Feasibility of comprehensive genomic profiling using endoscopic ultrasound-guided tissue acquisition with a 22-gauge Franseen needle.

Aim: Comprehensive genomic profiling (CGP) test for solid tumors is now increasingly utilized in clinical practice, especially in pancreatobiliary cancer, and specimens obtained by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are often submitted for tissue-based CGP test. In this study, we evaluated the feasibility of EUS-TA using a 22-gauge Franseen needle for the CGP test. Methods: Consecutive patients with solid tumors who underwent EUS-TA using a 22-gauge Franseen needle, and whose tissue samples were pre-checked for suitability for CGP test, were included in this single-center, retrospective analysis. The success rates of appropriate sample collection for CGP evaluated by pathologists (1st quality control) and CGP test (2nd quality control) were evaluated. In addition, The EUS-TA slides were evaluated for the tissue area and tumor area content, using the image software. Results: A total of 50 cases, with 78% of pancreatic cancer, were included in the analysis. A median of 3 passes of EUS-TA were performed with an adverse event rate of 4%. The success rates for 1st and 2nd quality control for CGP tests were 86% and 76%, respectively. The image analyses suggested EUS-TA specimen did not always fulfill CGP test criteria, with 18% of tissue area ≥16 mm2 and 38% of tumor area content ≥20%, even in cases with successful CGP tests. The suction method yielded a significantly larger amount of DNA but without a significant difference in the multivariate analysis. Conclusions: The present study demonstrated the feasibility of EUS-TA using a 22-gauge Franseen needle for CGP test.

Intraductal Papillary Mucinous Neoplasm Surveillance Leads to Early Diagnosis and Better Outcomes of Concomitant Cancer.

OBJECTIVE: To examine whether long-term surveillance of intraductal papillary mucinous neoplasms (IPMNs) leads to early diagnosis and better clinical outcomes of pancreatic ductal adenocarcinomas (PDACs) developing concomitantly with IPMNs. SUMMARY BACKGROUND DATA: Long-term image-based surveillance is recommended for patients with low-risk IPMNs. However, it is unknown whether the surveillance can improve surgical and survival outcomes of patients with concomitant PDACs. METHODS: Using a prospective single-institutional cohort of 4,620 patients with pancreatic cysts including 3,638 IPMN patients, we identified 63 patients who developed concomitant PDAC during long-term surveillance. We compared overall survival (OS) of 46 cases with concomitant PDAC to that of 460 matched cases diagnosed with non-IPMN-associated PDAC at the same institution. Multivariable hazard ratios and 95% confidence intervals (CIs) for overall mortality were computed using the Cox regression model with adjustment for potential confounders. RESULTS: Concomitant PDACs were identified at an earlier cancer stage compared to non-IPMN-associated PDACs with 67% and 38% cases identified at stage 2 or earlier, respectively (P<0.001) and 57% and 21% cases with R0 resection, respectively (P<0.001). Compared to non-IPMN-associated PDACs, concomitant PDACs were associated with longer OS (P=0.034) with a multivariable hazard ratio of 0.61 (95% CI, 0.39-0.96). The 5-year survival rate of patients with concomitant PDAC was higher compared to patients with non-IPMN-associated PDAC (34% vs. 18%, respectively; P=0.018). CONCLUSIONS: The surveillance for patients with IPMNs was associated with early identification of concomitant PDACs and longer survival of patients diagnosed with this malignancy.

Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography for hepatolithiasis in patients with hepaticojejunostomy.

BACKGROUND AND AIM: Balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) is an emerging procedure for pancreatobiliary diseases in patients with surgically altered anatomy. However, data on BE-ERCP for hepatolithiasis after hepaticojejunostomy (HJS) are still limited. METHODS: Stone removal success, adverse events and recurrence were retrospectively studied in consecutive patients who underwent BE-ERCP for hepatolithiasis after HJS between January 2011 and October 2022. Subgroup analysis was performed to compare clinical outcomes between patients who had undergone HJS over 10 years before (past HJS group) and within 10 years (recent HJS group). RESULTS: A total of 131 patients were included; 39% had undergone HJS for malignancy and 32% for congenital biliary dilation. Scope insertion and complete stone removal were successful in 89% and 73%, respectively. Early adverse events were observed in 9.9%. Four patients (3.1%) developed gastrointestinal perforation but could be managed conservatively. Hepatolithiasis recurrence rate was 17%, 20% and 31% in 1-year, 3-year, and 5-year after complete stone removal. The past HJS group was the only risk factor for failed stone removal (odds ratio 10.4, 95% confidence interval 2.99-36.5) in the multivariable analysis. Failed scope insertion (20%) and failed guidewire or device insertion to the bile duct (22%) were two major reasons for failed stone removal in the past HJS group. CONCLUSIONS: BE-ERCP for hepatolithiasis was effective and safe in cases with HJS but the complete stone removal rate was low in the past HJS group. Recurrent hepatolithiasis was common and careful follow up study is needed even after complete stone removal.

Skeletal muscle status and survival among patients with advanced biliary tract cancer.

BACKGROUND: Studies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes. METHODS: We identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change. RESULTS: Compared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15-2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07-2.14; Ptrend = 0.012), but not with PFS (Ptrend = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD. CONCLUSIONS: Skeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status.

Retrospective comparative study of new slim-delivery and conventional large-cell stents for stent-in-stent methods for hilar malignant biliary obstruction.

OBJECTIVES: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents. METHODS: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO. RESULTS: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group. CONCLUSION: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO.

Second Covered and Uncovered Self-Expandable Metal Stents for Recurrent Gastric Outlet Obstruction: A Retrospective Comparative Study.

Background: Endoscopic self-expandable metal stent (SEMS) placement is a current mainstay for malignant gastric outlet obstruction (GOO), but symptomatic recurrence due to initial SEMS dysfunction commonly occurs. We aimed to compare the safety and effectiveness of second SEMS for recurrent GOO (RGOO). Methods: Between April 2006 and December 2022, a total of 95 cases with malignant RGOO undergoing second endoscopic SEMS placement were enrolled. Technical and clinical success rates, RGOO, time to RGOO (TRGOO), stent patency rate, adverse events (AE), and overall survival (OS) were retrospectively compared between covered and uncovered SEMS (cSEMS/uSEMS) groups. Risk factors for TRGOO were also explored. Results: Baseline characteristics were well balanced between cSEMS (n = 48) and uSEMS (n = 47) groups, except for the causes of the initial SEMS dysfunction. High technical and clinical success rates with a similar incidence of AE (15% vs. 17%, p = 0.78) and OS (median of 101 vs. 102 days, p = 0.68) were achieved in both groups. There were no statistical differences in cumulative incidence of RGOO (19% vs. 13%, p = 0.58), TRGOO (median, not reached in both groups, p = 0.57), and stent patency rates at 1, 2, and 3 months between the groups (60%, 47% and 26%, respectively vs. 70%, 55% and 38%, respectively). However, TRGOO tended to be longer in cSEMS in cases with RGOO due to tumor ingrowth (median, not reached vs. 111 days, p = 0.19). A Cox regression analysis demonstrated that chemotherapy after second SEMS placement was significantly associated with an improved TRGOO (the hazard ratio of 0.27 [95% confidence interval, 0.08-0.93], p = 0.03). Conclusions: Regardless of the type of SEMS, second SEMS placement was similarly safe and effective for RGOO. The type of second SEMS might be considered based on the cause of initial SEMS dysfunction.

Clinical trajectory of intraductal papillary mucinous neoplasms progressing to pancreatic carcinomas during long-term surveillance: a prospective series of 100 carcinoma cases.

BACKGROUND: Trajectories of serological and morphological signatures have not been documented in pancreatic carcinogenesis related to intraductal papillary mucinous neoplasms (IPMNs). METHODS: Using a prospective cohort of 3437 IPMN patients, we identified 100 IPMN patients who developed pancreatic carcinomas during long-term surveillance. We examined serial changes of blood markers (carbohydrate antigen 19-9 [CA19-9], hemoglobin A1c [HbA1c], and pancreatic enzymes) and morphological features (worrisome features and high-risk stigmata) during the prediagnostic period of pancreatic carcinomas, overall and by carcinoma types (IPMN-derived vs. concomitant pancreatic carcinomas). RESULTS: CA19-9 elevation was observed in 39 patients and was associated with a metastatic stage. Compared to IPMN-derived carcinomas, concomitant carcinomas were more likely to represent CA19-9 elevation (60% vs. 30%, respectively; P = 0.005). HbA1c levels elevated only in 3 patients. Pancreatic enzyme elevation was observed in 18 patients with no differences in frequencies between the carcinoma types. All patients with elevated levels of blood markers had positive findings on cross-sectional imaging. High-risk stigmata or worrisome features were observed in all patients but one with concomitant carcinoma. The most common types of worrisome features were the main pancreatic duct dilatation and CA19-9 elevation in IPMN-derived and concomitant carcinomas, respectively. Compared to IPMN-derived carcinomas, concomitant carcinomas were less likely to harbor high-risk stigmata (16% vs. 86%, respectively; P < 0.001). CONCLUSIONS: The usefulness of currently available blood biomarkers was limited in early detection of pancreatic carcinomas related to IPMNs. Morphological alterations were well correlated with long-term risk of IPMN-derived carcinomas, but not with that of concomitant carcinomas.

Clinical Outcomes of Intraductal Papillary Mucinous Neoplasms With Dilatation of the Main Pancreatic Duct.

BACKGROUND & AIMS: Dilatation of the main pancreatic duct (MPD) has been a surgical indication for intraductal papillary mucinous neoplasms (IPMNs). Few studies have investigated long-term outcomes of IPMNs with MPD dilatation. METHODS: Among 3610 patients diagnosed with pancreatic cysts between 1994 and 2021, we identified 2829 IPMN patients, including 282 patients with MPD ≥5 mm, and examined short-term (≤6 months) and long-term risks of pancreatic carcinoma. Utilizing competing risks proportional hazards models, we estimated subdistribution hazard ratios for incidence of pancreatic carcinoma with adjustment for potential confounders. RESULTS: In analyses of short-term outcomes of the 282 patients with MPD dilatation, 72 (26%) patients were diagnosed with pancreatic carcinoma based on surgical or nonsurgical exploration. During long-term follow-up of 168 patients, we documented 24 (14%) patients diagnosed with pancreatic carcinoma (18 with IPMN-derived carcinoma and 6 with concomitant ductal adenocarcinoma). The patients with the MPD = 5-9.9 mm had cumulative incidence rates of pancreatic carcinoma diagnosis of 8.1% (95% confidence interval [CI], 4.3%-13.5%) and 10.0% (95% CI, 5.5%-15.9%) at 2 and 5 years, respectively; and the patients with the MPD ≥10 mm had the corresponding rates of 16.0% (95% CI, 3.6-36.5%) and 33.3% (95% CI, 10.3%-58.8%). The multivariable subdistribution hazard ratios were 2.78 (95% CI, 1.57-4.90) and 7.00 (95% CI, 2.58-19.0) for the MPD = 5-9.9 mm and ≥10 mm (vs <5 mm), respectively. CONCLUSIONS: IPMNs with MPD dilatation at baseline were associated with higher prevalence and incidence of pancreatic carcinoma compared with IPMNs with no MPD dilatation.

Acute Liver Failure Due to Hypereosinophilic Syndrome Accompanied by Duodenal Perforation.

A 78-year-old woman presenting with severe acute liver failure was admitted to our hospital. On screening for the etiology of acute liver failure, it was diagnosed as being due to idiopathic hypereosinophilic syndrome (eosinophil count reported as 4766/µL; 33.8% of the white blood cells). Her medical history included marked eosinophilia, as observed six months prior to this admission. Corticosteroid therapy was initiated. During the clinical course, duodenal perforation occurred but was managed promptly by appropriate surgery. A liver biopsy, following the initiation of corticosteroid therapy, revealed degenerating hepatic cells with mild eosinophilic infiltration. With corticosteroid therapy, the liver function improved.

A rare case of gallbladder cancer with multiple metastases to the colon.

Gallbladder cancer is often diagnosed with metastasis and is known to have poor prognosis. Although, gallbladder cancer often metastasizes to liver, lung, or lymph nodes, metastasis to gastrointestinal tract is not common. Several autopsy studies reported colorectal metastasis from gallbladder cancer, but most of these cases were supposed to be gastrointestinal invasion from peritoneal dissemination. We experienced a rare case of hematogenous colon metastasis from gallbladder cancer. Colonoscopy for a 76-year-old man who was diagnosed as gallbladder cancer revealed two 5-mm flatly elevated lesions with central erosion in the transverse and sigmoid colon. Endoscopic mucosal resection (EMR) revealed poorly differentiated adenocarcinoma in hematoxylin and eosin staining. Additional immunohistochemistry examination showed strongly positive CK7 expression with negative CDX2, and suggested colon metastases from gallbladder cancer. Despite the positive vertical margin in EMR specimens, autopsy finding denied colorectal invasion from peritoneal dissemination and proved vascular spread colon metastases. Gastrointestinal metastasis is often misdiagnosed as a primary tumor, and thus, it is important to recognize gallbladder cancer as a potential origin of gastrointestinal metastasis.

Site Specific Evaluation of Lymphatic Vessel Sclerosis in Lower Limb Lymphedema Patients.

BACKGROUND: Histological changes in the collecting lymphatics in patients with lymphedema are classified as Normal type, Ectasis type, Contraction type, and Sclerosis type (NECST) classification. In this study, we investigated the condition of the lymphatic vessels in different sites of the legs. PATIENTS AND METHODS: We prospectively investigated the lymphatic vessels of patients with lymphedema who underwent lymphaticovenous anastomosis (LVA) from August 8, 2014 to August 4, 2015 based on the NECST classification. Lymphedema was diagnosed using lymphoscintigraphy, indocyanine green (ICG) lymphography, and the International Society of Lymphology (ISL) Classification. The affected limbs were divided into four sites: proximal thigh (Site 1), distal thigh (Site 2), proximal crus (Site 3), and distal crus (Site 4). RESULTS: A total of 109 patients (205 limbs and 1028 lymphatics) were included in this study. Of the 109 patients, there were 100 women and 9 men with an average age of 61 years. The ratio of Ectasis type vessels increased toward the distal end of the limb with the highest occurrence rate being 54% at Site 4. As ISL stage, ICG stage, and lymphoscintigraphy stage advanced, so too did the ratio of Sclerosis type. In secondary lymphedema patients with lymphedema, the ratio of Ectasis type was more predominant in the distal end of the limb, whereas this tendency was not observed in primary lymphedema patients. CONCLUSIONS: Sclerotic lymphatics are more predominantly found in the proximal limb whereas nonsclerotic vessels are more often found toward the distal end. These findings help lymphatic surgeon determine incision sites.

Multi-site lymphatic venous anastomosis using echography to detect suitable subcutaneous vein in severe lymphedema patients.

BACKGROUND: The method of lymphatic venous anastomosis (LVA), including its indications or preoperative examinations, has not been established. The purpose of this study is to reveal the possible application of preoperative echography in surgical LVA outcome. METHODS: We performed a retrospective case-control study on patients with lower limb lymphedema who underwent LVA between August 15, 2013 and August 15, 2014. As a preoperative examination, we used venous echography to identify subcutaneous veins in the echo group, while we only used Accuvein visualizing system in the control group. The operation time, number of anastomoses, and limb circumference were compared between the two groups. RESULTS: Seventeen patients (34 limbs) were included in the echo group, and 21 patients (42 limbs) were included in the control group. The average follow-up period was 11.9 (6-16) and 12.4 (6-27) months, respectively. The average operation time in the echo group was 258.6 min, and that in the control group was 216.5 min. The average number of anastomoses was 9.8 and 7.0 in the echo and control group, respectively. The average time per anastomosis was 27.4 and 32.6 min, respectively. The diameter of the vein had a tendency to be larger in the echo group than in the control group. In 5.8% of the echo group, we observed a circumference increase, compared with 23.8% in the control group. CONCLUSIONS: Preoperative venous echography allowed surgeons to increase the number of anastomoses performed within the operating time, resulting in improvement of surgical outcomes.

Lymphaticovenous Anastomosis Releases the Lower Extremity Lymphedema-associated Pain.

BACKGROUND: We investigate the effectiveness of lymphaticovenous anastomosis (LVA) in releasing lymphedema-associated pain. METHODS: We performed a retrospective analysis. Subjects of this study included lower extremity lymphedema patients who presented persistent and constant degrees of pain in their lower limbs. LVA was performed under local anesthesia. The preoperative lower extremity pain and postoperative lower extremity pain were surveyed using the visual analog scale on a score from 0 to 10. The circumferences of the limbs were also recorded. RESULTS: A total of 8 patients (16 lower limbs) were included. The subjects included 1 man and 7 women, and their average age was 72 years. The average follow-up period was 17 months. The average preoperative and postoperative visual analog scale scores were 5.3 and 1.8, respectively. Moreover, 7 patients who had records of their lower extremity circumference observed an average changing rate of -4.7% in lower extremity lymphedema index after the surgery. CONCLUSION: LVA can release the pain in the affected limbs of lymphedema.

Multisite Lymphaticovenular Bypass Using Supermicrosurgery Technique for Lymphedema Management in Lower Lymphedema Cases.

BACKGROUND: The impact of lymphaticovenous anastomosis on lymphedema has yet to be defined. The authors investigated the clinical evidence regarding the effectiveness of lymphaticovenous anastomosis in lower limb lymphedema. METHODS: Eighty-four patients (162 limbs; 73 female and 11 male patients) with lower limb lymphedema who underwent multisite lymphaticovenous anastomosis in the authors' clinic between August of 2010 and May of 2014 were included in this retrospective study. Lymphedema was diagnosed using lymphoscintigraphy and indocyanine green lymphography. All lymphaticovenous anastomoses were performed under local anesthesia. The lymphatic vessels that were identified were classified using the normal, ectasis, contraction, and sclerosis type (NECST) classification. Limb circumference, subjective symptoms, and frequency of cellulitis were evaluated. RESULTS: The average patient age was 60 years (range, 24 to 94 years); mean postoperative follow-up period was 18.3 months (range, 6 to 51 months). The postoperative change rate in limb circumference indicated that 67 limbs (47.7 percent) were classified as improved, 35 (27.3 percent) were classified as stable, and 32 (25 percent) were classified as worse. Postoperative interview revealed improvement in subjective symptoms in 67 limbs (61.5 percent), no change in 38 (34.9 percent), and exacerbation in four (3.7 percent). The postoperative mean occurrence of cellulitis was decreased to 0.13 times per year compared with 0.89 preoperatively, which was statistically significant (p = 0.00084). Multiple regression analysis using the postanastomosis limb circumference and NECST classification confirmed the following results: change rate (percent) = -0.40 + (0.30 × N) + (-0.84 × E) + (0.22 × C) + (-0.61 × S). CONCLUSION: Lymphaticovenous anastomosis is effective for lower limb lymphedema, in point of limb circumference, subjective symptoms, and the frequency of cellulitis. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Modified lymph vessel flap transplantation for the treatment of refractory lymphedema: A case report.

Lymph vessel flap transplantation (LFT), lymphaticovenous anastomosis (LVA), or lymph node flap transfer are sometimes used to treat lymphedema that is resistant to conservative treatment. LFT harvested from the contralateral limb has been reported for the treatment of lymphedema. Here we report the use of modified LFT from the abdominal wall for the treatment of refractory lymphedema. Our patient was a 57-year-old patient with secondary lower limb lymphedema was previously treated with conservative therapy and lymphaticovenous anastomosis. We first examined the lymphatic function of the lower abdominal region in the patient using indocyanine green (ICG) lymphography. After confirming the good lymphatic function in the right abdominal region, we harvested the pedicled abdominal adiposal flap containing multiple abdominal lymph vessels and transferred it to the left groin region. The flap (20 × 10 cm2 ) was based on the superficial circumflex iliac artery perforator. We anastomosed one lymph vessel in the flap to that in the recipient site. We also performed multiple fibrotripsy using a 3-mm-diameter stainless steel stick inserted into small incisions. The postoperative course was uneventful. The circumference measurement was decreased by 2.2-13.5 cm at 1 year after the operation. The lower abdominal region has many lymph vessel networks and is thought to be a less risky donor site in patients with lymphedema than the lower limbs. Thus, LFT may be an option for the treatment of chronic lymphedema. © 2015 Wiley Periodicals, Inc. Microsurgery 36:695-699, 2016.

Case report: a new hybrid surgical approach for treating mosaic pattern secondary lymphedema in the lower extremities.

Two of the most common surgical lymph reconstructive interventions for the treatment of secondary lymphedema today are lymphaticovenous anastomosis (LVA) and lymph node transplant. However, neither of these approaches has proven enough evidence to be considered as an effective treatment measure. In this case report, we will introduce a "hybrid method" where combinations of these two conventional methods are used in treating a 52-year-old female patient who displays a mosaic pattern of aggravating secondary lymphedema. Preoperative indocyanine green lymphography assessment was used to identify the different stages of lymphedema within the symptomatic limbs. The application of the hybrid method has resulted in a faster improvement in limb circumference and tissue tenderness compared with when only LVA is performed and has resulted in successful recovery from lymphedema in our case. The hybrid method allows surgeons to select the most appropriate surgical approach for each region displaying a different severity staging of lymphedema, establishing a new order-made remedy for chronic secondary lymphedema patients.