Conversion therapy in advanced perihilar cholangiocarcinoma based on patient-derived organoids:A case report

BACKGROUND Patient-derived organoids(PDOs)have been demonstrated to predict the response to drugs in multiple cancer types.However,it remains unclear about its application in cholangiocarcinoma.CASE SUMMARY A 59-year-old woman was admitted to the hospital due to upper abdominal pain for over 8 months.According to relevant examinations,she was diagnosed as perihilar cholangiocarcinoma(pCCA)with intrahepatic metastasis and perihilar lymphatic metastasis.After multidisciplinary team discussion,percutaneous transhepatic cholangiodrainage was performed to relieve biliary obstruction,and puncture biopsy was conducted to confirm the pathological diagnosis.Transarterial chemoembolization with nab-paclitaxel was used in combination with toripalimab and lenvatinib,but the levels of tumor markers including alpha fetal protein,carcinoembryonic antigen,carbohydrate antigen 15-3 and cancer antigen 125 were still raised.The PDO for drug screening showed sensitive to gemcitabine and cisplatin.Accordingly,the chemotherapy regimen was adjusted to gemcitabine and cisplatin in combination with toripalimab and lenvatinib.After 4 cycles of treatment,the tumor was assessed resectable,and radical surgical resection was performed successfully.One year after surgery,the patient was still alive,and no recurrence or occurred.CONCLUSION PDOs for drug sensitivity contribute to screening effective chemotherapy drugs for advanced pCCA,promoting conversion therapy and improving the prognosis.

Pathologic complete response to conversion therapy in hepatocellular carcinoma using patient-derived organoids:A case report

BACKGROUND For primary liver cancer,the key to conversion therapy depends on the effectiveness of drug treatment.Patient-derived tumor organoids have been demonstrated to improve the efficacy of conversion therapy by identifying individualtargeted effective drugs,but their clinical effects in liver cancer remain unknown.CASE SUMMARY We described a patient with hepatocellular carcinoma(HCC)who achieved pathologic complete response(pCR)to conversion therapy guided by the patientderived organoid(PDO)drug sensitivity testing.Despite insufficiency of the remaining liver volume after hepatectomy,the patient obtained tumor reduction after treatment with the PDO-sensitive drugs and successfully underwent radical surgical resection.Postoperatively,pCR was observed.CONCLUSION PDOs contributes to screening sensitive drugs for HCC patients to realize the personalized treatment and improve the conversion therapy efficacy.

Cystic duct dilation through endoscopic retrograde cholangiopancreatography for treatment of gallstones and choledocholithiasis: Six case reports and review of literature

BACKGROUND Choledocholithiasis removal via endoscopic retrograde cholangiopancreatography(ERCP)then followed by laparoscopic cholecystectomy(LC)has gradually become the principal method in the treatment of gallstones and choledocholithiasis.We use ERCP through the cystic duct to treat gallstones combined with choledocholithiasis,with the aim to preserve the normal function of the gallbladder while simultaneously decreasing risk of biliary tract injury.CASE SUMMARY A total of six cases of patients diagnosed with gallstones and choledocholithiasis were treated with ERCP.The efficacy was evaluated via operation success rate,calculus removal rate,postoperative hospital stay and average hospitalization costs;the safety was evaluated through perioperative complication probability,gallbladder function detection and gallstones recrudesce.The calculus removal rate reached 100%,and patients had mild adverse events,including 1 case of postoperative acute cholecystitis and another of increased blood urinary amylase;both were relieved after corresponding treatment,the remaining cases had no complications.The average hospital stay and hospitalization costs were 6.16±1.47 d and 5194±696 dollars.The 3-11 mo follow-up revealed that gallbladder contracted well,without recurrence of gallstones.CONCLUSION This is the first batch of case reports for the treatment of gallstones and choledocholithiasis through ERCP approached by natural cavity.The results and effects of six reported cases proved that the new strategy is safe and feasible and is worthy of further exploration and application.

Efficacy and safety of laparoscopic radical resection following neoadjuvant therapy for pancreatic ductal adenocarcinoma:A retrospective study

BACKGROUND Multiple studies have demonstrated that neoadjuvant chemotherapy(NACT) can prolong the overall survival of pancreatic ductal adenocarcinoma(PDAC) patients. However, most studies have focused on open surgery following NACT.AIM To investigate the efficacy and safety of laparoscopic radical resection following NACT for PDAC.METHODS We retrospectively analyzed the clinical data of 15 patients with pathologically confirmed PDAC who received NACT followed by laparoscopic radical surgery in our hospital from December 2019 to April 2022. All patients underwent abdominal contrast-enhanced computed tomography(CT) and positron emission tomography-CT before surgery to accurately assess tumor stage and exclude distant metastasis.RESULTS All 15 patients with pancreatic cancer were successfully converted to surgical resection after NACT, including 8 patients with pancreatic head cancer and 7 patients with pancreatic body and tail cancer. Among them, 13 patients received the nab-paclitaxel plus gemcitabine regimen(gemcitabine 1000 mg/m^(2) plus nabpaclitaxel 125 mg/m^(2) on days 1, 8, and 15 every 4 wk) and 2 patients received the modified FOLFIRINOX regimen(intravenous oxaliplatin 68 mg/m^(2), irinotecan 135 mg/m^(2), and leucovorin 400 mg/m^(2) on day 1 and fluorouracil 400 mg/m^(2) on day 1, followed by 46-h continuous infusion of fluorouracil 2400 mg/m^(2)). After each treatment cycle, abdominal CT, tumor markers, and circulating tumor cell counts were reviewed to evaluate the treatment efficacy. All 15 patients achieved partial remission. The surgical procedures included laparoscopic pancreaticoduodenectomy(LPD, n = 8) and laparoscopic radical antegrade modular pancreatosplenectomy(L-RAMPS, n = 7). None of them were converted to a laparotomy. One patient with pancreatic head carcinoma was found to have portal vein involvement during the operation, and LPD combined with vascular resection and reconstruction was performed. The amount of blood loss and operation times of L-RAMPS vs LPD were 435.71 ± 32.37 m L vs 343.75 ± 145.01 m L and 272.52 ± 49.14 min vs 444.38 ± 68.63 min, respectively. The number of dissected lymph nodes was 16.87 ± 4.10, and 3 patients had positive lymph nodes. One patient developed grade B postoperative pancreatic fistula(POPF) after LRAMPS, and one patient experienced jaundice after LPD. None of the patients died after surgery. As of April 2022, progressive disease was noted in 4 patients, 2 patients had liver metastasis, and one had both liver metastasis and lymph node metastasis and died during the follow-up period.CONCLUSION Laparoscopic radical resection of PDAC after NACT is safe and effective if it is performed by a surgeon with rich experience in LPD and in a large center of pancreatic surgery.

Identification of hepatitis B virus and liver cancer bridge molecules based on functional module network

BACKGROUND The potential role of chronic inflammation in the development of cancer has been widely recognized.However,there has been little research fully and thoroughly exploring the molecular link between hepatitis B virus(HBV)and hepatocellular carcinoma(HCC).AIM To elucidate the molecular links between HBV and HCC through analyzing the molecular processes of HBV-HCC using a multidimensional approach.METHODS First,maladjusted genes shared between HBV and HCC were identified by disease-related differentially expressed genes.Second,the protein-protein interaction network based on dysfunctional genes identified a series of dysfunctional modules and significant crosstalk between modules based on the hypergeometric test.In addition,key regulators were detected by pivot analysis.Finally,targeted drugs that have regulatory effects on diseases were predicted by modular methods and drug target information.RESULTS The study found that 67 genes continued to increase in the HBV-HCC process.Moreover,366 overlapping genes in the module network participated in multiple functional blocks.It could be presumed that these genes and their interactions play an important role in the relationship between inflammation and cancer.Correspondingly,significant crosstalk constructed a module level bridge for HBV-HCC molecular processes.On the other hand,a series of non-coding RNAs and transcription factors that have potential pivot regulatory effects on HBV and HCC were identified.Among them,some of the regulators also had persistent disorders in the process of HBV-HCC including microRNA-192,microRNA-215,and microRNA-874,and early growth response 2,FOS,and Kruppel-like factor 4.Therefore,the study concluded that these pivots are the key bridge molecules outside the module.Last but not least,a variety of drugs that may have some potential pharmacological or toxic side effects on HBV-induced HCC were predicted,but their mechanisms still need to be further explored.CONCLUSION The results suggest that the persistent inflammatory environment of HBV can be utilized as an important risk factor to induce the occurrence of HCC,which is supported by molecular evidence.

Ileal pouch anal anastomosis with modified double-stapled mucosectomy-the experience in China

AIM:To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled mucosectomy.METHODS:From January 2002 to March 2011,fourtyfive patients underwent ileal pouch anal anastomosis with modified double-stapled mucosectomy technique and the clinical data obtained for these patients were reviewed.RESULTS:Patients with ulcerative colitis(n = 29) and familial adenomatous polyposis(n = 16) underwent ileal pouch-anal anastomosis with modified doublestapled mucosectomy.Twenty-eight patients underwent one-stage restorative proctocolectomy,ileal pouch anal anastomosis,protective ileostomy and the ileostomy was closed 4-12 mo postoperatively.Two-stage procedures were performed in seventeen urgent patients,proctectomy and ileal pouch anal anastomosis were completed after previous colectomy with ileostomy.Morbidity within the first 30 d of surgery occurred in 10(22.2%) patients,all of them could be treated conservatively.During the median follow-up of 65 mo,mild to moderate anastomotic narrowing was occurred in 4 patients,one patient developed persistent anastomotic stricture and need surgical intervention.Thirtyfive percent of patients developed at least 1 episode of pouchitis.There was no incontinence in our patients,the median functional Oresland score was 6,3 and 2 after 1 year,2.5 years and 5 years respectively.Nearly half patients(44.4%) reported "moderate functioning",37.7% reported "good functioning",whereas in 17.7% of patients "poor functioning" was observed after 1 year.Five years later,79.2% of patients with good function,16.7% with moderate function,only 4.2% of patients with poor function.CONCLUSION:The results of ileal pouch anal anastomosis with modified double-stapled mucosectomy technique are promising,with a low complication rate and good long-term functional results.

Sequential therapy with combined trans-papillary endoscopic nasopancreatic and endoscopic retrograde pancreatic drainage for pancreatic pseudocysts

BACKGROUND Endoscopic retrograde pancreatic drainage(ERPD)and stent implantation has become the major treatment method for pancreatic pseudocysts.However,it is associated with a high recurrence rate and infection.AIM To manage pancreatic pseudocysts by sequential therapy with endoscopic nasopancreatic drainage(ENPD)combined with ERPD and evaluate the treatment outcome.METHODS One hundred and sixty-two cases of pancreatic pseudocyst confirmed by endoscopic examination at our hospital between January 2014 and January 2020 were retrospectively analyzed.There were 152 cases of intubation via the duodenal papilla,of which 92 involved pancreatic duct stent implantation and 60 involved sequential therapy with combined ENPD and ERPD(two-step procedure).The success rate of the procedure,incidence of complications(infection,bleeding,etc.),recurrence,and length and cost of hospitalization were compared between the two groups.RESULTS The incidence of infection was significantly higher in the ERPD group(12 cases)than in the two-step procedure group(2 cases).Twelve patients developed infection in the ERPD group,and anti-infection therapy was effective in five cases but not in the remaining seven cases.Infection presented as fever and chills in the two-step procedure group.The reoperation rate was significantly higher in the ERPD group with seven cases compared with zero cases in the two-step procedure group(P<0.05).Similarly,the recurrence rate was significantly higher in the ERPD group(19 cases)than in the two-step procedure group(0 cases).CONCLUSION Sequential therapy with combined ENPD and ERPD is safe and effective in patients with pancreatic pseudocysts.

Heterozygosity of Knob-Associated Tandem Repeats and Knob Instability in Mitotic Chromosomes of Zea （Zea mays L. and Z. diploperennis Iltis Doebley）

Knobs are blocks of heterochromatin present on chromosomes of maize （Zea mays L.） and its relatives that have effects on the frequency of genetic recombination, as well as on chromosome behavior. Knob heterozygosity and instability in six maize inbred lines and one Z. diploperennis Iltis Doebley line were investigated using the fluorescence in situ hybridization （FISH） technique with knob-associated tandem repeats （180 bp and 350 bp （TR- 1）） as probes. Signals of seven heterozygous knobs containing 180- bp repeats and of one heterozygous knob containing TR- 1 were captured in chromosomes of all materials tested according to the results of FISH, which demonstrates that the 180-bp repeat is the main contributor to knob heterozygosity compared with the TR- 1 element. In addition, one target cell with two TR- 1 signals on one homolog of chromosome 2L, which was different from the normal cells in the maize inbred line GB57, was observed, suggesting knob duplication and an instability phenomenon in the maize genome.