Response of cholangiocarcinoma with epigastric metastasis to lenvatinib plus sintilimab: A case report and review of literature

BACKGROUND Cholangiocarcinoma(CCA)poses a significant clinical challenge due to its low radical resection rate and a propensity for high postoperative recurrence,resulting in a poor dismal.Although the combination of targeted therapy and immunotherapy has demonstrated notable efficacy in several solid tumors recently,however,its application in CCA remains underexplored and poorly documented.CASE SUMMARY This case report describes a patient diagnosed with stage IV CCA,accompanied by liver and abdominal wall metastases,who underwent palliative surgery.Subsequently,the patient received two cycles of treatment combining lenvatinib with sintilimab,which resulted in a reduction in abdominal wall metastasis,while intrahepatic metastasis displayed progression.This unexpected observation illustrates different responses of intrahepatic and extrahepatic metastases to the same therapy.CONCLUSION Lenvatinib combined with sintilimab shows promise as a potential treatment strategy for advanced CCA.Genetic testing for related driver and/or passenger mutations,as well as an analysis of tumor immune microenvironment analysis,is crucial for optimizing drug combinations and eventually addressing the issue of non-response in specific metastatic sites.

Learning curve of transumbilical suture-suspension single-incision laparoscopic cholecystectomy

AIM: To investigate the learning curve of transumbilical suture-suspension single-incision laparoscopic cholecystectomy (SILC). METHODS: The clinical data of 180 consecutive transumbilical suture-suspension SILCs performed by a team in our department during the period from August 2009 to March 2011 were retrospectively analyzed. Patients were divided into nine groups according to operation dates, and each group included 20 patients operated on consecutively in each time period. The surgical outcome was assessed by comparing operation time, blood loss during operation, and complications between groups in order to evaluate the improvement in technique.RESULTS: A total of 180 SILCs were successfully performed by five doctors. The average operation time was 53.58 ± 30.08 min (range: 20.00-160.00 min) and average blood loss was 12.70 ± 11.60 mL (range: 0.00-100.00 mL). None of the patients were converted to laparotomy or multi-port laparoscopic cholecystectomy. There were no major complications such as hemorrhage or biliary system injury during surgery. Eight postoperative complications occurred mainly in the first three groups (n = 6), and included ecchymosis around the umbilical incision (n = 7) which resolved without special treatment, and one case of delayed bile leakage in group 8, which was treated by ultrasound-guided puncture and drainage. There were no differences in intraoperative blood loss, postoperative complications and length of postoperative hospital stay among the groups. Bonferroni's test showed that the operation time in group 1 was significantly longer than that in the other groups (F = 7.257, P = 0.000). The majority of patients in each group were discharged within 2 d, with an average postoperative hospital stay of 1.9 ± 1.2 d. CONCLUSION: Following scientific principles and standard procedures, a team experienced in multi-port laparoscopic cholecystectomy can master the technique of SILC after 20 cases.

Perineural invasion of hilar cholangiocarcinoma in Chinese population: One center’s experience

BACKGROUND Hilar cholangiocarcinoma(HCCA)often produces perineural invasion(PNI)extending to extra-biliary sites,while significant confusion in the incidence of PNI in HCCA has occurred in the literature,and the mechanism of that procedure remains unclear.AIM To summarize the incidence of PNI in HCCA and to provide the distribution of nerve plexuses around hepatic portal to clinical surgeons.METHODS Reported series with PNI in HCCA since 1996 were reviewed.A clinicopathological study was conducted on sections from 75 patients with HCCA to summarize the incidence and modes of PNI.Immunohistochemical stains for CD34 and D2-40 in the cancer tissue were performed to clarify the association of PNI with microvessel and lymph duct.Sections of the hepatoduodenal ligament from autopsy cases were scanned and handled by computer to display the distribution of nerve plexuses around the hepatic portal.RESULTS The overall incidence of PNI in this study was 92%(69 of 75 patients),while the rate of PNI in HCCA in the literature ranging from 38%to 100%.The incidence of PNI did not show any remarkable differences among various differentiated groups and Bismuth-Corlette classification groups.Logistic regression analysis identified the depth of tumor invasion was the only factor that correlated significantly with PNI(P<0.01).In spite of finding tumor cells that could invade microvessels and lymph ducts in HCCA,we did not find tumor cells invaded nerves via microvessels or lymph ducts.Three nerve plexuses in the hepatoduodenal ligament and Glisson’s sheath were classified,and they all surrounded the great vessels very closely.CONCLUSION The incidence of PNI of HCCA in Chinese population is around 92%and correlated significantly with a depth of tumor invasion.It also should be considered when stratifying HCCA patients for further treatment.

Robotic resection of liver focal nodal hyperplasia guided by indocyanine green fluorescence imaging: A preliminary analysis of 23 cases

BACKGROUND Focal nodal hyperplasia(FNH)is a common benign tumor of the liver.It occurs mostly in people aged 40-50 years and 90%of the patients are female.FNH can be cured by local resection.How to locate and judge the tumor boundary in real time is often a challenge for surgeons.AIM To summarize the technique and feasibility of robotic resection of FNH guided by indocyanine green(ICG)fluorescence imaging.METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent robotic resection of liver FNH guided by ICG fluorescence imaging between May 1,2018 and September 30,2019 were retrospectively analyzed.ICG was injected through the median elbow vein in all the patients at a dose of 0.25 mg/kg 48 h before the operation.During the operation,the position of FNH in the liver was located in the fluorescence mode of the Da Vinci Si robot operating system and the tumor boundary was determined during the resection.RESULTS Among the 23 patients,there were 11 males and 12 females,with a mean age of 30.5±9.3 years.Twenty-two cases completed robotic resection,while one(4.3%)case converted to open surgery.In the robotic surgery group,the operation time was 35-340 min with a median of 120 min,the intraoperative bleeding was 10-800 m L with a median of 50 m L,and the postoperative hospital stay was 1-7 d with a median of 4 d.Biliary fistula occurred in two(8.7%)patients after robotic operation and they both recovered after conservative treatment.One(4.3%)patient received blood transfusion and there was no death in this study.The postoperative hospital stay in the small tumor group was significantly shorter than that in the large tumor group(P<0.05).CONCLUSION ICG fluorescence imaging can guide the surgeon to perform robotic resection of liver FNH by locating the tumor and displaying the tumor boundary in real time.It is a safe and feasible method to ensure the complete resection of the tumor.

Radioactive ^125I seed implantation for locally advanced pancreatic cancer:A retrospective analysis of 50 cases

BACKGROUND Pancreatic cancer is one of the common malignant tumors of the digestive system,and radical resection is the first choice of treatment for pancreatic cancer.If patients with locally advanced pancreatic cancer cannot be treated in time and effectively,their disease often develops rapidly and their survival period is very short.AIM To evaluate the therapeutic effect of ^125I seed implantation in patients with locally advanced pancreatic cancer.METHODS The demographics and perioperative outcomes of a consecutive series of patients who underwent ^125I seed implantation to treat locally advanced pancreatic cancer between January 1,2017 and June 30,2019 were retrospectively analyzed.According to the results of preoperative computed tomography or magnetic resonance imaging,the treatment planning system was used to determine the area and number of ^125I seeds implanted.During the operation,^125I seeds were implanted into the tumor under the guidance of intraoperative ultrasound,with a spacing of 1.5 cm and a row spacing of 1.5 cm.For patients with obstructive jaundice and digestive tract obstruction,choledochojejunostomy and gastroenterostomy were performed simultaneously.After operation,the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.RESULTS Among the 50 patients,there were 29 males and 21 females,with a mean age of 56.9±9.8 years.The main reason for the failure of radical resection was superior mesenteric artery invasion(37,74%),followed by superior mesenteric vein invasion(33,66%).Twenty-one(62%)patients underwent palliative surgery and postoperative pain relief occurred in 40(80%)patients.The estimated blood loss in operation was 107.4±115.3 mL and none of the patient received blood transfusion.The postoperative hospital stay was 7.5±4.2 d;one patient had biliary fistula and three had pancreatic fistula,all of whom recovered after conservative treatment.After operation,26 patients received chemotherapy and 24 did not.The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not(60.7%vs 35.9%,P=0.034).The mean overall survival of patients of the chemotherapy group and nonchemotherapy group was 14 and 11 mo,respectively(χ^2=3.970,P=0.046).CONCLUSION Radioactive ^125I seed implantation combined with postoperative chemotherapy can prolong the survival time,relieve pain,and improve the quality of life of patients with locally advanced pancreatic cancer.

The advanced development of molecular targeted therapy for hepatocellular carcinoma

Hepatocellular carcinoma(HCC),one of the most common malignant tumors in China,severely threatens the life and health of patients.In recent years,precision medicine,clinical diagnoses,treatments,and innovative research have led to important breakthroughs in HCC care.The discovery of new biomarkers and the promotion of liquid biopsy technologies have greatly facilitated the early diagnosis and treatment of HCC.Progress in targeted therapy and immunotherapy has provided more choices for precise HCC treatment.Multiomics technologies,such as genomics,transcriptomics,and metabolomics,have enabled deeper understanding of the occurrence and development mechanisms,heterogeneity,and genetic mutation characteristics of HCC.The continued promotion and accurate typing of HCC,accurate guidance of treatment,and accurate prognostication have provided more treatment opportunities and prolonged survival timelines for patients with HCC.Innovative HCC research providing an in-depth understanding of the biological characteristics of HCC will be translated into accurate clinical practices for the diagnosis and treatment of HCC.

Transumbilical single-incision endoscopic splenectomy:Report of ten cases

AIM: To investigate the feasibility and clinical application of transumbilical single-incision endoscopic splenectomy using conventional laparoscopic instruments.

Impact of resection margins on long-term survival after pancreaticoduodenectomy for pancreatic head carcinoma

BACKGROUND The impact of resection margin status on long-term survival after pancreaticoduodenectomy(PD) for patients with pancreatic head carcinoma remains controversial and depends on the method used in the histopathological study of the resected specimens. This study aimed to examine the impact of resection margin status on the long-term overall survival of patients with pancreatic head carcinoma after PD using the tumor node metastasis standard.METHODS Consecutive patients with pancreatic head carcinoma who underwent PD at the Chinese People's Liberation Army General Hospital between May 2010 and May 2016 were included. The impact of resection margin status on long-term survival was retrospectively analyzed.RESULTS Among the 124 patients, R0 resection was achieved in 85 patients(68.5%), R1 resection in 38 patients(30.7%) and R2 resection in 1 patient(0.8%). The 1-and 3-year overall survival(OS) rates were significantly higher for the patients who underwent R0 resection than the rates for those who underwent R1 resection(1-year OS rates: 69.4% vs 53.0%;3-year OS rates: 26.9% vs 11.7%). Multivariate analysis showed that resection margin status and venous invasion were significant risk factors for OS.CONCLUSION Resection margin was an independent risk factor for OS for patients with pancreatic head carcinoma after PD. R0 resection was associated with significantly better OS after surgery.

Single-incision vs three-port laparoscopic cholecystectomy:Prospective randomized study

AIM:To compare the clinical outcome of single-inci-sion laparoscopic cholecystectomy(SILC)with threeport laparoscopic cholecystectomy(TPLC). METHODS:Between 2009 and 2011,one hundred and two patients with symptomatic benign gallbladder diseases were randomized to SILC(n=49)or TPLC (n=53).The primary end point was post operative pain score(at 6 h and 7 d).Secondary end points were blood loss,operation duration,overall complications,postoperative analgesic requirements,length of hospital stay,cosmetic result and total cost.Surgical techniques were standardized and all operations were performed by one experienced surgeon,who had performed more than 500 laparoscopic cholecystectomies. RESULTS:One patient in the SILC group required conversion to two-port LC.There were no open conversions or major complications in either treatment groups.There were no differences in terms of esti-mated blood loss(mean±SD,14±6.0 mL vs 15±4.0 mL),operation duration(mean±SD,41.8±17.0 min vs 38.5±22.0 min),port-site complications(contusion at incision:5 cases vs 4 cases and hematoma at inci- sion:2 cases vs 1 case),total cost(mean±SD,12 075 ±1047 RMB vs 11 982±1153 RMB)and hospital stay (mean±SD,1.0±0.5 d vs 1.0±0.2 d),respectively. TPLC had a significantly worse visual analogue pain score at 8 h after surgery(mean±SD,3.5±1.6 vs 2.0 ±1.5),however,the scores were similar on day 7(mean ±SD,2.5±1.4 vs 2.0±1.3).Cosmetic satisfaction, as determined by a survey at 2 mo follow-up favored SILC(mean±SD,8±0.4 vs 6±0.2). CONCLUSION:SILC is a safe and feasible approach in selected patients.The main advantages are a better cosmetic result and less pain.

Laparoendoscopic single-site cholecystectomy vs three-port laparoscopic cholecystectomy: A large-scale retrospective study

AIM: To perform a large-scale retrospective comparison of laparoendoscopic single-site cholecystectomy (LESSC) and three-port laparoscopic cholecystectomy (TPLC) in a single institution. METHODS: Data were collected from 366 patients undergoing LESSC between January 2005 and July 2008 and were compared with the data from 355 patients undergoing TPLC between August 2008 and November 2011 in our department. Patients with body mass index greater than 35 kg/m2 , a history of major upper abdominal surgery, signs of acute cholecystitis, such as fever, right upper quadrant tenderness with or without Murphy's sign, elevated white blood cell count, imaging findings suggestive of pericholecystic fluid, gallbladder wall thickening > 4 mm, and gallstones > 3 cm, were excluded to avoid bias. RESULTS: Altogether, 298 LESSC and 315 TPLC patients met the inclusion criteria. The groups were well matched with regard to demographic data. There were no significant differences in terms of postoperative complications (contusion: 19 vs 25 and hematoma at incision: 11 vs 19), hospital stay (mean ± SD, 1.4 ± 0.2 d vs 1.4 ± 0.7 d) and visual analogue pain score (mean ± SD, 8 h after surgery: 2.3 ± 1.4 vs 2.3 ± 1.3 and at day 1: 1.2 ± 0.4 vs 1.3 ± 1.2) between the LESSC and TPLC patients. Four patients required the addition of extra ports and 2 patients were converted to open surgery in the LESSC group, which was not significantly different when compared with TPLC patients converted to laparotomy (2 vs 2). LESSC resulted in a longer operating time (mean ± SD, 54.8 ± 11.0 min vs 33.5 ± 9.0 min), a higher incidence of intraoperative gallbladder perforation (56 vs 6) and higher operating cost (mean ± SD, 1933.7 ± 64.4 USD vs 1874.7 ± 46.2 USD) than TPLC. No significant differences in operating time (mean ± SD, 34.3 ± 6.0 min vs 32.7 ± 8.7 min) and total cost (mean ± SD, 1881.3 ± 32.8 USD vs 1876.2 ± 33.4 USD) were found when the last 100 cases in the two groups were compared. A correlation was observed between reduced operating time of LESSC and increased experience (Spearman rank correlation coefficient, -0.28). More patients in the LESSC group expressed satisfaction with the cosmetic result (98% vs 85%). CONCLUSION: LESSC is a safe and feasible procedure in selected patients with benign gallbladder diseases, with the significant advantage of cosmesis.

Radioactive 125I seed implantation for pancreatic cancer with unexpected liver metastasis:A preliminary experience with 26 patients

BACKGROUND Preoperative diagnosis rate of pancreatic cancer has increased year by year.The prognosis of pancreatic cancer patients with unexpected liver metastasis found by intraoperative exploration is very poor,and there is no effective and unified treatment strategy.AIM To evaluate the therapeutic effect of radioactive 125I seed implantation for pancreatic cancer patients with unexpected liver metastasis.METHODS The demographics and perioperative outcomes of patients who underwent 125I seed implantation to treat pancreatic cancer with unexpected liver metastasis between January 1,2017 and June 1,2019 were retrospectively analyzed.During the operation,125I seeds were implanted into the pancreatic tumor under the guidance of intraoperative ultrasound,with a spacing of 1.5 cm and a row spacing of 1.5 cm.For patients with obstructive jaundice and digestive tract obstruction,choledochojejunostomy and gastroenterostomy were performed simultaneously.After operation,the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment.RESULTS Preoperative imaging evaluation of all patients in this study showed that the tumor was resectable without liver metastasis.There were 26 patients in this study,including 18 males and 8 females,aged 60.5±9.7 years.The most common tumor site was the pancreatic head(17,65.4%),followed by the pancreatic neck and body(6,23.2%)and pancreatic tail(3,11.4%).Fourteen patients(53.8%)underwent palliative surgery and postoperative pain relief occurred in 22 patients(84.6%).The estimated blood loss in operation was 148.3±282.1 mL and one patient received blood transfusion.The postoperative hospital stay was 7.6±2.8 d.One patient had biliary fistula,one had pancreatic fistula,and all recovered after conservative treatment.After operation,7 patients received chemotherapy and 19 did not.The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not(68.6%vs 15.8%,P=0.012).The mean overall survival of patients in the chemotherapy group and non-chemotherapy group was 16.3 mo and 10 mo,respectively(χ2=7.083,P=0.008).CONCLUSION Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time and relieve pain of pancreatic cancer patients with unexpected liver metastasis.

Leveraging machine learning techniques for predicting pancreatic neuroendocrine tumor grades using biochemical and tumor markers

BACKGROUND The incidence of pancreatic neuroendocrine tumors (PNETs) is now increasing rapidly. The tumor grade of PNETs significantly affects the treatment strategy and prognosis. However, there is still no effective way to non-invasively classify PNET grades. Machine learning (ML) algorithms have shown potential in improving the prediction accuracy using comprehensive data. AIM To provide a ML approach to predict PNET tumor grade using clinical data. METHODS The clinical data of histologically confirmed PNET cases between 2012 and 2018 were collected. A method of minimum P for the Chi-square test was used to divide the continuous variables into binary variables. The continuous variables were transformed into binary variables according to the cutoff value, while the P value was minimum. Four classical supervised ML models, including logistic regression, support vector machine (SVM), linear discriminant analysis (LDA) and multi-layer perceptron (MLP) were trained by clinical data, and the models were labeled with the pathological tumor grade of each PNET patient. The performance of each model, including the weight of the different parameters, were evaluated. RESULTS In total, 91 PNET cases were included in this study, in which 32 were G1, 48 were G2 and 11 were G3. The results showed that there were significant differences among the clinical parameters of patients with different grades. Patients with higher grades tended to have higher values of total bilirubin, alpha fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4. Among the models we used, LDA performed best in predicting the PNET tumor grade. Meanwhile, MLP had the highest recall rate for G3 cases. All of the models stabilized when the sample size was over 70 percent of the total, except for SVM. Different parameters varied in affecting the outcomes of the models. Overall, alanine transaminase, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4 affected the outcome greater than other parameters. CONCLUSION ML could be a simple and effective method in non-invasively predicting PNET grades by using the routine data obtained from the results of biochemical and tumor markers.

Association of tumor morphology with long-term prognosis after liver resection for patients with a solitary huge hepatocellular carcinoma-a multicenter propensity score matching analysis

Background:A solitary hepatocellular carcinoma(HCC)without macrovascular invasion and distant metastasis,regardless of tumor size,is currently classified as early-stage disease by the latest Barcelona Clinic Liver Cancer(BCLC)staging system.While the preferred treatment is surgical resection,the association of tumor morphology with long-term survival outcomes after liver resection for a solitary huge HCC of≥10 cm has not been defined.Methods:Patients who underwent curative liver resection for a solitary huge HCC were identified from a multicenter database.Preoperative imaging findings were used to define spherical-or ellipsoidal-shaped lesions with smooth edges as balloon-shaped HCCs(BS-HCCs);out-of-shape lesions or lesions of any shape with matt edges were defined as non-balloon-shaped HCCs(NBS-HCCs).The two groups of patients with BS-HCCs and NBS-HCCs were matched in a 1:1 ratio using propensity score matching(PSM).Clinicopathologic characteristics,long-term overall survival(OS)and recurrence-free survival(RFS)were assessed.Results:Among patients with a solitary huge HCC,74 pairs of patients with BS-HCC and NBS-HCC were matched.Tumor pathological features including proportions of microvascular invasion,satellite nodules,and incomplete tumor encapsulation in the BS-HCC group were lower than the NBS-HCC group.At a median follow-up of 50.7 months,median OS and RFS of all patients with a solitary huge HCC after PSM were 27.8 and 10.1 months,respectively.The BS-HCC group had better median OS and RFS than the NBS-HCC group(31.9 vs.21.0 months,P=0.01;and 19.7 vs.6.4 months,P=0.015).Multivariate analyses identified BS-HCC as independently associated with better OS(HR=0.592,P=0.009)and RFS(HR=0.633,P=0.013).Conclusions:For a solitary huge HCC,preoperative imaging on tumor morphology was associated with prognosis following resection.In particular,patients with BS-HCCs had better long-term survival following liver resection versus patients with large NBS-HCCs.

Abrogation of Hn RNP L enhances anti-PD-1 therapy efficacy via diminishing PD-L1 and promoting CD8^(+) T cell-mediated ferroptosis in castration-resistant prostate cancer

Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that target programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for human cancers with clinical benefit.However,many patients,especially prostate cancer,fail to respond to anti-PD-1/PD-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy.In the present study,analyzing the data from our prostate cancer tissue microarray,we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the PD-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC.Indeed,Hn RNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC cells.In addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells.Furthermore,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-PD-1 therapy in CRPC tumors.This study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.