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1.
Endosc Int Open ; 12(1): E116-E122, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38250162

ABSTRACT

Background and study aims To assess the outcomes of urgent endoscopic retrograde cholangiopancreatography (ERCP) performed with a single-use duodenoscope (SUD) in patients with moderate-to-severe cholangitis. Patients and methods Between 2021 and 2022 consecutive patients with moderate-to-severe cholangitis were prospectively enrolled to undergo urgent ERCP with SUD. Technical success was defined as the completion of the planned procedure with SUD. Multivariate analysis was used to identify factors related to incidence of adverse events (AEs) and mortality. Results Thirty-five consecutive patients (15 female, age 81.4±6.7 years) were enrolled. Twelve (34.3%) had severe cholangitis; 26 (74.3%) had an American Society of Anesthesiologists (ASA) score ≥3. Twenty-eight patients (80.0%) had a naïve papilla. Biliary sphincterotomy and complete stone clearance were performed in 29 (82.9%) and 30 patients (85.7%), respectively; in three cases (8.6%), concomitant endoscopic ultrasound-gallbladder drainage was performed. Technical and clinical success rates were 100%. Thirty-day and 3-month mortality were 2.9% and 14.3%, respectively. One patient had mild post-ERCP pancreatitis and two had delayed bleeding. No patient or procedural variables were related to AEs. ASA score 4 and leucopenia were related to 3-month mortality; on multivariate analysis, leukopenia was the only variable independently related to 3-month mortality (odds ratio 12.8; 95% confidence interval 1.03-157.2; P =0.03). Conclusions The results of this "proof of concept" study suggest that SUD use could be considered safe and effective for urgent ERCP for acute cholangitis. This approach abolishes duodenoscope contamination from infected patients without impairing clinical outcomes.

2.
Updates Surg ; 75(8): 2391-2394, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37843793

ABSTRACT

Hartmann's reversal as a staged procedure after emergency surgery is a major abdominal operation with undeniable skill-demanding steps. The robotic approach and its advantages seem to be a safe and feasible technique and could overcome necessary technical compromises of laparoscopy, ensuring a significant reduction in restoration failures or conversion.


Subject(s)
Laparoscopy , Robotic Surgical Procedures , Humans , Colostomy/methods , Feasibility Studies , Anastomosis, Surgical/methods , Laparoscopy/methods , Retrospective Studies , Postoperative Complications , Treatment Outcome
3.
Minerva Surg ; 78(6): 633-637, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37161866

ABSTRACT

BACKGROUND: Abdominal wall hernias and incisional hernias are a common benign disorder affecting quality of life, potentially leading to life-threatening complications. Laparoscopic IPOM (intraperitoneal onlay mesh) approach can offer good results in selected cases. METHODS: Patients who underwent laparoscopic incisional/ventral abdominal hernia repair operated with standardized technique and the same mesh, from January 2011 to December 2022, were retrospectively considered. RESULTS: Four hundred consecutive patients underwent laparoscopic abdominal wall repair. There were 255 ventral hernia (63%) and 145 (37%) primitive hernia (epigastric and umbilical). Mean size of the defect was 4.2 cm, W3 were 19 (4%). After a mean follow-up of 1906 days (range 45-4109), no mesh-related complications have been detected. There were 10 (2.5%) recurrences and 20 (5%) bulging. CONCLUSIONS: In this study we emphasized the role of patient selection and standardized technique which represents "the lesson" learned over a period of 15 years of activity. In this setting, we believe that laparoscopic approach can achieve very good results in abdominal wall repair.


Subject(s)
Hernia, Ventral , Laparoscopy , Humans , Surgical Mesh/adverse effects , Retrospective Studies , Quality of Life , Recurrence , Hernia, Ventral/surgery , Laparoscopy/adverse effects , Laparoscopy/methods
4.
Int J Surg ; 109(3): 244-254, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-37093069

ABSTRACT

BACKGROUND: The use of a simultaneous resection (SIMR) in patients with synchronous colorectal liver metastases (sCRLM) has increased over the past decades. However, it remains unclear when a SIMR is beneficial and when it should be avoided. The aim of this retrospective cohort study was therefore to compare the outcomes of a SIMR for sCRLM in different settings, and to assess which factors are independently associated with unfavorable outcomes. METHODS: To perform this retrospective cohort study, patients with sCRLM undergoing SIMR (2004-2019) were extracted from an international multicenter database, and their outcomes were compared after stratification according to the type of liver and colorectal resection performed. Factors associated with unfavorable outcomes were identified through multivariable logistic regression. RESULTS: Overall, 766 patients were included, encompassing colorectal resections combined with a major liver resection (n=122), minor liver resection in the anterolateral (n=407), or posterosuperior segments ('Technically major', n=237). Minor and technically major resections, compared to major resections, were more often combined with a rectal resection (29.2 and 36.7 vs. 20.5%, respectively, both P=0.003) and performed fully laparoscopic (22.9 and 23.2 vs. 6.6%, respectively, both P = 0.003). Major and technically major resections, compared to minor resections, were more often associated with intraoperative transfusions (42.9 and 38.8 vs. 20%, respectively, both P = 0.003) and unfavorable incidents (9.6 and 9.8 vs. 3.3%, respectively, both P≤0.063). Major resections were associated, compared to minor and technically major resections, with a higher overall morbidity rate (64.8 vs. 50.4 and 49.4%, respectively, both P≤0.024) and a longer length of stay (12 vs. 10 days, both P≤0.042). American Society of Anesthesiologists grades ≥3 [adjusted odds ratio (aOR): 1.671, P=0.015] and undergoing a major liver resection (aOR: 1.788, P=0.047) were independently associated with an increased risk of severe morbidity, while undergoing a left-sided colectomy was associated with a decreased risk (aOR: 0.574, P=0.013). CONCLUSIONS: SIMR should primarily be reserved for sCRLM patients in whom a minor or technically major liver resection would suffice and those requiring a left-sided colectomy. These findings should be confirmed by randomized studies comparing SIMR with staged resections.


Subject(s)
Colorectal Neoplasms , Laparoscopy , Liver Neoplasms , Humans , Retrospective Studies , Colorectal Neoplasms/pathology , Hepatectomy/adverse effects , Liver Neoplasms/surgery , Colectomy
5.
Minerva Surg ; 78(4): 361-370, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36883936

ABSTRACT

BACKGROUND: Incisional hernias (IH) are one of the major complications following abdominal surgery and the treatment of large abdominal hernias represents a challenge for the surgeon. We present our own modified open intraperitoneal mesh technique, named "IPOW technique" (intra-peritoneal mesh open repair without dissections). METHODS: We analyzed early postoperative complications (seroma, wound infection, hematoma) and the late ones (recurrence, chronic pain), in 50 unselected patients treated for IH and primary hernia (PH) larger than 5 cm using the proposed laparotomic technique. RESULTS: From January 2019 to September 2021, 50 unselected patients with, at least, one year of follow-up, with hernias ranging from 5 to 25 cm in width, were surgically repaired using IPOW technique. Mean Body Mass Index (BMI) was 29 (range 22-44). In our series, we report 2 (4%) complications and, after a mean follow-up of 847 days (range 481-1357), 2 (4%) recurrences. No patients reported chronic pain. CONCLUSIONS: In our experience, we consider IPOW technique easily reproducible, ensuring excellent results with a reduction of invasiveness, comparing to other techniques. Anyway, definitive conclusions require a larger number of patients.


Subject(s)
Chronic Pain , Hernia, Ventral , Incisional Hernia , Humans , Surgical Mesh , Hernia, Ventral/surgery , Incisional Hernia/surgery , Postoperative Complications/epidemiology
6.
Diagnostics (Basel) ; 12(5)2022 Apr 23.
Article in English | MEDLINE | ID: mdl-35626213

ABSTRACT

Despite the efforts made in the management of PDAC, the 5-year relative survival rate of pancreatic ductal adenocarcinoma (PDAC) still remains very low (10%). To date, precision oncology is far from being ready to be applied in cases of PDAC, although studies exploring the molecular and genetic alterations have been conducted, and the genomic landscape of PDAC has been characterized. This study aimed to apply a next-generation sequencing (NGS) laboratory-developed multigene panel to PDAC samples to find molecular alterations that could be associated with histopathological features and clinical outcomes. A total of 68 PDACs were characterized by using a laboratory-developed multigene NGS panel. KRAS and TP53 mutations were the more frequent alterations in 75.0% and 44.6% of cases, respectively. In the majority (58.7%) of specimens, more than one mutation was detected, mainly in KRAS and TP53 genes. KRAS mutation was significantly associated with a shorter time in tumor recurrence compared with KRAS wild-type tumors. Intriguingly, KRAS wild-type cases had a better short-term prognosis despite the lymph node status. In conclusion, our work highlights that the combination of KRAS mutation with the age of the patient and the lymph node status may help in predicting the outcome in PDAC patients.

7.
Updates Surg ; 74(2): 535-545, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35099776

ABSTRACT

Surgery has been the mainstay treatment for colorectal liver metastases (CRLM). Although the benefits of a laparoscopic approach have been evidenced by several comparative studies, the comparison between robotic and laparoscopic liver surgery has not been elucidated. Thus, in this study, we aim to analyze the short-term outcomes of a multicenter population that underwent robotic versus laparoscopic liver resection for CRLM. Consecutive patients with CRLM who were enrolled in the IGoMILS registry between November 2014 and June 2019 were retrospectively evaluated to compare robot-assisted procedures with laparoscopic procedures. Primary outcomes were postoperative morbidity and mortality, while secondary outcomes were length of hospital stay, operative time, and histological features of the surgical specimen. The effect size of surgical technique on resection margins was quantified using Hedges' g. In total, 1030 patients underwent minimally invasive liver surgery (MILS) for CRLM; of these, 77 (7.5%) underwent a robot-assisted approach (R-MILS), whereas 953 (92.5%) underwent a laparoscopic approach (L-MILS). Laparoscopy and robot-assisted surgery were comparable in terms of postoperative outcomes: specifically, complication rates, Comprehensive Complication Index (CCI®), intraoperative blood loss, conversion rate, operative time, and length of hospital stay did not differ significantly between the two groups. R-MILS showed a reduced rate of R1 resection margins (19.9 vs. 28.8%, p = 0.025) and wider surgical margins compared with L-MILS (8 vs. 3 mm, p < 0.001). The effect size of robot-assisted surgery was increased for posterosuperior lesions (g = 0.78) and difficult procedures (g = 1.92). As per our findings, it was determined that robot-assisted liver surgery offers some technical advantages over conventional laparoscopy, maintaining the benefits of minimally invasive surgery on short-term outcomes.


Subject(s)
Colorectal Neoplasms , Laparoscopy , Liver Neoplasms , Robotic Surgical Procedures , Colorectal Neoplasms/surgery , Humans , Length of Stay , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Margins of Excision , Minimally Invasive Surgical Procedures , Postoperative Complications/epidemiology , Postoperative Complications/surgery , Registries , Retrospective Studies , Treatment Outcome
8.
World J Surg ; 45(11): 3424-3435, 2021 11.
Article in English | MEDLINE | ID: mdl-34313830

ABSTRACT

BACKGROUND: The aim of the study was to evaluate perioperative outcomes and to evaluate factors influencing rative morbidity and adoption of minimally invasive technique in 1-team (1-T) versus two teams (2-T) management of synchronous colorectal liver metastases. METHODS: Within four referral centers, a group of 234 patients treated in 1-T centers was identified and compared with a group of 253 patients treated in 2-T. A nonparametric bootstrap process was applied to the original cohorts of 1-T group and 2-T group as a resampling method to obtain bootstrapped cohorts (155 patients per group). RESULTS: 33.5% of patients in 1-T boot group and 38.1% in the 2-T boot group were operated by laparoscopic approach. Multivariate analysis revealed that approach to primary tumor (laparoscopic or open) and intraoperative blood loss were independent prognostic factors for morbidity. Team approach did not show any significant correlation with incidence of postoperative complications nor with choice for laparoscopic approach. CONCLUSION: The optimization of team strategy for patients with SCRLM is not solely based on the adoption of a 1-T or 2-T approach, but should instead be based on the implementation of a standard protocol for management of these patients.


Subject(s)
Colorectal Neoplasms , Laparoscopy , Liver Neoplasms , Blood Loss, Surgical , Colorectal Neoplasms/surgery , Hepatectomy , Humans , Liver Neoplasms/surgery , Postoperative Complications/epidemiology , Treatment Outcome
9.
World J Gastroenterol ; 27(21): 2710-2726, 2021 Jun 07.
Article in English | MEDLINE | ID: mdl-34135550

ABSTRACT

Genetic alterations in pancreatic tumors can usually be classified in: (1) Mutational activation of oncogenes; (2) Inactivation of tumor suppressor genes; and (3) Inactivation of genome maintenance genes controlling the repair of DNA damage. Endoscopic ultrasound-guided fine-needle aspiration has improved pre-operative diagnosis, but the management of patients with a pancreatic lesion is still challenging. Molecular testing could help mainly in solving these "inconclusive" specimens. The introduction of multi-gene analysis approaches, such as next-generation sequencing, has provided a lot of useful information on the molecular characterization of pancreatic tumors. Different types of pancreatic tumors (e.g., pancreatic ductal adenocarcinomas, intraductal papillary mucinous neoplasms, solid pseudopapillary tumors) are characterized by specific molecular alterations. The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Carcinoma, Pancreatic Ductal/genetics , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans , Mutation , Oncogenes , Pancreatic Neoplasms/genetics
10.
Updates Surg ; 73(2): 753-762, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33394354

ABSTRACT

The COVID-19 pandemic has raised concerns about the negative impact of the fear of contagion on people's willingness to seek medical care and the subsequent effects on patients' prognosis. To date, not much is known about the outcomes of acute surgical diseases in this scenario. The aim of this multicenter observational study is to explore the effects of COVID-19 outbreak on the outcomes of patients who underwent surgery for peritonitis. Patients undergoing surgery for secondary peritonitis during the first COVID-19 surge in Italy (March 23-May 4, 2020-COVID period group) were compared with patients who underwent surgery during the same time interval of year 2019 (no-COVID period group). The primary endpoint was the development of postoperative complications. Logistic regression analysis was conducted to identify predictors of complications. Of the 332 patients studied, 149 were in the COVID period group and 183 were in the no-COVID period group. Patients in the COVID period group had an increased frequency of late presentations to the emergency departments (43% vs. 31.1%; P = 0.026) and a higher rate of postoperative complications (35.6% vs. 18%; P < 0.001). The same results were found in the subset analysis of patients with severe peritonitis at surgical exploration. The ASA score, severity of peritonitis, qSOFA score, diagnosis other than appendicitis, and COVID period resulted independent predictors of complications. During the COVID-19 pandemic patients with peritonitis had a higher rate of complicated postoperative courses, weighing on hospital costs and assistance efforts already pressured by the ongoing sanitary crisis.


Subject(s)
COVID-19/epidemiology , Peritonitis/surgery , Postoperative Complications/epidemiology , Adult , Emergencies , Female , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2
11.
Mol Biol Rep ; 47(10): 8235-8241, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32886326

ABSTRACT

Pancreatic adenocarcinoma (PDAC) is the most frequent histological type of malignancy in the pancreas. Extracellular matrix (ECM), plays a critical role during the process of human carcinogenesis and the possible diversity in matricellular proteins composition of ECM may have a significant impact on the clinical course of PDAC. Aim of this paper was to evaluate the expression of three matricellular proteins, including Periostin (POSTN), Tenascin (TNS) and Osteopontin (OPN), in PDAC from long-survival (LS) and non-long survival (NLS) patients. A total of 30 PDAC were analyzed, 15 from patients that survived more than 60 months after surgery (LS) and 15 that died from the disease within 24 (NLS). RNA was extracted and OPN, TNS and POSTN mRNA levels were evaluated by qRT-PCR. LS and NLS samples showed the same type of POSTN and TN isoforms. On the contrary, OPN seems to be preferentially expressed in NLS PDAC. Moreover, OPNb and OPNc isoforms were expressed exclusively in NLS samples. In conclusion, Our data led to hypothesize a possible relationship between the expression of different isoforms of each of these proteins and the clinical outcome of patients with PDAC.


Subject(s)
Adenocarcinoma , Cell Adhesion Molecules/biosynthesis , Neoplasm Proteins/biosynthesis , Osteopontin/biosynthesis , Pancreatic Neoplasms , Tenascin/biosynthesis , Adenocarcinoma/metabolism , Adenocarcinoma/mortality , Adenocarcinoma/surgery , Adult , Disease-Free Survival , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/surgery , Pilot Projects , Protein Isoforms/biosynthesis , Survival Rate
12.
J Laparoendosc Adv Surg Tech A ; 30(10): 1106-1109, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32762603

ABSTRACT

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a recent surgical advancement for increasing the rate of successful liver resection. This technique is particularly important for patients with advanced tumor burden in whom future liver remnant volume is estimated to be too small to meet hepatic metabolic demands. With increasing acceptance of laparoscopic liver surgery and the related experience, even complex liver resection techniques such as ALPPS have been performed laparoscopically to improve patient outcomes. However, conventional laparoscopy has certain technical limitations that can result in a lack of dexterity. By overcoming these limitations, robot-assisted laparoscopy could become the preferred procedure for complex liver resection. In this study, we describe the technique of fully robotic ALPPS with simultaneous left colectomy in a patient with stage IV colorectal cancer. We emphasize on the performance of the robotic platform during certain difficult steps of the procedure.


Subject(s)
Colectomy/methods , Colonic Neoplasms/surgery , Hepatectomy/methods , Laparoscopy/methods , Liver Neoplasms/surgery , Robotic Surgical Procedures/methods , Colonic Neoplasms/pathology , Female , Humans , Ligation , Liver Neoplasms/secondary , Middle Aged , Portal Vein/surgery
13.
Hepatobiliary Pancreat Dis Int ; 18(4): 389-394, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31230959

ABSTRACT

BACKGROUND: Borderline resectable pancreatic cancer may require extended resections in order to achieve tumor-free margins, especially in the case of up-front resections, but it is important to know the limits of surgical therapy in this disease. This study aimed to investigate the impact of extent of pancreatic and venous resection on short- and long-term outcomes in patients with pancreatic adenocarcinoma (PDAC). METHODS: This was a retrospective study from a prospectively maintained database of pancreatic resections for PDAC. Short- and long-term outcomes were analyzed in patients having borderline resectable PDAC submitted to up-front total pancreatectomy (TP) or pancreaticoduodenectomy (PD) with simultaneous portal vein (PV) and/or superior mesenteric vein (SMV) resection. Venous resections were carried out as tangential venous resection (TVR) or segmental venous resection (SVR). Patients were divided into 4 groups: (1) PD + TVR, (2) PD + SVR, (3) TP + TVR, (4) TP + SVR. Uni- and multivariate Cox regression analysis were performed to identify factors associated with survival. RESULTS: Ninety-nine patients were submitted to simultaneous pancreatic and venous resection for PDAC. Among them, 25 were submitted to PD + TVR (25.3%), 12 to PD + SVR (12.1%), 23 to TP + TVR (23.2%), and 39 to TP + SVR (39.4%). Overall, major morbidity (Clavien-Dindo grade ≥ IIIA) was 26.3%. Thirty- and 90-day mortality were 3% and 11.1%, respectively. There were no significant differences among groups in terms of short-term outcomes. Median overall survival of patients submitted to PD + TVR was significantly higher than those to TP+SVR (29.5 vs 7.9 months, P = 0.001). Multivariate analysis identified TP (HR = 2.11; 95% CI: 1.31-3.44; P = 0.002) and SVR (HR = 2.01; 95% CI: 1.27-3.15; P = 0.003) as the only independent prognostic factors for overall survival. CONCLUSIONS: Up-front TP associated to SVR was predictive of worse survival in borderline resectable PDAC. Perioperative treatments in high-risk surgical groups may improve such poor outcomes.


Subject(s)
Carcinoma, Pancreatic Ductal/surgery , Mesenteric Veins/surgery , Pancreatectomy , Pancreatic Neoplasms/surgery , Pancreaticoduodenectomy , Portal Vein/surgery , Aged , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Databases, Factual , Female , Humans , Male , Margins of Excision , Mesenteric Veins/pathology , Middle Aged , Pancreatectomy/adverse effects , Pancreatectomy/mortality , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Pancreaticoduodenectomy/adverse effects , Pancreaticoduodenectomy/mortality , Portal Vein/pathology , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
14.
J Transl Med ; 17(1): 61, 2019 02 28.
Article in English | MEDLINE | ID: mdl-30819202

ABSTRACT

BACKGROUND: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. METHODS: A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. RESULTS: We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. CONCLUSION: These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.


Subject(s)
Carcinogenesis/pathology , Diagnosis, Computer-Assisted , Extracellular Matrix/pathology , Pancreatic Neoplasms/pathology , Aged , Carcinogenesis/metabolism , Collagen/metabolism , Computer Simulation , Female , Fractals , Humans , Male , Middle Aged , Pancreas/metabolism , Pancreas/pathology , Pancreatic Neoplasms/metabolism , Pilot Projects , Pancreatic Neoplasms
15.
Int J Surg Pathol ; 27(1): 89-93, 2019 Feb.
Article in English | MEDLINE | ID: mdl-29996669

ABSTRACT

Carcinoma of the ampulla of Vater is an uncommon neoplasm and represents 0.5% of all gastrointestinal malignancies, being less common than carcinoma of the pancreas and bile ducts. The most common ampullary tumor is the adenocarcinoma with tubular growth pattern. Signet ring cell carcinoma is extremely rare. In this article, we report a case of signet ring cell carcinoma of the ampulla of Vater showing focal neuroendocrine amphicrine differentiation and intestinal phenotype, which occurred in a 49-year-old male who is still alive 7 years after surgery, without evidence of recurrence. This long-term survival might be attributed not only to the early stage of the disease but also to the neuroendocrine differentiation and the absence of genetic alterations.


Subject(s)
Ampulla of Vater/pathology , Carcinoma, Signet Ring Cell/pathology , Duodenal Neoplasms/pathology , Carcinoma, Signet Ring Cell/mortality , Cell Differentiation , Duodenal Neoplasms/mortality , Humans , Male , Middle Aged
16.
Arch Pathol Lab Med ; 142(4): 458-464, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29565213

ABSTRACT

CONTEXT: - Integration of the analysis of genetic markers with endoscopic ultrasound-guided fine-needle aspiration and cytologic evaluation has increased the accuracy of the preoperative diagnosis of pancreatic lesions. The application of high-throughput gene panel analysis using next-generation sequencing platforms is now offering a great opportunity for further improvements. OBJECTIVE: - To review the application of next-generation sequencing to the preoperative diagnosis of pancreatic lesions. DATA SOURCES: - For data acquisition, a PubMed search using the terms next-generation sequencing, pancreas, pancreatic lesions, pancreatic tumors, and EUS-FNA was performed covering the years 2000-2017. CONCLUSIONS: - KRAS remains the gene most widely studied for preoperative single-gene tests. Next-generation sequencing reliably allows analysis of multiple gene markers starting from limited amounts of DNA. The study of multigene panels has become a very attractive option for the management and preoperative risk stratification of patients with pancreatic cancer.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Pancreatic Ductal/diagnosis , High-Throughput Nucleotide Sequencing/methods , Pancreatic Neoplasms/diagnosis , Biomarkers, Tumor/genetics , Cytodiagnosis/methods , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans
17.
Pancreatology ; 18(1): 122-132, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29137857

ABSTRACT

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.


Subject(s)
Extracellular Matrix/metabolism , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Extracellular Matrix/genetics , Gene Expression Regulation, Neoplastic/physiology , Humans , Survival Analysis
18.
Cancer Biomark ; 21(2): 323-334, 2018 Feb 06.
Article in English | MEDLINE | ID: mdl-29103024

ABSTRACT

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing. SMAD4 and CDKN2A/p16 was tested using immunohistochemistry. MGMT promoter methylation was investigated. RESULTS: Tumors from "LS" have a lower prevalence of KRAS and TP53 mutations and had more frequently SMAD4 retained expression, if compared with that of patients died within 24 months from surgery. The survival of patients with wild-type KRAS and TP53 tumors was more than twice longer than that of patients bearing KRAS and TP53 mutations (90.2 vs. 41.1 months). Patients with KRAS wild-type tumors and that retained SMAD4 expression had a survival twice longer than cases with alterations in both genes (83.8 vs. 36.7 months). Eleven tumors (39.3%) showed MGMT methylation. CONCLUSIONS: Our data indicate that absence of KRAS, TP53 and SMAD4 genetic alterations may identify a subset of pancreatic carcinomas with better outcome.


Subject(s)
Adenocarcinoma/genetics , Carcinoma, Pancreatic Ductal/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Smad4 Protein/genetics , Tumor Suppressor Protein p53/genetics , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Aged , Cancer Survivors , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mutation , Proto-Oncogene Proteins p21(ras)/metabolism , Smad4 Protein/metabolism , Tumor Suppressor Protein p53/metabolism
19.
J Gastrointest Oncol ; 8(6): 1037-1045, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29299364

ABSTRACT

BACKGROUND: The recurrence rate, related to the unpredictable behavior of gastrointestinal stromal tumors (GISTs), continues to be a major topic of investigation, since no actual risk evaluation scales have proven to be exceedingly effective in predicting prognosis. We therefore focus in this study on investigating the predictive variables of disease recurrence. METHODS: Between September 2004 and January 2011, 34 patients, 18 males and 16 females with a median age of 62 (range, 27-87) years, underwent operations for primary, localized and advanced GISTs. Immunohistochemical profile, KIT and the platelet-derived growth factor receptor-alpha (PDGFR-α) gene mutations, tumor size, tumor site, mitotic index, synchronous tumors, adjuvant therapy, symptoms and gender were considered and analyzed as predictive variables. The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for tumor dimension to predict recurrence. RESULTS: The median follow-up (FU) was 20 months (range, 6-86 months). A first-line adjuvant therapy was performed in nine patients. Disease relapse occurred in five cases. The tumor size and the mitotic index were the strongest predictive factors (P<0.001). The optimal maximum value for the tumor size was 7 cm [area under the curve (AUC) =0.955]. CONCLUSIONS: In light of the most recent evidence, a tumor size of 7 cm should be considered the threshold value for malignancy, and smaller GISTs with low mitotic counts as tumors with a low-grade risk.

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