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Il tumore del pancreas si attesta come l'ottava causa di morte nel mondo, con oltre 40.000 nuovi casi attesi negli USA nel 2014.In Italia rappresenta il 3% di tutti i tumori in entrambi i sessi costituendo la quarta causa di morte per tumore nella donna e la quinta negli uomini. Si registra, quasi per tutte e neoplasie, un gradiente di incidenza nord-sud con una maggiore incidenza al nord del paese. Il carcinoma pancreatico è più frequente tra sesto e settimo decennio e colpisce maggiormente il sesso maschile. La prognosi è ancora oggi estremamente infausta, sia a causa della diagnosi spesso tardiva della malattia, sia in rapporto alle scarse possibilità terapeutiche, senza alcun significativo aumento di sopravvivenza nel corso degli ultimi anni.

Context Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with few effective therapies. Although next-generation sequencing (NGS) further clarified the genomic complexity of PDAC, genes or pathways that specifically drive tumour progression or metastasis are not well understood. Objective Our challenge is to implement a whole transcriptome massively parallel sequencing (RNASeq) study to better understand the PDAC molecular biology for diagnosis and prognosis of PDAC. Methods We collected a total of 17 PDAC samples by ultrasound-guided biopsy or by surgical specimen for RNA extraction. Fourteen samples were analyzed by RNASeq, performed at 75x2 bp on a HiScanSQ Illumina platform. To study gene expression profiling related to poor outcome, we first studied differentially expressed genes between “poor” (overall survival 36 months; n=3) prognosis in a total of 6 PDAC sample. Results The relative presence of tumor cells in the sample was evaluated based on the presence of KRAS mutation. A total of 211 genes were differentially expressed. Genes involved in the p53 signalling pathway (CSNK1G1, TGFA), the Wnt/β-catenin (DKK1, WNT7B, WNT10A), insulin-like growth factor system (IGF2) and EGF receptor signalling pathway (EGF) were highly upregulated in “poor” PDAC samples. Interestingly, we found a strong overexpression of CA125/MUC16, recently demonstrated to be involved in PDCA and ovarian cancer invasion by stimulating matrix metalloproteinases 7. Conclusion Components of p53 signalling pathway, Wnt/β-catenin pathways, insulin-like growth factor system and MUC16 might be useful molecular markers in PDCA as their overexpression seems to be related with cancer growth, invasion and prognosis. Further validation of the role of these genes is necessary for translation in clinical practice., JOP. Journal of the Pancreas, Vol 14, N° 5S (2013): September (Suppl.) - p. 528-602

Context We merged clinical history of a locally advanced pancreatic cancer (LAPC) patient with data obtained from a whole transcriptome massively parallel sequencing (RNASeq). Case report A 56-year-old man with histological diagnosis of LAPC. After obtained informed consent, we collected a fragment of pancreatic lesion. Patient received 6 induction cycles treatment with gemcitabine and oxaliplatin (GEMOX) from November 2011, followed by chemoradiotherapy with bi-weekly gemcitabine 50 mg/m2 for 6 weeks. CT-scan demonstrated partial response, so patient received additional 12 cycles of GEMOX, with further response, which currently persist since 17 months (to 3.8 cm vs. 2.5 cm). At the same time, the RNASeq was performed at 75x2 bp on a HiScanSQ (Illumina Inc., San Diego, CA, USA) platform. Single nucleotide variants (SNVs) were detected with SNVMix2 and filtered on dbSNP, 1000 Genomes Project, and Cosmic databases. Non-synonymous SNVs were analyzed with SNPs&GO and PROVEAN. We highlighted the major oncogenic hits of LAPC, confirming KRAS mutations, CDKN2A and SMAD4 deletions. RNASeq analysis showed a somatic mutation p.H672D involving the catalytic domain of hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, not yet reported neither in the COSMIC nor in the ICGC databases. Furthermore, 4 new genomic rearrangements leading to fusion genes emerged: 2 in-frame gene fusions regulating RAS-MAPK and apoptotic pathways (ANKRD44-GULP1 on chromosome 2; ATXN10-TMEM49; chromosome 22 and 17) and 2 out-of-frame fusions [t(15;3) and t(19;22)] leading to SMAD3-KIAA1143 and LTBP4-SPATS2L, both disrupting genes of the TGFbeta pathway. Conclusion We found a novel somatic alteration involving HMGCR in LAPC. Due to the key role of HMGCR in cellular transformation, we hypothesize a strong potential in the development and outcome of LAPC, whose the optimal treatment remains to be elucidated. Trials that integrate RNASeq data with clinical options are needed., JOP. Journal of the Pancreas, Vol 14, N° 5S (2013): September (Suppl.) - p. 528-602

Context Patients with locally advanced pancreatic cancer are usually treated with chemoradiotherapy and rarely they became resectable. Herein, we present the case of a patient with locally advanced pancreatic cancer. Case report A 56-year-old man was observed in October 2011 because of high blood levels of CA 19.9 (>230 U/mL) and the presence of a pancreatic mass of the uncinate process (diameter 3.8x3.5 cm) revealed by US and CT scan. An US-guided biopsy allowed the diagnosis of well differentiated pancreatic adenocarcinoma, biliopancreatic type. CT scan showed a vascular involvement of both superior mesenteric vein and artery. The disease was defined as locally advanced unresectable pancreatic cancer. The patient started chemotherapy with gemcitabine and oxaliplatin. Five months later, CT scan re-evaluation of the disease showed a stable disease. Thus, a protocol of radio-chemotherapy was suggested. Eight months later from diagnosis, the mass was still unresectable. Other eight cycles of gemcitabine and oxaliplatin were performed. In February 2013 a further CT scan evaluation demonstrated a smaller lesion (3.5x2.2 cm) and also the vascular involvement was decreased, still without a normal fat plane between the tumor and the vessels. Another cycle of gemcitabine and oxaliplatin was completed. At the end of May 2013, the 18FDG-PET was negative; CT scan demonstrated a further decreased of the mass (maximum diameter: 2.5 cm) while the mesenteric vessels involvement still remained. Moreover, the genomic characteristics of the patient DNA were different from other the pancreatic cancer. Because of the long-term survival of the young patient, the partial regression of the disease and the genomic characteristics of the tumor, a surgical approach was indicated. The patient underwent to a total pancreatectomy with splenectomy plus segmental resection of portal mesenteric trunk. Pathological diagnosis confirmed a well-differentiated ductal pancreatic carcinoma, biliopancreatic type (T4), with R0 resection. Conclusion Our case suggests that there are locally advanced pancreatic cancers in which chemoradiotherapy can allow surgical pancreatic resection probably because they have particular genomic characteristics., JOP. Journal of the Pancreas, Vol 14, N° 5S (2013): September (Suppl.) - p. 528-602

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a 5-year survival rate of 4%. Even if some genetic hits leading to PDAC development are known, a deeper knowledge of the genetic landscape of tumor is necessary to identify druggable targets. Methods: PDAC samples from 14 localized and advanced cases of pancreatic adenocarcinomas were collected by ultrasound-guided biopsy used for DNA and RNA extraction. High resolution copy number analysis was performed on Affymetrix SNP array 6.0 and analyzed with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). Whole transcriptome massively parallel sequencing was performed at 75x2 bp on a HiScanSQ Illumina platform. An average of 7,3x107 reads per sample were generated, with a mean read depth of 50X. Single nucleotide variants (SNVs) were detected with SNVMix2 and compared with genetic variation databases (dbSNP, 1000genomes, Cosmic). Non-synonimous SNVs were analyzed with SNPs&GO and SIFT to predict disease association. Results: Whole transcriptome sequencing showed that PDAC samples exhibited a mean of 145 (range: 61-240) non-synonimous SNVs, of which 16 on average are potentially disease-related. 9/14 patients exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 copy number alterations per patient, while 5 patients did not show any copy number gain or loss. Most frequent gains were observed in 18q11.2 involving GATA6 (3/14) and 19q13 targeting AKT2 (3/14) while hotspot deleted regions were found on 18q21 (7/14), 17p13 (6/14), 9p21.3 (6/14), 15q (5/14) and 1q35 (4/14). Merging copy number and RNAseq data we highlighted the major oncogenic hits of PDAC, confirming the prevalence (9/14) of KRAS mutations, in one case also NRAS (G13D), and the central role of the three oncosuppressor CDKN2A (mutated in 3 cases and deleted in 6 cases, either in hetero- or homozygosity), SMAD4 (altered by either point mutation or gene deletion in 8/14 cases), and TP53 (lost in 7/14 samples). We identified novel pathogenic single nucleotide variants and frameshift mutations, and inter- and intra-chromosomal translocation events that give rise to chimeric fusion transcripts. Even if the mutation profile was heterogeneous in different patients the signaling pathways affected were shared, and included KRAS/MAPK, TGFbeta and integrin signaling, proliferation and apoptosis, DNA damage response, and epithelial to mesenchymal transition. New oncogenic alterations emerged, as ARID1A that was inactivated by somatic mutation (G91R and P1425fs) or copy number loss in 6 patients, NOTCH2 and HMGCR, that displayed pathogenic mutations in 15-20% of the analyzed patients. Conclusions: Next generation sequencing combined with high resolution cytogenetic analysis can improve the understanding of carcinogenesis and highlight new biomarkers for early diagnosis and potential therapeutic targets in PDAC.

Context Assessment of response after chemotherapy (CTH) for pancreatic cancer (PC) is currently based on RECIST criteria. In 2007 Choi et al. published a new classification system. Objectives To evaluate the accuracy of the two classification systems for radiological response to CTH in patients affected by advanced PC. Methods From 2006 to 2011, 61 untreated patients affected by advanced pancreatic adenocarcinoma underwent palliative CTH. Thirty-seven (60.7 %) had a locally advanced PC and 24 (39.3%) a metastatic disease. All patients were treated with a bemcitabine-based CTH. We assessed radiological response after three months of first-line therapy applying both RECIST criteria and Choi’s criteria, which consider changes both in size and in density at CT. We evaluated the accuracy in restaging, comparing the class of response with overall survival (OS). OS was calculated with Kaplan-Meier method. The concordance with the two classification systems was evaluated with Kendall’s test. The accuracy in restaging was assessed through log rank test. Results At restaging, using RECIST criteria, we registered 6 (9.8%) patients with partial response (PR), 32 (52.5%) with stable disease (SD), and 23 (37.7%) with disease progression (PD). Instead Choi’s criteria assessed 18 PR (29.5%), 12 SD (19.7%) and 31 PD (50.8%). The concordance test showed that the two systems matched (Pvs. 9 months; P=0.009; RR=2.3). Conclusions Choi’s criteria seem to better assess radiological response of CTH in PC patients than RECIST criteria. Due to the small number of patients, larger prospective studies are needed., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

Context Pancreatic cancer (PC) is the fourth leading cause of cancer deaths. The molecular mechanisms involved in the high tumorigenicity of PC are not yet well-known. Methods Pancreatic tumor samples from 14 patients were collected by ultrasound-guided biopsy and used for DNA extraction. High resolution copy number analysis was performed on Affymetrix SNP array 6.0 and analyzed with segmentation algorithm against a reference of 270 Ceu HapMap individuals (Partek Genomic Suite). Results Nine out of 14 patients exhibited both macroscopic and cryptic cytogenetic alterations, with a mean of 10 copy number alterations (CNA) per patient, while 5 patients did not show any copy number gain or loss. Deletions outnumbered amplifications by more than 2 folds. The chromosomes showing more copy number gains were chromosomes 12, 18, 19, while chromosomes 6, 9, 17 and 18 were most frequently deleted. In particular, deletions on 9p21 encompassed CDKN2A and 2B tumor suppressor genes, that on chromosome 18q21 overlapped with SMAD4, the one on chromosome 6p21 included RUNX2, while TP53 and MAP2K4 were the target genes deleted on chromosome 17p13. Amplified regions on chromosome 12p12 encompassed KRAS and ETV6 genes, the one on chromosome 18q11 overlapped with GATA6, while that on 19q13 included AKT2. We observed that the number of alterations correlates with the clinical course, and in particular that patients with none to few alterations (≤6) showed a median time to disease progression and a median overall survival significantly longer than those having a high number of CNA (>6), with a time to disease progression of 13.7 vs. 4.1 months (P=0.015) and an overall survival of 14.6 vs. 4.8 months (P=0.035). Conclusions High resolution cytogenetic analysis by SNP-array has the potential to uncover the genetic alterations carried by pancreatic tumors, and find new markers related to patient prognosis., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

Context Pancreatic cancer (PC) is characterized by a 5-year survival rate of 4%. The molecular mechanisms involved in the high tumorigenicity of PC are not yet well-known. Methods PC samples from 7 localized and advanced cases of pancreatic adenocarcinomas were collected by ultrasound-guided biopsy. Whole transcriptome RNA libraries were sequenced at 75x2 bp on a HiScanSQ Illumina platform. An average of 4.5x107 reads per sample were generated, with a mean read depth of 40. Sequences were mapped to the human genome (build hg19) and the single nucleotide variants (SNVs) were detected with SNVMix2 tool. The SNVs were compared with genetic variations databanks (dbSNP, 1000genomes, Cosmic) in order to highlight the novel variants. The non-synonimous SNVs were considered at the protein level and analyzed with SNPs&GO, in order to predict whether a variation is disease-related or neutral. Results Pancreatic adenocarcinomas exhibited a mean of 139 (range: 65-252) non-synonimous SNVs, of which 12 on average are potentially disease-related. We found mutations in oncogenes and tumor suppressor genes known to be related to pancreatic tumors, as 4/7 patients exhibited KRAS oncogenic variants (p.G12D, R or V) two of which carried also mutations either in SMAD4 or PIK3CA, one patient showed both TP53 and CDKN2A inactivating mutations and one a mutation in SMARCA4. Novel disease-related SNVs were found in genes regulating cell cycle progression and proliferation, apoptosis, TGFbeta and integrin-signaling, epithelial to mesenchymal transition and nucleotide excision repair. Of interest some genes were mutated in multiple patients, as CBLC that regulates intracellular signalling by multiple tyrosine kinase genes. Conclusions Next generation sequencing analysis, through the identification of the oncogenic alterations carried by tumor cells, can improve the understanding of pancreatic carcinogenesis and highlight new biomarkers for early diagnosis and potential therapeutic targets in pancreatic cancer., JOP. Journal of the Pancreas, Vol 13, N° 5S (2012): September (Suppl.) - p. 548-650

Context We report a case of clinical benefit and RP with GemOx in patient with cystadenocarcinoma of pancreas with ovarian metastasis. Case report In July 2008 a 42-year-old woman complained of abdominal pain and constipation. The CT scan and the MR showed the presence of two bilateral ovarian mass with pancreatic extension. The patient arrived then to our hospital and ECOG PS was 2. She underwent bilateral ovarian and womb resection. During surgery peritoneal carcinosis, a pancreatic mass and multiple abdominal lesions were found. Multiple biopsies of pancreatic lesion and other abdominal lesions documented mucinous cystadenocarcinoma of pancreas, with ovarian and peritoneal metastases. In December 2008 the patient started chemotherapy (CHT) with gemcitabine 1000 mg/m2/dL and oxaliplatin 100 mg/m2/d2 every 2 weeks (GemOx). After 6 cycles of CHT a CT scan showed a stable disease. Clinical conditions were good (ECOG 0) so we decided to continue the medical treatment with other 6 cycles of CHT. In August 2009 a CT scan showed a reduction of the abdominal mass, and a surgical resection was then possible. The patient underwent distal pancreatic resection, regional lymphadenectomy and splenectomy. Pathologic examination documented biliopancreatic well differentiated adenocarcinoma. Surgical margins presented malignant cells and mucoid areas without cells. After surgery we decided to continue CHT with gemcitabine as "adjuvant treatment" for other 3 cycles, CT scan showed no disease, clinical conditions were good and the patient stopped the treatment. Actually there is no evidence or relapse. Conclusion As reported in literature, GemOx is associated with improvement in PFS and clinical benefit in patient with advanced pancreatic cancer. This is an interesting case where GemOx leaded inoperable pancreatic cancer to a operable cancer.

// Sandra Durante 1, * , Silvia Vecchiarelli 2, * , Annalisa Astolfi 1 , Elisa Grassi 2 , Riccardo Casadei 3 , Donatella Santini 4 , Riccardo Panzacchi 4 , Claudio Ricci 3 , Salvatore Serravalle 5 , Giuseppe Tarantino 1 , Mirella Falconi 6 , Gabriella Teti 6 , Valentina Indio 1 , Andrea Pession 5 , Francesco Minni 3 , Guido Biasco 1, 2 , Mariacristina Di Marco 2 1 Giorgio Prodi Cancer Research Centre, University of Bologna, Bologna, Italy 2 Department of Experimental, Diagnostic and Specialty Medicine University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy 3 Department of Medical and Surgical Sciences, University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna, Italy 4 Pathology Unit, Sant'Orsola-Malpighi Hospital, Bologna, Italy 5 Department of Medical and Surgical Sciences, “Lalla Seragnoli” Hematology-Oncology Unit, University of Bologna, Bologna, Italy 6 DIBINEM—Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy * These authors contributed equally to this work Correspondence to: Annalisa Astolfi, email: annalisa.astolfi@unibo.it Keywords: PDA, IPMN, chromosome 3, NGS, PIK3CA Received: April 11, 2016 Accepted: August 10, 2016 Published: August 22, 2016 ABSTRACT Background: Intraductal papillary mucinous neoplasm (IPMN) is the most common cystic preneoplastic lesion of pancreatic cancer. We used an approach coupling high resolution cytogenetic analysis (Affymetrix Oncoscan FFPE Array) with clinically-oriented bioinformatic interpretation of data to understand the most relevant alterations of precursor lesions at different stages to identify new diagnostic markers. Results: We identified multiple copy number alterations, particularly in lesions with severe dysplasia, with 7 IPMN with low-intermediate dysplasia carrying a nearly normal karyotype and 13 IPMN with complex Karyotype (> 4 alterations), showing high grade dysplasia. A specific gain of chromosome arm 3q was found in IPMN with complex Karyotype (92%). This gain of 3q is particularly interesting for the presence of oncogenes such as PIK3CA, GATA2 and TERC that are part of pathways that deregulate cell growth and promote disease progression. Quantitative PCR and FISH analysis confirmed the data . Further demonstration of the overexpression of the PIK3CA gene supports the identification of this alteration as a possible biomarker in the early identification of patients with IPMN at higher risk for disease progression. Materials and methods: High resolution cytogenetic analysis was performed in 20 formalin fixed paraffin embedded samples of IPMN by Oncoscan FFPE assay. Results were validated by qPCR and FISH analysis. Conclusions: The identification of these markers at an early stage of disease onset could help to identify patients at risk for cancer progression and new candidates for a more specific targeted therapy.

// Silvia Vecchiarelli 1, * , Francesco Passiglia 2, * , Armida D’Incecco 3, * , Marianna Gallo 4 , Antonella De Luca 4 , Elisa Rossi 5 , Federica D’Inca 1 , Gabriele Minuti 1 , Lorenza Landi 1 , Chiara Bennati 1 , Michela Spreafico 1 , Manolo D’Arcangelo 1 , Valentina Mazza 1 , Nicola Normanno 4 and Federico Cappuzzo 1 1 Department of Oncology and Hematology, AUSL della Romagna, Ravenna, Italy 2 Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy 3 Medical Oncology and Immunotherapy, University Hospital of Siena, Siena, Italy 4 Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori "Fondazione G Pascale"-IRCCS, Naples, Italy 5 Fondazione Ricerca Traslazionale, Rome, Italy * These authors contributed equally to this work Correspondence to: Federico Cappuzzo, email: federico.cappuzzo@auslromagna.it Keywords: PD-L1; immunotherapy; biomarkers; non-small-cell lung cancer Received: November 28, 2017 Accepted: February 27, 2018 Published: April 03, 2018 ABSTRACT Background: This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome. Methods: Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p -value. Results: Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort ( p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months ( p = 0.062) and 8.8 vs 9.3 months ( p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant ( p = 0.063). Conclusions: This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations.

The aim of the current study was to implement whole transcriptome massively parallel sequencing (RNASeq) and copy number analysis to investigate the molecular biology of pancreatic ductal adenocarcinoma (PDAC). Samples from 16 patients with PDAC were collected by ultrasound‑guided biopsy or from surgical specimens for DNA and RNA extraction. All samples were analyzed by RNASeq performed at 75x2 base pairs on a HiScanSQ Illumina platform. Single‑nucleotide variants (SNVs) were detected with SNVMix and filtered on dbSNP, 1000 Genomes and Cosmic. Non‑synonymous SNVs were analyzed with SNPs&GO and PROVEAN. A total of 13 samples were analyzed by high resolution copy number analysis on an Affymetrix SNP array 6.0. RNAseq resulted in an average of 264 coding non‑synonymous novel SNVs (ranging from 146‑374) and 16 novel insertions or deletions (In/Dels) (ranging from 6‑24) for each sample, of which a mean of 11.2% were disease‑associated and somatic events, while 34.7% were frameshift somatic In/Dels. From this analysis, alterations in the known oncogenes associated with PDAC were observed, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (93.7%) and inactivation of cyclin‑dependent kinase inhibitor 2A (CDKN2A) (50%), mothers against decapentaplegic homolog 4 (SMAD4) (50%), and tumor protein 53 (TP53) (56%). One case that was negative for KRAS exhibited a G13D neuroblastoma RAS viral oncogene homolog mutation. In addition, gene fusions were detected in 10 samples for a total of 23 different intra‑ or inter‑chromosomal rearrangements, however, a recurrent fusion transcript remains to be identified. SNP arrays identified macroscopic and cryptic cytogenetic alterations in 85% of patients. Gains were observed in the chromosome arms 6p, 12p, 18q and 19q which contain KRAS, GATA binding protein 6, protein kinase B and cyclin D3. Deletions were identified on chromosome arms 1p, 9p, 6p, 18q, 10q, 15q, 17p, 21q and 19q which involve TP53, CDKN2A/B, SMAD4, runt‑related transcription factor 2, AT‑rich interactive domain‑containing protein 1A, phosphatase and tensin homolog and serine/threonine kinase 11. In conclusion, genetic alterations in PDCA were observed to involve numerous pathways including cell migration, transforming growth factor‑β signaling, apoptosis, cell proliferation and DNA damage repair. However, signaling alterations were not observed in all tumors and key mutations appeared to differ between PDAC cases.

Cystic lymphangioma is a type of benign tumor originating from the lymph vessels. The tumor commonly occurs in childhood, in the head or neck regions, and retroperitoneal localization and presentations in adulthood are rare. Determining a pre-operative diagnosis is often challenging, and in the majority of cases, a diagnosis is only possible subsequent to the histological examination of the surgical specimen. A radical resection is the recommended treatment for cystic lymphangioma, and recurrence is usually due to an incomplete excision of the mass. The present study reports 2 cases of cystic lymphangioma, localized in the pancreatic gland and duodenal wall respectively, which were treated with surgical resection. The study also briefly reviews the literature regarding the differential diagnosis of retroperitoneal cystic masses.