Hepatic histopathology and postoperative outcome after preoperative chemotherapy for Chinese patients with colorectal liver metastases

AIM: To assess the effects of preoperative treatment on the hepatic histology of non-tumoral liver and the postoperative outcome. METHODS: One hundred and six patients underwent hepatic resection for colorectal metastases between 1999 and 2009. The surgical specimens were reviewed with established criteria for diagnosis and grading of pathological hepatic injury. The impact of preoperative therapy on liver injury and postoperative outcome was analyzed.alone, whereas 42 patients (39.6%) received neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%) and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%) had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the perioperative complication rate was not significantly different between the oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated with more steatosis, sinusoidal dilation and steatohepatitis than the surgery group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and mortality (9.1% vs 0% P = 0.02). CONCLUSION: Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone. However, the preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI can cause pathological changes and tends to increase perioperative morbidity and mortality.

Tumour response following preoperative chemotherapy is affected by body mass index in patients with colorectal liver metastases

BACKGROUND Colorectal cancer is the third most prevalent malignancy globally and ranks second in cancer-related mortality,with the liver being the primary organ of metastasis.Preoperative chemotherapy is widely recommended for initially or potentially resectable colorectal liver metastases(CRLMs).Tumour pathological response serves as the most important and intuitive indicator for assessing the efficacy of chemotherapy.However,the postoperative pathological results reveal that a considerable number of patients exhibit a poor response to preoperative chemotherapy.Body mass index(BMI)is one of the factors affecting the tumori-genesis and progression of colorectal cancer as well as prognosis after various antitumour therapies.Several studies have indicated that overweight and obese patients with metastatic colorectal cancer experience worse prognoses than those with normal weight,particularly when receiving first-line chemotherapy regimens in combination with bevacizumab.AIM To explore the predictive value of BMI regarding the pathologic response following preoperative chemotherapy for CRLMs.METHODS A retrospective analysis was performed in 126 consecutive patients with CRLM who underwent hepatectomy following preoperative chemotherapy at four different hospitals from October 2019 to July 2023.Univariate and multivariate logistic regression models were applied to analyse potential predictors of tumour pathological response.The Kaplan-Meier method with log rank test was used to compare progression-free survival(PFS)between patients with high and low BMI.BMI<24.0 kg/m^(2) was defined as low BMI,and tumour regression grade 1-2 was defined as complete tumour response.RESULTS Low BMI was observed in 74(58.7%)patients and complete tumour response was found in 27(21.4%)patients.The rate of complete tumour response was significantly higher in patients with low BMI(29.7%vs 9.6%,P=0.007).Multivariate analysis revealed that low BMI[odds ratio(OR)=4.56,95%confidence interval(CI):1.42-14.63,P=0.011],targeted therapy with bevacizumab(OR=3.02,95%CI:1.10-8.33,P=0.033),preoperative carcinoembryonic antigen level<10 ng/mL(OR=3.84,95%CI:1.19-12.44,P=0.025)and severe sinusoidal dilatation(OR=0.17,95%CI:0.03-0.90,P=0.037)were independent predictive factors for complete tumour response.The low BMI group exhibited a significantly longer median PFS than the high BMI group(10.7 mo vs 4.7 mo,P=0.011).CONCLUSION In CRLM patients receiving preoperative chemotherapy,a low BMI may be associated with better tumour response and longer PFS.

Stent placement followed by preoperative chemotherapy and elective surgery for acute malignant colorectal obstruction: Six cases of report

BACKGROUND The self-expandable metal stent is used as a bridge to surgery in the treatment of acute malignant colorectal obstruction(AMCO). However, recent studies have shown inferior long-term outcomes and increased risk of tumor dissemination after stent placement. In addition, the optimal interval between stent placement and surgery is not clear. The aim of the current study was to present a new strategy for AMCO: stent placement followed by preoperative chemotherapy and elective surgery.CASE SUMMARY Six patients were diagnosed as acute obstruction. There was one patient with descending cancer, four with sigmoid cancers and one with rectal cancer. The obstructive symptoms of these six patients were relieved within 3 d after stent placement. After receiving two cycles of preoperative chemotherapy, consisting of modified infusional fluorouracil, leucovorin and oxaliplatin [modified FOLFOX6(mFOLFOX6)], they underwent elective surgery of primary tumor resection. None of the 6 patients received colostomy or colonic lavage during surgery. There was no complication of anastomotic leak, ileus or surgical site infection after surgery. In addition, the patients had low operation time and blood loss, adequate lymph nodes harvest and fast postoperative recovery.CONCLUSION The two-cycle mFOLFOX6 preoperative chemotherapy and elective surgery after stent placement is a safe and feasible strategy in the management of AMCO.

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

Phase Ⅱ study of docetaxel,cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer

AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric cancer.METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria,were treated with 4 cycles of docetaxel(60 mg/m2),cisplatin(60 mg/m2) and capecitabine(1.875 mg/m2 orally on day 1-14,two daily doses) repeated every three weeks,followed by surgery.Primary end point was the feasibility and toxicity/safety profile of DCC,secondary endpoints were pathological complete resection rate and pathological complete response(p CR) rate.RESULTS All of the patients(51) were assessable for the feasibility and safety of the regimen.The entire preoperative regimen was completed by 68.6% of the patients.Grade Ⅲ/Ⅳ febrile neutropenia occurred in 10% of all courses.Three patients died due to treatment related toxicity(5.9%),one of them(also) because of refusing further treatment for toxicity.Of the 45 patients who were evaluable for secondary endpoints,four developed metastatic disease and 76.5% received a curative resection.In 3 patients a p CR was seen(5.9%),two patients underwent a R1 resection(3.9%).CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding.The high occurrence of febrile neutropenia is of concern.To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colonystimulating factor(G-CSF) should be explored.A curative resection rate of 76.5% is acceptable.The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

Impact of homogeneous pathologic response to preoperative chemotherapy in patients with multiple colorectal liver metastases

AIM To analyze the homogeneity of pathologic response to preoperative chemotherapy(PRPC) after chemotherapy in patients with multiple liver metastases(LM).METHODS From September 2011 to August 2014,patients with at least two LM undergoing preoperative chemotherapy prior to resection were included in this retrospective,single-center study. The endpoints were PRPC homogeneity(according to both the Rubbia-Brandt and MD Anderson classifications),the impact of PRPC on the MDT decision,factors associated with homogeneous PRPC and overall survival of patients with vs. without homogeneous PRPC.RESULTS seventy-three patients with a total of 88 liver resections(including 15 two-stage procedures) were included in the study. The homogeneous PRPC rate was 55% according to the Rubbia-Brandt classification and 53% according to the MD Anderson classification. The MDT decision was modified by the PRPC in only 2.7% of patients(n = 2). CONCLUSION The PRPC was homogeneous in only one half of patients and had very little influence on the MDT decision.

Comprehensive Analysis of Key mRNAs and lncRNAs in Osteosarcoma Response to Preoperative Chemotherapy with Prognostic Values

Objective:Osteosarcoma is one of the most common types of bone sarcoma with a poor prognosis.However,identifying the predictive factors that contribute to the response to neoadjuvant chemotherapy remains a significant challenge.Methods:A public data series(GSE87437)was downloaded to identify differentially expressed genes(DEGs)and differentially expressed lncRNAs(DElncRNAs)between osteosarcoma patients that do and do not respond to preoperative chemotherapy.Subsequently,functional analysis of the transcriptome expression profile,regulatory networks of DEGs and DElncRNAs,competing endogenous RNAs(ceRNA)and protein-protein interaction networks were performed.Furthermore,the function,pathway,and survival analysis of hub genes was performed and drug and disease relationship prediction of DElncRNA was carried out.Results:A total of 626 DEGs,26 DElncRNAs,and 18 hub genes were identified.However,only one gene and two lncRNAs were found to be suitable as candidate gene and lncRNAs respectively.Conclusion:The DEGs,hub genes,candidate gene,and candidate lncRNAs screened out in this context were considered as potential biomarkers for the response to neoadjuvant chemotherapy of osteosarcoma.

Predictive value of serum alpha-fetoprotein for tumor regression after preoperative chemotherapy for rectal cancer

BACKGROUND Preoperative therapy is widely used in locally advanced rectal cancer.It can improve local control of rectal cancer.However,there are few indicators that can predict the effect of preoperative chemotherapy accurately.AIM To investigate whether the increase in serumα-fetoprotein(AFP)can predict better efficacy of preoperative chemotherapy.METHODS This was a retrospective study.We analyzed 125 patients admitted between 2017 and 2019 with locally advanced rectal cancer.All patients received six cycles of preoperative chemotherapy(mFOLFOX6 every 2 wk).Serum AFP of 26 patients rose slightly after three or four cycles of chemotherapy,and fell to normal again within 2 mo.The other 99 patients had a normal level of serum AFP during chemotherapy.Patients were divided into two groups(AFP risen and AFP normal).According to postoperative pathology,we compared tumor regression and complete response rate between the two groups.The primary outcome measure was the tumor regression grade(TRG)after chemotherapy.The difference in pathological complete response between the two groups was also investigated.RESULTS There were no tumor progression and distant metastasis in both groups during preoperative chemotherapy.Patients in the AFP risen group achieved better TRG 0/1 than those in the AFP normal group(61.5%vs 39.4%).The increase in AFP was a significant predictor for better tumor regression[χ2=4.144,odds ratio(OR)=2.666,P=0.04].In the AFP risen group,the complete response rate was 30.8%,which was higher than in the AFP normal group(30.8%vs 12.1%,χ2=4.542,OR=3.251,P=0.03).CONCLUSION Patients with a slight increase in serum AFP can achieve better tumor regression during preoperative chemotherapy,and are more likely to achieve pathological complete response.

Effect of preoperative bronchial artery infusion chemotherapy on the tumor malignancy of patients with stage IIIA non-small cell lung cancer

Objective:To investigate the effect of preoperative bronchial artery infusion chemotherapy on the tumor malignancy of patients with stage IIIA non-small cell lung cancer.Methods:99 patients with stage IIIA non-small cell lung cancer who underwent surgical treatment in our hospital between January 2015 and August 2018 were chosen as the research subjects, and the preoperative adjuvant therapies were reviewed and used to divide them into the control group (n=51) who received conventional neoadjuvant chemotherapy and the study group (n=48) who received neoadjuvant chemotherapy combined with bronchial artery infusion chemotherapy. The differences in the expression levels of NSCLC-related proliferation, invasion and apoptosis genes in intraoperative lesion tissues were compared between the two groups.Results: NSCLC-related proliferation genes CD137L, dlk1, EZH2 and WT1 mRNA expression in lesion tissues of study group were lower than those of control group whereas DCLAK11 mRNA expression was higher than that of control group;NSCLC-related invasion genes ALX1, periostin and RAC1 mRNA expression were lower than those of control group whereas DAL-1 mRNA expression was higher than that of control group;NSCLC-related apoptosis genes Survivin, Livin, bcl-2 and Bag-1 mRNA expression were lower than those of control group.Conclusion: Preoperative bronchial artery infusion chemotherapy can further inhibit the malignant biological behaviors of cancer cells in patients with stage IIIA NSCLC.

Skeletal muscle mass and quality before preoperative chemotherapy influence postoperative long-term outcomes in esophageal squamous cell carcinoma patients

BACKGROUND Previous reports have focused on muscle mass as a prognostic factor in esophageal cancer.AIM To investigate how preoperative body type influences the prognosis of patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemotherapy(NAC)and surgery.METHODS The subjects were 131 patients with clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma who underwent subtotal esophagectomy after NAC.Skeletal muscle mass and quality were calculated based on computed tomography images prior to NAC,and their statistical association with long-term outcomes was examined retrospectively in this case-control study.RESULTS The disease-free survival rates in the low psoas muscle mass index(PMI)group vs the high PMI group were 41.3%vs 58.8%(P=0.036),respectively.In the high intramuscular adipose tissue content(IMAC)group vs the low IMAC group,the disease-free survival rates were 28.5%vs 57.6%(P=0.021),respectively.The overall survival(OS)rates for the low PMI group vs the high PMI group were 41.3%vs 64.5%(P=0.008),respectively,and for the high IMAC group vs the low IMAC group,they were 29.9%vs 61.9%(P=0.024),respectively.Analysis of the OS rate revealed significant differences in patients aged 60 years or older(P=0.018),those with pT3 or above disease(P=0.021),or those with lymph node metastasis(P=0.006),aside from PMI and IMAC.Multivariate analysis demonstrated that pT3 or above hazard ratio(HR):1.966,95%confidence interval(CI):1.089-3.550,(P=0.025),lymph node metastasis(HR:2.154,95%CI:1.118-4.148,P=0.022),low PMI(HR:2.266,95%CI:1.282-4.006,P=0.005),and high IMAC(HR:2.089,95%CI:1.036-4.214,P=0.022)were significant prognostic factors for esophageal squamous cell carcinoma.CONCLUSIONSkeletal muscle mass and quality before NAC in patients with esophageal squamous cellcarcinoma are significant prognostic factors for postoperative OS.

HCV infection, B-cell non-Hodgkin's lymphoma and immunochemotherapy: Evidence and open questions

There is plenty of data confirming that hepatitis C virus (HCV) infection is a predisposing factor for a B-cell non-Hodgkin's lymphoma (B-NHL) outbreak, while relatively few reports have addressed the role of HCV in affecting B-NHL patients' outcome. HCV infection may influence the short-term outcome of B-NHL because of the emergence of severe hepatic toxicity (HT) during immunochemotherapy. Furthermore, the long term outcome of HCV-related liver disease and patients' quality of life will possibly be affected by Rituximab maintenance, multiple-lines of toxicity during chemotherapy and hematopoietic stem cell transplantation. In this review, data dealing with aggressive and low-grade B-NHL were separately analyzed. The few retrospective papers reporting on aggressive B-NHL patients showed that HCV infection is a risk factor for the outbreak of severe HT during treatment. This adverse event not infrequently leads to the reduction of treatment density and intensity. Existing papers report that low-grade B-NHL patients with HCV infection may have a more widespread disease, more frequent relapses or a lower ORR compared to HCV-negative patients. Notwithstanding, there is no statistical evidence that the prognosis of HCV-positive patients is inferior to that of HCV-negative subjects. HCV-positive prospective studies and longer follow-up are necessary to ascertain if HCV-positive B-NHL patients have inferior outcomes and if there are long term sequels of immunochemotherapies on the progression of liver disease.

Effect of preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy on the expression of oncogene in advanced gastric cancer after surgical resection

Objective: To study the effect of preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy on the expression of oncogene in advanced gastric cancer after surgical resection. Methods: The patients who were diagnosed with advanced gastric cancer in our hospital during the period of March 2015 to October 2017 were randomly divided into the combined group received preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy, control group received conventional chemotherapeutic drugs intraperitoneal chemotherapy. The tumor markers in serum were measured before and after chemotherapy, and the expression of oncogenes in the lesion was measured after operation. Results: After chemotherapy, the levels of CEA, CA199, G17 and TK1 in the serum of the two groups were significantly decreased and the decreasing trend of CEA, CA199, G17 and TK1 in the serum of the combined group was more significant than that of the control group. The mRNA expression of CyclinD1, FRA-1, Bmi-1, c-Met, HER-2, CAT-D, MMP2, MMP7 in gastric cancer of combined group were significantly lower than the control group, and the mRNA expression of PTEN, p16, KISS-1, Caspase-3, TSPYL-5, TIMP1, RECK were significantly higher than that of the control group. Conclusion: Preoperative Brucea javanica oil emulsion + conventional chemotherapeutic drugs intraperitoneal chemotherapy can more significantly regulate the expression of oncogene in gastric cancer than conventional chemotherapy drugs.

Preoperative bowel preparation does not favor the management of colorectal anastomotic leak

BACKGROUND Controversy exists regarding the impact of preoperative bowel preparation on patients undergoing colorectal surgery. This is due to previous research studies,which fail to demonstrate protective effects of mechanical bowel preparation against postoperative complications. However, in recent studies, combination therapy with oral antibiotics(OAB) and mechanical bowel preparation seems to be beneficial for patients undergoing an elective colorectal operation.AIM To determine the association between preoperative bowel preparation and postoperative anastomotic leak management(surgical vs non-surgical).METHODS Patients with anastomotic leak after colorectal surgery were identified from the 2013 and 2014 Colectomy Targeted American College of Surgeons National Surgical Quality Improvement Program(ACS-NSQIP) database and were employed for analysis. Every patient was assigned to one of three following groups based on the type of preoperative bowel preparation: first groupmechanical bowel preparation in combination with OAB, second groupmechanical bowel preparation alone, and third group-no preparation.RESULTS A total of 652 patients had anastomotic leak after a colectomy from January 1,2013 through December 31, 2014. Baseline characteristics were assessed and found that there were no statistically significant differences between the three groups in terms of age, gender, race, American Society of Anesthesiologists score,and other preoperative characteristics. A χ~2 test of homogeneity was conducted and there was no statistically/clinically significant difference between the three categories of bowel preparation in terms of reoperation.CONCLUSION The implementation of mechanical bowel preparation and antibiotic use in patients who are going to undergo a colon resection does not influence the treatment of any possible anastomotic leakage.

EFFECT OF PREOPERATIVE CHEMOTHERAPY ON METASTASIZED LYMPH NODES IN PATIENTS WITH ADVANCED ESOPHAGEAL CARCINOMA

Objective To investigate the effect and clinical value of preoperative chemotherapy on the treatment of metastasized lymph nodes in patients with advanced esophageal carcinoma. Methods We studied the pathological results of primary lesions and lymph nodes of 97 patients with advanced esophageal cancer between 1996 and 1999,62 patients were treated by preoperative chemotherapy and 35 patients were treated by surgery only. Results The metas- tasized rate and degree of mediastinum in preoperative group were 16.1% and 4.7% ,whereas 65.7% and 34.2% in the surgery only group (P<0.05) ;That of abdomen in preoperative group were 25.8% and 6.6% ,whereas 48.6% and 12.0% in the surgery only group (P<0.05). Conclusion Preparative chemotherapy is effective not only against the primary lesions but also the metastasized lymph nodes. The lower complete response rate of the metastasized lymph may account for the unsatisfied long-term results. Whole resection of primary lesions and lymph nodes are still very important for a better prognosis even for patients who have a good response for the preoperative chemotherapy.

Prognostic factors in resectable cholangiocarcinoma patients: Carcinoembryonic antigen, lymph node, surgical margin and chemotherapy

AIM: To evaluate outcomes in resectable cholangiocarcinoma patients and to determine prognostic factors. METHODS: A retrospective study was conducted among newly-diagnosed cholangiocarcinoma patients from January 2009 to December 2011 who underwent curative resection in Srinakarind Hospital (a 1000-bed university hospital). Two hundred and sixty-three cholangiocarcinoma patients with good performance were enrolled. These patients had pathological reports with clear margins or microscopic margins. Prognostic factors which included clinical factors, serum liver function test as well as serum tumor makers at presentation,tumor data, and receiving adjuvant chemotherapy were determined by uniand multivariate analysis. RESULTS: The median overall survival time was 17 mo (95%CI: 13.2-20.7); and 1-, 2-, and 3year survival rates were 65.5%, 45.2% and 35.4%. Serum albumin levels, serum carcinoembryonic antigen (CEA) levels, staging classifications by American Joint Committee on cancer, pathological tumor staging, lymph node metastases, tumor grading, surgical margin status, and if adjuvant chemotherapy was administered, were shown to be significant prognostic factors of resectable cholangiocarcinoma by univariate analysis. Multivariate analysis, however, established that only abnormal serum CEA [hazard ratio (HR) 1.68; P = 0.027] and lymph node metastases (HR 2.27; P = 0.007) were significantly associated with a decrease in overall survival, while adjuvant chemotherapy (HR 0.71; P = 0.067) and surgical margin negative (HR 0.72; P = 0.094) tended to improve survival time. CONCLUSION: Serum CEA and lymph node metastases which were associated with advanced stage tumors become strong negative prognostic factors in cholangiocarcinoma.

Metastatic appendiceal cancer treated with Yttrium 90 radioembolization and systemic chemotherapy:A case report

BACKGROUND Primary appendiceal cancers are rare,and they generally present with liver and/or peritoneal metastases.Currently there are no guidelines to treat metastatic appendiceal cancer,and hence they are treated as metastatic colorectal cancer.Combining Yttrium 90(Y-90)radioembolization(RE)with systemic chemotherapy early in the treatment of right sided colon cancers has been shown to improve survival.Based on this data,a combination of systemic chemotherapy and Y-90 RE was used to treat a case of metastatic appendiceal cancer.CASE SUMMARY A 76-year-old male presented to the emergency room with progressive right lower quadrant pain.A Computed Tomography of the abdomen and pelvis was performed which showed acute appendicitis and contained perforation.Urgent laparoscopic appendectomy was then followed by histological analysis,which was significant for appendiceal adenocarcinoma.After complete workup he underwent right hemicolectomy and lymph node dissection.He received adjuvant chemotherapy as the local lymph nodes were positive.Follow-up imaging was significant for liver metastasis.Due to rapid growth of the liver lesions and new peritoneal nodules,the patient was treated with a combination of Y-90 RE and folinic acid,fluorouracil,and irinotecan with bevacizumab and not microwave ablation as previously planned.Follow up imaging demonstrated complete response of the liver lesions.At 12-mo follow-up,the patient continued to enjoy good quality of life with no recurrent disease.CONCLUSION Utilization of Y-90 RE concomitantly with systemic chemotherapy early in the treatment of appendiceal cancer may provide improved control of this otherwise aggressive cancer.

Conversion of Unresectable to Resectable Liver Metastases from Colorectal Carcinoma Using Hepatic Arterial Chronomodulated Chemotherapy: A Case Report and Short Literature Review

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.

Portal thrombosis and steatosis after preoperative chemotherapy with FOLFIRI-bevacizumab for colorectal liver metastases

In order to discuss the role of preoperative chemo- therapy for colorectal liver metastases, which is used frequently before hepatic resection, even in patients with resectable disease at presentation, we herein report the development of two complications, partial portal vein thrombosis and hepatic steatosis with Iobular inflammation, during the course of preoperative chemotherapy with FOLFIRI plus bevacizumab for colorectal liver metastases, which recognition led to timely discontinuation of chemotherapy as well as a change in the surgical strategy to resect the tumors and the damaged liver through advanced techniques. We conclude that duration of treatment and drug doses and combinations may impact the development of chemotherapy-induced liver injury. Surgeons and medical oncologists must work together to devise safe, rational, and oncologically appropriate treatments for patients with multiple colorectal liver metastases, and to improve the understanding of the pathogenesis of chemotherapyinduced liver injury.

Complete response of gallbladder cancer treated with gemcitabine and cisplatin chemotherapy combined with durvalumab:A case report and review of literature

BACKGROUND Gallbladder cancer(GBC)is the most common and aggressive subtype of biliary tract cancer(BTC)and has a poor prognosis.A newly developed regimen of gemcitabine,cisplatin,and durvalumab shows promise for the treatment of advanced BTC.However,the efficacy of this treatment for GBC remains unclear.CASE SUMMARY In this report,we present a case in which the triple-drug regimen exhibited marked effectiveness in treating locally advanced GBC,thus leading to a long-term survival benefit.A 68-year-old man was diagnosed with locally advanced GBC,which rendered him ineligible for curative surgery.Following three cycles of therapy,a partial response was observed.After one year of combined therapy,a clinical complete response was successfully achieved.Subsequent maintenance therapy with durvalumab monotherapy resulted in a disease-free survival of 9 months for the patient.The patient experienced tolerable toxicities of reversible grade 2 nausea and fatigue.Tolerable adverse events were observed in the patient throughout the entirety of the treatment.CONCLUSION The combination of gemcitabine and cisplatin chemotherapy with durvalumab was proven to be an effective treatment approach for advanced GBC,with manageable adverse events.Further research is warranted to substantiate the effectiveness of the combined regimen in the context of GBC.

四君子汤对小鼠膀胱癌化疗的减毒增效作用

目的探讨中药四君子汤对小鼠膀胱癌化疗的减毒增效作用。方法采用小鼠膀胱癌细胞接种于T 739小鼠皮下,动物随机分为8组:对照组,丝裂霉素C(mitomycinC ,MMC)常规剂量组,MMC小剂量组,四君子汤大剂量组,四君子汤中剂量组,四君子汤小剂量组,联合用药(四君子汤大剂量+MMC常规剂量)A组,联合用药(四君子汤大剂量+MMC小剂量)B组;每组于接种癌细胞2 4h后分别给药;用药14天后分别检测各组小鼠的抑瘤率、腹腔巨噬细胞活性,观察小鼠荷瘤生存时间及治疗7天后血白细胞数的变化。结果四君子汤大剂量组的荷瘤小鼠生存时间与对照组比较差异有显著性(P <0 .0 5 ) ,而四君子汤中、小剂量组与对照组比较差异无显著性(P >0. 0 5 ) ;MMC常规组的抑瘤率最高,但荷瘤生存时间与对照组比较差异无显著性(P >0 . 0 5 ) ;联合用药B组的小鼠荷瘤生存时间最长,达到(32 7±1 3)天,与其他各组比较差异均有显著性(P <0 . 0 5 ) ;联合用药B组除抑瘤率低于MMC常规组及联合用药A组,血白细胞数及巨噬细胞活性均优于MMC各剂量组及联合用药A组,差异均有显著性(P <0 . 0 5 )。结论四君子汤联合小剂量MMC化疗可以有效抑制小鼠膀胱肿瘤生长,具有增效减毒之作用。