Diagnosis and treatment of bacterial peritonitis in patients with gastrointestinal cancer: an observational multicenter study.

Background: Bacterial peritonitis (BP) in patients with gastrointestinal (GI) cancer has been poorly described, and its prevalence is unknown. Objectives: This study aimed to evaluate in patients with both GI cancer and ascites the prevalence of BP, associated features, mechanisms, prognosis, and the diagnostic performance of neutrophil count in ascites. Design: A retrospective, multicenter, observational study. Methods: All patients with GI cancer and ascites who underwent at least one paracentesis sample analyzed for bacteriology over a 1-year period were included. BP was defined by a positive ascites culture combined with clinical and/or biological signs compatible with infection. Secondary BP was defined as BP related to a direct intra-abdominal infectious source. Results: Five hundred fifty-seven ascites from 208 patients included were analyzed. Twenty-eight patients had at least one episode of BP and the annual prevalence rate of BP was 14%. Among the 28 patients with BP, 19 (65%) patients had proven secondary BP and 17 (59%) patients had multi-microbial BP, mainly due to Enterobacterales. A neutrophil count greater than 110/mm3 in ascites had negative and positive predictive values of 96% and 39%, respectively, for the diagnosis of BP. The median survival of patients with BP was 10 days (interquartile range 6-40) after the diagnosis. Conclusion: BP is not rare in patients with GI cancer and is associated with a poor short-term prognosis. When a patient with GI cancer is diagnosed with BP, a secondary cause should be sought. Further studies are needed to better define the best management of these patients.

Ampullary tumors: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, ACHBT, AFC, SFRO, RENAPE, SNFCP, AFEF, SFP, SFR).

BACKGROUND: Management of ampullary tumors (AT) is challenging because of a low level of scientific evidence. This document is a summary of the French intergroup guidelines regarding the management of AT, either adenoma (AA) or carcinoma (AC), published in July 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: A collaborative work was conducted under the auspices of French medical, endoscopic, oncological and surgical societies involved in the management of AT. Recommendations are based on recent literature review and expert opinions and graded in three categories (A, B, C), according to quality of evidence. RESULTS: Accurate diagnosis of AT requires at least duodenoscopy and EUS. All patients should be discussed in multidisciplinary tumor board before treatment. Surveillance may only be proposed for small AA in familial adenomatous polyposis. For AA, endoscopic papillectomy is the preferred option only if R0 resection can be achieved. When not possible, surgical papillectomy should be considered. For AC beyond pT1a N0, pancreaticoduodenectomy is the procedure of choice. Adjuvant monochemotherapy (gemcitabine, 5FU) may be proposed. For aggressive tumors (pT3/T4, pN+, R1, poorly differentiated AC, pancreatobiliary differentiation) with high risk of recurrence, 6 months polychemotherapy (CAPOX/FOLFOX for the intestinal subtype and mFOLFIRINOX for the pancreatobiliary or the mixed subtype) may be a valid alternative. Clinical and radiological follow up is recommended for 5 years. CONCLUSIONS: These guidelines help to homogenize and highlight unmet needs in the management of AA and AC. Each individual case should be discussed by a multidisciplinary team.

Clinical care pathways of patients with biliary tract cancer: A French nationwide longitudinal cohort study.

BACKGROUND: Although the incidence of BTC is raising, national healthcare strategies to improve care lack. We aimed to explore patient clinical care pathways and strategies to improve biliary tract cancer (BTC) care. METHODS: We analysed the French National Healthcare database of all BTC inpatients between January 1, 2017 and December 31, 2021. Multinomial logistic regression adjusted odds ratios (aOR) were used to identify healthcare organisation factors that influenced access to curative care both overall and in a longitudinal sensibility analysis using optimal matching and hierarchical ascending classification to detect a subgroup of curative-care patients with a high survival over a two-year period. RESULTS: A total of 19,825 new BTC patients and three clinical care pathways (CCP) were identified: 'Palliative care' (PC-CCP), 'Non-curative Care' (NCC-CCP) and 'Curative Care' (CC-CCP) involving 7669 (38.7%), 7721 (38.9%) and 4435 (22.4%) patients respectively. Out of 1200 centers involved in BTC treatment, 84%, 11% and 5% were of low- (<15 patients/year), medium- (15-30 patients/year) and high-volume (>30 patients/year) respectively. Among patient, tumor and hospital factors, BTC management in academic (aOR: 2.32; 95%CI: 1.98-2.71), private (2.51; 2.22-2.83), semi-private (2.25; 1.91-2.65) and in high- (2.09; 1.81-2.42) or medium-volume (1.49; 1.33-1.68) centers increased probability to CC-CCP. These results were maintained in a longitudinal cluster of 2363 (53%) CC-CCP patients presenting a higher two-year survival compared with the rest [96.4% (95.1; 97.6) vs. 38.8% (36.3; 41.4), log-rank p < 0.001]. CONCLUSIONS: Among factors subject to healthcare policy improvement, the volume and type of centers managing BTC strongly influenced access to curative care.

Biliary tract cancers: French national clinical practice guidelines for diagnosis, treatments and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACABi, ACHBPT).

INTRODUCTION: This document is a summary of the French intergroup guidelines of the management of biliary tract cancers (BTC) (intrahepatic, perihilar and distal cholangiocarcinomas, and gallbladder carcinomas) published in September 2023, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS: This collaborative work was conducted under the auspices of French medical and surgical societies involved in the management of BTC. Recommendations were graded in three categories (A, B and C) according to the level of scientific evidence until August 2023. RESULTS: BTC diagnosis and staging is mainly based on enhanced computed tomography, magnetic resonance imaging and (endoscopic) ultrasound-guided biopsy. Treatment strategy depends on BTC subtype and disease stage. Surgery followed by adjuvant capecitabine is recommended for localised disease. No neoadjuvant treatment is validated to date. Cisplatin-gemcitabine chemotherapy combined to the anti-PD-L1 inhibitor durvalumab is the first-line standard of care for advanced disease. Early systematic tumour molecular profiling is recommended to screen for actionable alterations (IDH1 mutations, FGFR2 rearrangements, HER2 amplification, BRAFV600E mutation, MSI/dMMR status, etc.) and guide subsequent lines of treatment. In the absence of actionable alterations, FOLFOX chemotherapy is the only second-line standard-of-care. No third-line chemotherapy standard is validated to date. CONCLUSION: These guidelines are intended to provide a personalised therapeutic strategy for daily clinical practice. Each individual BTC case should be discussed by a multidisciplinary team.

Closure of gastrointestinal perforations using an endoloop system and a single-channel endoscope: description of a simple, reproducible, and standardized method.

BACKGROUND: Several endoscopic treatments for iatrogenic perforations are currently available, with some limitations in terms of size, location, complexity, or cost. Our aims were to introduce a novel technique for closure, using an endoloop and clips, to assess its rate of technical success and post-resection complications. METHODS: For closure of large perforations (diameter ≥ 10 mm), two similar techniques were implemented, using a single-channel endoscope. An endoloop was deployed through the operating channel or towed by an endoclip alongside the endoscope. Several clips were utilized to fix it on the muscular layer of defect's margins. The defect was closed, by fastening the loop either directly or after being reattached to the mobile hook. RESULTS: This analysis included eleven patients (72% women, median age 68 years). Eight colorectal, one appendiceal, and two gastric lesions were resected, with a median perforation size of 15 mm. As confirmed by computed tomography, closure of wall defects was achieved successfully in all cases, using a median of 6 clips. Pneumoperitoneum was evacuated in 4 cases. The median hospitalization duration was 4 days, prophylactic antibiotics being prescribed for a median of 7 days. One patient had a small abdominal collection, without requiring drainage, while another presented post-resection bleeding from the mucosal defect. CONCLUSION: The novel techniques, utilizing a single-channel endoscope, clips, and an endoloop, ensuring an edge-to-edge suture of muscular layer, proved to be safe, reproducible, and easy to implement. They exhibit an excellent technical success rate and a minimal incidence of non-severe complications.

CT and MRI of Gastrointestinal Stromal Tumors: New Trends and Perspectives.

Gastrointestinal stromal tumors (GISTs) are defined as mesenchymal tumors of the gastrointestinal tract that express positivity for CD117, which is a c-KIT proto-oncogene antigen. Expression of the c-KIT protein, a tyrosine kinase growth factor receptor, allows the distinction between GISTs and other mesenchymal tumors such as leiomyoma, leiomyosarcoma, schwannoma and neurofibroma. GISTs can develop anywhere in the gastrointestinal tract, as well as in the mesentery and omentum. Over the years, the management of GISTs has improved due to a better knowledge of their behaviors and risk or recurrence, the identification of specific mutations and the use of targeted therapies. This has resulted in a better prognosis for patients with GISTs. In parallel, imaging of GISTs has been revolutionized by tremendous progress in the field of detection, characterization, survival prediction and monitoring during therapy. Recently, a particular attention has been given to radiomics for the characterization of GISTs using analysis of quantitative imaging features. In addition, radiomics has currently many applications that are developed in conjunction with artificial intelligence with the aim of better characterizing GISTs and providing a more precise assessment of tumor burden. This article sums up recent advances in computed tomography and magnetic resonance imaging of GISTs in the field of image/data acquisition, tumor detection, tumor characterization, treatment response evaluation, and preoperative planning.

Impact of surgery after endoscopically resected high-risk T1 colorectal cancer: results of an emulated target trial.

BACKGROUND AND AIMS: We aimed to compare the long-term outcomes of patients with high-risk T1 colorectal cancer (CRC) resected endoscopically who received either additional surgery or surveillance. METHODS: We used data from routine care to emulate a target trial aimed at comparing 2 strategies after endoscopic resection of high-risk T1 CRC: surgery with lymph node dissection (treatment group) versus surveillance alone (control group). All patients from 14 tertiary centers who underwent an endoscopic resection for high-risk T1 CRC between March 2012 and August 2019 were included. The primary outcome was a composite outcome of cancer recurrence or death at 48 months. RESULTS: Of 197 patients included in the analysis, 107 were categorized in the treatment group and 90 were categorized in the control group. From baseline to 48 months, 4 of 107 patients (3.7%) died in the treatment group and 6 of 90 patients (6.7%) died in the control group. Four of 107 patients (3.7%) in the treatment group experienced a cancer recurrence and 4 of 90 patients (4.4%) in the control group experienced a cancer recurrence. After balancing the baseline covariates by inverse probability of treatment weighting, we found no significant difference in the rate of death and cancer recurrence between patients in the 2 groups (weighted hazard ratio, .95; 95% confidence interval, .52-1.75). CONCLUSIONS: Our study suggests that patients with high-risk T1 CRC initially treated with endoscopic resection may not benefit from additional surgery.

CT and MRI of abdominal cancers: current trends and perspectives in the era of radiomics and artificial intelligence.

Abdominal cancers continue to pose daily challenges to clinicians, radiologists and researchers. These challenges are faced at each stage of abdominal cancer management, including early detection, accurate characterization, precise assessment of tumor spread, preoperative planning when surgery is anticipated, prediction of tumor aggressiveness, response to therapy, and detection of recurrence. Technical advances in medical imaging, often in combination with imaging biomarkers, show great promise in addressing such challenges. Information extracted from imaging datasets owing to the application of radiomics can be used to further improve the diagnostic capabilities of imaging. However, the analysis of the huge amount of data provided by these advances is a difficult task in daily practice. Artificial intelligence has the potential to help radiologists in all these challenges. Notably, the applications of AI in the field of abdominal cancers are expanding and now include diverse approaches for cancer detection, diagnosis and classification, genomics and detection of genetic alterations, analysis of tumor microenvironment, identification of predictive biomarkers and follow-up. However, AI currently has some limitations that need further refinement for implementation in the clinical setting. This review article sums up recent advances in imaging of abdominal cancers in the field of image/data acquisition, tumor detection, tumor characterization, prognosis, and treatment response evaluation.

Comparison Between Radial and Femoral Artery Access for Transarterial Chemoembolisation in Patients With Hepatocellular Carcinoma.

PURPOSE: The purpose of this study was to compare the technical success rate, the selectivity of transarterial chemoembolisation (TACE), the complication rate, the radiation dose given to the patients and the hospitalization stay between TACE performed using femoral artery approach (FAA) and TACE performed using radial artery approach (RAA) in patients with hepatocellular carcinoma (HCC). METHODS: Between June 2020 and April 2022, 49 patients with HCC who underwent 116 TACEs (75 using FAA and 41 using RAA) were included. Differences in technical success rate, selectivity of micro-catheterization, radiation dose given to the patients, fluoroscopy time, hospitalization stay duration, and complication rate were compared between FAA and RAA using Fisher exact or Student t tests. RESULTS: No differences in technical success rates were found between RAA (93%; 39/41 TACEs) and FAA (100%; 75/75 TACEs) (P = .12). There were no differences between the two groups in terms of selectivity of catheterization, radiation dose, fluoroscopy time and hospitalization stay duration. Five patients had Grade 2 complications (hematoma) after FAA vs. one patient with one Grade 1 complication (radial artery occlusion) after RAA (5/75 [7%] vs. 1/41 [2%], respectively; P = .42). No major arterial access site complications occurred with FAA or RAA. CONCLUSIONS: This study confirms that RAA is a safe approach that does not compromise the technical efficacy and the selectivity of TACE compared to FAA in patients with HCC.

Preoperative Endoscopic Ultrasound-Guided Hepaticogastrostomy for Definite Biliary Drainage in Hilar Cholangiocarcinoma Laparoscopic Resection: A Hybrid Minimal-Invasive Technique.

BACKGROUND AND STUDY AIMS: Laparoscopic approach of perihilar cholangiocarcinoma (PHC) is still challenging. We report the original use of a endoscopic hepaticogastrostomy (EHG) for definite biliary drainage in order to avoid biliary reconstruction. PATIENTS AND METHODS: A 70-year-old man presenting with jaundice was referred for resection of a Bismuth type IIIa PHC. Repeated endoscopic retrograde cholangiopancreatography failed to drain the future liver remnant, enabling only right anterior liver section drainage. EHG was performed three weeks before surgery. A hepatogastric anastomosis was created, placing a half-coated self-expanding endoprosthesis between biliary duct of segment 2 and the lesser gastric curvature. RESULTS: A laparoscopic right hepatectomy extended to segment 1, common bile duct, and hepatic pedicle lymphadenectomy was performed. The left hepatic duct was sectioned and ligated downstream to the biliary confluence of segment 2-3 and 4 allowing exclusive biliary flow through the EHG. The patient was disease free at 12 months, postoperative outcomes were uneventful except three readmissions for acute cholangitis due to prosthesis obstruction. CONCLUSIONS: EHG may be used as definite biliary drainage technique in laparoscopic PHC resection, at the expense of prosthesis obstruction and cholangitis.

Burden of grade 3 or 4 liver injury associated with immune checkpoint inhibitors.

Background & Aims: There is concern about the burden of liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). Methods: In a retrospective cohort study, we evaluated the likelihood of grade 3/4 liver injury, of grade 3/4 cholestatic liver injury, and of liver failure, as per the Common Terminology Criteria for Adverse Events (CTCAE) version 5, following treatment with ICIs. We compared these occurrences with a group of cancer patients who were propensity-matched and treated with conventional chemotherapy. For all ICI patients experiencing grade 3/4 liver injury, we conducted a causality assessment using the RUCAM method and examined patient outcomes. Results: Among 952 patients (median [IQR] age 66 [57-73] years, 64% males) who were treated with ICI between January 1, 2015, and December 31, 2019, a total of 86 (9%) progressed to grade 3/4 liver injury, and liver failure was not observed. Anti-PD-(L)1/anti-CTLA-4 antibodies combinations (adjusted hazard ratio 3.36 [95% CI: 1.67-6.79]; p <0.001), and chronic hepatitis B (adjusted hazard ratio 5.48 [95% CI: 1.62-18.5]; p = 0.006], were independent risk factors. Liver injury was attributed to ICI treatment in 19 (2.0%) patients. Patients with ICI toxicity typically presented with granulomatous hepatitis or cholangiocyte inflammation. ICI withdrawal was associated with cancer progression and mortality. Re-introduction of ICI was not associated with recurrent grade 3/4 liver injury. Compared with matched patients treated with conventional, non-ICI-based chemotherapy, anti-PD-(L)1/anti-CTLA-4 combinations (p <0.001) and anti-PD-(L)1 monotherapies (p = 0.053) increased the risk of grade 3/4 liver injury and of grade 3/4 cholestatic liver injury, respectively. Conclusions: An increased risk of grade 3/4 liver injury under anti-PD-(L)1/anti-CTLA-4 antibodies was observed, whereas no substantial increase in the likelihood of liver failure occurred even after treatment reintroduction. Impact and implications: There is concern about liver injury in patients with cancer exposed to immune checkpoints inhibitors (ICIs). We investigated the burden of grade 3/4 liver injury after treatment with ICIs in a multicentric cohort of patients with cancer. Overall, a 9% incidence of grade 3/4 liver injury was detected after ICIs, and direct ICI hepatotoxicity was demonstrated in 2% of patients. Anti-PD-(L)1/Anti-CTLA-4 antibody combinations, and chronic HBV infection were independent risk factors. ICI withdrawal for grade 3/4 liver injury was associated with cancer progression. Re-introduction of ICI treatment was not associated with recurrent grade 3/4 liver injury.

Cinematic Rendering of Gastrointestinal Stromal Tumors: A Review of Current Possibilities and Future Developments.

Gastrointestinal stromal tumors (GISTs) are defined as CD117-positive primary, spindled or epithelioid, mesenchymal tumors of the gastrointestinal tract, omentum, or mesentery. While computed tomography (CT) is the recommended imaging modality for GISTs, overlap in imaging features between GISTs and other gastrointestinal tumors often make radiological diagnosis and subsequent selection of the optimal therapeutic approach challenging. Cinematic rendering is a novel CT post-processing technique that generates highly photorealistic anatomic images based on a unique lighting model. The global lighting model produces high degrees of surface detail and shadowing effects that generate depth in the final three-dimensional display. Early studies have shown that cinematic rendering produces high-quality images with enhanced detail by comparison with other three-dimensional visualization techniques. Cinematic rendering shows promise in improving the visualization of enhancement patterns and internal architecture of abdominal lesions, local tumor extension, and global disease burden, which may be helpful for lesion characterization and pretreatment planning. This article discusses and illustrates the application of cinematic rendering in the evaluation of GISTs and the unique benefit of using cinematic rendering in the workup of GIST with a specific emphasis on tumor characterization and preoperative planning.

A preoperative computed tomography radiomics model to predict disease-free survival in patients with pancreatic neuroendocrine tumors.

IMPORTANCE: Imaging has demonstrated capabilities in the diagnosis of pancreatic neuroendocrine tumors (pNETs), but its utility for prognostic prediction has not been elucidated yet. OBJECTIVE: The aim of this study was to build a radiomics model using preoperative computed tomography (CT) data that may help predict recurrence-free survival (RFS) or OS in patients with pNET. DESIGN: We performed a retrospective observational study in a cohort of French patients with pNETs. PARTICIPANTS: Patients with surgically resected pNET and available CT examinations were included. INTERVENTIONS: Radiomics features of preoperative CT data were extracted using 3D-Slicer® software with manual segmentation. Discriminant features were selected with penalized regression using least absolute shrinkage and selection operator method with training on the tumor Ki67 rate (≤2 or >2). Selected features were used to build a radiomics index ranging from 0 to 1. OUTCOME AND MEASURE: A receiving operator curve was built to select an optimal cutoff value of the radiomics index to predict patient RFS and OS. Recurrence-free survival and OS were assessed using Kaplan-Meier analysis. RESULTS: Thirty-seven patients (median age, 61 years; 20 men) with 37 pNETs (grade 1, 21/37 [57%]; grade 2, 12/37 [32%]; grade 3, 4/37 [11%]) were included. Patients with a radiomics index >0.4 had a shorter median RFS (36 months; range: 1-133) than those with a radiomics index ≤0.4 (84 months; range: 9-148; P = .013). No associations were found between the radiomics index and OS (P = .86).

Adjuvant chemotherapy benefit according to T and N stage in small bowel adenocarcinoma: a large retrospective multicenter study.

BACKGROUND: Small bowel adenocarcinoma is a rare cancer, and the role of adjuvant chemotherapy for localized disease is still debated. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for localized small bowel adenocarcinoma between 1996 and 2019 from 3 French cohort studies. Prognostic and predictive factors of adjuvant chemotherapy efficacy were analyzed for disease-free survival and overall survival. The inverse probability of treatment weighting method was applied in the Cox regression model using the propensity score derived from multivariable logistic regression. RESULTS: A total of 354 patients were included: median age, 63.5 years; duodenum location, 53.5%; and tumor stage I, II, and III in 31 (8.7%), 144 (40.7%), and 179 (50.6%) patients, respectively. The adjuvant chemotherapy was administered in 0 (0%), 66 (48.5%), and 143 (80.3%) patients with stage I, II, and III, respectively (P < .0001). In the subgroup analysis by inverse probability of treatment weighting method, a statistically significant disease-free survival and overall survival benefit in favor of adjuvant chemotherapy was observed in high-risk stage II (T4 and/or <8 lymph nodes examined) and III (T4 and/or N2) but not for low-risk stage II (T3 and ≥8 lymph nodes examined) and III (T1-3/N1) tumors (Pinteraction < .05). Furthermore, tumor location in jejunum and ileum was also a statistically significant predictive factor of response to adjuvant chemotherapy in stage II and III tumors (Pinteraction < .05). CONCLUSION: In localized small bowel adenocarcinoma, adjuvant chemotherapy seems to provide a statistically significant survival benefit for high-risk stage II and III tumors and for jejunum and ileum tumor locations.

Non eosinophilic chronic stricturing esophagitis: Lessons from thirty eight cases.

BACKGROUND AND AIMS: The endoscopic workup of dysphagia can lead to the diagnosis of atypical esophagitis, with thickened esophageal mucosa, strictures, mucosal exudates, furrows, and sloughing. While these aspects suggest eosinophilic esophagitis, pathology might not report the presence of eosinophils, but rather chronic inflammation, with spongiosis, parakeratosis, and lymphocytic infiltrate. We aimed to report the management of this disease and assess the prevalence of associated dermatological conditions. METHODS: We retrospectively evaluated the medical records of our patients with non-eosinophilic stricturing esophagitis for clinical, endoscopy, and pathology data. Patients were evaluated by a dermatologist. A blood immunoassay and skin biopsy were performed if needed. RESULTS: Thirty-eight patients (twenty-six women) were included in the study. The median age at onset of symptoms was 56.5 years, with a median duration of symptoms of two years. Thirty-five patients presented with dysphagia at diagnosis and eighteen with weight loss. At endoscopy, a single esophageal stenosis was diagnosed in 19 patients, localized in the upper third in 22 patients. Thirty patients received endoscopic treatment (dilatation in 29/38 and local triamcinolone injection in 11/38 patients). In 21 patients, oral, skin or vulvo-anal lesions were found on dermatological examination. Nineteen patients received systemic treatment, including corticosteroids, immunosuppressive drugs and plasmapheresis. Five patients developed esophageal squamous cell carcinoma. CONCLUSION: The management of non-eosinophilic chronic stricturing esophagitis is challenging, because of a low contribution of esophageal biopsies and the refractory nature of the strictures. In our experience, a dermatological evaluation helped in 55% of cases to introduce a systemic treatment, leading to limit the use of endoscopic dilatation. Endoscopic follow-up is needed, considering the significant risk of esophageal squamous cell carcinoma.

Achalasia and Hiatal Hernia: A Rare Association and a Therapeutic Challenge.

Background/Aims: Achalasia and hiatal hernia are rarely associated. The aim of the current study is to explore the clinical and manometric findings in patients with achalasia and hiatal hernia, and to determine if the presence of a hiatal hernia should influence therapeutic management in patients with achalasia. Methods: This retrospective single center analysis included a group of patients with achalasia and hiatal hernia (study group) and a group of matched patients with achalasia but no hiatal hernia (control group). We recorded demographic, clinical, endoscopic, and manometric parameters and compared initial presentation and treatment outcomes between the groups. Results: Between 2015 and 2022, achalasia was diagnosed in 294/1513 (19.4%) patients. Concomitant hiatal hernia was identified in 13/294 (4.4%) patients. Compared to patients with achalasia and no hiatal hernia, patients in the study group had lower Eckardt scores at baseline (5.4 ± 2.0 vs 7.8 ± 2.4; P = 0.005) but similar integrated relaxation pressure. Following treatment, patients in the study and control group had similar clinical success and prevalence of gastroesophageal reflux symptoms. Conclusions: Hiatal hernia is rarely associated with achalasia. The presence of a hiatal hernia should not influence treatment decisions in patients with achalasia.

Beyond atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma: overall efficacy and safety of tyrosine kinase inhibitors in a real-world setting.

Background: In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapeutic sequence is still unclear and no second-line agent has proven its efficacy. Objectives: The aim of this retrospective multicenter real-world cohort study was to provide an evaluation of the efficacy and safety of the use of second-line tyrosine kinase inhibitors (TKIs) in this population. Methods: All patients with advanced HCC, treated in first-line setting by atezolizumab-bevacizumab, and who received at least one dose of treatment with TKI were included in this study. All the data were retrospectively collected from medical records. The primary outcome was progression-free survival (PFS). Secondary outcomes were overall survival (OS), overall global survival (OGS), and safety. A total of 82 patients were included in this study. Results: Patients were assigned to the regorafenib group (n = 29, 35.4%) or other TKI (sorafenib n = 41, lenvatinib n = 8, or cabozantinib n = 4) group (n = 53). PFS was not significantly different between the two groups [2.6 versus 2.8 months, HR 1.07 (95% CI: 0.61-1.86), p = 0.818]. Median PFS rates were 2.6, 4.4, and 2.8 months in sorafenib-, lenvatinib-, and cabozantinib group, respectively. OS was statistically different between the regorafenib group and other TKI group [15.8 versus 7.0 months, HR 0.40 (95% CI: 0.20-0.79), p = 0.023]. When adjusting on confounding factors, there was still a difference in OS favoring the regorafenib group (adjusted hazard ratio 0.35, p = 0.019). OGS of patients who received regorafenib was improved compared to other TKI [18.6 versus 15.0 months, HR 0.42 (95% CI: 0.22-0.84), p = 0.036]. Twenty percent of patients had grade 3 and none had grade 4 or 5 adverse events. In patients who experienced disease progression and fit for a third-line treatment, 80% and 50% received cabozantinib in regorafenib group and other TKI group, respectively. Conclusion: Efficacy of any TKI in the second-line setting was not affected by atezolizumab-bevacizumab treatment as first-line therapy. The safety profile in the second-line setting was consistent with the results shown in pivotal studies. PFS rates of patients were similar, regardless of TKI type. Regorafenib was associated with better OS and OGS rates compared to other TKI. These data need to be confirmed in prospective comparative studies.