Neoadjuvant transcatheter arterial chemoembolization and systemic chemotherapy for the treatment of undifferentiated embryonal sarcoma of the liver in children

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a rare and aggressive mesenchymal tumor in children.Herein,we describe our experience in neoadjuvant therapy(NAT)and subsequent surgery for the treatment of UESL in children.AIM To evaluate the efficacy of NAT and explore a new choice for successful operation of UESL in children.METHODS We retrospectively analyzed six patients newly diagnosed with unresectable UESL who received NAT and then surgery at our center between January 2004 and December 2019.The tumor was considered unresectable if it involved a large part of both lobes of the liver or had invaded the main hepatic vessels or inferior vena cava.The NAT included preoperative transcatheter arterial chemoembol ization(TACE)and systemic chemotherapy.The patients were 4 boys and 2 girls with a mean age of 7 years.The longest tumor at presentation ranged from 8.6 to 14.8 cm(mean,12 cm).Extrahepatic metastases were present in 2 cases.Preoperative systemic chemotherapy was administered 3 wk after TACE.Tumor resection was performed 3 wk after one or two cycles of NAT.The patients received systemic chemotherapy after surgery.RESULTS All patients successfully underwent NAT and complete resection.The tumor volumes decreased by 18.2%–68.7%,with a mean decrease of 36%after 1 cycle of NAT(t=3.524,P=0.017).According to the Response Evaluation Criteria In Solid Tumors criteria,4 patients had a partial response and underwent surgery,while 2 had stable disease and received another cycle of NAT before surgery.Massive tumor necrosis was seen on pathological examination of the surgical specimen:>90%necrosis in two,>50%necrosis in three,and 25%necrosis in 1,with an average of 71.8%.Post-NAT complications included fever,nausea and vomiting,and mild bone marrow suppression.Elevated alanine transaminase levels occurred in all patients,which returned to normal within 7–10 d after treatment.No cardiac or renal toxicity,severe hepatic dysfunction,bleeding and nontarget embolization were observed in the patients.The median follow-up period was 8 years with an overall survival of 100%.CONCLUSION NAT effectively reduced tumor volume,cleared the tumor margin,and caused massive tumor necrosis.This may be a promising choice for successful surgery of UESL in children.

A case of advanced intrahepatic cholangiocarcinoma successfully treated with chemosensitivity test-guided systemic chemotherapy

Intrahepatic cholangiocarcinoma （ICC） is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin （CDDP）. A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography （CT） showed low-density masses of 50 and 15 mm in diameter, respectively in segment w of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months afcer initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion.After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

Efficacy comparison between hepatic arterial infusion chemotherapy plus systemic chemotherapy used as first-line and non-first-line treatments for the patients of colorectal cancers with unresectable hepatic metastases

Objective: The combination of hepatic arterial chemotherapy(HAIC) and systemic chemotherapy(SYC) has potential effect on colorectal cancer(CRC) patients with unresectable hepatic metastasis. The aim of this retrospective study was to investigate the efficacy and safety of this combined therapeutic regimen on Chinese patients based on single institute experiences. Methods: All 54 patients of this retrospective analysis were diagnosed with CRC with unresectable liver metastasis and received combined HAIC and SYC. Among the patients, 23 of them received HAIC plus SYC when they developed liver metastases as first-line treatment(Group 1), and 31 patients received HAIC plus SYC as non-first-line treatment(Group 2). The different efficacy in two groups was analyzed by SPSS 19.0. Results: The overall response rate(ORR) were 52.2% and 25.8% respectively in Groups 1 and 2(P = 0.047), and the disease control rate(DCR) were 65.2% and 35.5% respectively in Groups 1 and 2(P = 0.031). The median progression-free survival(PFS) were 6.8 and 3.3 months(P = 0.002), the median hepatic progression-free survival(H-PFS) were 8.8 and 3.7 months(P = 0.001), and the median overall survival(OS) were 18.8 and 13.7 months(P = 0.121) in Groups 1 and 2, respectively. No fatal reaction was observed and no significant difference of adverse reaction was found in two groups. Grade 3/4 toxic effects included neutropenia(9.7% in Group 2 only), gastrointestinal reaction(8.7% in Group 1 and 6.5% in Group 2), stomatitis(6.5% in Group 2 only) and hyperbilirubinemia(4.3% in Group 1 only). Conclusion: HAIC combined with SYC showed promising efficacy and safe profiles on CRC patients with unresectable liver metastases.

Is it relevant that intra-arterial chemotherapy may be effective for advanced pancreatic cancer?

Unresectable pancreatic cancers have an extremely dismal prognosis and chemoresistant nature. The treatment of pancreatic cancer is still problematic. Gemcitabine is a promising new agent that has been studied recently for palliation of advanced pancreatic cancer. However,the response rates have been highly variable,and are often irreproducible. To improve this low response rate,various treatments are needed because no standard treatment exists. Intra-arterial chemotherapy is considered to take advantage of the first pass effect of the drug,generating higher local drug concentrations in tumor cells with lower toxicity. Regional intra-arterial chemotherapy may provide high levels of cytostatic concentrations within the tumor and,simultaneously,a low rate of systemic side effects compared with systemic administration of anti-neoplastic drugs. Intra-arterial chemotherapy has been introduced as an alternative treatment for advanced pancreatic cancer. Further clinical trials of this method should be subjected to a prospective randomized controlled study for advanced pancreatic cancer.

Intraperitoneal chemotherapy and its evolving role in management of gastric cancer with peritoneal metastases

Advanced gastric cancer （GC） has been recognized as lethal disease when peritoneal metastases （PM） occurred.There is no standard treatment for advanced GC with PM.Until 1980s,the therapeutic arena for these patients had remained stagnant,with no therapeutic approach having shown a survival gain in GC with PM.However,cytoreductive surgery （CRS） with peritonectomy procedures and intraperitoneal chemotherapy （IPC） promising new combined therapeutic approach to achieve disease control for GC with PM.The recent publications changed the GC with PM treatment landscape by providing an evidence that CRS and IPC led to prolongation in overall survival （OS）.This review will provide an overview of the evolving role of CRS and IPC in the management of advanced GC with PM in the current era.

Thermal ablation in colorectal liver metastases: Lack of evidence or lack of capability to prove the evidence?

Many studies suggest that combined multimodality treatments including ablative therapies may achieve better outcomes than systemic chemotherapy alone in patients with colorectal liver metastases. Nevertheless, ablative therapies are not yet considered as effective options because their efficacy has never been proved by randomized controlled trials (RCT). However, there are in literature no trials that failed in demonstrating the effectiveness of ablative treatments: what are lacking, are the trials. All the attempts to organize phase III studies on this topic failed as a result of non accrual. Just one prospective RCT comparing radiofrequency ablation combined with systemic chemotherapy vs chemotherapy alone has been published. It was designed as a phase III study, but it was closed early because of slow accrual, and was downscaled to phase II study, with the consequent limits in drawing definite conclusions on the benefit of combined treatment. However, the combination treatment met the primary end point of the study and obtained a significantly higher 3-year progression-free survival than systemic chemotherapy alone. It is very unlikely that ultimate efficacy of ablation treatments will ever be tested again, and the best available evidence points toward a benefit for the combination strategy using ablative treatments and chemotherapy.

Clinical and therapeutic considerations of rectal lymphoma: A case report and literature review

Primary rectal lymphoma is a rare presentation of gastrointestinal lymphomas. Its clinical presentation is indistinguishable from that of rectal carcinoma. Although surgical resection is often technically feasible, optimal therapy for colorectal lymphoma has not yet been identified.We report a case of primary rectal lymphoma (nonHodgkin's large cell lymphoma of type B) with high-grade features that disappeared completely after chemoradiotherapy. This case underlines that primary treatment with systemic chemotherapy and involved-field radiotherapy can be successful for rectal lymphoma, with surgery reserved for complications and chemotherapy failures.

Clinical study of FOLFOX4 regimen for patients of advanced hepatocellular carcinoma

Objective:The aim of our study was to observe the efficiency and toxicity of oxaliplatin (L-OHP) combined with CF/5-FU in patients with advanced primary hepatocellular carcinoma.Methods:Twenty patients with advanced primary hepatocellular carcinoma had recurrence/metastasis after multiple courses of TACE (cisplatin and epirubicin,etc.).All patients were treated with FOLFOX4 regimen of the combination of oxaliplatin and leucovorin and 5-fluorouracil.Treatment was repeated every 2 weeks until disease progression or unacceptable adverse effects occurred.The efficiency was evaluated according to RECIST criteria,and toxicities according to American National Cancer Institute Common Toxicity Criteria (NCI CTC),respectively.Results:Twenty patients were assessable for the objective efficiency and for toxicity.No patient achieved complete response (CR),4 patients were partial response (PR),8 patients were stable disease (SD),8 patients were disease progression (PD);Time to tumor progression (TTP) of the patients ranged from 1.5 to 4.8 months,median TTP was 2.2 months;Overall survival (OS) of the patients ranged from 3 to 10.2 months,median OS was 5 months.The 2 patients' serum AFP level decreasing.Sixteen patients relieved the symptoms obviously,stabilized or raised up Karnofsky Score.The toxicities were mainly grade I-II arrest of bone marrow (50%),mild neurotoxicity (30%) and mild reaction of gastrointestinal tract (40%).Conclusion:FOLFOX4 regimen is effective and safe for patients with advanced primary hepatocellular carcinoma.It can be worthy of further clinical investigation.

Current treatment strategies for patients with only peritoneal cytology positive stage IV gastric cancer

Gastric cancer(GC)is one of the most common malignancies worldwide and surgery remains the only potentially curative treatment option for it.Although a significant proportion of GC patients are found with distant metastases already at the initial diagnosis.Peritoneal dissemination is the most common site of metastases.Positive peritoneal cytology(Cy1)is associated with poor long-term outcomes;thus,these patients are considered as stage IV even if macroscopic carcinomatosis is absent.Currently,there is no clear evidence for the most optimal treatment for this distinct subpopulation of the stage IV cohort.Available strategies vary from palliative chemotherapy to upfront gastrectomy.This comprehensive review summarized current evidence of different treatment strategies for Cy1 GC including roles of surgery,systemic and intraperitoneal chemotherapy.

Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer:From Preclinical Findings to Current Clinical Practice

Epithelial ovarian cancer (EOC) is the sixth most common malignancy in women. Ovarian tumors consist of several clinical and pathological entities that share an anatomic site. The gold standard treatment, both in front-line and in adjuvant setting, is represented by carboplatin/paclitaxel combination. Conversely, the second-line treatment is not well defined. The response to platinum is the major prognostic factor for survival. In this review we discuss the current views on platinum-refractory/resistant patient treatment only, which includes patients progressing or relapsing within 6 months from the last platinum-based course. Concerning this subgroup, the activity of several conventional drugs was confirmed in different trials without a significant impact in terms of overall survival. In the last years particular emphasis was given to targeted anti-angiogenetic therapy which produced a survival improvement with an acceptable toxicity profile. New “ad hoc” approaches, with a major attention to outcome-predictive factors, are eagerly awaited.

Comparison of regional arterial chemotherapy and systemic intravenous chemotherapy for advanced pancreatic cancer:a systematic review and meta-analysis

Chemotherapy is the mainstay of treatment for advanced pancreatic cancer(stageⅢ/Ⅳ).However,conventional systemic intravenous chemotherapy(SIC)has been unsatisfactory for pancreatic cancer.In recent years,regional arterial infusion chemotherapy(RAIC)has been clinically used as a new chemotherapy regimen for the treatment of advanced pancreatic cancer,but its efficacy is controversial.The purpose of this study was to evaluate the clinical efficacy and safety of RAIC.We searched literatures in databases such as PubMed,EMBASE,Cochrane Library,Web of Science,and CNKI.After screening,this meta-analysis finally included 9 randomized controlled trials(RCTs)with 444 patients(230 RAIC and 214 SIC).We used the Cochrane Risk of Bias 2.0 tool to assess risk of bias for included RCTs.Outcomes were overall survival(OS),overall response rate(ORR),adverse events rate(AER),and pain remission rate.Outcome indicators used relative risk(RR)and its 95%confidence interval(CI)as effect analysis statistics.The results showed that RAIC had some advantages over SIC in terms of ORR,OS,incidence of leukopenia,and pain remission.In conclusion,compared with SIC,RAIC has better clinical efficacy and lower toxicity in the treatment of advanced pancreatic cancer.

Liver metastasis of pancreatic cancer: the new choice at the crossroads

In recent years,the incidence of pancreatic cancer has increased markedly both in China and internationally.For patients with pancreatic cancer,surgical resection remains the only effective method of obtaining a cure and long-term survival,although only few patients can expect this benefit.