Background Gallbladder cancer is a rare neoplasm with a poor prognosis. Early diagnosis and correct treatment strategy is important. The aim of this study was to identify predictors for incidental ...gallbladder cancer. Methods Data from cholecystectomies registered in the nationwide Swedish Register for Gallstone Surgery between 2007 and 2014 were analyzed for incidental gallbladder cancer. Exclusion criteria were patients with a gallbladder not sent for histopathology, preoperative suspicion of polyps/gallbladder cancer, and indication for operation for other reasons than gallstone disease. Predictive factors for incidental gallbladder cancer were identified using multivariable logistic regression. Results A total of 86,154 procedures were registered in the Swedish Register for Gallstone Surgery. Of these, 36,355 patients were included in the analysis, and 215 of the included patients had incidental gallbladder cancer (0.59%). Mean age was 70 ± 11 years for index cases and 54 ± 16 years for the control group, and 80% of cases and 60% of controls were female. Predictors for incidental gallbladder cancer were older age (odds ratio = 1.08; P < .001), female sex (odds ratio = 3.58; P < .001), previous cholecystitis (odds ratio = 1.37; P = .045), and the combination of acute cholecystitis without jaundice (odds ratio = 1.39; P = .041) and jaundice without acute cholecystitis (odds ratio = 2.02; P = .009). A preoperative risk model including these factors gave an area under receiver operating characteristic curve of 0.82. By adding macroscopic evaluation of the gallbladder by the surgeon, the area under receiver operating characteristic curve increased to 0.87. Intraoperatively suspected gallbladder cancer was confirmed as cancer in 31% of the cases. Conclusion Incidental gallbladder cancer is more likely to be diagnosed in older patients, women, and after previous cholecystitis. Jaundice and acute cholecystitis were also shown to be important risk factors. Intraoperative inspection of the gallbladder improved the risk model.
Ischemia/reperfusion may lead to graft dysfunction in heart transplantation (HT). The purpose of this study was to evaluate the influence of ischemic and reperfusion time on acute cellular rejection ...(ACR) within the first‐year post‐HT and on long‐term outcomes. Data were collected from 331 patients (mean age 49 ± 12 y, 28% females) who underwent HT 1988‐2016. Endomyocardial biopsies obtained within the first year after HT were graded according to the 2004‐ISHLT‐WF. We classified the patients by ischemic time </≥4 hours and further by reperfusion time </≥90 minutes. Primary endpoint was ACR ≥ 2R within one‐year post‐HT. A multiple logistic regression analysis was used to adjust for potential confounders. Secondary endpoint was long‐term survival. There were 56 (17%) patients who received donor hearts with ischemic time >4 hours, and of these, 31 (55%) patients had reperfusion with CPB ≥90 minutes. Ischemia >4 hours had an increased risk of ACR ≥ 2R during the first year (adjusted OR = 3.1, P = .016); however, an extended reperfusion ≥90 minutes reduced the risk (adjusted OR = 0.25, P = .024). The conditional probability of surviving 10 years post‐transplant, given that the patients already survived first year, was inferior for recipients with ischemia ≥ 4 hours and reperfusion <90 minutes, 59%, compared with the other groups 83%, P = .016. Prolonged reperfusion appears to reduce the risk for ACR ≥ 2R and improve long‐term survival.
The International Society for Heart and Lung Transplantation (ISHLT) guidelines advise against inappropriate weight match (IWM) for heart transplant, defined as donor weight <70% of recipient's ...weight. Few studies have explored in detail this size-matching recommendation, especially with regard to body mass index (BMI) and gender matching. We aimed to determine whether any difference could be observed between size-matching in obese and non-obese recipients with regard to mortality after cardiac transplantation.
Data from 52,455 adult heart transplants (recipients ≥18 years of age) between 1994 and 2013 were obtained from the ISHLT Registry. We defined the following subgroups of patients based on BMI: underweight, BMI <18.5; non-obese, BMI 18.5 to 30; and obese, BMI >30. The end-points were all-cause 30-day mortality and cumulative mortality.
IWM was associated with increased 30-day mortality (odds ratio OR = 1.20, 95% confidence interval CI 1.01 to 1.43, p = 0.041) and cumulative mortality (hazard ratio HR = 1.14, 95% CI 1.07 to 1.22, p < 0.001). In non-obese recipients, IWM was associated with increased 30-day mortality (OR = 1.89, 95% CI 1.48 to 2.41, p < 0.001) as well as cumulative mortality (HR = 1.27, 95% CI 1.15 to 1.41, p < 0.001), whereas, for obese recipients, IWM was not associated with 30-day or cumulative mortality. Male recipients of female allografts (HR = 1.08, 95% CI 1.04 to 1.12, p < 0.001) as well as female recipients of male allografts (HR = 1.07, 95% CI 1.02 to 1.13, p = 0.003) had increased cumulative mortality compared with gender-matched transplants. There was no interaction between IWM and gender mismatch.
Our results indicate that donor weight <70% of recipient weight increases mortality in non-obese heart transplant recipients, but not in obese transplant recipients. Gender mismatch increases mortality independently of weight match.
Heart transplantation is life saving for patients with end-stage heart disease. However, a number of factors influence how well recipients and donor organs tolerate this procedure. The main objective ...of this study was to develop and validate a flexible risk model for prediction of survival after heart transplantation using the largest transplant registry in the world.
We developed a flexible, non-linear artificial neural networks model (IHTSA) and classification and regression tree to comprehensively evaluate the impact of recipient-donor variables on survival over time. We analyzed 56,625 heart-transplanted adult patients, corresponding to 294,719 patient-years. We compared the discrimination power with three existing scoring models, donor risk index (DRI), risk-stratification score (RSS) and index for mortality prediction after cardiac transplantation (IMPACT). The accuracy of the model was excellent (C-index 0.600 95% CI: 0.595-0.604) with predicted versus actual 1-year, 5-year and 10-year survival rates of 83.7% versus 82.6%, 71.4%-70.8%, and 54.8%-54.3% in the derivation cohort; 83.7% versus 82.8%, 71.5%-71.1%, and 54.9%-53.8% in the internal validation cohort; and 84.5% versus 84.4%, 72.9%-75.6%, and 57.5%-57.5% in the external validation cohort. The IHTSA model showed superior or similar discrimination in all of the cohorts. The receiver operating characteristic area under the curve to predict one-year mortality was for the IHTSA: 0.650 (95% CI: 0.640-0.655), DRI 0.56 (95% CI: 0.56-0.57), RSS 0.61 (95% CI: 0.60-0.61), and IMPACT 0.61 (0.61-0.62), respectively. The decision-tree showed that recipients matched to a donor younger than 38 years had additional expected median survival time of 2.8 years. Furthermore, the number of suitable donors could be increased by up to 22%.
We show that the IHTSA model can be used to predict both short-term and long-term mortality with high accuracy globally. The model also estimates the expected benefit to the individual patient.
Periampullary cancer is a term for cancers arising in or in close proximity to the pancreas. Pancreatic cancer is the 3
leading cause of cancer death for both sexes and while surgery is the only ...option for cure, chemotherapy is given in both the adjuvant and palliative settings. The aim of this study was to investigate any sex and gender differences in patients with pancreatic and other periampullary adenocarcinomas enrolled in a prospective, observational trial.
The study cohort consists of the first 100 patients, 49 women and 51 men, enrolled in the Chemotherapy, Host Response and Molecular dynamics in Periampullary cancer (CHAMP) study, an ongoing study of patients undergoing neoadjuvant, adjuvant or first-line palliative chemotherapy treatment. Twenty-five patients had surgery with curative intent and subsequent adjuvant treatment, and 75 patients were treated with palliative chemotherapy. Data regarding health-related quality of life (HRQoL, EORTC-QLQ-C30) at baseline, demographic and clinicopathological factors were examined and stratification by treatment intention according to sex. Overall survival (OS) was calculated through Kaplan-Meier analysis.
There was a statistically significant difference between male and female patients treated with curative intent, with fewer women having undergone surgery (18 vs 7, p = 0.017), also after adjustment for age, tumor location and performance status. No statistical differences were found between the sexes regarding age, comorbidities, or clinicopathological factors. Before start of chemotherapy treatment, health-related quality of life (HRQoL) was lower in female than in male patients. However, HRQoL was not associated with performance status in female patients, whereas in male patients several HRQoL indicators were significantly positively associated with poorer performance status at baseline.
This study shows no clear differences between the sexes regarding biological factors concluding that gender bias might be responsible for the discrepancy between men and women being offered curative surgery. The observed difference between women and men regarding the association between HRQoL and performance status is unprecedented. Altogether these findings underline the importance of taking gender into consideration when assessing eligibility for curative surgery in order to improve biological outcome and decrease suffering in both sexes.
NCT03724994.
Background
Biliary complications during pregnancy is an important issue. The aim of this study was to examine if there is an increased risk to perform cholecystectomy during pregnancy in patients ...with previous bariatric surgery in comparison to other females subjected to cholecystectomy.
Methods
The Nationwide Swedish Registry for Gallstone Surgery (GallRiks) and the Scandinavian Obesity Surgery Registry (SOReg) were combined. Female patients 18–45 years old were included. The study group was patients with a history of bariatric surgery whom were pregnant at the time of cholecystectomy. This group was compared with pregnant patients without previous bariatric surgery and non-pregnant with and without previous bariatric surgery.
Results
In total, 21,314 patients were included and 292 underwent surgery during pregnancy. From 1282 patients identified in both registers, 16 patients were pregnant at the time of cholecystectomy. Acute cholecystectomy was performed in 5922 (28%) non-pregnant and 199 (68%) pregnant (
p
< 0.001), including 11/16 (69%) pregnant with previous bariatric surgery. When comparing all pregnant patients, those with previous bariatric surgery had longer operative time (
p
= 0.031) and length of stay (
p
= 0.043), but no differences were seen when only comparing patients with an acute indication for surgery. There was no difference in complications comparing pregnant patients with previous bariatric surgery with non-pregnant, both with and without previous bariatric surgery.
Conclusions
Cholecystectomy during pregnancy in patients with previous bariatric surgery seems to be safe. The increased risk seen in the non-pregnant group after previous bariatric surgery is not seen in pregnancy, possibly due to an optimization of the circumstances at surgery.
Background
Pancreatic ductal adenocarcinoma has the lowest survival rate among all major cancers and is the third leading cause of cancer-related mortality. The stagnant survival statistics and ...dismal response rates to current therapeutics highlight the need for more efficient preclinical models. Patient-derived organoids (PDOs) offer new possibilities as powerful preclinical models able to account for interpatient variability. Organoid development can be divided into four different key phases: establishment, propagation, drug screening and response prediction. Establishment entails tailored tissue extraction and growth protocols, propagation requires consistent multiplication and passaging, while drug screening and response prediction will benefit from shorter and more precise assays, and clear decision-making tools.
Conclusions
This review attempts to outline the most important challenges that remain in exploiting organoid platforms for drug discovery and clinical applications. Some of these challenges may be overcome by novel methods that are under investigation, such as 3D bioprinting systems, microfluidic systems, optical metabolic imaging and liquid handling robotics. We also propose an optimized organoid workflow inspired by all technical solutions we have presented.
Distal cholangiocarcinoma is an aggressive malignancy with a dismal prognosis. Diagnostic and prognostic biomarkers for distal cholangiocarcinoma are lacking. The aim of the present study was to ...identify differentially expressed proteins between distal cholangiocarcinoma and normal bile duct samples.
A workflow utilizing discovery mass spectrometry and verification by parallel reaction monitoring was used to analyze surgically resected formalin-fixed, paraffin-embedded samples from distal cholangiocarcinoma patients and normal bile duct samples. Bioinformatic analysis was used for functional annotation and pathway analysis. Immunohistochemistry was performed to validate the expression of thrombospondin-2 and investigate its association with survival.
In the discovery study, a total of 3057 proteins were identified. Eighty-seven proteins were found to be differentially expressed (q < 0.05 and fold change ≥ 2 or ≤ 0.5); 31 proteins were upregulated and 56 were downregulated in the distal cholangiocarcinoma samples compared to controls. Bioinformatic analysis revealed an abundance of differentially expressed proteins associated with the tumor reactive stroma. Parallel reaction monitoring verified 28 proteins as upregulated and 18 as downregulated in distal cholangiocarcinoma samples compared to controls. Immunohistochemical validation revealed thrombospondin-2 to be upregulated in distal cholangiocarcinoma epithelial and stromal compartments. In paired lymph node metastases samples, thrombospondin-2 expression was significantly lower; however, stromal thrombospondin-2 expression was still frequent (72%). Stromal thrombospondin-2 was an independent predictor of poor disease-free survival (HR 3.95, 95% CI 1.09-14.3; P = 0.037).
Several proteins without prior association with distal cholangiocarcinoma biology were identified and verified as differentially expressed between distal cholangiocarcinoma and normal bile duct samples. These proteins can be further evaluated to elucidate their biomarker potential and role in distal cholangiocarcinoma carcinogenesis. Stromal thrombospondin-2 is a potential prognostic marker in distal cholangiocarcinoma.
Aims
Intermittently scanned continuous glucose monitoring (isCGM) systems have not been thoroughly evaluated during in-hospital stay, and there are concerns about accuracy during various conditions. ...Patients undergoing pancreatoduodenectomy have an increased risk of hyperglycaemia after surgery which is aggravated by parenteral nutrition therapy. This study aims to evaluate glycaemic control and safety during insulin infusion in a surgical non-ICU ward, using a hybrid glucose monitoring approach with isCMG and periodic point-of-care (POC) testing.
Methods
We prospectively included 100 patients with a resectable pancreatic tumour. After surgery, continuous insulin infusion was initiated when POC glucose was > 7 mmol/l and titrated to maintain glucose between 7 and 10 mmol/l. Glucose was monitored with isCGM together with intermittent POC, every 3–6 h. Median absolute relative difference (MARD) and hypoglycaemic events were evaluated. Mean glucose was compared with a historic control (
n
= 100) treated with multiple subcutaneously insulin injections, monitored with POC only.
Results
The intervention group (isCGM/POC) had significantly lower POC glucose compared with the historic control group (8.8 ± 2.2 vs. 10.4 ± 3.4 mmol/l,
p
< 0.001). MARD was 17.8% (IQR 10.2–26.7). isCGM readings were higher than POC measurements in 91% of the paired cases, and isCGM did not miss any hypoglycaemic event. About 4.5% of all isCGM readings were < 3.9 mmol/l, but only six events were confirmed with POC, and none was < 3.0 mmol/l.
Conclusions
A hybrid approach with isCGM/POC is a safe and effective treatment option in a non-ICU setting after pancreatoduodenectomy.
Mortality after elective pancreatic surgery in modern high-volume centers is very low. Morbidity remains high, affecting 20-40% of patients. Late postpancreatectomy hemorrhage is a rare but ...potentially lethal complication. The exceptionality in our case lies in the underlying mechanism of its clinical presentation. It is a demonstration of the difficulties associated with finding the source of bleeding in late postpancreatectomy hemorrhage.
An 82-year-old White female was diagnosed with a periampullary malignancy and underwent pancreatoduodenectomy. Postoperatively, the patient suffered from an anastomotic leak in the hepaticojejunostomy, which was treated with percutaneous pigtail drains in the abdomen and in the biliary tract. On the fourth postoperative week she presented blood in both drains and in her stool. Given our knowledge about the biliary anastomotic leak, this presentation led us to suspect an intraluminal source (biliary tract or gastrojejunostomy) with blood leaking through the insufficient hepaticojejunostomy into the abdominal cavity. Upper tract endoscopy and computed tomography angiography were, however, unremarkable. Further investigation with conventional angiography identified the bleeding source at the gastroduodenal artery stump, which was successfully coiled. Hence, the gastroduodenal artery stump was bleeding into the insufficient hepaticojejunostomy, filling up the biliary tree and the small intestine. After coiling of the artery, the remainder of the postoperative care was uneventful.
Postpancreatectomy hemorrhage presents a major clinical challenge after pancreatoduodenectomy, with significant morbidity and high risk for mortality. The treating physician must be alert and active in the investigation and treatment of the bleeding source to ensure a successful outcome.
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