Laboratory scoring system to predict hepatic indocyanine green clearance ability during fluorescence imaging-guided laparoscopic hepatectomy

BACKGROUND Indocyanine green(ICG)fluorescence played an important role in tumor localization and margin delineation in hepatobiliary surgery.However,the preoperative regimen of ICG administration was still controversial.Factors associated with tumor fluorescence staining effect were unclear.AIM To investigate the preoperative laboratory indexes corelated with ICG fluorescence staining effect and establish a novel laboratory scoring system to screen specifical patients who need ICG dose adjustment.METHODS To investigate the predictive indicators of ICG fluorescence characteristics in patients undergoing laparoscopic hepatectomy from January 2018 to January 2021 were included.Blood laboratory tests were completed within 1 wk before surgery.All patients received 5 mg ICG injection 24 h before surgery for preliminary tumor imaging.ImageJ software was used to measure the fluorescence intensity values of regions of interest.Correlation analysis was used to identify risk factors.A laboratory risk model was established to identify individuals at high risk for high liver background fluorescence.RESULTS There were 110 patients who were enrolled in this study from January 2019 to January 2021.The mean values of fluorescence intensity of liver background(FI-LB),fluorescence intensity of gallbladder,and fluorescence intensity of target area were 18.87±17.06,54.84±33.29,and 68.56±36.11,respectively.The receiver operating characteristic(ROC)curve showed that FI-LB was a good indicator for liver clearance ability[area under the ROC curve(AUC)=0.984].Correlation analysis found pre-operative aspartate aminotransferase,alanine aminotransferase,gammaglutamyl transpeptidase,adenosine deaminase,and lactate dehydrogenase were positively associated with FI-LB and red blood cell,cholinesterase,and were negatively associated with FI-LB.Total laboratory risk score(TLRS)was calculated according to ROC curve(AUC=0.848,sensitivity=0.773,specificity=0.885).When TLRS was greater than 6.5,the liver clearance ability of ICG was considered as poor.CONCLUSION Preoperative laboratory blood indicators can predict hepatic ICG clearance ability.Surgeons can adjust the dose and timing of ICG preoperatively to achieve better liver fluorescent staining.

Pancreatic neuroendocrine tumors:A review of serum biomarkers,staging,and management

Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.

Intraoperative radiofrequency ablation combined with ^(125)iodine seed implantation for unresectable pancreatic cancer

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.

Functional anatomical hepatectomy guided by indocyanine green fluorescence imaging in patients with localized cholestasis:Report of four cases

BACKGROUND Liver cancer is a malignant tumor with a high incidence.At present,the most effective treatment is laparoscopic hepatectomy(LH).Indocyanine green fluorescence imaging(ICG-FI)has become an important tool in LH,and the most common fluorescent types of tumors are total fluorescence,partial fluorescence,and rim fluorescence.CASE SUMMARY We presented four cases of LH guided by ICG-FI in which we also observed the fourth special fluorescent type.When the tumor or intrahepatic stone compresses the adjacent bile duct to cause local cholestasis,the liver segment or subsegment with obstructed bile drainage will show strong fluorescence.Complete removal of the lesion together with the fluorescent liver parenchyma may help reduce the risk of tumor or stone recurrence.CONCLUSION This type of partial fluorescence can indicate local biliary compression,and the resection method is related to bile drainage,which may be called functional anatomical hepatectomy and ensures radical resection of the lesion.

Analysis of lycopodiastrum casuarinoides transcriptome discovers lycodine-type alkaloid biosynthetic genes and genetic markers

OBJECTIVE o facilitate the basic acquaintance with the bioactive lycodine-type alkaloids biosynthetic pathways,we conducted the transcriptome analysis of L.casuarinoides by illumina sequencing.METHODS The plant of L.casuarinoides was collected and was subjected to RNA isolation,cDNA library construction,and illumina sequencing before bioinformatics analysis.After sequencing,the clean reads were obtained for de novo assembly by using Trinity software,and then further processed with TGICL sequencing clustering software to generate unigenes,The unigenes are aligned by Blast X alignment to six public protein database.In addition,all unigenes are functionally annotated by GO,KEGG and characterized putative genes involved in lycopodium alkaloids biosynthesis.RESULTS In total,124,524 high-quality unigenes were obtained with an average sequence length of 601 bp.Among the L.casuarinoides transcripts,61,304 showed significant similarity(E-value<1 e-5) to the known proteins in the public database.Among the total 124 524 unigenes,47,538 open reading frame(ORFs) were predicted.Based on the bioinformatics analysis,all possible enzymes involved in the Lycodine-type alkaloids biosynthetic pathway of L.casuarinoides were identified,including primary amine oxidase(PAO),and Malonly-CoA decarboxylase.In addition,a total of 64 putative cytochrome P450(CYP450) and 827 transcription factors were selected as the candidates of Lycodine-type alka.loids modifiers.Furthermore,a total of 13 352 simple sequence repeats(SSRs) were identified from the 124,524 unigenes,of which dinucleotide motifs AG/CT(50.1%),were the most abundant.CONCLU.SION This transcriptome analysis of L.casuarinoides,provides many valuable candidate genes involv.ing in the biosynthesis of novel secondary metabolites but also lays the foundation for genetic diversity analysis via SSRs markers in L.casuarinoides.

Mining lycodine-type alkaloid biosynthetic genes and genetic markers from transcriptome of Lycopodiastrum casuarinoides

Objective:Lycopodiastrum casuarinoides,a fern of the Lycopodiaceae family,is a traditional Chinese medicine,which has similar efficacy to that of Huperzia serrata in treating rheumatoid arthritis(RA).However,they are different in the contents and compositions of lycopodium alkaloids.In this study,the biosynthesis related genes of lycopodium alkaloids and genetic markers are discovered in L.casuarinoides transcriptome.Methods:The plant of L.casuarinoides was collected and was subjected to the RNA isolation,c DNA library construction,high throughput RNA sequencing and bioinformatics analysis.Results:Totally 124,524 high-quality unigenes were assembled from RNA sequencing reads,with an average sequence length of 601 bp.Among the L.casuarinoides transcripts,61,304 shared the significant similarity(E-value<10-5)with existing protein sequences in the public databases.From 124,524 unigenes,47,538 open reading frames(ORFs)were predicted.Based on the bioinformatics analysis,all possible enzyme genes involved in the lycodine-type alkaloids biosynthetic pathway of L.casuarinoides were identified,including lysine decarboxylase(LDC),primary amine oxidase(PAO),malonyl-Co A decarboxylase,etc.Sixty-four putative cytochrome p450(CYP)and 827 putative transcription factors were selected from the transcriptome unigenes as the candidates of lycodine-type alkaloids biosynthesis modifiers.Furthermore,13,352 simple sequence repeats(SSRs)were identified from 124,524 unigenes,of which dinucleotide motifs AG/CT were the most abundant(50.1%).Meanwhile,we confirmed the amplification effectiveness of25 PCR primer pairs for randomly selected SSRs.Conclusion:We obtained the comprehensive transcriptomic information from the high throughput RNA sequencing and bioinformatics analysis,which provided a valuable resource of transcript sequences of L.casuarinoides in public databases.