Risk factors to differentiate between benign proximal biliary strictures and perihilar cholangiocarcinoma

BackgroundThe aim of this study was to evaluate potential risk factors associated with benign lesions and perihilar cholangiocarcinoma (PHC) in patients presenting with proximal biliary strictures (PBS).MethodsPatients with PBS who were referred to a specialist HPB centre between 2008 and 2016 were identified. Patients with primary sclerosing cholangitis, metastatic PHC or hilar obstruction by a peripheral tumour were excluded. The final diagnosis was determined either by (1) resection histology or (2) combination of biopsy and clinical course. Multivariable analysis of clinical, laboratory and radiological data was undertaken to identify independent predictors of benign and malignant lesions.Results155 consecutive patients were identified, including 25 patients (16%) with benign PBS. Abdominal pain (odds ratio [OR] 3.36; p = 0.027), serum CA19.9 < 100 U/ml (OR 10.35; p = 0.001), and absence of mass on imaging (OR 4.66; p = 0.004) were all associated with the presence of benign lesions on multivariable analysis.ConclusionsThis study has identified several independent variables that may differentiate between benign and malignant proximal biliary strictures. A larger multi-institutional study would be warranted to validate these findings, and to develop a risk score to stratify patients with suspected PHC.     

CA 19-9 to differentiate benign and malignant masses in chronic pancreatitis: is there any benefit?

Background  The role of the tumor marker CA 19-9 in differentiating benign from malignant masses in chronic pancreatitis has not been extensively studied. Aim  This study aims at assessing the accuracy of CA 19-9 in differentiating inflammatory head masses in chronic pancreatitis from superimposed carcinomas on chronic pancreatitis. Methods  The data of 84 consecutive patients who had mass lesions in chronic pancreatitis were analyzed to determine the sensitivity, specificity and predictive values at cut-off values of 37, 100, 200 and 300 U/mL. Receiver operating characteristic (ROC) curves were used to assess the sensitivity and specificity. Results  There were 50 benign masses and 34 malignancies. The overall sensitivity and specificity of CA 19-9 for cancer was 68% and 70%, respectively. There was a higher positivity of CA 19-9 in cancers than in benign masses (23/34; 68% versus 15/50; 30%, P<0.01) with cut-off values of 37 U/mL. Higher positivity rates were obtained in cancers using other cut-off values such as 100, 200 and 300 U/mL. Values over 300 U/mL were 100% specific for malignancy, but occurred in only 5 (of whom had distant metastases) of 34 patients. Conclusion  CA 19-9 level in excess of 300 U/mL in mass lesions in chronic pancreatitis was always indicative of malignancy.     

CA-125, but not galectin-3, complements CA 19-9 for discriminating ductal adenocarcinoma versus non-malignant pancreatic diseases

Background/objectivesCA 19-9 is the gold standard biomarker of pancreatic adenocarcinoma despite several weaknesses in particular a high rate of false positives or negatives. CA-125 corresponding to MUC16 and galectin-3, a lectin able to interact with mucin-associated carbohydrates, are tumor-associated proteins. We investigated whether combined measurement of CA 19-9, galectin-3 and CA-125 may help to better discriminate pancreatic adenocarcinoma versus non-malignant pancreatic diseases.MethodsWe evaluated by immunohistochemistry the expression of MUC4, MUC16 (CA-125) and galectin-3 in 31 pancreatic adenocarcinomas. We measured CA 19-9, CA-125 and Gal-3 in the serum from patients with pancreatic benign diseases (n = 58) or adenocarcinoma (n = 44). Clinical performance of the 3 biomarkers for cancer diagnosis and prognosis was analyzed.ResultsBy immunohistochemistry, MUC16 and Gal-3 were expressed in 74% and 84% of adenocarcinomas versus 0% and 3.2% in peri-tumoral regions, respectively. At the serum level, CA 19-9 and CA125 were significantly higher in patients with pancreatic adenocarcinoma whereas Gal-3 levels did not differ. The performance of CA 19-9 for cancer detection was higher than those of CA-125 or Gal-3 by ROC analysis. However, CA-125 offers the highest specificity for malignancy (81%) because of an absence of false positives among type 2 diabetic patients. Cancer deaths assessed 6 or 12 months after diagnosis varied according to the initial CA-125 level (p < 0.006).ConclusionGal-3 is not an interesting biomarker for pancreatic adenocarcinoma detection. CA 19-9 alone exhibits the best performance but measuring CA-125 provides complementary information in terms of diagnosis and prognosis.     

CA19.9 decrease >15% is a predictor of favourable outcome in patients treated for advanced pancreatic carcinoma: analysis of two independent cohorts

BackgroundAlthough carbohydrate antigen 19.9 (CA19.9) is widely used in pancreatic adenocarcinoma (PA), no consensual cut-off value of CA19.9 decrease has been established for treatment monitoring.MethodsThis was a retrospective study including patients with a baseline CA19.9 ≥ 37 UI/ml and with locally advanced or metastatic PA from two French centers. CA19.9 measurements were performed at baseline and first CT-scan evaluation. The aim was to use a training set to determine the best cut-off of CA19.9 decrease for predicting progressive disease (PD) and to analyze its performance in an independent validation cohort.ResultsA total of 95 and 93 patients were included in the training and validation sets, respectively. A ≤15% CA19.9 decrease was the best cut-off for predicting PD with a sensitivity (Se) = 68% and a specificity (Sp) = 90%. In the validation set, this threshold was associated with Se = 76% and Sp = 83%. A >15% CA19.9 decrease was significantly associated with improved PFS (median 8.3 versus 3.1 months, p < 0.0001) and OS (median 14 versus 7.2 months, p < 0.0001). A >15% CA19.9 decrease was also identified as a factor independently associated with OS (HRa = 0.25, 95% CI:0.14–0.44).ConclusionsA CA 19.9 decrease >15% is a favourable predictor of outcome in patients treated for advanced PA.     

Mucormycosis in children with haematological malignancies is a salvageable disease: a report from the Israeli Study Group of Childhood Leukemia

Mucormycosis has emerged as an increasingly important cause of morbidity and mortality in immunocompromised patients, but contemporary data in children are lacking. We conducted a nationwide multicentre study to investigate the characteristics of mucormycosis in children with haematological malignancies. The cohort included 39 children with mucormycosis: 25 of 1136 children (incidence 2·2%) with acute leukaemias prospectively enrolled in a centralized clinical registry in 2004–2017, and an additional 14 children with haematological malignancies identified by retrospective search of the databases of seven paediatric haematology centres. Ninety-two percent of mucormycosis cases occurred in patients with acute leukaemias. Mucormycosis was significantly associated with high-risk acute lymphoblastic leukaemia (OR 3·75; 95% CI 1·51–9·37; P = 0·004) and with increasing age (OR 3·58; 95% CI 1·24–9·77; P = 0·01). Fifteen patients (38%) died of mucormycosis. Rhinocerebral pattern was independently associated with improved 12-week survival (OR 9·43; 95% CI 1·47–60·66; P = 0·02) and relapsed underlying malignancy was associated with increased 12-week mortality (OR 6·42; 95% CI, 1·01–40·94; P = 0·05). In patients receiving frontline therapy for their malignancy (n = 24), one-year cumulative mucormycosis-related mortality was 21 ± 8% and five-year overall survival was 70 ± 8%. This largest paediatric population-based study of mucormycosis demonstrates that children receiving frontline therapy for their haematological malignancy are often salvageable.     

A novel smartphone scleral-image based tool for assessing jaundice in decompensated cirrhosis patients

Background and Aim

Serum bilirubin is an established marker of liver disease. Reliable tools for non-invasive assessment of jaundice in cirrhosis patients, at risk of clinical decompensation, are highly desirable. While smartphone-based imaging has been described in neonatal jaundice, it has not been investigated in advanced cirrhosis patients.

Methods

We included 46 hospitalized patients with acute cirrhosis decompensation and jaundice. Scleral images using an Android smartphone were taken to derive “Scleral Color Values (SCV),” which were matched with same day serum bilirubin measurements. In 29 patients, repeat SCV and bilirubin measurements were performed over time. We analyzed the relationship of SCV and its dynamics with serum bilirubin, clinical scores, and patient outcomes.

Results

Of 46 patients, 26 (57%) had alcoholic hepatitis as the decompensation precipitant. Seven patients died during admission; a further 12 following hospital discharge. SCV had an excellent linear correlation with serum bilirubin (rho = 0.90, P < 0.001); changes in SCV and serum bilirubin across different time points, were also closely associated (rho = 0.77, P < 0.001). SCV correlated significantly with CLIF Consortium Acute Decompensation score (rho = 0.38, P < 0.001) and grade of Acute-on-Chronic Liver Failure (rho = 0.42, P = 0.039). SCV was higher in patients who died, however, not significantly (86.1 [IQR 83.0–89.7] vs 82.3 [IQR 78.5–83.3], P = 0.22). The associations of SCV with clinical parameters mirrored those of serum bilirubin.

Conclusion

Smartphone-based assessment of jaundice shows excellent concordance with serum bilirubin and is associated with clinical parameters in acute cirrhosis decompensation. This approach offers promise for remote assessment of cirrhosis patients at-risk of decompensation, post hospital discharge.     

Early cytomegalovirus infections following allogeneic stem cell transplantation: a comparison between non-malignant and malignant haematological disorders

Abstract

The haematological indications for allogeneic stem cell transplantation can be broadly divided into non-malignant and malignant disorders. We compared the incidence and risk factors for post-transplant cytomegalovirus (CMV) infections between these two biologically diverse subgroups of haematological conditions. Out of 105 allogeneic transplants, 64 and 41 were for underlying non-malignant and malignant indications respectively. CMV infections were significantly more frequent (P=0·016) in the malignant subgroup. Pre-transplant recipient CMV seropositivity in both subgroups (negative versus positive; non-malignant,P=0·023; malignant, p<0·001), donor seropositivity (P=0·002) and acute graft-versus-host disease (GVHD) (P=0·02) in the non-malignant subgroup and ≥3 courses of previous cytotoxic therapy (P=0·023) in the malignant subgroup were found to be associated with an increased risk of CMV infections. On multivariate analysis, donor seropositivity in the non-malignant patients (negative versus positive,P=0·022; odds ratio: 0·18) and recipient seropositivity in patients with malignancies (negative versus positive; P=0·001, odds ratio: 0·01) were identified to be significant factors for risk of CMV infection.     

Expression of GNAZ,encoding the Gαz protein,predicts survival in mantle cell lymphoma

Mantle cell lymphoma (MCL), a malignancy of B-lymphocytes, has a poor prognosis. It is thus necessary to improve the understanding of the pathobiology of MCL and identify factors contributing to its aggressiveness. Our studies, based on Affymetrix data from 17 MCL biopsies, real-time quantitative polymerase chain reaction data from 18 sorted primary MCL cells and 108 MCL biopsies compared to non-malignant tissue, reveals that GNAZ expression predicts poor clinical outcome of MCL patients (Cox regression, P = 0·014) and lymphocytosis (Mann-Whitney, P = 0·011). We show that GNAZ translates to Gα_z protein – a signalling molecule within the G-protein coupled receptor network. Our findings suggest that GNAZ/Gα_z contribute to the MCL pathobiology.     

Persistent elevation of serum CA 19-9 with no evidence of malignant disease

BackgroundSerum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases.AimsIn this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed.PatientsNine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one.MethodsRoutine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission.ResultsSerum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2–7 years) serum CA 19-9 values were persistently elevated in all patients.ConclusionsOur study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.     

Natural course of benign adrenal incidentalomas in subjects with extra-adrenal malignancy

Patients with extra-adrenal malignancies are diagnosed increasingly with benign adrenal tumors, as well as non-oncology subjects. We aimed to demonstrate the natural course of adrenal adenomas in terms of mass size and hormonal status in oncology and non-oncology subjects. We also compared the characteristics and behavior of adrenal adenomas with adrenal malignancies. In our registry of adrenal tumors (n = 335), we prospectively evaluated 29 oncology subjects (EAM+) and age, gender, and follow-up duration matched 110 non-oncology subjects (EAM−) with adrenal adenomas. Median follow-up was 24 months. We also included 16 subjects with adrenal malignancies (primary; 3 and metastasis; 13). Tumor size was followed-up with CT or MRI at 6th and 12th months and annually in subsequent visits. Hormonal assessment was repeated at the 6th month after the initial visit and annually in subsequent visits. Initial tumor size, mean increase in tumor size, and number of subjects who showed mass enlargement or developed subclinical Cushing Syndrome were comparable (P > 0.05) between EAM+ and EAM− groups. Subjects with malignant adrenal tumors were older (P = 0.06), had larger tumors at presentation (P < 0.001), and showed mass enlargement during a shorter follow-up duration (P < 0.001). Oncology subjects with adrenal adenomas featured similar baseline and follow-up parameters in terms of mass enlargement and development of subclinical Cushing Syndrome when compared with non-oncology subjects. Malignant adrenal tumors were characterized with large, rapidly growing tumors of older ages. Conservative approach can be suggested to oncology subjects for adrenal adenomas unless clinical and radiological suspicion of adrenal malignancy is present.     

Incidence and predictive factors for malignancies in 136 Japanese patients with dermatomyositis,polymyositis and clinically amyopathic dermatomyositis

The aim of this study was to define the standardized incidence ratio (SIR) of malignancy and the potential risk factors of concomitant malignancies in patients with inflammatory myopathies, including clinically amyopathic dermatomyositis (CADM). A total of 145 patients diagnosed with either dermatomyositis/polymyositis (DM/PM) or CADM at our institute between 1984 and 2002 were enrolled in the study. The demographic, clinical and laboratory features of the patients at the time of DM/PM or CADM diagnosis were compared between patients with and without malignancies, respectively. Multivariate analysis by logistic regression was used to determine the independent risk factors for the development of malignancies in DM/PM patients. Malignancy was found in 17 of 70 patients with DM (24%), three of 15 patients with CADM (20%), and three of 51 patients with PM (6%). Gastric cancer (8/23) was the most common malignancy. Compared with general population, the SIR of malignancies was 13.8 (range 9.0–21.1). The patients who developed malignancies were older (61.5 vs. 51.1 years; P < 0.005), presented more often with dysphagia (61 vs. 15%; P < 0.0001) and were less likely to have the complication of interstitial lung disease (30 vs. 60%; P < 0.05). These features were independent predictive factors for developing malignancies in multiple logistic regression analysis. The results of our study confirm that CADM in addition to DM was associated with high rates of malignancy among our patient cohort.     

Malignancy in scleroderma patients from south west England: a population-based cohort study

The pathophysiological relationship between scleroderma and malignancy remains poorly understood. Although some previous studies have demonstrated an increased malignancy risk in patients with scleroderma, others have been inconclusive. We aimed to determine if patients with scleroderma had an increased risk of malignancy compared to an age- and sex-matched local South West England population, and if there were any important differences between scleroderma patients with and without malignancy. Methods of this study are as follows. Notes were obtained on all local scleroderma patients (n = 68) locally, and those diagnosed with malignancy verified by contacting each patient’s general practitioner. Expected malignancy figures were obtained from age- and sex-stratified regional prevalence data provided by the South West Cancer Intelligence Service registry. Among the patients, 22.1% with scleroderma were identified with concurrent malignancy. Affected sites were of the breast (n = 5), haematological system (n = 5), skin (n = 4), and unknown primary (n = 1). Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95% CI 1.77–5.20, p = 0.01). In particular, this risk was the highest for haematological malignancies (RR = 18.5, 95% CI 6–43, p = 0.03), especially for non-Hodgkin’s lymphoma (RR = 25.8, 95% CI 5–75, p = 0.10). The majority of patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9 years). Age of >70 and patients with limited scleroderma were significant risk factors for a patient with scleroderma to have a concurrent malignancy; however, no increased risk was found in patients with any particular pattern of organ involvement, cytotoxic usage or serology. To conclude, in this small patient cohort, we have found that scleroderma is associated with an increased risk of malignancy. This risk is statistically significant in patients with limited scleroderma. Patients who are elderly and those with limited disease should be closely scrutinized at follow-up appointments.     

Peripheral blood late mixed chimerism in leucocyte subpopulations following allogeneic stem cell transplantation for childhood malignancies: does it matter?

The impact of persistent mixed chimerism (MC) after haematopoietic stem cell transplantation (HSCT) remains unclarified. We investigated the incidence of MC in peripheral blood beyond day +50 after HSCT and its impact on rejection, chronic graft‐versus‐host disease (c‐GvHD) and relapse in 161 children receiving allogeneic HSCT for haematological malignancies. The 1‐year incidence of late MC was 26%. Spontaneous conversion to complete donor chimerism (CC) occurred in 43% of patients as compared to 62% after donor lymphocyte infusions. No graft rejection occurred. The 1‐year incidence of c‐GvHD was 20 ± 7% for MC, and 18 ± 4% for CC patients (P = 0·734). The 3‐year cumulative incidence of relapse (CIR) according to chimerism status at days +50 and +100 was 22 ± 4% for CC patients vs. 22 ± 8% for MC patients (day +50; P = 0·935) and 21 ± 4% vs. 20 ± 7% (day +100; P = 0·907). Three‐year CIRs in patients with persistent MC and patients with CC/limited MC were comparable (8 ± 7% vs. 19 ± 4%; P = 0·960). HSCT for acute leukaemia or myelodysplastic syndrome as secondary malignancies (hazard ratio (HR) 4·7; P = 0·008), for AML (HR 3·0; P = 0·02) and from mismatched donors (HR 3·1; P = 0·03) were independent factors associated with relapse. Our data suggest that late MC neither protects from c‐GvHD nor does it reliably predict impending disease relapse.     

The inverse association of incident cardiovascular disease with plasma bilirubin is unaffected by adiponectin

Objective

Bilirubin may protect against atherosclerotic cardiovascular disease (CVD). The heme oxygenase pathway is crucial for bilirubin generation, and is stimulated by adiponectin. We tested the relationship of plasma bilirubin with adiponectin, and determined whether the association of incident CVD with bilirubin is modified by adiponectin.

Methods

A community-based prospective nested case–control study (PREVEND cohort) was carried out in 87 non-diabetic men who developed a first cardiovascular event (cases) and 94 controls during a median follow-up of 6.1 (2.8–10.6) years.

Results

In all subjects combined, bilirubin was positively related to adiponectin (r = 0.205, P = 0.006). Age-adjusted incident CVD was inversely associated with bilirubin (hazard ratio (HR): 0.80 (95% CI 0.65–0.99), P = 0.048), independently of adiponectin (HR: 0.78 (95% CI 0.63–0.97), P = 0.027). Adiponectin did not modify the association of CVD with bilirubin (interaction term: P = 0.65). After additional adjustment for CVD risk factors, neither the association of incident CVD with bilirubin nor with adiponectin remained significant (P > 0.20 for both), and there was again no interaction between bilirubin and adiponectin on CVD risk (P = 0.67).

Conclusion

Bilirubin is related to adiponectin, but the association of bilirubin with CVD risk is largely unaffected by adiponectin.     

Carbohydrate antigen 19‐9 is extremely elevated in polycystic liver disease

Background/Aims: Carbohydrate antigen 19‐9 (CA19‐9) is used as a biomarker to differentiate benign from malignant gastrointestinal disorders. We examined the value of CA19‐9 measurement in polycystic livers after observing high CA19‐9 cyst fluid levels in a benign polycystic liver case. Methods: We determined CA19‐9 levels in serum (n=120) and hepatic cyst fluid (n=81), from patients with polycystic livers (n=109) and simple hepatic cysts (n=24). Further, we analysed CA19‐9 expression in normal and polycystic liver tissue (n=17). Results: Cyst fluid CA19‐9 levels from both polycystic livers and simple hepatic cysts were extremely high (median 91 000 U/ml, range 14–15 870 000 U/ml; median 85 000 U/ml, range 332–1 744 000 U/ml respectively). Serum CA19‐9 levels were significantly higher in polycystic liver patients (median 30 U/ml, range 0–1200 U/ml) compared with patients with simple hepatic cysts (median 10 U/ml, range 3–200 U/ml, P=0.0011). Serum CA19‐9 levels correlated with those in cyst fluid (r=0.3979, P=0.0399), polycystic liver volume (r=0.3870, P=0.0025) and the size of the largest cyst (simple cysts group; r=0.5319, P=0.0280). Cyst epithelia showed strong CA19‐9 expression. Evacuation of cyst fluid in four patients resulted in a dramatic decrease in the serum CA19‐9 levels (60–95%). Conclusions: CA19‐9 levels are high in the cyst fluid and serum of polycystic liver disease patients due to production and secretion by cyst epithelia. It does not reflect malignancy in these patients and may be of value as a biomarker for intervention efficiency assessment.     

A nationwide analysis of clinical trial participation for common hepato-pancreato-biliary malignancies demonstrates survival advantages for subsets of trial patients but disparities in and infrequency of enrollment

BackgroundWe describe factors associated with trial enrollment for patients with hepato-pancreato-biliary (HPB) malignancies. We analyzed the association and effect of trial enrollment on overall survival (OS).MethodsThe National Cancer Database (2004–2017) was queried for common HPB malignancies (pancreatic adenocarcinoma [PDAC] & neuroendocrine tumors, hepatocellular carcinoma [HCC], biliary tract cancers [BTC]). Multivariable logistic regression was used to identify factors associated with trial enrollment. OS was analyzed by multivariable Cox regression. Inverse-probability-weighted Cox regression was utilized to determine the effect of trial enrollment on OS.ResultsA total of 1573 (0.3%) of 511,639 patients were enrolled in trials; pancreatic malignancy: 1214 (0.4%); HCC: 217 (0.14%); BTC: 106 (0.15%). HCC and BTC were associated with lower likelihood of enrollment compared with pancreatic malignancy. Black and Hispanic patients were less likely to be enrolled compared to White patients. Treatment at academic facilities and metastatic disease were associated with higher likelihood of enrollment. Enrollment was associated with higher OS for PDAC, metastatic HCC, and metastatic BTC. Trial enrollment exhibited an OS advantage for PDAC and metastatic HCC.ConclusionNationally, fewer than 1% of patients with HPB malignancies were enrolled in clinical trials. There are racial, sociodemographic, and facility-based disparities in trial enrollment.     

Secondary acute lymphoblastic leukaemia is constitutional and probably not related to prior therapy

Very little is known about secondary acute lymphoblastic leukaemia (s‐ALL). This retrospective analysis studied a cohort of s‐ALL patients treated at a single centre between 1994 and 2013, while comparing therapy‐associated ALL (t‐ALL) and antecedent malignancy ALL (am‐ALL) patients. Thirty‐two patients with s‐ALL were identified. The overall incidence was 9·4% among ALL adults while T‐cell s‐ALL was rare (12% of s‐ALLs). The median time interval between two malignant diagnoses was 5·3 years (range: 0·1–28). In contrast to previous reports, most of the s‐ALLs were CD10 +  and without KMT2A (MLL) abnormalities. The overall survival (OS) rates of the entire cohort at 12 and 24 months from ALL diagnosis was 49% and 25%, respectively. Most patients (n = 23, 72%) received prior chemo‐/radio‐therapy for their first malignancy (t‐ALL) and only 9 (28%) did not (am‐ALL). No significant difference was found in the incidence of B‐/T‐ lineage ALL, extramedullary disease, blood count, and the rate of Philadelphia‐positive ALL, nor in the rates of complete remission (P = 0·55) and OS (P = 0·97). This similarity, together with high incidence of family malignancy in both groups, raise the possibility that s‐ALL patients may have an inherent predisposition to malignancies and a history of previous therapy may be of lesser importance in the pathogenesis of s‐ALL.     

Impact of graft-versus-lymphoma effect on outcomes after reduced intensity conditioned-alemtuzumab allogeneic haematopoietic stem cell transplantation for patients with mature lymphoid malignancies

Allogeneic haematopoietic stem cell transplant (allo-HSCT) offers potentially curative therapy for patients with relapsed/refractory lymphoid malignancies. Reduced-intensity conditioning (RIC) with Alemtuzumab reduces transplant-related mortality and graft-versus-host disease (GvHD), but may be associated with increased risk of relapse. With the aim of studying the effect of GVHD and donor lymphocyte infusions (DLI) on relapse, we performed a retrospective study of 288 patients (57% non-Hodgkin lymphoma, 24% Hodgkin lymphoma and 19% chronic lymphocytic leukaemia; 58% were relapsed/refractory) who underwent RIC-Alemtuzumab-HSCT between 2000 and 2012. Median follow-up time for survivors was 64 months. Five-year overall survival, relapse incidence, GvHD/relapse-free survival and non-relapse mortality were 47%, 33%, 37% and 28% respectively. Cumulative incidence of grade II-IV acute and extensive chronic GvHD was 22% and 21% at 100 days and 5 years respectively. On multivariate analysis, presence of GvHD (P = 0·03) and unrelated donor type (P = 0·03) were protective of relapse. 62/288 patients received DLI for either mixed donor chimerism (prophylactic DLI, n = 37) or clinical relapse (therapeutic DLI, n = 25). Prophylactic and therapeutic DLI successfully converted the patient to full or stable mixed donor chimerism in 78% and 56% of patients respectively. These data demonstrate good long-term outcomes and support the concept of the graft-vs-lymphoma effect as a key protective factor against relapse following RIC-Alemtuzumab allo-HSCT for patients with mature lymphoid malignancies.     

Genetic copy number alterations and IL-13 expression differences in papillary thyroid cancers and benign nodules

Thyroid nodules were the extremely common endocrine tumors, in which papillary thyroid carcinomas (PTCs) were the most prevalent endocrine malignancy, representing 80–90% of all thyroid malignancies. It was still a dilemma to discriminate PTCs and benign thyroid nodules. With a new molecular genetics technology of Multiplex ligation-dependent probe amplification (MLPA), we investigated 13 PTC and 14 benign nodule tissue samples. The results showed that PTCs had more genetic copy number alteration than benign nodules (P < 0.001). Receiver operating characteristic (ROC) curve analysis suggested that genomic aberrations would provide a moderate accuracy method to discriminate PTCs and benign nodules. The gain of interleukin 13 (IL-13) gene obviously identified the great difference between PTCs and benign nodules. Immunohistochemistry also confirmed significantly higher IL-13 expression in the PTCs (P < 0.001). The current study showed that MLPA should be an effective method to diagnose PTCs and benign thyroid nodules, and also provided a clue to another relationship between IL-13 and PTCs. ZeFei Zhao and Qing Wei contributed equally to this work.     

Hidden work in hepatopancreaticobiliary surgery: the contemporary demands of non-operative patient management

BackgroundIncreasing use is now made of modalities other than surgery (including endoscopy and interventional radiology) in the care of patients with hepatopancreaticobiliary (HPB) diseases. However, the care of and responsibility for patients managed non-operatively continues to reside with surgical services. This investigation was undertaken to quantify the implications of non-operative patient related admissions our HPB unit over a 24 month period.MethodsTotal admissions from Jan 2018–Dec 2019 in a tertiary HPB unit were analyzed to determine HPB-related non-operative admissions. Cost analysis was also undertaken.ResultsThere were 1528 admissions in 1029 patients for non-operative indications out of a total of 2576 admissions to the HPB unit. Of these, 707 were for diagnoses related to underlying HPB or upper gastrointestinal diagnoses. Patients were primarily treated with an interventional radiology procedure (n = 180), diagnostic or therapeutic endoscopy (n = 287), palliation (n = 57), symptomatic management (n = 152), other (n = 31). Patient age ≥80 (p < 0.05), acute admission (p < 0.01) and the presence of a stage 4 cancer diagnosis (p < 0.01) were associated with non-operative admission.ConclusionOver half of patient admissions are for non-operative management. The contemporary HPB unit is responsible for providing surgical intervention as well as coordinating multidisciplinary care of patients with HPB disease.