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Background and Objectives: Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to improve outcomes. We evaluated risk factors of focal pancreatic lesions (FPLs) in asymptomatic individuals at hereditary high risk for PC. Methods: This is an observational single-institution cohort study conducted over a period of 5 years. Surveillance was performed through imaging studies (EUS or magnetic resonance imaging/magnetic resonance cholangiopancreatography) and serum biomarkers. We collected demographic characteristics and used univariate and multivariate logistic regression models to evaluate associations between potential risk factors and odd ratios (ORs) for FPL development. Results: A total of 205 patients completed baseline screening. Patients were followed up to 53 months. We detected FPL in 37 patients (18%) at baseline; 2 patients had lesions progression during follow-up period, 1 of them to PC. Furthermore, 13 patients developed new FPLs during the follow-up period. Univariate and multivariate analyses revealed that new-onset diabetes (NOD) is strongly associated with the presence of FPL (OR, 10.94 [95% confidence interval, 3.01-51.79; P < 0.001]; OR, 9.98 [95% confidence interval, 2.15-46.33; P = 0.003]). Follow-up data analysis revealed that NOD is also predictive of lesions progression or development of new lesions during screening (26.7% vs. 2.6%; P = 0.005). Conclusions: In a PC high-risk cohort, NOD is significantly associated with presence of FPL at baseline and predictive of lesions progression or new lesions during surveillance.
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Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.
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BACKGROUND: Given the favourable prognosis of patients with gastric mucosa-associated lymphoid tissue (MALT) lymphoma, treatment-related toxicity should be minimised. We aimed to evaluate the efficacy of 4 Gy radiotherapy given in a response-adapted approach. METHODS: We conducted a single-centre, single-arm, prospective trial at MD Anderson Cancer Center (Houston, TX, USA) of response-adapted ultra-low-dose radiotherapy. Eligible patients were 18 years or older and had newly diagnosed or relapsed Helicobacter pylori-negative gastric MALT lymphoma, with stage I-IV disease. Given the expected low toxicity profile of treatment, performance status was not an exclusion criterion. Patients received external beam photon-based radiotherapy for a total dose of 4 Gy in two fractions. Patients with a complete response to 4 Gy via endoscopy and imaging at 3-4 months were observed; patients with a partial response were re-evaluated in 6-9 months. Residual disease at 9-13 months or stable or progressive disease at any time required additional treatment with 20 Gy. The primary endpoint was gastric complete response at 1 year (second evaluation timepoint) after 4 Gy treatment. All analyses were performed as intention to treat. This trial is registered at ClinicalTrials.gov (NCT03680586) and is complete and closed to enrolment. FINDINGS: Between March 27, 2019, and Oct 12, 2021, we enrolled 24 eligible patients. The median age of participants was 67 years (IQR 58-74; range 40-85); 15 (63%) were female and nine (37%) male; 18 (75%) were White, four (17%) Asian, and two (8%) Hispanic; 20 (83%) had stage I disease, one (4%) stage II, and three (13%) stage IV. Median follow-up time was 36 months (IQR 26-42). 20 patients (83%) had a complete response to 4 Gy (16 at 3-4 months, four at 9-13 months); two patients received 20 Gy for symptomatic stable disease at 3-4 months and two for residual disease at 9-13 months; all had a complete response. The 3-year local control rate was 96% (95% CI 88-100), with one local relapse at 14 months after 4 Gy radiotherapy salvaged successfully with 20 Gy. One patient with stage IV disease had a distant relapse. The most common adverse events were grade 1 nausea (nine [38%] of 24 patients who received 4 Gy and two [50%] of four patients who received 20 Gy) and grade 1 abdominal pain (five [21%] of 24 and zero of four, respectively). No grade 3 or worse adverse events were noted, including no treatment-related deaths. INTERPRETATION: Most patients had a complete response after 4 Gy radiotherapy; all who required an additional 20 Gy had a complete response within 12 months. This response-adapted strategy could be used to select patients who would benefit from additional radiotherapy and spare others potential associated toxicity. FUNDING: National Cancer Institute.
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Lymphoma, B-Cell, Marginal Zone , Radiotherapy Dosage , Stomach Neoplasms , Humans , Lymphoma, B-Cell, Marginal Zone/radiotherapy , Male , Female , Middle Aged , Stomach Neoplasms/radiotherapy , Stomach Neoplasms/pathology , Aged , Pilot Projects , Adult , Prospective Studies , Treatment Outcome , Aged, 80 and overABSTRACT
In this 14th document in a series of papers entitled "Controversies in Endoscopic Ultrasound" we discuss various aspects of EUS-guided biliary drainage that are debated in the literature and in practice. Endoscopic retrograde cholangiography is still the reference technique for therapeutic biliary access, but EUS-guided techniques for biliary access and drainage have developed into safe and highly effective alternative options. However, EUS-guided biliary drainage techniques are technically demanding procedures for which few training models are currently available. Different access routes require modifications to the basic technique and specific instruments. In experienced hands, percutaneous transhepatic cholangiodrainage is also a good alternative. Therefore, in this paper, we compare arguments for different options of biliary drainage and different technical modifications.
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OBJECTIVES: Clinical presentation and outcomes of esophageal candidiasis (EC) in cancer patients are scarcely studied in the azole era, as is the correlation between clinical, endoscopic, and histopathological EC manifestations. METHODS: We retrospectively reviewed the risk factors, clinical features, and outcomes of pathology-documented EC cases at MD Anderson Cancer Center. We further assessed associations between presence of symptoms, standardized 4-stage endoscopic grade (Kodsi classification), histopathological data, and fluconazole treatment failure. RESULTS: Among 323 cancer patients with EC, 89% had solid tumors, most commonly esophageal cancer (29%). Thirty-three percent of EC patients were asymptomatic. The proportion of symptomatic EC patients significantly increased with endoscopic grade (P = 0.005). Among 202 patients receiving oral fluconazole, 27 (13%) had treatment failure. Underlying esophageal disease was the only independent predictor of fluconazole treatment failure (odds ratio: 3.88, P = 0.005). Endoscopic grade correlated significantly with Candida organism burden (Correlation coefficient [ρ] = 0.21, P < 0.01) and neutrophilic inflammation (ρ = 0.18, P < 0.01). Candida invasion of the squamous mucosal layer was associated with treatment failure (P = 0.049). CONCLUSIONS: EC was predominantly encountered in patients with solid tumors. One-third of EC patients were asymptomatic, challenging traditional symptom-based diagnosis. The development of integrated clinicopathological scoring systems could further guide the therapeutic management of cancer patients with EC.
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Antifungal Agents , Candidiasis , Fluconazole , Humans , Male , Female , Middle Aged , Retrospective Studies , Candidiasis/microbiology , Candidiasis/pathology , Candidiasis/drug therapy , Candidiasis/epidemiology , Aged , Fluconazole/therapeutic use , Antifungal Agents/therapeutic use , Adult , Aged, 80 and over , Risk Factors , Neoplasms/complications , Neoplasms/pathology , Candida/isolation & purification , Candida/classification , Esophageal Diseases/pathology , Esophageal Diseases/microbiology , Esophageal Diseases/drug therapy , Treatment Failure , Esophageal Neoplasms/pathology , Esophageal Neoplasms/microbiologyABSTRACT
Efforts to improve the prognosis for patients with locally advanced esophageal or gastroesophageal junction (GEJ) adenocarcinoma have focused on neoadjuvant approaches to increase the pathological complete response (pathCR) rate, improve surgical resection, and prolong event-free and overall survival (OS). Building on the recent evidence that PD-1 inhibition plus chemotherapy improves the OS of patients with metastatic GEJ adenocarcinoma, we evaluated whether the application of this strategy in the neoadjuvant setting would improve the pathological response. This single-center phase I/II trial evaluated the safety, toxicity, and efficacy of neoadjuvant atezolizumab with oxaliplatin and 5-fluorouracil (modified FOLFOX) followed by esophagectomy followed by atezolizumab. The primary objective goal was to achieve 20% pathCR. From the twenty enrolled patients, eighteen underwent resection and two (10%, 95% CI: 1.24-31.7%) achieved pathCR. After a median follow-up duration of 40.7 months, 11 patients had disease recurrence and 10 had died. The median disease-free and OS were 28.8 (95% CI: 14.7, NA) and 38.6 months (95% CI: 30.5, NA), respectively. No treatment-related adverse events led to death. Although modified FOLFOX plus atezolizumab did not achieve the expected pathCR, an acceptable safety profile was observed. Our results support the continued development of a more refined strategy (neoadjuvant chemotherapy plus perioperative immunotherapy/targeted agents) with molecular/immune profiling in parallel.
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PURPOSE: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum. METHODS AND MATERIALS: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT. RESULTS: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove was pathologically confirmed with no evidence of damage to the duodenum. CONCLUSIONS: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit to translate into clinically improved tumor control.
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BACKGROUND: Stereotactic body radiotherapy (SBRT) has the potential to ablate localised pancreatic ductal adenocarcinoma. Selective dismutase mimetics sensitise tumours while reducing normal tissue toxicity. This trial was designed to establish the efficacy and toxicity afforded by the selective dismutase mimetic avasopasem manganese when combined with ablative SBRT for localised pancreatic ductal adenocarcinoma. METHODS: In this adaptive, randomised, double-blind, placebo-controlled, phase 1b/2 trial, patients aged 18 years or older with borderline resectable or locally advanced pancreatic cancer who had received at least 3 months of chemotherapy and had an Eastern Cooperative Oncology Group performance status of 0-2 were enrolled at six academic sites in the USA. Eligible patients were randomly assigned (1:1), with block randomisation (block sizes of 6-12) with a maximum of 24 patients per group, to receive daily avasopasem (90 mg) or placebo intravenously directly before (ie, within 180 min) SBRT (50, 55, or 60 Gy in five fractions, adaptively assigned in real time by Bayesian estimates of 90-day safety and efficacy). Patients and physicians were masked to treatment group allocation, but not to SBRT dose. The primary objective was to find the optimal dose of SBRT with avasopasem or placebo as determined by the late onset EffTox method. All analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT03340974, and is complete. FINDINGS: Between Jan 25, 2018, and April 29, 2020, 47 patients were screened, of whom 42 were enrolled (median age was 71 years [IQR 63-75], 23 [55%] were male, 19 [45%] were female, 37 [88%] were White, three [7%] were Black, and one [2%] each were unknown or other races) and randomly assigned to avasopasem (n=24) or placebo (n=18); the placebo group was terminated early after failing to meet prespecified efficacy parameters. At data cutoff (June 28, 2021), the avasopasem group satisfied boundaries for both efficacy and toxicity. Late onset EffTox efficacy response was observed in 16 (89%) of 18 patients at 50 Gy and six (100%) of six patients at 55 Gy in the avasopasem group, and was observed in three (50%) of six patients at 50 Gy and nine (75%) of 12 patients at 55 Gy in the placebo group, and the Bayesian model recommended 50 Gy or 55 Gy in five fractions with avasopasem for further study. Serious adverse events of any cause were reported in three (17%) of 18 patients in the placebo group and six (25%) of 24 in the avasopasem group. In the placebo group, grade 3 adverse events within 90 days of SBRT were abdominal pain, acute cholangitis, pyrexia, increased blood lactic acid, and increased lipase (one [6%] each); no grade 4 events occurred. In the avasopasem group, grade 3-4 adverse events within 90 days of SBRT were acute kidney injury, increased blood alkaline phosphatase, haematoma, colitis, gastric obstruction, lung infection, abdominal abscess, post-surgical atrial fibrillation, and pneumonia leading to respiratory failure (one [4%] each).There were no treatment-related deaths but one late death in the avasopasem group due to sepsis in the setting of duodenal obstruction after off-study treatment was reported as potentially related to SBRT. INTERPRETATION: SBRT that uses 50 or 55 Gy in five fractions can be considered for patients with localised pancreatic ductal adenocarcinoma. The addition of avasopasem might further enhance disease outcomes. A larger phase 2 trial (GRECO-2, NCT04698915) is underway to validate these results. FUNDING: Galera Therapeutics.
Subject(s)
Adenocarcinoma , Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Radiosurgery , Humans , Male , Female , Aged , Adenocarcinoma/radiotherapy , Adenocarcinoma/drug therapy , Pancreatic Neoplasms/radiotherapy , Pancreatic Neoplasms/drug therapy , Radiosurgery/adverse effects , Bayes Theorem , Carcinoma, Pancreatic Ductal/radiotherapy , Carcinoma, Pancreatic Ductal/drug therapy , Double-Blind Method , Antineoplastic Combined Chemotherapy Protocols/therapeutic useABSTRACT
Accurate delivery of stereotactic body radiotherapy (SBRT) to pancreatic tumors relies on successful EUS-guided placement of fiducial markers. The aim of this study is to report the technical feasibility and safety of EUS-guided fiducial placement and to evaluate the characteristics and technical benefit of SBRT in a cohort of patients with pancreatic cancer (PC). A retrospective chart review was performed for all (n = 82) PC patients referred for EUS-guided fiducial placement by a single endosonographer at a tertiary cancer center. Data regarding EUS-related technical details, SBRT characteristics, adverse events, and continuous visibility of fiducials were recorded and analyzed. Most patients included in the study had either locally advanced disease (32 patients, 39%) or borderline resectable disease (29 patients, 35%). Eighty-two PC patients underwent the placement of 230 fiducial markers under EUS guidance. The technical success rate of the fiducial placement was 98%. No immediate EUS-related adverse events were reported. The average time to the simulation CT after fiducial placement was 3.1 days. Of the 216 fiducial markers used for the SBRT delivery, 202 fiducial markers were visible on both the simulation CT and the cone beam CT scan. A median dose of 40cGY was given to all the patients in five fractions. Of these, 41% of the patients reported no SBRT-related toxicities during the follow-up. Fatigue and nausea were the most reported SBRT-related toxicities, which were seen in 35% of the patients post-SBRT. Our results demonstrate that EUS-guided fiducial placement is safe and effective in target volume delineation, facilitating SBRT delivery in PC patients. Further clinical trials are needed to determine the SBRT-related survival benefits in patients with pancreatic cancer.
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Introduction: The tumor microbiome (TM) has been linked to pancreatic cancer prognosis. Specific microbes can confer tumor resistance to therapies. Early knowledge of the TM at time of diagnosis would be clinically relevant for precision therapy based on microbial composition. However, it is difficult to define the TM prior to surgical resection. Methods: In this pilot feasibility study, patients underwent Endoscopic Ultrasound-Fine Needle Aspiration (EUS-FNA) biopsy of pancreatic adenocarcinoma. These samples were analyzed using 16S rRNA and internal transcribed spacer (ITS) sequencing for characterization of the tumor bacteria and fungi. Result: After in silico decontamination and comparison to non-matched tumor, we were able to characterize the TM in biopsies, which was comparable to the TM from surgical specimens. Discussion: EUS-FNA biopsy may represent a feasible modality to characterize the pancreatic TM prior to surgical resection with proper decontamination strategies and improvements in matched controls.
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Adenocarcinoma , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , RNA, Ribosomal, 16S/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration , BacteriaABSTRACT
The discovery of botulinum toxin A (BTX)'s therapeutic properties has led to studies evaluating its usefulness in multiple medical disorders. Its use in the gastrointestinal (GI) tract has been studied for 30 years. Multiple databases, including PubMed, AccessMedicine, ClinicalKey, Cochrane Library, Embase, and Medline, were used to review research from case series to randomized controlled trials on BTX use in the GI tract. This article reviews the current literature on the efficacy of BTX and the strength of recommendations for or against its use in various disorders, including cricopharyngeal dysphagia, achalasia, nonachalasia motility disorders, gastroparesis, obesity, sphincter of Oddi disorders, chronic anal fissure, chronic idiopathic anal pain, and anismus. The appeal of BTX comes from its simplicity of administration, good safety profile, and reliability in decreasing muscular tone. However, there are several drawbacks that limit its use, including the lack of long-term efficacy and/or limited data in many GI disorders.
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A definite pathologic diagnosis of intrapancreatic metastasis is crucial for the management decision, i.e., curative or palliative surgery versus chemotherapy or conservative/palliative therapy. This review focuses on the appearance of intrapancreatic metastases on native and contrast-enhanced transabdominal ultrasound and endoscopic ultrasound. Differences and similarities in relation to the primary tumor, and the differential diagnosis from pancreatic carcinoma and neuroendocrine neoplasms are described. The frequency of intrapancreatic metastases in autopsy studies and surgical resection studies will be discussed. Further emphasis is placed on endoscopic ultrasound-guided sampling to confirm the diagnosis.
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INTRODUCTION: Gastroesophageal adenocarcinoma is relatively common in elderly patients as the incidence increases with age. However, the optimal treatment approach is not well established in this group of patients. The aim of this study is to review our experience for localized gastroesophageal adenocarcinoma in patients aged ≥80 years and to assess association between patient characteristics, clinical factors, and overall survival (OS) in order to optimize the therapeutic approaches for this population. METHODS: Patients ≥80 years old treated for localized gastroesophageal adenocarcinoma were retrospectively analyzed. Survival curves were estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression models were applied to assess the association between patient characteristics and OS. Factors that were significant in the multivariate model were included in the final reduced model. RESULTS: 127 patients ≥80 years old, were included in this study with median age of 83 years. The median follow-up time was 3.2 years, and median OS was 2.5 years (95% CI: 2.0-3.1 years). Independent prognostic factors for OS were Eastern Cooperative Oncology Group (ECOG) performance status (PS) (p = 0.003), baseline clinical stage (p = 0.01), and surgery (p = 0.001). ECOG PS, tumor location, baseline stage, tumor grade, and surgery were included in the final reduced model. CONCLUSION: Surgical treatment can improve survival in elderly patients. Therapeutic decisions should be based on the patients' general condition rather that age alone.
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Adenocarcinoma , Aged , Humans , Aged, 80 and over , Prognosis , Retrospective Studies , Adenocarcinoma/drug therapy , Proportional Hazards ModelsABSTRACT
Image fusion of CT, MRI, and PET with endoscopic ultrasound and transabdominal ultrasound can be promising for GI malignancies as it has the potential to allow for a more precise lesion characterization with higher accuracy in tumor detection, staging, and interventional/image guidance. We conducted a literature review to identify the current possibilities of real-time image fusion involving US with a focus on clinical applications in the management of GI malignancies. Liver applications have been the most extensively investigated, either in experimental or commercially available systems. Real-time US fusion imaging of the liver is gaining more acceptance as it enables further diagnosis and interventional therapy of focal liver lesions that are difficult to visualize using conventional B-mode ultrasound. Clinical studies on EUS guided image fusion, to date, are limited. EUS-CT image fusion allowed for easier navigation and profiling of the target tumor and/or surrounding anatomical structure. Image fusion techniques encompassing multiple imaging modalities appear to be feasible and have been observed to increase visualization accuracy during interventional and diagnostic applications.
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Patients with esophageal cancer undergoing esophagectomy have an improved survival over time, however adverse events associated with the use of a gastric conduit are increasingly being reported. Delayed gastric emptying (DGE) is an esophagectomy-related complication which can decreased quality of life by causing debilitating gastrointestinal symptoms and malnutrition. The aim of our study was to evaluate the effect of endoscopic intrapyloric botulinum (BT) injection in combination with pyloric balloon dilation in patients with DGE following distal esophagectomy at our tertiary cancer center. Patients with a prior history of distal esophagectomy who had also undergone endoscopic BT injection with pyloric balloon dilation by a single endoscopist between 2007 and 2017 were included in the study. One hundred units of BT were injected endoscopically into the pylorus in four quadrants using an injection needle. Following BT injection, a standard through-the-scope balloon was passed to the pylorus and inflated to a maximum diameter of 12−20 mm. For patients who underwent repeat procedures, the symptomatic outcomes were assessed and documented by the endoscopist; for the other patients, the electronic medical records were reviewed. A total of 21 patients undergoing 44 endoscopic intrapyloric botox injections combined with balloon dilatations were identified. The patients underwent the procedures at a median of 22 months (range, 1−108 months) after esophagectomy. The procedures were performed only once in 43% of the patients; 43% patients underwent the procedure twice, while 14% had it multiple times (>2). Overall, intrapyloric BT injection coupled with balloon dilation was a safe procedure, without any major immediate or delayed (1 month) procedure-related adverse events. Eighteen patients (85%) reported a significant overall improvement in symptoms from the initial presentation. One patient (5%) showed no improvement, whereas in two (10%) patients responses were not available. In our particular cohort of patients, the interventions of endoscopic intrapyloric BT injection with pyloric balloon dilation proved to be very beneficial, leading to significant symptomatic improvement. The balloon dilation after BT injection might have resulted in better diffusion of the BT into the pyloric sphincter complex, possibly increasing its therapeutic effects. Further prospective studies are needed to validate these results.
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BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P < 0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).
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Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Precision Medicine , Retrospective Studies , Imaging, Three-Dimensional , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/genetics , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Organoids/pathology , Pancreatic NeoplasmsABSTRACT
EUS-guided biliary drainage (EUS-BD) has recently gained widespread acceptance as a minimally invasive alternative method for biliary drainage. Even in experienced endoscopy centers, ERCP may fail due to inaccessibility of the papillary region, altered anatomy (particularly postsurgical alterations), papillary obstruction, or neoplastic gastric outlet obstruction. Biliary cannulation fails at first attempt in 5%-10% of cases even in the absence of these factors. In such cases, alternative options for biliary drainage must be provided since biliary obstruction is responsible for poor quality of life and even reduced survival, particularly due to septic cholangitis. The standard of care in many centers remains percutaneous transhepatic biliary drainage (PTBD). However, despite the high technical success rate with experienced operators, the percutaneous approach is more invasive and associated with poor quality of life. PTBD may result in long-term external catheters for biliary drainage and carry the risk of serious adverse events (SAEs) in up to 10% of patients, including bile leaks, hemorrhage, and sepsis. PTBD following a failed ERCP also requires scheduling a second procedure, resulting in prolonged hospital stay and additional costs. EUS-BD may overcome many of these limitations and offer some distinct advantages in accessing the biliary tree. Current data suggest that EUS-BD is safe and effective when performed by experts, although SAEs have been also reported. Despite the high number of clinical reports and case series, high-quality comparative studies are still lacking. The purpose of this article is to report on the current status of this procedure and to discuss the tools and techniques for EUS-BD in different clinical scenarios.
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BACKGROUND AND AIMS: Esophageal function testing is an integral component of the evaluation of refractory GERD and esophageal motility disorders. This review summarizes the current technologies available for esophageal function testing, including the functional luminal imaging probe (FLIP), high-resolution esophageal manometry (HRM), and multichannel intraluminal impedance (MII) and pH monitoring. METHODS: We performed a MEDLINE, PubMed, and MAUDE database literature search to identify pertinent clinical studies through March 2021 using the following key words: esophageal manometry, HRM, esophageal impedance, FLIP, MII, and esophageal pH testing. Technical data were gathered from traditional and web-based publications, proprietary publications, and informal communications with pertinent vendors. The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. RESULTS: FLIP is a high-resolution impedance planimetry system used for pressure and dimension measurement in the esophagus, pylorus, and anal sphincter. FLIP provides complementary information to HRM for esophageal motility disorders, especially achalasia. The Chicago classification, based on HRM data, is a widely adopted algorithmic scheme used to diagnose esophageal motility disorders. MII detects intraluminal bolus movement and, combined with pH measurement or manometry, provides information on acid and non-acid gastroesophageal reflux and bolus transit in patients with refractory GERD and for preoperative evaluation for anti-reflux procedures. CONCLUSIONS: Esophageal function testing techniques (FLIP, HRM, and MII-pH) have diagnostic and prognostic value in the evaluation of esophageal motility disorders and refractory GERD. Newer technologies and classification systems have enabled an increased understanding of these diseases.