Genomic studies have revealed subtypes of pancreatic ductal adenocarcinoma (PDA) based on their molecular features, but different studies have reported different classification systems. It is a ...challenge to obtain high-quality, freshly frozen tissue for clinical analysis and determination of PDA subtypes. We aimed to redefine subtypes of PDA using a large number of formalin-fixed and paraffin-embedded PDA samples, which are more amenable to routine clinical evaluation.
We collected PDA samples from 309 consecutive patients who underwent surgery from September 1996 through December 2010 at 4 academic hospitals in Europe; nontumor tissue samples were not included. Samples were formalin fixed and paraffin embedded. DNA and RNA were isolated; gene expression, targeted DNA sequencing, and immunohistochemical analyses were performed. We used independent component analysis to deconvolute normal, tumor, and microenvironment transcriptome patterns in samples. We devised classification systems from an unsupervised analysis using a consensus clustering approach of our data set after removing normal contamination components. We associated subtypes with overall survival and disease-free survival of patients using Cox proportional hazards regression with estimation of hazard ratios and 95% confidence interval. We used The Cancer Genome Consortium and International Cancer Genome Consortium PDA data sets as validation cohorts.
We validated the previously reported basal-like and classical tumor-specific subtypes of PDAs. We identified features of the PDA, including microenvironment gene expression patterns, that allowed tumors to be categorized into 5 subtypes, called pure basal like, stroma activated, desmoplastic, pure classical, and immune classical. These PDA subtypes have features of cancer cells and immune cells that could be targeted by pharmacologic agents. Tumor subtypes were associated with patient outcomes, based on analysis of our data set and the International Cancer Genome Consortium and The Cancer Genome Consortium PDA data sets. We also observed an exocrine signal associated with acinar cell contamination (from pancreatic tissue).
We identified a classification system based on gene expression analysis of formalin-fixed PDA samples. We identified 5 PDA subtypes, based on features of cancer cells and the tumor microenvironment. This system might be used to select therapies and predict patient outcomes. We found evidence that the previously reported exocrine-like (called ADEX) tumor subtype resulted from contamination with pancreatic acinar cells.
ArrayExpress accession number: E-MTAB-6134.
A 63-year-old male presented to our oncological hospital with a one-year evolving abdominal pain, with an abdominal mass feeling. Contrast-enhanced computed tomography displayed two soft tissue ...masses, one at the mesentery root and the second around the pancreatic tail; at the same time the patient presented with hyperlipasemia. Endoscopic biopsy for the pancreatic mass and surgical biopsy of the mesenteric one were performed in order to narrow diagnosis. No neoplastic cells but only dense fibro-inflammatory changes with immunoglobulin G4 (IgG4)-positive plasma cell inclusions were observed for both biopsies. A diagnostic and therapeutic strategy based on high suspicion of IgG4-related disease was adopted, with good clinical and imaging response to corticotherapy.
Background and objectives
The aim of this study was to evaluate the role of indocyanine green (ICG) fluorescence imaging (FI) for the ex vivo detection of metastatic lymph nodes (LNs) in advanced ...stage ovarian cancer (AOC).
Methods
Paraffin‐embedded LNs from patients included in a previous ICG‐FI study (Protocol NCT01834469) were further assessed for fluorescence. Intravenous injection of ICG was delivered intraoperatively. Tumor‐to‐background ratios (TBRs) were calculated.
Results
A total of 675 LNs from 19 patients were analyzed. The mean LN number per patient was 29.3 (median: 24; range 2‐77). Seventy‐three LNs were malignant (10.8%), 602 were benign (89.2%). The mean TBR of all LNs was 1.5 (SD 0.8). With a cut‐off TBR of 1.3, the sensitivity, specificity, positive predictive, and negative predictive values of ICG‐FI for retroperitoneal LNs were 80%, 41%, 2.8%, and 99%, respectively. On univariate analysis, only the fluorescence ratio (TBR ≥ 1.3) was correlated with malignancy at pathology (P = 0.03). No predictive factors of pathological LN status were found on multivariate analysis.
Conclusions
Ex vivo ICG‐FI of retroperitoneal LNs in AOC had good sensitivity but poor specificity. However, its high negative predictive value could make it an appropriate complementary tool to focus pathological analysis on fluorescent LNs.
Background
Low anterior resection (LAR) with total mesorectal excision (TME) for mid and low rectal cancer is standard of care, reducing local recurrence and enhancing long-term survival. However, ...this surgery is associated with a constellation of major defecatory problems that are collectively referred to as low anterior resection syndrome (LARS). The aims of this study were to evaluate the frequency of LARS in patients who have undergone LAR and to assess the impact of LARS on long-term quality of life (QoL).
Methods
This was a single-center prospective survey study on patients who underwent LAR and TME for low or mid rectal cancer between 2007 and 2015. LARS score and QLQ-C30 questionnaires were used to evaluate patient’s bowel functions and quality of life, respectively. Associations between LARS and QoL were evaluated.
Results
Fifty-seven patients out of 65 eligible agreed to participate in the study. Forty-three (66%) patients returned complete questionnaires. Five patients (11.6%) had no LARS, 7 had minor LARS (16.3%), and 31 had major LARS (72.1%). In univariate analysis, BMI > 30 kg/m
2
was predictive of major LARS (
p
= 0.047). Major LARS did not impair global QoL (
p
= 0.75), function scores, or social scales, and was not associated with any of the symptom scores except for diarrhea (
p
= 0.02).
Conclusion
LARS is a frequent occurrence after LAR and TME for rectal cancer (72.1%) and is more prevalent in morbidly obese patients. However, the occurrence of LARS does not appear to have a direct impact on QoL except for the occurrence of diarrhea.
Nodal staging is used in colorectal cancer (CRC) to determine which patients should receive adjuvant chemotherapy. The aim of this study was to evaluate the role of indocyanine green fluorescence ...imaging (ICG-FI) in sentinel lymph node (SLN) detection compared to the standard technique.
Twenty patients with CRC admitted for elective colectomy were included (NCT01995591). Ex vivo SLN detection was performed using patent blue (PB) and free ICG injected around the tumor.
Identification rates were 95% (19/20) for both techniques. Sensitivity was 43% for PB and 57% for ICG. Correlation between the techniques was 83%. FI was more sensitive in patients with body mass index (BMI) >25 kg/m(2) Serial section analysis did not allow for up-staging of patients.
The use of ICG-FI is superior to the blue dye technique in patients with a BMI >25 kg/m(2) However, the sensitivity of ICG-FI in SLN detection remains low, with a high rate of false-negative results.
Resectability of hepatocellular carcinoma in patients with chronic liver disease is dramatically limited by the need to preserve sufficient remnant liver in order to avoid postoperative liver ...insufficiency. Preoperative treatments aimed at downsizing the tumor and promoting hypertrophy of the future remnant liver may improve resectability and reduce operative morbidity. Here we report the case of a patient with a large hepatocellular carcinoma arising from chronic liver disease. Preoperative treatment, including tumor downsizing with transarterial radioembolization and induction of future remnant liver hypertrophy with right portal vein embolization, resulted in a 53% reduction in tumor volume and compensatory hypertrophy in the contralateral liver. The patient subsequently underwent extended right hepatectomy with no postoperativesigns of liver decompensation. Pathological examination demonstrated a margin-free resection and major tumor response. This new therapeutic sequence, combining efficient tumor targeting and subsequent portal vein embolization, could improve the feasibility and safety of major liver resection for hepatocellular carcinoma in patients with liver injury.
Peritoneal carcinomatosis (PC) refers to malignant epithelial cells that spread to the peritoneum, principally from abdominal malignancies. Until recently, PC prognosis has been considered ill-fated, ...with palliative therapies serving as the only treatment option. New locoregional treatments are changing the outcome of PC, and imaging modalities have a critical role in early diagnosis and disease staging, determining treatment decision making strategies. The aim of this review is to provide a practical approach for detecting and characterizing peritoneal deposits in cross-sectional imaging modalities, taking into account their appearances, including the secondary complications, the anatomical characteristics of the peritoneal cavity, together with the differential diagnosis with other benign and malignant peritoneal conditions. Among the cross-sectional imaging modalities, computed tomography (CT) is widely available and fast; however, magnetic resonance (MR) performs better in terms of sensitivity (92% vs. 68%), due to its higher contrast resolution. The appearance of peritoneal deposits on CT and MR mainly depends on the primary tumour histology; in case of unknown primary tumour (3-5% of cases), their behaviour at imaging may provide insights into the tumour origin. The timepoint of tumour evolution, previous or ongoing treatments, and the peritoneal spaces in which they occur also play an important role in determining the appearance of peritoneal deposits. Thus, knowledge of peritoneal anatomy and fluid circulation is essential in the detection and characterisation of peritoneal deposits. Several benign and malignant conditions show similar imaging features that overlap those of PC, making differential diagnosis challenging. Knowledge of peritoneal anatomy and primary tumour histology is crucial, but one must also consider clinical history, laboratory findings, and previous imaging examinations to achieve a correct diagnosis. In conclusion, to correctly diagnose PC in cross-sectional imaging modalities, knowledge of peritoneal anatomy and peritoneal fluid flow characteristics are mandatory. Peritoneal deposit features reflect the primary tumour characteristics, and this specificity may be helpful in its identification when it is unknown. Moreover, several benign and malignant peritoneal conditions may mimic PC, which need to be considered even in oncologic patients.
The antimicrobial susceptibility of Helicobacter pylori strains isolated from HIV‐positive individuals is not well characterized. This study aimed to measure the prevalence and long‐term trends ...associated with primary H. pylori antibiotic resistance, evaluate correlations with antibiotic consumption, and compare predictors for H. pylori antibiotic resistance between HIV‐positive and HIV‐negative individuals. In this longitudinal registry study, we evaluated consecutive adults with and without HIV infection, naïve to H. pylori treatment, who underwent upper gastrointestinal endoscopy and had a positive H. pylori culture, with susceptibility testing available, between 2004 and 2015. Outpatient antibiotic consumption data were based on nationwide aggregated numbers. H. pylori was isolated from gastric biopsies of 3008/8321 patients, 181/477 (37.9%) were HIV‐positive and 2827/7844 (36.0%) HIV‐negative. Overall cohort mean prevalence of H. pylori primary antibiotic resistance was 11.1% for clarithromycin, 17.8% levofloxacin, and 39.4% metronidazole. The prevalence of H. pylori primary resistance was significantly higher for these three drugs in HIV‐positive individuals across the study period. Linear regression showed that the prevalence of clarithromycin and levofloxacin resistance correlated with the country aggregate daily dose consumption of macrolides and quinolones, respectively. Multivariable regression analysis showed that HIV infection is a strong independent risk factor for multiple H. pylori antibiotic resistance. In summary, HIV infection is a risk factor for carrying multi‐resistant H. pylori strains and this is correlated with antibiotic consumption. Empirical therapies should be avoided in HIV‐positive individuals. These data highlight the need to implement ongoing monitoring of H. pylori antimicrobial susceptibility among HIV‐positive individuals. The study is registered at ISRCTN registry, number 13466428: https://www.isrctn.com/ISRCTN13466428.
Primary antibiotic resistance was almost two‐fold more common among Helicobacter pylori strains isolated from HIV‐positive individuals over 12 years of observation: AIDS > AIDS‐free > HIV‐negative. This may be due to increased antibiotic consumptions and other factors. *p‐value after Bonferroni correction.
PDF
