Mattia Garancini

Combined hepatocellular‐cholangiocarcinoma: A population‐level analysis of an uncommon primary liver tumor

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) is a rare primary liver cancer. Our aims were to analyze the demographic, clinical, and pathological characteristics of cHCC‐CC at a population level and to investigate the effects of these features as well as different management strategies on the prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for 1988‐2009. Data analyses were performed with chi‐square tests, analyses of variance, Kaplan‐Meier curves, and Cox proportional hazards regression. Four hundred sixty‐five patients with cHCC‐CC, 52,825 patients with hepatocellular carcinoma (HCC), and 7181 patients with cholangiocarcinoma (CC) were identified. cHCC‐CC was more common in patients who were white, male, and older than 65 years. Treatment was more frequently nonsurgical/interventional. Patients with cHCC‐CC, HCC, and CC had 5‐year overall survival (OS) and disease‐specific survival rates of 10.5%, 11.7%, and 5.7% (P < 0.001) and 17.8%, 21.0%, and 11.9% (P < 0.001), respectively. For cHCC‐CC patients, an increasing invasiveness of the therapeutic approach was significantly associated with prolonged survival (P < 0.001). In a multivariate model, black race, a distant SEER stage, and a tumor size of 5.0 to 10.0 cm were independently associated with lower survival for cHCC‐CC patients; a year of diagnosis after 1995 and surgical treatment with minor hepatectomy, major hepatectomy (MJH), or liver transplantation (LT) were independently associated with better survival for cHCC‐CC patients. Patients diagnosed with cHCC‐CC, HCC, and CC and treated with LT had 5‐year OS rates of 41.1%, 67.0%, and 29.0%, respectively (P < 0.001). In conclusion, cHCC‐CC patients appear to have intermediate demographic, clinical, and survival characteristics in comparison with HCC and CC patients. cHCC‐CC patients undergoing LT showed inferior survival in comparison with HCC patients, and the role and indications for LT in cHCC‐CC have yet to be defined. At this time, MJH may be considered the best therapeutic approach for such patients. Liver Transpl 20:952–959, 2014.

Surgical treatment of liver metastases of gastric cancer: state of the art

BackgroundThe prognosis of patients with liver metastases from gastric cancer (LMGC) is dismal, and little is known about prognostic factors in these patients; so justification for surgical resection is still controversial. Furthermore the results of chemotherapy for these patients are disappointing. The purpose of this study was to review recent outcomes of hepatectomy for LMGC and to determine the suitable candidates for surgery, assessing the surgical results and clinicopathologic features. Moreover we compare these results with those obtained with alternative treatments.

An alternative approach in endocrine pathology research: MALDI-IMS in papillary thyroid carcinoma

To the Editor, Many different molecular techniques (polymerase chain reaction (PCR), DNA sequencing, fluorescence in situ hybridization (FISH)) have been introduced in thyroid pathology [1]. Fewer studies evaluated the role of proteomic analysis in the research of new useful targets [2, 3]. Matrixassisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a unique technology that explores the spatial distribution of biomolecules directly in situ, thus integrating molecular and morphological information. Therefore, we are investigating the potential role of MALDIIMS in detecting new diagnostic targets in papillary thyroid carcinoma (PTC). We have addressed the issue of molecular stratification of PTC in a small cohort of samples, evaluating both the genomic profile of the main genes of interest (BRAF, N-H-K RAS point mutations, and PAX8/PPARγ or RET/PTC rearrangements) and the proteomic profile shown byMALDIIMS analysis. We have collected ex vivo cytological specimens (see “Technical Note”), in order to analyse a sample perfectly mimicking the in vivo fine-needle aspiration (FNA) biopsy, while respecting the ethical requirements. Unsupervised proteomic analysis of the samples was followed by comparison with histopathology and genetic classification of the patients (Table 1). Data generated by MALDI-IMS were submitted to hierarchical cluster analysis (HCA), in order to evaluate the different proteomic expressions in the cases under study. HCA allowed to cluster proteomic spectra based on their similarity on a dendrogram: spectra showing comparable features were grouped under the same node of the dendrogram; then, it was possible to select nodes and assign them a specific colour (Fig. 1) [4]. Node A groups together three cytological specimens (two collected from patient 1 and one from patient 2), all histologically diagnosed as hyperplastic benign nodules. Node B groups together specimens collected from patients 3, 4 and 5, who were affected by PTC comparable for stage and histotype (Table 1). Node C, instead, groups a microcarcinoma (follicular variant (fv) of PTC), from patient 6, and a nodule histologically classified as uncertain malignant potential (UMP) tumour (patient 7). The last one, originated in a multinodular goitre environment and showed ambiguous morphological features, defined as borderline between a hyperplastic nodule and an “incipient” fv,PTC. The three distinct nodes (A, B, C) generated by HCA analysis confirmed that MALDI-IMS can potentially discriminate between benign and malignant thyroid lesions. Moreover, the homologies between cases 6 and 7 highlight that MALDI-IMS is able to identify a PTC even when the classic diagnostic morphological aspects are still unclear and ambiguous (mild nuclear clearing, rare grooves, no pseudoinclusions). This finding is in agreement Veronica Mainini and Fabio Pagni equally contributed to this paper.

Proteomics in thyroid cytopathology: Relevance of MALDI-imaging in distinguishing malignant from benign lesions.

Several proteomic strategies are used extensively for the purpose of biomarker discovery and in order to obtain insights into the molecular aspects of cancers, using either body fluids or tissue as samples. Among them, MALDI‐imaging can be applied to cytological thyroid specimens to investigate the molecular signatures of different pathological conditions and highlight differences in the proteome that are of relevance for diagnostic and pathogenetic research. In this study, 26 ex‐vivo fine needle aspirations from benign thyroid nodules (n = 13) and papillary thyroid carcinomas (n = 13) were analyzed by MALDI‐imaging. Based on the specific protein signatures capable of distinguishing the aforementioned patients, MALDI‐imaging was able to correctly assign, in blind, the specimens from ten additional FNABs to a malignant or benign class, as later confirmed by the morphological classification. Moreover, some proteins presented a progressive overexpression in malignant phenotypes when compared with Hashimotos thyroiditis and hyperplastic/follicular adenoma. This data not only suggests that a MALDI‐imaging based approach can be a valuable tool in the diagnosis of thyroid lesions but also in the detection of proteins that have a possible role in the promotion of tumorigenic activity.

Bleeding in Hepatic Surgery: Sorting through Methods to Prevent It

Liver resections are demanding operations which can have life threatening complications although they are performed by experienced liver surgeons. The parameter “Blood Loss” has a central role in liver surgery, and different strategies to minimize it are a key to improve results. Moreover, recently, new technologies are applied in the field of liver surgery, having one goal: safer and easier liver operations. The aim of this paper is to review the different principal solutions to the problem of blood loss in hepatic surgery, focusing on technical aspects of new devices.

Proteomic profiles of thyroid tumors by mass spectrometry-imaging on tissue microarrays.

The current study proposes the successful use of a mass spectrometry-imaging technology that explores the composition of biomolecules and their spatial distribution directly on-tissue to differentially classify benign and malignant cases, as well as different histotypes. To identify new specific markers, we investigated with this technology a wide histological Tissue Microarray (TMA)-based thyroid lesion series. Results showed specific protein signatures for malignant and benign specimens and allowed to build clusters comprising several proteins with discriminant capabilities. Among them, FINC, ACTB1, LMNA, HSP7C and KAD1 were identified by LC-ESI-MS/MS and found up-expressed in malignant lesions. These findings represent the opening of further investigations for their translation into clinical practice, e.g. for setting up new immunohistochemical stainings, and for a better understanding of thyroid lesions. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.

Consecutive concomitant laparoscopic splenectomy and cholecystectomy: an Italian experience of 30 patients and proposition of a technique.

INTRODUCTION With recent advancements in the field of minimally invasive surgery, combined laparoscopic procedure is now being performed for treating coexisting abdominal pathologies during the same surgery. In some patients, spleen disorders are associated with gallbladder stones. Conventional surgery requires a wide upper abdominal incision for correct exposure of both organs. The aim of this study was to assess the feasibility and outcomes of concomitant laparoscopic treatment for coexisting spleen and gallbladder diseases. MATERIALS AND METHODS Thirty consecutive laparoscopic splenectomy (LS) plus laparoscopic cholecystectomy (LC) have been performed in our department between January 2000 and December 2009 (24% of 125 LS performed in this period). There were 11 female patients and 19 male patients, with a median age of 16.2 years (range: 4-55). Indications were hereditary spherocytosis for 22 cases, idiopathic thrombocytopenic purpura for 3 cases, thalassemia for 4 cases, and sickle cell disease for 1 case. Patients were operated on using right semilateral position, tilting the table from right to left, using a five-trocar technique in 25 cases and a four-trocar technique in the last 5 cases. Cholecystectomy was performed first, then splenectomy was achieved, and spleen was removed in an Endobag. RESULTS One patient required conversion to open procedure (3.3%) because of splenomegaly. Average operative time was 150 minutes (range: 90-240). Average length of stay was 3.5 days (range: 3-11). Mean blood loss was 60  mL (range: 30-500). Transfusion rate was 3.3%. Mean spleen size and weight were, respectively, 16.5  cm and 410  g. No perioperative mortality occurred in the series. We reported 3 cases of hemoperitoneum, of which one managed conservatively. The results using four trocars were comparable to those with five trocars. CONCLUSION With increasing institutional experience, concomitant laparoscopic splenectomy and cholecystectomy is a safe and feasible procedure and may be considered for coexisting spleen and gallbladder diseases. The four-trocar technique guarantees good results.

Solid cell nests of the thyroid gland: morphological, immunohistochemical and genetic features

The correct identification of solid cell nests (SCNs) is an important issue in thyroid pathology because of the spectrum of differential diagnoses of this type of lesion.

Challenging diagnosis of ileal gastrointestinal stromal tumor presenting with obscure digestive bleeding.

We report a case of a patient observed in emergency condition for recurrent episodes of massive obscure gastrointestinal bleeding that required surgical control. At laparotomy we found an ileal mass with the characteristics of a gastrointestinal stromal tumor (GIST) at histopathological analysis. GISTs should always be considered as a possible cause of obscure gastrointestinal bleeding, although they are often difficult to diagnose preoperatively. Laparotomy is sometimes the only way to obtain a diagnosis. Starting from this case, we reviewed the literature about GISTs, focusing our attention on their diagnosis and the possible surgical and nonsurgical therapies.

Hepatic resection beyond barcelona clinic liver cancer indication: When and how

Hepatocellular carcinoma (HCC) is the main common primary tumour of the liver and it is usually associated with cirrhosis. The barcelona clinic liver cancer (BCLC) classification has been approved as guidance for HCC treatment algorithms by the European Association for the Study of Liver and the American Association for the Study of Liver Disease. According to this algorithm, hepatic resection should be performed only in patients with small single tumours of 2-3 cm without signs of portal hypertension (PHT) or hyperbilirubinemia. BCLC classification has been criticised and many studies have shown that multiple tumors and large tumors, as wide as those with macrovascular infiltration and PHT, could benefit from liver resection. Consequently, treatment guidelines should be revised and patients with intermediate/advanced stage HCC, when technically resectable, should receive the opportunity to be treated with radical surgical treatment. Nevertheless, the surgical treatment of HCC on cirrhosis is complex: The goal to be oncologically radical has always to be balanced with the necessity to minimize organ damage. The aim of this review was to analyze when and how liver resection could be indicated beyond BCLC indication. In particular, the role of multidisciplinary approach to assure a proper indication, of the intraoperative ultrasound for intra-operative restaging and resection guidance and of laparoscopy to minimize surgical trauma have been enhanced.