Project description:ObjectiveAutoimmune pancreatitis (AIP) is a treatable form of chronic pancreatitis that has been increasingly recognised over the last decade. We set out to better understand the current burden of AIP at several academic institutions diagnosed using the International Consensus Diagnostic Criteria, and to describe long-term outcomes, including organs involved, treatments, relapse frequency and long-term sequelae.Design23 institutions from 10 different countries participated in this multinational analysis. A total of 1064 patients meeting the International Consensus Diagnostic Criteria for type 1 (n=978) or type 2 (n=86) AIP were included. Data regarding treatments, relapses and sequelae were obtained.ResultsThe majority of patients with type 1 (99%) and type 2 (92%) AIP who were treated with steroids went into clinical remission. Most patients with jaundice required biliary stent placement (71% of type 1 and 77% of type 2 AIP). Relapses were more common in patients with type 1 (31%) versus type 2 AIP (9%, p<0.001), especially those with IgG4-related sclerosing cholangitis (56% vs 26%, p<0.001). Relapses typically occurred in the pancreas or biliary tree. Retreatment with steroids remained effective at inducing remission with or without alternative treatment, such as azathioprine. Pancreatic duct stones and cancer were uncommon sequelae in type 1 AIP and did not occur in type 2 AIP during the study period.ConclusionsAIP is a global disease which uniformly displays a high response to steroid treatment and tendency to relapse in the pancreas and biliary tree. Potential long-term sequelae include pancreatic duct stones and malignancy, however they were uncommon during the study period and require additional follow-up. Additional studies investigating prevention and treatment of disease relapses are needed.
Project description:BackgroundCharacterized by spindle cell composition in hepatocellular carcinoma tumor, sarcomatoid hepatocellular carcinoma (SHC) is a rare malignant with poor prognosis. In this study, we aimed to evaluate the clinical and pathological features of SHC and establish a nomogram that can predict long-term outcomes of the disease.MethodsWe retrospectively analyzed 63 patients who were diagnosed with SHC between October 2007 and November 2016 and used immunohistochemistry (IHC) to assessed various markers in liver samples. The clinical data and the histological and pathological findings were collected and used to build a nomogram to predict survival.ResultsThe median overall survival (OS) and the recurrence-free survival (RFS) in SHC were 23.2 and 8.4 months, respectively. High expression levels of tyrosine-protein kinase Met (17/63, 27.0%) were associated with poorer RFS (P=0.040). A panel of markers, consisting heat-shock protein 70 (HSP70), glutamine synthetase (GS), and glypican-3 (GPC3), merged as an independent risk factor for treatment outcomes. The nomogram, which including this panel of markers, predicted OS times with a concordance-index (C-index) score of 0.758 (95% CI: 0.672-0.843) in the training set and 0.832 (95% CI: 0.712-0.952) in the validation set. The use of the nomogram showed marked improvements in the prediction of patient outcomes compared with conventional staging systems (P<0.05).ConclusionsDiagnosis of SHC is rare and has a relatively poor prognosis. A panel of markers HSP70, GS and GPC3 served as an independent prognostic factor for SHC.
Project description:BackgroundThe growing demand for surgical resection in elderly patients with hepatocellular carcinoma highlights the need to understand the impact of preoperative frailty on surgical outcomes. The aim of this multicentre cohort study was to investigate the association between frailty and short- and long-term outcomes after hepatic resection among elderly patients with hepatocellular carcinoma.MethodsA multicentre analysis was conducted on elderly patients with hepatocellular carcinoma (aged greater than or equal to 70 years) who underwent curative-intent resection at ten Chinese hospitals from 2012 to 2021. Frailty was assessed using the Clinical Frailty Scale (with frailty defined as a Clinical Frailty Scale score greater than or equal to 5). The primary outcomes were overall survival and recurrence-free survival; secondary outcomes encompassed postoperative 30-day morbidity and mortality, and 90-day mortality. The outcomes between patients with and without preoperative frailty were compared.ResultsOf the 488 elderly patients, 148 (30.3%) were considered frail. Frail patients experienced significantly higher 30-day morbidity (68.9% (102 of 148) versus 43.2% (147 of 340)), 30-day mortality (4.1% (6 of 148) versus 0.6% (2 of 340)), and 90-day mortality (6.1% (9 of 148) versus 0.9% (3 of 340)) compared with non-frail patients (all P < 0.010). During a median follow-up of 37.7 (interquartile range 20.4-57.8) months, frail patients demonstrated significantly worse median overall survival (41.6 (95% c.i. 32.0 to 51.2) versus 69.7 (95% c.i. 55.6 to 83.8) months) and recurrence-free survival (27.6 (95% c.i. 23.1 to 32.1) versus 42.7 (95% c.i. 34.6 to 50.8) months) compared with non-frail patients (both P < 0.010). Multivariable Cox regression analysis revealed frailty as an independent risk factor for decreased overall survival (HR 1.61; P = 0.001) and decreased recurrence-free survival (HR 1.32; P = 0.028).ConclusionFrailty is significantly associated with adverse short-term and long-term outcomes after resection in elderly patients with hepatocellular carcinoma. The findings suggest that frailty assessment should be incorporated into perioperative and postoperative evaluation for elderly patients undergoing hepatocellular carcinoma resection.
Project description:BackgroundThere is no consensus on the effect of sorafenib dosing on efficacy and toxicity in elderly patients with hepatocellular carcinoma (HCC). Older patients are often empirically started on low-dose therapy with the aim to avoid toxicities while maximising clinical efficacy. We aimed to verify whether age impacts on overall survival (OS) and whether a reduced starting dose impacts on OS or toxicity experienced by the elderly.MethodsIn an international, multicentre cohort study, outcomes for those aged <75 or ≥75 years were determined while accounting for common prognostic factors and demographic characteristics in univariable and multivariable models.ResultsFive thousand five hundred and ninety-eight patients were recruited; 792 (14.1%) were aged ≥75 years. The elderly were more likely to have larger tumours (>7 cm) (39 vs 33%, p < 0.01) with preserved liver function (67 vs 57.7%) (p < 0.01). No difference in the median OS of those aged ≥75 years and <75 was noted (7.3 months vs 7.2 months; HR 1.00 (95% CI 0.93-1.08), p = 0.97). There was no relationship between starting dose of sorafenib 800 mg vs 400 mg/200 mg and OS between those <75 and ≥75 years. The elderly experienced a similar overall incidence of grade 2-4 sorafenib-related toxicity compared to <75 years (63.5 vs 56.7%, p = 0.11). However, the elderly were more likely to discontinue sorafenib due to toxicity (27.0 vs 21.6%, p < 0.01). This did not vary between different starting doses of sorafenib.ConclusionsClinical outcomes in the elderly is equivalent to patients aged <75 years, independent of dose of sorafenib prescribed.
Project description:AimsChildren presenting with hypertrophic cardiomyopathy (HCM) in infancy are reported to have a poor prognosis, but this heterogeneous group has not been systematically characterized. This study aimed to describe the aetiology, phenotype, and outcomes of infantile HCM in a well-characterized multicentre European cohort.Methods and resultsOf 301 children diagnosed with infantile HCM between 1987 and 2019 presenting to 17 European centres [male n = 187 (62.1%)], underlying aetiology was non-syndromic (n = 138, 45.6%), RASopathy (n = 101, 33.6%), or inborn error of metabolism (IEM) (n = 49, 16.3%). The most common reasons for presentation were symptoms (n = 77, 29.3%), which were more prevalent in those with syndromic disease (n = 62, 61.4%, P < 0.001), and an isolated murmur (n = 75, 28.5%). One hundred and sixty-one (53.5%) had one or more co-morbidities. Genetic testing was performed in 163 (54.2%) patients, with a disease-causing variant identified in 115 (70.6%). Over median follow-up of 4.1 years, 50 (16.6%) underwent one or more surgical interventions; 15 (5.0%) had an arrhythmic event (6 in the first year of life); and 48 (15.9%) died, with an overall 5 year survival of 85%. Predictors of all-cause mortality were an underlying diagnosis of IEM [hazard ratio (HR) 4.4, P = 0.070], cardiac symptoms (HR 3.2, P = 0.005), and impaired left ventricular systolic function (HR 3.0, P = 0.028).ConclusionsThis large, multicentre study of infantile HCM describes a complex cohort of patients with a diverse phenotypic spectrum and clinical course. Although overall outcomes were poor, this was largely related to underlying aetiology emphasizing the importance of comprehensive aetiological investigations, including genetic testing, in infantile HCM.
Project description:Hepatocellular carcinoma (HCC) is the most common malignancy in the elderly worldwide, but it is also common among younger individuals in areas with endemic hepatitis B virus infection. The differences in long-term oncological prognosis of young versus elderly patients after R0 liver resection for HCC were explored in this study. Using a Chinese multicentre database, consecutive patients who underwent R0 liver resection for HCC between 2007 and 2019 were analysed retrospectively. After excluding middle-aged (36-69 years old) patients, overall survival (OS), cancer-specific survival (CSS), and recurrence were compared between young (35 years or younger) and elderly (70 years or older) patients using propensity score matching (PSM). Among 531 enrolled patients, there were 192 (36.2 per cent) and 339 (63.8 per cent) patients categorized as young and elderly respectively. PSM created 140 pairs of matched patients. In the PSM cohort, 5-year OS was comparable for young versus elderly patients (51.7 versus 52.3 per cent, P = 0.533). Young patients, however, had a higher 5-year cumulative recurrence rate (62.1 versus 51.6 per cent, P = 0.011) and a worse 5-year CSS rate (54.0 versus 64.3 per cent, P = 0.034) than elderly patients. On multivariable Cox regression analyses, young patient age remained independently associated with an increased recurrence rate (hazard ratio 1.62, P = 0.016) and a decreased CSS rate (hazard ratio 1.69, P = 0.021) compared with older age. Following R0 liver resection for HCC, younger patients were at a higher risk of recurrence, and elderly patients had a better CSS rate. Thus, enhanced surveillance for HCC recurrence should be implemented for young patients.
Project description:Background and aimsTo evaluate long-term outcomes and prognostic factors of laparoscopic microwave ablation as a first-line treatment for hepatocellular carcinoma located at the liver surface not feasible for percutaneous ablation.Methods51 consecutive patients receiving laparoscopic microwave ablation in our center between January 11, 2012, and July 31, 2014, were enrolled. Technique effectiveness (complete ablation or incomplete ablation) was evaluated 1 month postprocedure. Procedure-related complications were recorded. The influences of patients' baseline characteristics on recurrence-free survival and overall survival were analyzed after a median follow-up of 34.0 (ranging 19.0-49.0) months.ResultsComplete ablation was gained in 47 (92.2%) of the 51 patients. No patients died within 30 days of microwave ablation procedure. A total of 3 (5.9%) cases of complications were observed. Tumor progression/recurrence were observed in 40 patients (78.4%). The median recurrence-free survival and median overall survival of the total cohort was 11.0 months (95% confidence interval: 7.573-14.427) and 34.0 months (95% confidence interval: 27.244-40.756), respectively. Multivariate analysis identified alanine transaminase level and tumor number as independent significant prognosticators of recurrence-free survival whereas α-fetoprotein level as significant prognosticators of overall survival.ConclusionsAs a first-line treatment, laparoscopic microwave ablation provides high technique effectiveness rate and is well tolerated in patients with hepatocellular carcinoma located at liver surface. Alanine transaminase and tumor number were significant predictors of recurrence-free survival, whereas α-fetoprotein level was significant predictor of overall survival. Laparoscopic microwave ablation might serve as a rational treatment option for patients with hepatocellular carcinoma with tumors at the liver surface, which merits validation in future perspective studies.
Project description:BackgroundThe 2-week schedule of hypofractionated radiotherapy as a salvage treatment for hepatocellular carcinoma (HCC) has previously exhibited promising results; this study aimed to assess its long-term clinical outcomes in patients with recurrent HCC ineligible for curative treatments.MethodsWe retrospectively enrolled 77 patients (84 lesions) with HCC who were treated with hypofractionated radiotherapy between December 2008 and July 2013. Primary inclusion criteria were HCC unsuitable for curative treatments and HCC located within 2 cm of a critical normal organ. We administered 3.5-5 Gy/fraction for 2 weeks, resulting in a total dose of 35-50 Gy.ResultsThe median follow-up period was 33.6 (range, 4.8-78.3) months. The 3- and 5-year overall survival rates were 52.3% and 40.9%, respectively, and local control rates were 79.5% and 72.6% in all treated lesions, respectively. The 5-year local control rate was better in the higher radiation dose group than in the lower radiation dose group (50 Gy: 79.7% vs. < 50 Gy: 66.1%); however, the difference was not statistically significant (P = 0.493). We observed grade ≥ 3 hepatic toxicity in 2 (2.6%) patients and grade 3 gastrointestinal bleeding in 1 (1.3%) patient. However, grade ≥ 4 toxicity was not observed after hypofractionated radiotherapy.ConclusionsThe 2-week schedule of hypofractionated radiotherapy for recurrent HCC exhibited good local control and acceptable treatment-related toxicity during the long-term follow-up period. Thus, this fractionation schedule can be a potential salvage treatment option for recurrent HCC, particularly for tumors located close to a radiosensitive gastrointestinal organ.
Project description:BackgroundTrauma to the pancreas is rare but associated with significant morbidity. Currently available management guidelines are based on low-quality evidence and data on long-term outcomes is lacking. This study aimed to evaluate clinical characteristics and patient-reported long-term outcomes for pancreatic injury.MethodsA retrospective cohort study evaluating treatment for pancreatic injury in 11 centers across 5 European nations over >10 years was performed. Data relating to pancreatic injury and treatment were collected from hospital records. Patients reported quality of life (QoL), changes to employment and new or ongoing therapy due to index injury.ResultsIn all, 165 patients were included. The majority were male (70.9%), median age was 27 years (range: 6-93) and mechanism of injury predominantly blunt (87.9%). A quarter of cases were treated conservatively; higher injury severity score (ISS) and American Association for the Surgery of Trauma (AAST) pancreatic injury scores increased the likelihood for surgical, endoscopic and/or radiologic intervention. Isolated, blunt pancreatic injury was associated with younger age and pancreatic duct involvement; this cohort appeared to benefit from non-operative management. In the long term (median follow-up 93; range 8-214 months), exocrine and endocrine pancreatic insufficiency were reported by 9.3% of respondents. Long-term analgesic use also affected 9.3% of respondents, with many reported quality of life problems (QoL) potentially attributable to side-effects of opiate therapy. Overall, impaired QoL correlated with higher ISS scores, surgical therapy and opioid analgesia on discharge.ConclusionsPancreatic trauma is rare but can lead to substantial short- and long-term morbidity. Near complete recovery of QoL indicators and pancreatic function can occur despite significant injury, especially in isolated, blunt pancreatic injury managed conservatively and when early weaning off opiate analgesia is achieved.
Project description:BackgroundMany patients with Crohn's disease (CD) require fecal diversion. To understand the long-term outcomes, we performed a multicenter review of the experience with retained excluded rectums.MethodsWe reviewed the medical records of all CD patients between 1990 and 2014 who had undergone diversionary surgery with retention of the excluded rectum for at least 6 months and who had at least 2 years of postoperative follow-up.ResultsFrom all the CD patients in the institutions' databases, there were 197 who met all our inclusion criteria. A total of 92 (46.7%) of 197 patients ultimately underwent subsequent proctectomy, while 105 (53.3%) still had retained rectums at time of last follow-up. Among these 105 patients with retained rectums, 50 (47.6%) underwent reanastomosis, while the other 55 (52.4%) retained excluded rectums. Of these 55 patients whose rectums remained excluded, 20 (36.4%) were symptom-free, but the other 35 (63.6%) were symptomatic. Among the 50 patients who had been reconnected, 28 (56%) were symptom-free, while 22(44%) were symptomatic. From our entire cohort of 197 cases, 149 (75.6%) either ultimately lost their rectums or remained symptomatic with retained rectums, while only 28 (14.2%) of 197, and only 4 (5.9%) of 66 with initial perianal disease, were able to achieve reanastomosis without further problems. Four patients developed anorectal dysplasia or cancer.ConclusionsIn this multicenter cohort of patients with CD who had fecal diversion, fewer than 15%, and only 6% with perianal disease, achieved reanastomosis without experiencing disease persistence.