Maria Gomez Galdon

Cellular angiofibroma of the vulva: a clinicopathological study of two cases with documentation of some unusual features and review of the literature.

Background:  Cellular angiofibroma (CA) of the vulva is a recently described condition, whose clinical and pathological features are poorly known.

Fluorescence imaging after intraoperative intravenous injection of indocyanine green for detection of lymph node metastases in colorectal cancer.

PURPOSE This short communication aims at reporting the potential role of ICG fluorescence imaging after an intraoperative IV injection in the detection of lymph nodes (LNs) of a colorectal cancer origin. PATIENTS AND METHODS Two patients who were included in a protocol study evaluating the role of ICG in the detection of peritoneal metastases of colorectal origin (Protocol NCT-01995591) also had fluorescent LNs at exploration with a dedicated near-infrared camera system (Photodynamic Eye, PDE; Hamamatsu Photonics, Hamamatsu, Japan). An IV injection of ICG was delivered intraoperatively at 0.25 mg/kg. All LNs were also explored for their fluorescence, and tumor to background ratio (TBR) was calculated with IC-Calc 2.0 program. RESULTS One patient had two retroperitoneal lymph node metastases and one mesocolic on a pre-operative work-up. The three tumoural lymph nodes at histopathology were hyperfluorescent in comparison to other uninvolved LNs. One patient had no pre-operatively known LN metastases and had one epigastric hyperfluorescent LN discovered at intraoperative exploration. This LN of 6 mm in size was malignant at histopathology. CONCLUSION This is the first report about tumoural LN of colorectal cancer origin detected by fluorescence imaging with intraoperative IV free-ICG injection. ICG fluorescence imaging by intraoperative IV injection represents an easy method for detecting metastatic LNs in colorectal cancer. This proof of concept should lead to further research in this field.

Ex vivo detection of tumoral lymph nodes of colorectal origin with fluorescence imaging after intraoperative intravenous injection of indocyanine green.

The aim of this study was to investigate the potential role of indocyanine green (ICG) fluorescence imaging after intraoperative intravenous (IV) injection for the “ex vivo” detection of metastatic lymph nodes (mLNs) of colorectal cancer origin.

Radioembolisation and portal vein embolization before resection of large hepatocellular carcinoma.

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 postoperative signs 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.

Selective internal radiation therapy (SIRT) before partial hepatectomy or radiofrequency destruction for treatment of hepatocellular carcinoma in cirrhotic patients: a feasibility and safety pilot study

BACKGROUND/PURPOSE Preoperative selective internal radiation therapy (SIRT) may improve the results of partial hepatectomy (PH) or radiofrequency destruction (RF) for hepatocellular carcinoma (HCC) in patients with cirrhosis. The aim of this study was to evaluate the feasibility and safety of this combined approach. METHODS Patients with cirrhosis and HCC selected for PH or RF were prospectively included and systematically proposed for preoperative SIRT. Feasibility and safety of SIRT and post-SIRT PH or RF were assessed. RESULTS Thirty patients were included. SIRT was contraindicated in seven, due to lack of access to tumour artery or to hepato-pulmonary shunts. SIRT was performed in 23 patients without significant complications. Post-SIRT, surgery was refuted in seven patients, due to tumour progression or the patients deteriorating condition. After surgery, major complications were observed in 2/16 patients (12.5%) and one patient died 52 days post-surgery. A major tumour pathological response was seen in most patients who underwent surgery after SIRT. CONCLUSIONS On intention-to-treat basis, the overall feasibility of combining preoperative SIRT and surgery was limited. Preoperative SIRT did not increase expected operative morbidity, but post-SIRT, a third of patients were refuted for surgery. Accurate selection criteria and potential long-term oncological benefit of this approach remains to be determined. ClinicalTrials.gov NCT01686880.

Sequential tumor-directed and lobar radioembolization before major hepatectomy for hepatocellular carcinoma

Preoperative radioembolization may improve the resectability of liver tumor by inducing tumor shrinkage, atrophy of the embolized liver and compensatory hypertrophy of non-embolized liver. We describe the case of a cirrhotic Child-Pugh A patient with a segment IV hepatocellular carcinoma requiring a left hepatectomy. Preoperative angiography demonstrated 2 separated left hepatic arteries, for segment IV and segments II-III. This anatomic variant allowed sequential radioembolizations, delivering high-dose 90Yttrium (160 Gy) to the tumor, followed 28 d later by lower dose (120 Gy) to segments II-III. After 3 mo, significant tumor response and atrophy of the future resected liver were obtained, allowing uneventful left hepatectomy. This case illustrates that, when anatomic disposition permits it, sequential radioembolizations, delivering different 90Yttrium doses to the tumor and the future resected liver, could represent a new strategy to prepare major hepatectomy in cirrhotic patients, allowing optimal tumoricidal effect while reducing the toxicity of the global procedure.

Leiomyomatosis peritonealis disseminata: case report and review of the literature.

Abstract Leiomyomatosis peritonealis disseminata (LPD) is typically a benign and rare disorder found in female patients, prior to menopause. It can be found in the subperitoneal or peritoneal spaces and is represented by multiple different sized myomatous nodules (smooth muscle tumors). Additionally, it has also been found in women after menopause as well as in men. Despite the fact that high levels of estrogen and progesterone play a significant role in this disorder, the mechanism behind LPD development and a definitive therapeutic concept has yet to be conceived. This disorder is mostly found incidentally during imaging or surgery as it is often an asymptomatic condition. The present case reports an incident of LPD, clinically similar to peritoneal metastases, in a patient with a past history of dermatofibrosarcoma of Darier and Ferrand.

Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.

Ex vivo indocyanine green fluorescence imaging for the detection of lymph node involvement in advanced-stage ovarian cancer: POP et al.

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).

Stratification of Pancreatic Ductal Adenocarcinomas Based on Tumor and Microenvironment Features

BACKGROUND & AIMS 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.