Correlation of Ultrasound Scores with Endoscopic Activity in Crohn's Disease: A Prospective Exploratory Study.

BACKGROUND AND AIMS: Intestinal ultrasound [IUS] is widely accepted as a reliable tool to monitor Crohn's disease [CD]. Several IUS scores have been proposed, but none has been formally accepted by international organizations. Our aim here was to compare the available scores regarding their correlation with endoscopic activity. METHODS: Consenting CD patients undergoing ileocolonoscopy at our Unit between September 2021 and February 2023 were included. Endoscopic activity was defined as SES-CD ≥ 3 or Rutgeerts score ≥ i2b for operated patients. IUS was performed within 6 weeks of endoscopy and scored with IBUS-SAS, BUSS, Simple-US and SUS-CD scores. All correlations were performed using Spearman's rank coefficient [rho = ρ]. Receiver operating characteristic [ROC] curves were compared with the Hanley and McNeil method. RESULTS: Of 73 CD patients, 45 [61.6%] presented endoscopic activity, of whom 22 were severe [30.1%]. All IUS scores showed a significant positive correlation with endoscopy [p < 0.0001], with IBUS-SAS ranking the highest [ρ = 0.87]. Similarly, IBUS-SAS was the most highly correlated with clinical activity [ρ = 0.58]. ROC analysis of IBUS-SAS for any endoscopic activity showed the highest area under the curve (0.95 [95% confidence interval 0.87-0.99]), with sensitivity of 82.2% and specificity of 100% for a cut-off value of 25.2. IBUS-SAS was statistically superior to all the other scores in detecting severe endoscopic activity [SES-CD ≥ 9 or Rutgeerts i4]. CONCLUSIONS: All IUS scores provided solid correlation with endoscopy and clinical symptoms. IBUS-SAS outperformed the others due to a more granular description that might help in stratifying different levels of disease activity. Therefore, the use of IBUS-SAS in centres with well-founded expertise in IUS can be suggested.

Understanding fatigue in primary biliary cholangitis: From pathophysiology to treatment perspectives.

Fatigue is considered one of the most frequent and debilitating symptoms in primary biliary cholangitis (PBC), affecting over 50% of PBC patients. One in five patients with PBC suffer from severe fatigue, which significantly impairs quality of life. Fatigue is made up of a central and a peripheral component, whose pathophysiology is still greatly unresolved. Central fatigue is characterised by a lack of self-motivation and can manifest both in physical and mental activities (lack of intention). Peripheral fatigue includes neuromuscular dysfunction and muscle weakness (lack of ability). Peripheral fatigue could be explained by an excessive deviation from aerobic to anaerobic metabolism leading to excessive lactic acid accumulation and therefore accelerated decline in muscle function and prolonged recovery time. As opposed to itching, and with the exception of end-stage liver disease, fatigue is not related to disease progression. The objective of this review is to outline current understanding regarding the pathophysiology of fatigue, the role of comorbidities and contributing factors, the main tools for fatigue assessment, the failed therapeutic options, and future treatment perspectives for this disabling symptom. Since fatigue is an extremely common and debilitating symptom and there is still no licensed therapy for fatigue in PBC patients, further research is warranted to understand its causative mechanisms and to find an effective treatment.

Higher volume growth rate is associated with development of worrisome features in patients with branch duct-intraductal papillary mucinous neoplasms.

BACKGROUND: Branch duct-intraductal papillary mucinous neoplasms (BD-IPMNs) are the most common pancreatic cystic tumours and have a low risk of malignant transformation. Current guidelines only evaluate cyst diameter as an important risk factor but it is not always easy to measure, especially when comparing different methods. On the other side, cyst volume is a new parameter with low inter-observer variability and is highly reproducible over time. AIM: To assess both diameter and volume growth rate of BD-IPMNs and evaluate their correlation with the development of malignant characteristics. METHODS: Computed tomography scans and magnetic resonance imaging exams were retrospectively reviewed. The diameter was measured on three planes, while the volume was calculated by segmentation: The volume of the entire cyst was determined by manually drawing a region of interest along the edge of the neoplasm on each consecutive slice covering the whole lesion; therefore, a three-dimensional volume of interest was finally obtained with the calculated value expressed in cm3. Changes in size over time were measured. The development of worrisome features was evaluated. RESULTS: We evaluated exams of 98 patients across a 40.5-mo median follow-up time. Ten patients developed worrisome features. Cysts at baseline were significantly larger in patients who developed worrisome features (diameters P = 0.0035, P = 0.00652, P = 0.00424; volume P = 0.00222). Volume growth rate was significantly higher in patients who developed worrisome features (1.12 cm3/year vs 0 cm3/year, P = 0.0001); diameter growth rate was higher as well, but the difference did not always reach statistical significance. Volume but not diameter growth rate in the first year of follow-up was higher in patients who developed worrisome features (0.46 cm3/year vs 0 cm3/year, P = 0.00634). CONCLUSION: The measurement of baseline volume and its variation over time is a reliable tool for the follow-up of BD-IPMNs. Volume measurement could be a better tool than diameter measurement to predict the development of worrisome features.

Stevens-Johnson Syndrome and Herpes Simplex Type 1 Infection during Adalimumab Therapy for Crohn's Disease.

Stevens-Johnson syndrome (SJS) is a severe mucocutaneous adverse drug reaction with a relatively high mortality rate. SJS is described during herpes simplex virus type 1 (HSV1) infection and, rarely, even during adalimumab therapy. We report the case of a patient with Crohn's disease who developed SJS during an HSV1 infection and a contemporaneous anti-TNFα therapy with adalimumab. Remission was achieved with suspension of adalimumab and high doses of intravenous steroids and antivirals. Patients with HSV1 infection and on adalimumab therapy have a combined risk of SJS and should be monitored closely.

Computed tomography or contrast-enhanced ultrasonography for follow-up of liver metastases after Cyberknife therapy?: A prospective pilot study.

OBJECTIVES: Contrast-enhanced ultrasonography (CEUS) allows the study of vascularization of secondary liver lesions. The Cyberknife (Accuray, Inc, Sunnyvale, CA) is a therapeutic method that allows a tumor target to be subjected to a high radiant dose gradient. This prospective pilot study aimed to demonstrate the concordance of CEUS versus contrast-enhanced computed tomography (CECT) in determining the stability or disease progression of secondary liver lesions after treatment with the Cyberknife. METHODS: Twenty-four patients were consecutively enrolled, and 3 different operators evaluated the CEUS images and the intermodality concordance with CECT. All patients received CEUS at 1 and 2 months after the Cyberknife therapy. The intermodality agreement was evaluated by the Cohen κ coefficient and a multivariate analysis according to the method of Janson and Olsson (Educ Psychol Meas 2001; 61:277-289). RESULTS: Forty secondary liver lesions were detected and treated. Forty-one CECT and 51 CEUS examinations were performed without any adverse events in the 24 patients. The intermodality agreement rates, calculated for the operators as Cohen κ values, were κ = 1.00, 0.881, and 0.767, respectively. The multivariate analysis of intermodality agreement showed an almost perfect value (ι = 0.841). CONCLUSIONS: This pilot study found excellent diagnostic correspondence between CEUS and CECT in the evaluation of local disease stability or progression after Cyberknife therapy in liver metastases. These findings suggest that CEUS could play an important role in the surveillance of these patients because of its high accuracy and reproducibility, thus reducing the need for CECT.

Metabolic Signature of Primary Biliary Cholangitis and Its Comparison with Celiac Disease.

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by ongoing inflammatory destruction of the interlobular bile ducts, eventually leading to chronic cholestasis and biliary cirrhosis. This study primarily aims to define the metabolomic signature of PBC after comparison with healthy controls (HC). Second, it aims to evaluate the possible metabolic association between PBC and celiac disease (CD), an immune-mediated disorder frequently associated with PBC. Serum and urine samples from 20 PBC, 21 CD, and 19 sex-matched HC subjects were collected. 1H nuclear magnetic resonance (NMR) spectra for all samples were acquired, and multivariate statistics were used to evaluate the differences among the three groups and to provide information about the involved metabolites. The classification accuracies to discriminate PBC and HC groups were 78.9-84.6% for serum and 76.9% for urine. In comparison to HC, PBC patient sera were characterized by altered levels ( p value <0.05) of pyruvate, citrate, glutamate, glutamine, serine, tyrosine, phenylalanine, and lactate. PBC patient urine showed lower levels ( p value <0.05) of trigonelline and hippurate with respect to HC. Furthermore, the NMR metabolomic fingerprint was able to cluster PBC with respect to CD patients, and the classification accuracies in the discriminations between these groups were 81.9-91.7% for serum and 77.7% for urine. Our results show that PBC displays a unique metabolomic fingerprint, which led to speculation about an impaired energy metabolism, probably associated with an altered gut microbiota. PBC and CD showed two distinct metabolic fingerprints. These data could provide clues for the comprehension of the PBC pathogenetic mechanisms and the detection of novel therapeutic targets.

Chemotherapy for hepatocellular carcinoma: The present and the future.

Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver. Its relationship to chronic liver diseases, in particular cirrhosis, develops on a background of viral hepatitis, excessive alcohol intake or metabolic steatohepatitis, leads to a high incidence and prevalence of this neoplasia worldwide. Despite the spread of HCC, its treatment it's still a hard challenge, due to high rate of late diagnosis and to lack of therapeutic options for advanced disease. In fact radical surgery and liver transplantation, the most radical therapeutic approaches, are indicated only in case of early diagnosis. Even local therapies, such as transarterial chemoembolization, find limited indications, leading to an important problem regarding treatment of advanced disease. In this situation, until terminal HCC occurs, systemic therapy is the only possible approach, with sorafenib as the only standard treatment available. Anyway, the efficacy of this drug is limited and many efforts are necessary to understand who could benefit more with this treatment. Therefore, other molecules for a targeted therapy were evaluated, but only regorafenib showed promising results. Beside molecular target therapy, also cytotoxic drugs, in particular oxaliplatin- and gemcitabine-based regimens, and immune-checkpoint inhibitors were tested with interesting results. The future of the treatment of this neoplasia is linked to our ability to understand its mechanisms of resistance and to find novel therapeutic targets, with the objective to purpose individualized approaches to patients affected by advanced HCC.

Percutaneous ultrasound-guided fiducial marker placement for liver cancer robotic stereotactic radio-surgery treatment: A comparative analysis of three types of markers and needles.

BACKGROUND AND STUDY AIMS: Percutaneous placement of fiducial markers is required to perform stereotactic body radiation therapy (SBRT) for liver neoplastic lesions. This prospective trial was designed to evaluate the feasibility and safety of percutaneous ultrasound-guided placement of three different types of markers in patients with liver cancer referred for SBRT. PATIENTS AND METHODS: Fifty patients underwent percutaneous ultrasound-guided implantation of a fiducial marker in the liver. Three sizes of needles were used: 25 gauge (G), 22G, and 17G. The 25G and 22G needles contained gold anchor markers of 0.28×10mm and 0.4 ×10mm size, respectively. In contrast, the 17G needle contained a gold grain marker of 1×4mm. Each patient received 1-6 markers, depending on lesion size and numbers. Technical feasibility and the occurrence of adverse events were registered. Computed tomography scans were acquired prior to SBRT to evaluate the location, visibility, or complications related to the markers. RESULTS: A total of 163 needles were used to deliver 163 markers in 50 patients. No major complications occurred. Minor complication occurrence rate was 12%. The total complication occurrence for all type of markers was 8.5%. No complications were observed with the use of the gold anchor marker of 0.4 ×10mm size. Variance analysis of the three markers showed a significant difference in the frequency of complications amongst the three markers (p<0.01). CONCLUSION: Percutaneous ultrasound-guided placement of fiducial markers for SBRT of liver neoplastic lesions is safe and feasible. In our series, the 22G needle showed some advantage in terms of handling and safety when compared with the 25G and 17G needles. In addition, the gold anchor marker of 0.4 ×10mm size displayed a lower percentage of displacement.

Metabolomic analysis with 1H-NMR for non-invasive diagnosis of hepatic fibrosis degree in patients with chronic hepatitis C.

BACKGROUND: The assessment of fibrosis degree in liver diseases is based on several non-invasive techniques, but none has been accurate. AIM: This study employed proton nuclear magnetic resonance spectroscopy to identify metabolic profiles in serum and urine, specific for different fibrosis degree in chronic hepatitis C patients. METHOD: 71 plasma, 73 serum, and 578 urine samples were collected. All samples were analyzed using 1H-NMR spectroscopy technique and three different NMR spectra were acquired for each serum/plasma sample. The data analyses were performed by partial least square regression, principal component analysis, and Monte Carlo cross-validation in a supervised methodology. RESULTS: The cross-validation test correctly assigned each sample to its specific donor with 98.44% accuracy for urine samples and 65% for serum/plasma samples. Advanced fibrosis and cirrhosis were recognized with 71% sensitivity for CPMG plasma spectra and 69% specificity for NOESY serum spectra. Accuracy for NOESY serum spectra was 68%. Noesy spectra recognized advanced fibrosis and cirrhosis with 71% sensitivity, 30% specificity, and 50% accuracy in urine samples. CONCLUSION: Metabolomic analysis of urine spectra using 1H-NMR spectroscopy can recognize a specific individual profile in all patients with chronic hepatitis C. However, this method cannot yet differentiate with sufficient accuracy, patients with advanced fibrosis from patients with milder disease.

Gastric and duodenal polyps in familial adenomatous polyposis patients: Conventional endoscopy vs virtual chromoendoscopy (fujinon intelligent color enhancement) in dysplasia evaluation.

AIM: To test the fujinon intelligent color enhancement (FICE) in identifying dysplastic or adenomatous polyps in familial adenomatous polyposis (FAP) patients. METHODS: Seventy-six consecutive FAP patients, already treated by colectomy and members of sixty-five families, were enrolled. A FICE system for the upper gastro-intestinal tract with an electronic endoscope system and a standard duodenoscope (for side-viewing examination) were used by two expert examiners. Endoscopic resection was performed with diathermic loop for polyps ≥ 6 mm and with forceps for polyps < 6 mm. Formalin-fixed biopsy specimens were analyzed by two expert gastrointestinal pathologists blinded to size, location and number of FAP-associated fundic gland polyps. RESULTS: Sixty-nine (90.8%) patients had gastric polyps (34 only in the corpus-fundus, 7 only in the antrum and 28 in the whole stomach) and 52 (68.4%) in duodenum (7 in the bulb, 35 in second/third duodenal portion, 10 both in the bulb and the second portion of duodenum). In the stomach fundus after FICE evaluation, 10 more polyps were removed from 10 patients for suspicious features of dysplasia or adenomas, but they were classified as cystic fundic gland after histology. In the antrum FICE identified more polyps than traditional endoscopy, showing a better tendency to identify adenomas and displastic areas. In the duodenum FICE added a significant advantage in identifying adenomas in the bulb and identified more polyps in the II/III portion. CONCLUSION: FICE significantly increases adenoma detection rate in FAP patients but does not change any Spigelman stage and thus does not modify patient's prognosis and treatment strategies.

Factors Predictive of Improved Abdominal Ultrasound Visualization after Oral Administration of Simethicone.

Ultrasonography is a non-invasive, accurate and low-cost technique used to study the upper abdomen, but it has reduced reliability in the study of the pancreas and retroperitoneum. Simethicone is a well-known emulsifying agent that has been used to improve ultrasonographic visualization. The aim of this study was to identify anthropometric parameters that are able to predict a good response to simethicone in improving ultrasonographic visualization of abdominal structures. One hundred twenty-seven patients were recruited. After basal examination, their anthropometric parameters were collected. Patients with an incomplete upper abdominal examination because of gastrointestinal gas have greater body mass index, waist circumference and abdominal wall thickness. In our study, the best anthropometric parameter for identifying patients with poor visualization at abdominal ultrasound examination is waist circumference. Using a cutoff of 84 cm, we can identify patients with poor visibility at abdominal ultrasound examination (group B) with a sensitivity of 90%.

Therapeutic usability of two different fiducial gold markers for robotic stereotactic radiosurgery of liver malignancies: A pilot study.

AIM: To assess how the application of different types of markers affects the tracking accuracy of CyberKnife's. METHODS: Fifteen patients were recruited and subjected to the ultrasound-guided placement of markers. Two different type of needles 25 gauge (G) and 17 G containing two different fiducial marker, gold notched flexible anchor wire 0.28 mm × 10 mm (25 G needle) and gold cylindrical grain 1 mm × 4 mm (17 G), were used. Seven days after the procedure, a CyberKnife planning computed tomography (CT) for the simulation of radiation treatment was performed on all patients. A binary CT score was assigned to the fiducial markers visualization. Also, the CT number was calculated for each fiducial and the values compared with a specific threshold. RESULTS: For each patient from 1 to 5, intra-hepatic markers were placed (one in 2 patients, three in 8 patients, four in 3 patients, and five in 2 patients). A total of 48 needles were used (thirty-two 17 G and sixteen 25 G) and 48 gold markers were placed (32 Grain shaped markers and 16 Gold Anchor). The result showed that the CT visualization of the grain markers was better than the anchor markers (P = 5 × 10(-9)). Furthermore, the grain markers were shown to present minor late complications (P = 3 × 10(-6)), and the best CT threshold number (P = 0.0005). CONCLUSION: The study revealed that the Gold Anchor fiducial marker is correlated with a greater number of late minor complications and low visualization by the CT.

Assessment of liver fibrosis in primary biliary cholangitis: Comparison between indirect serum markers and fibrosis morphometry.

BACKGROUND: The accuracy of non-invasive methods for the quantification of liver fibrosis in primary biliary cholangitis (PBC) is still debated. AIMS: To determine the histo-morphometric measurement of fibrotic tissue and to explore the possible association between indirect markers (APRI, FORNS, FIB-4, and Lok) and morphometry. METHODS: Retrospective analysis of medical data from patients with PBC, on whom needle liver biopsy was performed as part of the diagnostic assessment. One section of each biopsy stained with Sirius red was used for calculating the percentage of collagen. Quantitative measure of fibrotic tissue (fibrosis morphometry) was calculated as a percentage of collagen content by digital image analysis. Morphometry results were divided into four groups reflecting Ludwig's staging and compared with values for indirect serum markers. RESULTS: 50 PBC patients were enrolled (86% females, mean age 57 ± 12.30 years), 19 were Ludwig's stage I (38%), 14 stage II (28%), 12 stage III (24%), and five stage IV (10%). Morphometry results were significantly different among Ludwig stages (p<0.05). No significant differences were found for indirect serum markers. A significant correlation was found between morphometry results and indirect serum markers tested (p<0.05). CONCLUSION: In our cohort, the histo-morphometric values of fibrotic tissue increased progressively with Ludwig's stages of PBC, while non-invasive markers did not.

Survival after laparoscopic and open surgery for colon cancer: a comparative, single-institution study.

BACKGROUND: Some recent studies have suggested that laparoscopic surgery for colorectal cancer may provide a potential survival advantage when compared with open surgery. This study aimed to compare cancer-related survivals of patients who underwent laparoscopic or open resection of colon cancer in the same, high volume tertiary center. METHODS: Patients who had undergone elective open or laparoscopic surgery for colon cancer between January 2002 and December 2010 were analyzed. A clinical database was prospectively compiled. Survival analysis was calculated by using the Kaplan-Meier method. RESULTS: A total of 460 resections were performed. There were no significant differences between the laparoscopic (n = 227) and the open group (n = 233) apart from tumor stage: stage I tumors were more frequent in the laparoscopic group whereas stage II tumors were more frequent in the open group. The mean number of harvested lymph nodes was significantly higher in the laparoscopic than in the open group (20.0 ± 0.7 vs 14.2 ± 0.5, P < 0.01). The 5-year cancer-related survival for patients undergoing laparoscopic resection was significantly higher than that following open resections (83.1% vs 68.5%, P = 0.01). By performing a stage-to-stage comparison, we found that the improvement in survival in the laparoscopic group occurred mainly in patients with stage II tumors. CONCLUSIONS: Our study shows a survival advantage for patients who had undergone laparoscopic surgery for stage II colon cancer. This may be correlated with a higher number of harvested lymph nodes and thus a better stage stratification of these patients.

Laparoscopic total gastrectomy using the transorally inserted anvil (OrVil™): a preliminary, single institution experience.

Laparoscopic total gastrectomy (LTG) is not a commonly performed procedure due to the difficulty associated with surgical reconstruction. We present our preliminary results after intracorporeal circular stapling esophagojejunostomy using the newly developed transorally inserted anvil (OrVil™, Covidien, MA, USA). Between 2008 and June 2013, 51 patients underwent laparoscopic gastrectomy with D2 lymph node dissection for gastric cancer. A total of 12 patients underwent LTG: of these, 5 received an intracorporeal linear side-to-side esophagojejunal anastomosis and the remaining 7 underwent intracorporeal circular stapling esophagojejunostomy using the OrVil™ system. Short-term outcomes were compared between the two groups. There were no intraoperative complications or conversions to open surgery in any patients. The mean operative time was significantly shorter in the OrVil™ than in the side-to-side group (261.4 ± 12.0 vs 333.0 ± 15.0 minutes, respectively, p = 0.005). Postoperative fluorography revealed no anastomosis leakage or stenosis in either groups. All patients resumed an oral liquid diet on postoperative day 5 and the mean postoperative hospital stay was 9 days. Intracorporeal circular stapling esophagojejunostomy using the OrVil™ system is technically feasible and safe in LTG. This technique may be considered a simple and time-saving alternative to the side-to-side linear esophagojejunostomy.

Endoscopic ultrasonography for surveillance of individuals at high risk for pancreatic cancer.

Pancreatic cancer is a highly lethal disease with a genetic susceptibility and familial aggregation found in 3%-16% of patients. Early diagnosis remains the only hope for curative treatment and improvement of prognosis. This can be reached by the implementation of an intensive screening program, actually recommended for individuals at high-risk for pancreatic cancer development. The aim of this strategy is to identify pre-malignant precursors or asymptomatic pancreatic cancer lesions, curable by surgery. Endoscopic ultrasound (EUS) with or without fine needle aspiration (FNA) seems to be the most promising technique for early detection of pancreatic cancer. It has been described as a highly sensitive and accurate tool, especially for small and cystic lesions. Pancreatic intraepithelial neoplasia, a precursor lesion which is highly represented in high-risk individuals, seems to have characteristics chronic pancreatitis-like changes well detected by EUS. Many screening protocols have demonstrated high diagnostic yields for pancreatic pre-malignant lesions, allowing prophylactic pancreatectomies. However, it shows a high interobserver variety even among experienced endosonographers and a low sensitivity in case of chronic pancreatitis. Some new techniques such as contrast-enhanced harmonic EUS, computer-aided diagnostic techniques, confocal laser endomicroscopy miniprobe and the detection of DNA abnormalities or protein markers by FNA, promise improvement of the diagnostic yield of EUS. As the resolution of imaging improves and as our knowledge of precursor lesions grows, we believe that EUS could become the most suitable method to detect curable pancreatic neoplasms in correctly identified asymptomatic at-risk patients.

Totally laparoscopic versus open gastrectomy for gastric cancer: a matched cohort study.

BACKGROUND: The role of laparoscopic surgery for the treatment of gastric cancer is still controversial, particularly in terms of oncologic efficacy. The aim of this study was to compare short-term outcomes of laparoscopic and open resection for gastric cancer at a single Western institution. SUBJECTS AND METHODS: This study was designed as a matched cohort study from a prospective gastric cancer database. Forty-one patients undergoing laparoscopic gastrectomy for gastric cancer between June 2008 and January 2012 were matched with 41 patients undergoing open gastrectomy in the same time period. Patient pairing was done according to age, gender, type of gastrectomy (subtotal or total), and tumor stage via a randomized statistical method. The short-term outcomes and oncologic adequacy of the laparoscopic and open procedures were compared. A D2 lymph node dissection was performed in the majority of patients in both groups. RESULTS: The two study groups were similar with respect to patient and tumor characteristics. Laparoscopic procedures were associated with a decreased blood loss (118.7 versus 312.4 mL, P<.005), incidence of surgery-unrelated complications (3 versus 9 patients, P<.05), and duration of hospital stay (8.1 versus 11.5 days, P<.05) but increased operative time for both subtotal (223.5 versus 158.2 minutes, P<.001) and total (298.1 versus 185.5 minutes, P<.001) gastrectomies. The mean number of retrieved lymph nodes after D2 dissection was similar: 30.0 for laparoscopic and 29.7 for open patients. CONCLUSIONS: Within the limitations of a nonrandomized analysis, this study shows that the laparoscopic approach is a safe and oncologically adequate option for the treatment of gastric cancer, which compares favorably with open gastrectomy in short-term outcomes.