Pre-operative factors that can predict neoplastic polypoid lesions of the gallbladder

AIM:To investigate the preoperative factors that can predict neoplastic polypoid lesions of the gallbladder(PLGs) as well as malignant PLGs.METHODS:A retrospective analysis was conducted on the 210 consecutively enrolled patients who underwent cholecystectomy due to a PLG larger than 10 mm,as was determined by preoperative trans-abdominal ultrasonography or endoscopic ultrasonography.We ana-lyzed the medical,laboratory,radiologic data and the pathologic results.RESULTS:In 210 cases,146 had non-neoplastic polyps(69.5%) and 64 cases were neoplastic polyps(30.5%).An older age(≥ 65 years),the presence of diabetes mellitus(DM) and the size of polyp(≥ 15 mm) were revealed to be independent predictive variables for neoplastic polyps with odd ratios(OR) of 2.27(P = 0.044),2.64(P = 0.021) and 4.94(P < 0.01),respectively.Among the neoplastic PLGs,an older age(≥ 65 years),the presence of DM and polyp size(≥ 15 mm) were associated with malignancy with ORs of 4.97(P = 0.005),6.13(P = 0.001) and 20.55(P < 0.001),respectively.CONCLUSION:Among patients with PLGs larger than 10 mm in size,higher risk groups such as elderly patients more than 65 years old,those with DM or a large polyp size(≥ 15 mm) should be managed by cholecystectomy.

Optimal biliary drainage for inoperable Klatskin's tumor based on Bismuth type

AIM： To investigate differences in the effects of biliary drainage procedures in patients with inoperable Klatskin＇s tumor based on Bismuth type, considering endoscopic retrograde biliary drainage （ERBD）, external percutaneous transhepatic biliary drainage （EPTBD） and internal biliary stenting via the PTBD tract （IPTBD）. METHODS： The initial success rate, cumulative patency rate, and complication rate were compared retrospectively, according to the Bismuth type and ERBD, EPTBD, and IPTBD. Patency was defined as the duration for adequate initial bile drainage or to the point of the patient＇s death associated with inadequate drainage. RESULTS： One hundred thirty-four patients （93 men, 41 women; 21 Bismuth type Ⅱ, 47Ⅲ, 66 Ⅳ; 34 ERBD, 66 EPTBD, 34 IPTBD） were recruited. There were no differences in demographics among the groups. Adequate initial relief of jaundice was achieved in 91% of patients without a significant difference in the results among different procedures or Bismuth types. The cumulative patency rates for ERBD and IPTBD were better than those for EPTBD with Bismuth type Ⅲ. IPTBD provided an excellent response for Bismuth type IV. However, there was no difference in the patency rate among drainage procedures for Bismuth type Ⅱ. Procedure-related cholangitis occurred less frequently with EPTBD than with ERBD and IPTBD. CONCLUSION： ERBD is recommended as the firstline drainage procedure for the palliation of jaundice in patients with inoperable Klatskin＇s tumor of Bismuth type Ⅱ or Ⅲ, but IPTBD is the best option for Bismuth type Ⅳ.

Biliary drainage for obstructive jaundice caused by unresectable hepatocellular carcinoma: the endoscopic versus percutaneous approach

BACKGROUND: For palliative treatment of the obstructive jaundice associated with unresectable hepatocellular carcinoma (HCC), percutaneous transhepatic biliary drainage (PTBD) or endoscopic retrograde biliary drainage (ERBD) has been performed. PTBD is preferred as an initial procedure. Little is known about the better option for patients with obstructive jaundice caused by unresectable HCC. METHODS: Sixty patients who had received ERBD or PTBD for the palliative treatment of obstructive jaundice caused by unresectable HCC between January 2006 and May 2010 were included in this retrospective study. Successful drainage, drainage patency, and the overall survival of patients were evaluated. RESULTS: Univariate analysis revealed that the overall frequency of successful drainage was higher in the ERBD group (22/29, 75.9%) than in the PTBD group (15/31, 48.4%) (P=0.029); but multivariate analysis showed marginal significance (P=0.057). The duration of drainage patency was longer in the ERBD group than in the PTBD group (82 vs 37 days, respectively, P=0.020). Regardless of what procedure was performed, the median survival time of patients who had a successful drainage was much longer than that of the patients who did not have a successful drainage (143 vs 38 days, respectively, P<0.001).CONCLUSION: Besides PTBD, ERBD may be used as the initial treatment option to improve obstructive jaundice in patients with unresectable HCC if there is a longer duration of drainage patency after a successful drainage.

Risk factors of organ failure in cholangitis with bacteriobilia

AIM: To identify the risk factors for organ failure(OF) in cholangitis with bacteriobilia.METHODS: This study included 182 patients with acute cholangitis who underwent percutaneous transhepatic biliary drainage between January 2005 and April 2013. We conducted a retrospective analysis of comprehensive clinical and laboratory data.RESULTS: There were 24 cases(13.2%) of OF and five deaths(2.7%). Bile culture was positive for microbial growth in 130 out of 138(94.2%) patients. In multivariate analysis of 130 patients with positivebile cultures, significant predictive factors for OF were the presence of extended-spectrum beta-lactamase(ESBL) organisms in blood cultures, pre-existing renal dysfunction, and choledocholithiasis as an etiology, with odds ratios of 15.376, 6.319, and 3.573, respectively. We developed a scoring system with a regression coefficient of each significant variable. The OF score was calculated using the following equation:(2.7 × ESBL organisms in blood cultures) +(1.8 × pre-existing renal dysfunction) +(1.3 × choledocholithiasis). This scoring system for predicting OF was highly specific(99.1%) and had a positive predictive value of 86.2%.CONCLUSION: ESBL organisms in blood cultures, preexisting renal dysfunction, and choledocholithiasis are risk factors for OF in cholangitis with bacteriobilia. The OF scoring system may aid clinicians to identify a poor prognosis group.

Safety of endoscopic ultrasound-guided ethanol ablation for pancreatic cystic lesions: A single-center experience of 214 patients

Background:Endoscopic ultrasound-guided ethanol ablation(EUS-EA)for pancreatic cystic lesions(PCLs)has been used in recent years as a feasible treatment modality for low malignant probability PCLs or patients considered high-risk for surgery.The present study aimed to confirm the safety of EUS-EA and to find predictive factors for adverse event(AE).Methods:A retrospective review was performed from the prospectively maintained database of patients who underwent EUS-EA for PCLs from June 2006 to April 2018 at Seoul National University Hospital.The primary outcomes of the study were the rates of AEs and severe AEs by EUS-EA.The secondary outcome was the predictive factors of AEs including acute pancreatitis and abdominal pain.Results:A total of 214 patients were evaluated and the diagnoses of PCLs according to cystic fluid analysis and clinical features were as follows:serous cystic neoplasm(32.2%),mucinous cystic neoplasm(26.6%),branch duct type intraductal papillary mucinous neoplasm(BD-IPMN)(29.4%),and pseudocyst(11.7%).Three patients(1.4%)experienced severe AEs.Overall,AEs occurred in 71(33.2%)patients.BD-IPMN(OR:2.87;95%CI:1.05–7.84;P=0.040),multilocular cysts(OR:3.59;95%CI:1.09–11.85;P=0.036),suspected ethanol leakage during procedure(OR:10.68;95%CI:1.98–57.53;P=0.006),and sticky cystic fluid(OR:3.83;95%CI:1.20–12.24;P=0.024)were predictive factors for post-procedural acute pancreatitis.PCLs of uncinate process(OR:2.99;95%CI:1.22–7.35;P=0.017)and PCLs with exophytic portion(OR:3.70;95%CI:1.96–7.01;P<0.001)were predictive factors for post-procedural abdominal pain.Conclusions:EUS-EA is a safe procedure with a very low rate of severe AEs.It seems possible to predict the AEs according to the features of the procedure and PCLs.

Clobenpropit enhances anti-tumor effect of gemcitabine in pancreatic cancer

AIM: To evaluate the anti-tumor effect of clobenpropit, which is a specific H3 antagonist and H4 agonist, in combination with gemcitabine in a pancreatic cancer cell line.

Folfirinox chemotherapy prolongs stent patency in patients with malignant biliary obstruction due to unresectable pancreatic cancer

Background:Stent insertion for biliary decompression to relieve jaundice and subsequent biliary infection is necessary for patients with biliary obstruction caused by pancreatic cancer,and it is important to keep the stent patent as long as possible.However,few studies have compared stent patency in terms of chemotherapy in patients with pancreatic cancer.This study aimed to evaluate the differences in stent patency in terms of recently evolving chemotherapy.Methods:Between January 2015 and May 2017,161 patients with pancreatic cancer who had undergone biliary stent insertion with a metal stent were retrospectively analyzed.The relationship between chemotherapy and stent patency was assessed.Additionally,overall survival according to the treatment,risk factors for stent patency,and long-term adverse events were evaluated.Results:Median stent patency was 42 days for patients with the best supportive care and 217 days for patients with chemotherapy(conventional gemcitabine-based chemotherapy and folfirinox)(P<0.001).Furthermore,the folfirinox group showed the longest median stent patency and overall survival,with 283 days and 466 days,respectively(P<0.001)despite higher adverse events rate.Patients who underwent folfirinox chemotherapy after stent insertion had better stent patency in multivariate analysis(HR=0.26;95%CI:0.12–0.60;P=0.001).Conclusions:Compared with patients who received best supportive care only,patients who underwent chemotherapy after stent insertion had better stent patency.More prolonged stent patency can be expected for patients with folfirinox than conventional gemcitabine-based chemotherapy.

Comparison of efficacy between adjuvant chemotherapy and chemoradiation therapy for pancreatic cancer: AJCC stage-based approach

BACKGROUND The adjuvant treatment for patients with resected pancreatic cancer(PC)is not yet standardized.Because the prognosis differs according to the American Joint Committee on Cancer(AJCC)stage,a tailored approach to establish more aggressive treatment plans in high-risk patients is necessary.However,studies comparing the efficacy of adjuvant treatment modalities according to the AJCC stage are largely lacking.AIM To compare the efficacy of chemotherapy and chemoradiation therapy according to AJCC 8th staging system in patients with PC who underwent surgical resection.METHODS A total of 335 patients who underwent surgical resection and adjuvant treatment for PC were included.Patients were divided into three groups:Chemoradiation therapy(CRT)group,systemic chemotherapy(SCT)group and combined treatment of chemoradiation plus chemotherapy therapy(CRT-SCT)group.The primary outcomes were differences in overall survival(OS)between the three groups.The secondary outcomes were differences in recurrence-free survival,recurrence pattern and adverse events between the three groups.RESULTS Patients received CRT(n=65),SCT(n=62)and CRT-SCT(n=208).Overall median OS was 33.3 mo(95%confidence interval(CI):27.4-38.6).In patients with stage I/II,the median OS was 27.0 mo(95%CI:2.06-89.6)in the CRT group,35.8 mo(95%CI:26.9-NA)in the SCT group and 38.6 mo(95%CI:33.3-55.7)in the CRT SCT group.Among them,there was no significant difference in OS between the three groups.In 59 patients with stage III,median OS in the SCT group[19.0 mo(95%CI:12.6-NA)]and the CRT-SCT group[23.4 mo(95%CI:22.0-44.4)]was significantly longer than that in the CRT group[17.7 mo(95%CI:6.8-NA);P=0.011 and P<0.001,respectively].There were no significant differences in incidence of locoregional and distant recurrences between the three groups(P=0.158 and P=0.205,respectively).Incidences of grade 3 or higher hematologic adverse events were higher in the SCT and CRT-SCT groups than in the CRT group.CONCLUSION SCT and CRT-SCT showed significantly longer OS and recurrence-free survival than CRT in patients with AJCC stage III,while there was no significant difference in OS between the CRT,SCT and CRT-SCT groups in patients with AJCC stage I/II.Different adjuvant therapy according to AJCC stage can be applied in patients with PC.

Comparison of cytological and histological preparations in the diagnosis of pancreatic malignancies using endoscopic ultrasoundguided fine needle aspiration

BACKGROUND:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) has become a crucial diagnostic technique for pancreatic malignancies.The specimen obtained by EUS-FNA can be prepared for either cytological or histological examinations.This study was to compare diagnostic performance of cytological and histological preparations using EUSFNA in the same lesions when pancreatic malignancies were suspected.METHODS:One hundred and eighteen patients who underwent EUS-FNA for suspected pancreatic malignancies were consecutively enrolled.All procedures were conducted by a single echoendoscopist under the same conditions.Four adequate preparations were obtained by 22-gauge needles with 20 to-and-fro movements for each pass.The 4 preparations included 2 cytological and 2 histological specimens.The pathologic reviews of all specimens were conducted independently by a single experienced cytopathologist.Sensitivity,specificity,and accuracy of the 2 preparations were compared.RESULTS:The enrolled patients consisted of 62 males(52.5%),with the mean age of 64.6±10.5 years.Surgery was performed in 23(19.5%) patients.One hundred and sixteen(98.3%) lesions were classified as malignant,while 2(1.7%) were benign.Sensitivity of cytology and histology were 87.9% and 81.9%,respectively,with no significant difference(P=0.190).Accuracy was also not significantly different.Cytological preparation was more sensitive when the size of lesion was <3 cm(86.7% vs 68.9%,P=0.033).CONCLUSIONS:Our results suggested that the diagnostic performances of cytological and histological preparations are not significantly different for the diagnosis of pancreatic malignancies.However,cytological preparation might be more sensitive for pancreatic lesions <3 cm.

Multicenter phase Ⅱ trial of modified FOLFIRINOX in gemcitabine-refractory pancreatic cancer

AIM To evaluate the efficacy and safety of modified FOLFIRINOX as a second-line treatment for gemcitabine(GEM)-refractory unresectable pancreatic cancer(PC).METHODS This study was a prospective, multicenter, one-arm, open-label, phase Ⅱ trial. Patients with unresectable PC, who showed disease progression during GEMbased chemotherapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin(RIO; irinotecan 120 mg/m^2 and oxaliplatin 60 mg/m^2), which was set according to the phase Ⅰ study of FOLFIRINOX. The objective response rate(ORR), disease control rate(DCR), progressionfree survival(PFS), overall survival(OS), adverse events were evaluated. Additionally, changes in quality of life(QoL) were assessed using a questionnaire on QoL.RESULTS Between August 2015 and May 2016, a total of 48 patients were enrolled. The median follow-up time was 259 d with a median of 8.5 cycles. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval(CI): 3.7-7.9] and median OS was 9.0 mo(95%CI: 6.4-11.6). Neutropenia(64.6%) was the most common grade 3-4 adverse event, followed by febrile neutropenia(16.7%). Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment(45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).CONCLUSION FOLFIRINOX with RIO showed acceptable toxicity and promising efficacy for GEM-refractory unresectable PC. However, this treatment requires careful observation of treatment-related hematologic toxicities.

Huge encrusted ureteral stent forgotten for over 25 years:A case report

BACKGROUND Ureteral stent insertion is a relatively non-invasive procedure commonly used in the field of urology to resolve urinary obstruction.However,they are sometimes forgotten and the risk of complications increases with time.CASE SUMMARY A 43-year-old woman with a history of recurrent urinary tract infections visited our hospital for evaluation of persistent left flank pain,and lower urinary tract symptoms despite anti-biotic treatment.She had received urological surgery in her teens but did not know the details of her surgery.Kidney,ureter,and bladder X-ray and abdominopelvic computed tomography revealed a forgotten left ureteral stent with huge encrustation at both ends and a severely dilated left kidney with parenchymal thinning.In order to remove the ureteral stent,a laparoscopic nephroureterectomy was planned.The ureteral stent was successfully removed,and she was discharged after recovery.The patient was followed up for two years after surgery and did not show any signs of long-term complications.CONCLUSION Long indwelling stents can cause dire complications requiring radical interventions.Stent registry systems,novel stent material development,and proper patient education is important for complication prevention.

Revision of bilateral self-expandable metallic stents placed using the stent-in-stent technique for malignant hilar biliary obstruction

Background: Endoscopic biliary decompression using bilateral self-expandable metallic stent(SEMS) placed using the stent-in-stent(SIS) technique is considered favorable for unresectable malignant hilar biliary obstruction(MHBO). However, occlusion of the bilateral SIS placement is frequent and revision can be challenging. This study was performed to investigate the efficacy, the long-term patency and the appropriate approach for revision of occluded bilateral SIS placement in unresectable MHBO. Methods: From January 2011 to July 2016, thirty-eight patients with unresectable MHBO underwent revision of occluded bilateral SIS placement. Clinical data including success rates and patency of revision, were retrospectively analyzed. Results: The technical success rate of revision was 76.3%. The clinical success rate of revision was 51.7% and mean patency of revision was 49.1 days. No significant predictive factor for clinical failure of revision was observed. The cell size of SEMS was not found to have significant effects on clinical success rates or revision patency. Conclusions: Revision of occluded bilateral SIS placement for MHBO showed fair patency and clinical success rate. Revision method and cell size of SEMS were not found to influence clinical outcomes.

Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent

BACKGROUND： Bilateral stent-in-stent （SIS） self-expandable metal stent placement is technically chghallenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent. METHODS： Thirty-one patients who underwentlbilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilarl obstruction （Bismuth types Ⅱ, Ⅲ, Ⅳ） with different etiologies. RESULTS： Sixteen （51.6%） patients were male. The mean age of the patients was 67.0±14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma （58.1%） and gallbladder cancer （29.0%）. Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence （MOC） than those with MOC （95.2% vs 60.0%, P=0.03）. Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC （50.0% vs 19.0%, P=0.11）. Median time to recurrent biliary obstruction was 188 days and median survival was 175 days. CONCLUSIONS： The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients.

Effect of external beam radiotherapy on patency of uncovered metallic stents in patients with inoperable bile duct cancer

BACKGROUND： Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer（BDC）, maintenance of patency is still unsatisfactory.We tried to assess the effectiveness and safety of external beam radiotherapy（EBRT） for prolonging stent patency in patients having uncovered metallic stents.METHOD： We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT（RT group） and 32 did not（non-RT group）.RESULTS： No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group（140.7±51.3 vs136.4±34.9 days, P=0.94）, the difference was not statistically significant. There were a lower rate of stent occlusion（27.8% vs50.0% of patients, P=0.12） and a longer overall survival（420.1 ±73.2 vs 269.1±41.7 days, P=0.11） in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ（55.6% vs 53.1% of patients, P=0.91）. There was no serious adverse reaction in both groups（P=0.99）.CONCLUSIONS： EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials withrefined protocols for better efficacy are expected.

Acetylsalicylic acid for metal stent in malignant distal common bile duct obstruction:A randomized controlled trial

Background:Endoscopic biliary drainage is the treatment of choice for patients with malignant distal common bile duct obstruction.Self-expandable metal stents have clinical advantages including an increased duration of patency that may be prolonged by acetylsalicylic acid(ASA)use.The aim of this study was to investigate whether ASA had a positive effect on the patency of self-expandable metal stents compared with placebo.Methods:This prospective,multicenter,double-blinded,and randomized placebo-controlled trial was conducted from October 2017 to May 2020 in Korea.Patients who underwent palliative endoscopic biliary drainage with self-expandable metal stents for malignant distal bile duct obstruction were enrolled,and allocated to ASA treatment or placebo.The study outcomes were the rate of stent dysfunction at 6 months,duration of stent patency,risk factors for stent dysfunction,and any adverse events.Results:Interim analysis included 24 and 28 patients in the ASA and placebo groups,respectively.There was no significant difference between the ASA and placebo groups in stent dysfunction(25.0%vs.20.7%,P=0.761)or the duration of stent patency(150.97±10.55 vs.158.07±8.70 days,P=0.497).Six patients experienced suspected ASA-related adverse events,and there was one lethal case.Conclusions:ASA did not prolong stent patency.This study was terminated early because of the possibility of serious adverse events related to ASA treatment of these patients receiving palliative care.

Spontaneous rupture of adrenal myelolipoma as a cause of acute flank pain:A case report

BACKGROUND Adrenal myelolipoma is a rare,benign,non-functioning mass that occurs in the adrenal gland.It is composed of an admixture of hematopoietic elements and mature adipose tissue,similar to bone marrow.Even at large sizes,adrenal myelolipomas are usually asymptomatic and often incidentally found by ultrasonography or computed tomography(CT)scan.This paper describes an unusual case of adrenal myelolipoma presenting as flank pain.CASE SUMMARY A 50-year-old male with severe right flank pain underwent a CT scan revealing a huge mass extending into the suprarenal space.The mass showed a fat component with retroperitoneal hemorrhage.The tumor was treated laparoscopically,and pathologic examination revealed features of myelolipoma originating from the adrenal gland.CONCLUSION Adrenal myelolipomas are generally asymptomatic and can be treated conservatively.However,rupture and hemorrhage of the tumor can cause symptoms requiring surgical removal.

Electroacupuncture for abdominal pain relief in patients with acute pancreatitis:A three-arm randomized controlled trial

Background: Electroacupuncture(EA) may reduce the severity of acute pancreatitis(AP) and provide additional pain relief in patients with chronic pancreatitis. However, the ability of EA to relieve pain in patients with AP has not been well documented.Objective: This study was undertaken to compare the pain-relieving effects of EA and conventional treatment in patients with AP.Design, setting, participants and interventions: This study was conducted using a randomized, controlled,three-arm, parallel-group and multi-center design. Patients diagnosed with AP were randomly and equally assigned to EA1, EA2 or control groups. All participants received conventional standard-of-care therapy for AP. Local EA alone was administered in EA1, and local plus distal EA was given in EA2.Local EA included two abdominal acupoints, while distal EA included twelve peripheral acupoints. EA groups underwent one session of EA daily for 4 days(days 1–4), or until pain was resolved or discharged.Main outcome measures: The primary outcome measure was the change in the visual analogue scale(VAS;0–100) pain score between baseline and day 5.Results: Eighty-nine participants were randomized into EA1, EA2 and control groups, and 88(EA1, 30;EA2, 29;control, 29) were included in the full-analysis set. VAS score change(median [interquartile range]) on day 5 was(12.3 ± 22.5) in the EA1 group,(10.3 ± 21.5) in the EA2 group, and(8.9 ± 15.2) in the control group. There were not significant differences in the change in VAS score among treatments(P = 0.983). However, time to food intake was significantly shorter in the EA group(EA1 + EA2) than in the control group(median 2.0 days vs 3.0 days), with a hazard ratio of 0.581(P = 0.022;95% CI,0.366–0.924). No significant adverse events occurred.Conclusion: EA treatment did not significantly reduce pain after 4 days of treatment in patients with AP-associated abdominal pain but significantly reduced time to first food intake.