HAI+radiotherapy,11.7% ,22/188),and single treatment group(Cryosurgery,HAL,or HAI,1.0%,2/195). The combination of targeting therapy played an important role to the increasing number of sequential resection during 1978 through 1992.The 5-year survival of the 55 patients with sequential resection was as nigh as 60.8%.By the end of June 1993,13 patients survived more than 5 years, the longest being 15 years.展开更多
A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic r...A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) revealed that the density of the entire pancreas had decreased,and showed dilatation of the common bile duct (CBD) and the main pancreatic duct (MPD). Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites,liver metastasis,or peritoneal dissemination was observed. The entire pancreas was a hard mass,and a needle biopsy was obtained from the head,body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed,and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However,the patient suffered relatively severe side effects,and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response (CR) after 3 treatments. Therefore,weekly chemotherapy was stopped and was changed to monthly administration. To date,for 4 years after chemotherapy,the tumor has not reappeared.展开更多
文摘1.Introduction Hepatocellular carcinoma(HCC)is the most common primary malignancy of the liver.HCC is the sixth most frequently diagnosed cancer and the third leading cause of cancer-relatedmortality worldwide.[1]Partial hepatectomy is recommended for patients with early stage HCC.[2]A large proportion of patients with HCC inChina are diagnosed in the intermediate to advanced HCC stages,rendering them ineligible for hepatectomy due to aspects such as liver dysfunction,insufficient residual liver volume,or surgical technique.
文摘Treatment of locally advanced unresectable pancreatic cancer remains a major clinical challenge due to pronounced heterogeneity and resistance to standard regimens.Increasing evidence highlights the critical role of the tumor microenvironment(TME)in shaping therapeutic response and driving drug resistance.In this minireview,we summarize recent advances in TME phenotyping and its potential to guide precision therapy.A four-dimensional framework integrating stromal,immune,genomic,and metabolic features has been proposed to better characterize TME heterogeneity.Preclinical and clinical studies indicate that strategies targeting the stroma,modulating immunity,or exploiting genomic vulnerabilities such as homologous recombination deficiency may enhance the efficacy of chemotherapy,immunotherapy,and targeted agents.Dynamic biomarkers,including circulating tumor DNA and carbohydrate antigen 19-9,also show promise for real-time therapy adaptation,although their clinical application remains limited.By synthesizing current evidence,we emphasize the importance of individualized treatment strategies that account for TME complexity.While encouraging,the translation of multiomics phenotyping and biomarker monitoring into routine clinical practice requires standardization,prospective validation,and integration of novel technologies.Future research should focus on establishing reproducible TME-guided models to enable dynamic and personalized therapy for patients with unresectable pancreatic cancer.
基金Supported by The Health Commission of Zhejiang Provence,China,No.WKJ-ZJ-2136.
文摘BACKGROUND Palliative care for unresectable pancreatic cancer(PC)focuses mainly on the symptoms of the disease,including abdominal pain,obstructive jaundice,and malnutrition.Biliary stent placement using endoscopic retrograde cholangiopan-creatography(ERCP)to relieve biliary obstruction has become an internationally recognized treatment.Although a few studies have evaluated the efficacy of endoscopic pancreatic duct stenting in advanced PC,no consensus exists on the use of endoscopic treatment to relieve pain and improve nutritional status.METHODS Patients with unresectable PC were recruited.The participants were randomized into two groups:The double-stent group underwent ERCP with a fully-covered self-expandable metallic biliary stent(FCSEMS)and a pancreatic duct stent,while the single-stent group underwent ERCP with an FCSEMS only.Abdominal pain,nutritional status,and incidence of adverse events were compared between the two groups using the SPSS software.RESULTS Seventy-eight patients with unresectable PC were included in the analysis(40 and 38 in the double-and single-stent groups,respectively).The median pain scores of patients in the double-stent group were lower than those in the single-stent group at 1(0 vs 2.5,P=0.002),2(0 vs 3,P<0.001),3(0 vs 4,P<0.001),and 6 months(0 vs 4,P<0.001)after ERCP.Total serum protein levels in patients in the double-stent group were higher than those in the single-stent group(66.6±8.4 g/L vs 60.4±4.0 g/L,P=0.046)6 months postoperatively.The body mass index(BMI)of patients in both groups decreased at six months.However,the BMI in the single-stent group was higher than that in the double-stent group(P<0.001).CONCLUSION Early pancreatic duct stenting reduces abdominal pain and improves nutritional status in patients with unre-sectable PC without reducing the technical success rate or increasing the incidence of adverse events.
基金Supported by the Health Industry Research Program of Gansu Province,No.GSWSKY2021-043the Youth Science and Technology Foundation of Gansu Province,No.22JR11RA002the Natural Science Foundation of Gansu Province,No.22JR5RA008.
文摘BACKGROUND The treatment of gastric cancer remains highly challenging,particularly in cases of unresectable locally advanced or metastatic disease.Although chemotherapy and immunotherapy have shown some efficacy in such patients,significant limitations persist in extending survival and enhancing safety.To address these challenges,we designed an innovative first-line quadruple conversion therapy regimen that integrates a programmed cell death protein 1(PD-1)inhibitor with chemotherapy,and we successfully implemented this therapy regimen in the treatment of a patient with unresectable locally advanced gastric adenocarcinoma.CASE SUMMARY We report the case of a 55-year-old male who was diagnosed with unresectable locally advanced gastric adenocarcinoma and presented with intermittent epigastric pain and multiple lymph node metastases in the abdominal cavity,with the metastasis being notably large in size.The tumor tissue was negative for human epidermal growth factor receptor 2 by immunohistochemistry.Considering the patient's status,the multidisciplinary team decided to administer sintilimab in combination with albumin-bound paclitaxel(nab-paclitaxel),S-1,and oxaliplatin as a quadruple drug conversion therapy.After 4 cycles of conversion therapy,the patient's epigastric pain was significantly alleviated,his stool color normalized,the volume of the primary tumor and lymph node metastases was markedly reduced,and the tumor marker levels decreased to within the normal range.The patient subsequently underwent laparoscopic total gastrectomy with abdominal lymph node dissection,and postoperative pathological biopsy revealed a pathological complete response and R0 resection,after which the patient recovered to an excellent physical status.CONCLUSION To the best of our knowledge,this is the first reported case of unresectable locally advanced gastric adenocar-cinoma successfully treated with quadruple therapy with a PD-1 inhibitor and chemotherapy as a first-line conversion regimen.This first-line conversion therapy with the quadruple regimen may be effective and safe for unresectable locally advanced gastric adenocarcinoma.
文摘The Zhang et al’s study addresses an important clinical question of timing and role of salvage surgery post-downstaging procedures in patients with advanced hepatocellular carcinoma wherein different modalities like trans arterial chemoembolization,tyrosine kinase inhibitors,and anti-programmed cell death 1 antibodies have been used as downstaging procedure.Although proper selection of patients is a pre-requisite for salvage related liver failure.
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.
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 retrospectively evaluate the prognosis of patients with hepatocellular carcinoma （HCC） with or without a history of therapy for HCC following transcatheter arterial embolization （TAE）. METHODS： One hundred and twenty-one patients with HCC treated with TAE from 1992 to 2004 in our hospital were enrolled in this study. Eighty-four patients had a history of treatment for HCC, while 37 did not. At the time of entry, patients with extra-hepatic metastasis, portal vein tumor thrombosis, or Child-Pugh class C were excluded. TAE was repeated when recurrence of HCC was diagnosed by elevated tumor markers, or ultrasonography or dynamic computed tomography findings. RESULTS： Tumor size was larger and the number of tumors was fewer in patients without past treatment （P〈0.01）. However, there were no differences in tumor node metastasis （TNM） stage or survival rate between the 2 groups. A bilobular tumor and high level of α-fetoprotein （AFP） （〉100 ng/mL） were factors related to a poor prognosis in patients with a history of HCC. CONCLUSION： The prognosis following TAE is similar between HCC patients with and without past treatment. Early diagnosis of HCC or recurrent HCC and obtaining good local control against HCC before entry to a repeated TAE course can improve prognosis.
文摘Objective：To evaluate the efficacy and tolerability of sorafenib combined with cryoablation in treating unresectable hepatocellular carcinoma （HCC）.Methods：Patients with unresectable advanced HCC received cryoablation and sorafenib at a dose of 400 mg twice daily in 4-week cycles on the same day of the cryoablation.Tumor response,median overall survival and the median time to radiological progression were calculated and the toxicity was evaluated.Results：Seventy-eight patients with unresectable HCC were involved in this study.The median age was 52 years （range,22-81 years）.The Eastern Cooperative Oncology Group （ECOG） performance status scores were 0 （39.7%）,1 （55.1%）,and 2 （5.1%）.Nine （11.5%） patients were at Barcelona clinic liver cancer （BCLC） stage A,twenty-four （30.8%） patients were at stage B and 45 （57.7%） patients were at stage C.Five （6.4%） achieved partial responses,and 34 （43.6%） achieved stable disease.The median time to progression （TTP） for all enrolled patients was 6.6 months and the median overall survival （OS） was 12.2 months.Conclusion：Cryoablation combined with sorafenib demonstrates good efficacy and acceptable tolerability in treating unresectable advanced HCC patients.
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.
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AIM: To assess optimum endoscopic biliary drainage (EBD) in cases with unresectable pancreatic cancer in the era of gemcitabine (GEM). METHODS: Thirty patients with unresectable pancreatic cancer, who presented with jaundice and underwent chemotherapy using GEM after EBD were included in this study (GEM group). Fifteen cases with the same clinical manifestation and stage of pancreatic cancer treated with EBD alone were also included as controls. A covered metallic stent (CMS) or a plastic stent (PS) was used for EBD. The mean survival time (MST) in each group, risk factors of survival time, type of stent used and associated survival time, occlusion rate of stent, patency period of stent, and risk factors of stent occlusion were evaluated. RESULTS: MST in the GEM group was longer than that in the control (9.9 mo vs 6.2 mo). In the GEM group, the survival time was not different between those who underwent metallic stenting and those who underwent plastic stenting. Stent occlusion occurred in 60% of the PS group and 7% of the CMS group. The median stent patency in the PS-GEM group and the CMS-GEM group was 5 mo and 7.5 mo, respectively. Use of a PS was the only risk factor of stent occlusion. CONCLUSION: A CMS is recommended in cases presenting with jaundice due to unresectable pancreatic cancer, since the use of a CMS makes it possible to continue chemotherapy using GEM without repetition of stent replacement.
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.
基金This work was supported by the Science and Technology Development Fund,Macao SAR(No.0053-2021-AGJ)the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao(No.SKL-QRCM-IRG2023-011)the Natural Science Foundation of Sichuan Province(No.2023NSFSC1783).
文摘Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.
文摘Despite unquestionable progress has been made inresection of small and large hepatocellular carcinoma'(HCC),the dismal outcome of unresectable HCC remains a great challenge.Fortunately,the progress of multidisciplinary approach,particularly with new treatment modalities,has provided a new hope for unresectable HCC.This paper reports 477 patients with surgically verified unresectable HCC treated by different modalities, sequential resection was done in 55 patients(11.5%)due to marked shrinkage of the tumor.Patients treated with hepatic artery ligation(HAL),cannulation with infusion (HAI)and plus intraarterial targeting therapy(131I-antiHCC Ferritin IgG,131I-antiHCC monoclonal antibody,or 131I-Lipiodol)has higher sequential resection rate(33. 0%,31/94)when compared with other combination treatment(HAL+HAI,HAL+HAI+radiotherapy,11.7% ,22/188),and single treatment group(Cryosurgery,HAL,or HAI,1.0%,2/195). The combination of targeting therapy played an important role to the increasing number of sequential resection during 1978 through 1992.The 5-year survival of the 55 patients with sequential resection was as nigh as 60.8%.By the end of June 1993,13 patients survived more than 5 years, the longest being 15 years.
文摘A 68-year-old female visited a local clinic with epigastralgia. A routine laboratory test revealed jaundice and liver dysfunction. She was referred to this hospital. Abdominal computed tomography (CT) and endoscopic retrograde cholangio-pancreatography (ERCP) revealed that the density of the entire pancreas had decreased,and showed dilatation of the common bile duct (CBD) and the main pancreatic duct (MPD). Pancreatic cancer was diagnosed by cytological examination analyzing the pancreatic juice obtained by ERCP. When jaundice had decreased the tumor was observed via laparotomy. No ascites,liver metastasis,or peritoneal dissemination was observed. The entire pancreas was a hard mass,and a needle biopsy was obtained from the head,body and tail of the pancreas. These biopsies diagnosed a poorly differentiated adenocarcinoma. Hepaticojejunostomy was thus performed,and postoperative progress was good. Chemotherapy with 1000 mg/body per week of gemcitabine was administered beginning 15 d postoperatively. However,the patient suffered relatively severe side effects,and it was necessary to change the dosing schedule of gemcitabine. Abdominal CT revealed a complete response (CR) after 3 treatments. Therefore,weekly chemotherapy was stopped and was changed to monthly administration. To date,for 4 years after chemotherapy,the tumor has not reappeared.
