Alessandro Paniccia

Characteristics of 10-Year Survivors of Pancreatic Ductal Adenocarcinoma

IMPORTANCE To our knowledge, this study reports on the largest cohort of long-term survivors (LTSs) (≥10 years) following a diagnosis of pancreatic ductal adenocarcinoma (PADC) and identifies the characteristics associated with LTS. OBJECTIVE To determine patient, tumor, surgical, and sociodemographic characteristics associated with LTS. DESIGN, SETTING, AND PARTICIPANTS A nationwide retrospective cohort study of patients with invasive PADC (International Classification of Diseases for Oncology, Third Edition codes 8140/3, 8500/3, 8021/3, and 8035/3) was conducted using data collected in the National Cancer Database (NCDB). A multivariable logistic regression model of factors significantly associated with LTS was developed and used to generate a nomogram predicting the likelihood of surviving at least 10 years from initial diagnosis. Data collected from more than 1500 academic centers and community hospitals in the United States and Puerto Rico were assessed. Patients included were those with histologically proven PADC who underwent pancreatic surgical resection aimed at removal of the primary tumor between January 1, 1998, and December 31, 2002 (n = 11,917). The initial cohort (n = 70,915) excluded noninvasive tumors or tumors with unknown histology (n = 11,696) and was limited to patients who underwent surgical resection (n = 47,302 excluded). Analysis was conducted from January 1, 1998, to December 31, 2011. EXPOSURES Pancreatic ductal adenocarcinoma. MAIN OUTCOMES AND MEASURES Long-term survival, defined as surviving at least 10 years from initial diagnosis. RESULTS Of the 11,081 patients with complete survival information, 431 individuals (3.9%) were LTSs. Significant predictors of LTS included (determined using odds ratio [OR]; 95% CI), in order of importance, lymph node positivity ratio (0%: 4.6; 3.4-6.4), adjuvant chemotherapy (2.4; 2.0-3.0), pathologic T stage (T1: 3.1; 1.8-5.6), patient age (50-60 years: 3.4; 1.8-6.7), tumor grade (well differentiated: 2.2; 1.5-3.0), surgical margin (negative: 1.9; 1.4-2.6), pathologic M stage (M = X: 5.6; 2.1-22.8), tumor size (<2 cm: 1.7; 1.2-2.5), educational level (>86% high school graduates: 1.7; 1.2-2.4), and insurance status according to the patients zip code (private: 2.0; 95% CI, 0.9-5.1). The model C index was 0.768. Based on our nomogram, patients with the most favorable characteristics had an 18.1% chance of LTS. Furthermore, survival curves demonstrated that the probability of dying following initial diagnosis of PADC reached a plateau of approximately 10% per year after 7 years of survival. CONCLUSIONS AND RELEVANCE Although PADC remains a deadly disease, long-term survival is possible, even beyond the 10-year mark. Our adjusted analysis identified lymph node ratio, administration of adjuvant chemotherapy, and pathologic T stage as being the top 3 variables associated with LTS of PADC. In addition, our easy-to-use nomogram may be able to identify potential LTS among patients with resected PADC.

Identification of CD112R as a novel checkpoint for human T cells

Zhu et al. report the identification of CD112R as a new coinhibitory receptor of the TIGIT–DNAM-1 family for human T cells.

Neoadjuvant FOLFIRINOX Application in Borderline Resectable Pancreatic Adenocarcinoma: A Retrospective Cohort Study

Abstract5-Fluorouracile, oxaliplatin, irinotecan, and leucovorin (FOLFIRINOX) has not been extensively used in the neoadjuvant setting because of concerns with safety and toxicity. We evaluated our institutional experience with neoadjuvant FOLFIRINOX in borderline resectable pancreatic adenocarcinoma (BRPAC). The primary endpoints were completion of therapy to surgery and negative resection margin (R0) rate.Patients with BRPAC treated with neoadjuvant FOLFIRINOX were retrospectively analyzed. Between August 2011 and September 2013, 20 patients with BRPAC treated with neoadjuvant FOLFIRINOX were identified.Most patients (88.8%) completed FOLFIRINOX therapy and underwent resection. Abutment of venous structures was identified in 13 cases (72.2%), while short segment portal vein encasement in 3 cases (16.6%) with concomitant arterial involvement in 3 cases (16.6%). Isolated superior mesenteric artery abutment was identified in 2 cases (11.2%). Patients received a median of 4 cycles of FOLFIRINOX. There was 1 case of progression. Vascular resection was performed in 9 cases (52.9%). Preoperative radiation therapy was used in 8 patients (44%). All patients underwent margin negative resection (R0). Histopathologic treatment response was evident in 10 cases (58.8%).Neoadjuvant FOLFIRINOX was generally safe and the expected toxicity did not prevent surgery allowing for a high rate of R0 resection.

Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC.

Antenna coupling explains unintended thermal injury caused by common operating room monitoring devices.

Introduction: Unintended thermal injury from patient monitoring devices (eg, electrocardiogram pads, neuromonitoring leads) results in third-degree burns. A mechanism for these injuries is not clear. The monopolar “bovie” emits radiofrequency energy that transfers to nearby, nonelectrically active cables or wires without direct contact by capacitive and antenna coupling. The purpose of this study was to determine if, and to what extent, radiofrequency energy couples to common patient monitoring devices. Materials and Methods: In an ex vivo porcine model, monopolar radiofrequency energy was delivered to a handheld “bovie” pencil. Nonelectrically active neuromonitoring and cardiac-monitoring leads were placed in proximity to the monopolar pencil and its cord. Temperature changes of tissue touched by the monitoring lead were measured using a thermal camera immediately after a 5-second activation. The energy-device cords were then separated by 15 cm, the power was reduced from 30 W coag to 15 W coag and different cord angulation was tested. An advanced bipolar device, a plasma-based device, and an ultrasonic device were also tested at standard settings. Results: The neuromonitoring lead increased tissue temperature at the insertion site by 39±13°C (P<0.001) creating visible char at the skin. The electrocardiogram lead raised tissue temperature by 1.3±0.5°C (P<0.001). Decreasing generator power from 30 W to 15 W and separating the bovie cord from the neuromonitoring cord by 15 cm significantly reduced the temperature change (39±13°C vs. 26±5°C; P<0.001 and 39±13°C vs. 10±5°C; P<0.001, respectively). Lastly, monopolar energy increased tissue temperatures significantly more than argon beam energy (34±15°C), advanced bipolar energy (0.2±0.4°C), and ultrasonic energy (0±0.3°C) (all P<0.001). Conclusions: Stray energy couples to commonly used patient monitoring devices resulting in potentially significant thermal injury. The handheld bovie cord transfers energy via antenna coupling to neuromonitoring leads that can raise tissue temperatures over 100°F (39°C) using standard settings. The most effective ways to decrease this energy coupling is to reduce generator power, increase the separation between wires, or utilize lower voltage energy devices such as ultrasonic or bipolar energy.

Surgical Margin in Hepatic Resections for Colorectal Metastasis: Should We Care?

Many studies seek to define the appropriate margin width necessary to confer the best survival advantage following hepatic resection for colorectal metastatic disease. The ability to achieve at least a 1-cm tumor-free margin has historically represented one of the strongest prognostic factors determining overall outcomes and has been a necessary condition for resectability. With the advent of modern chemotherapy, the importance of surgical margin width is increasingly questioned and our understanding of its impact is evolving concomitantly to the improvement and the widespread use of more effective systemic chemotherapeutic agents. Although achieving a microscopic margin-negative resection (R0) remains the goal of surgical resection, specific tumor biology factors should be consider in deciding on the appropriate margin width. In this review, we summarize the most recent evidence regarding the importance of the surgical margin in hepatic resection for colorectal metastasis in the era of modern chemotherapy.

Diagnostic Operation of the Liver and Techniques of Hepatic Resection

Abstract The indications for liver resection are various and include benign or malignant, as well as primary or secondary, conditions of the liver. The surgeon performing liver resection must have a clear understanding of the liver functional anatomy and must always strive for the resection of the minimum amount of liver parenchyma necessary to achieve appropriate removal of the pathologic lesion(s) with appropriate margins. The techniques of liver resection have varied minimally throughout the years, with the exception of the introduction of new instrumentation dedicated to liver parenchymal transection, and the popularization of laparoscopy in the armamentarium of the liver surgeon. A few fundamental principles must always be adhered to and includes extremely careful preoperative patient selection aimed at ensuring an adequate functional liver remnant with good vascular inflow, vascular outflow, and biliary drainage. In this chapter, we present an overview of the liver functional anatomy and illustrate the most common techniques of liver biopsy and liver parenchymal transection and their associated complications.

Development of Cancer Vaccine and Targeted Immune Checkpoint Therapies

Pancreatic cancer is one of the deadliest cancer types, and current therapeutic strategies are often unsatisfactory. Therefore, novel approaches are necessary to fight against this challenging disease. Great progress has been made recently in cancer immunotherapy, which is revolutionizing our clinical approaches to cancer treatment. However, few single immunotherapeutic approaches are successful in treating pancreatic cancer. In pancreatic cancer, the unique immunosuppressive microenvironment with massive stromal cells, poses great challenges. Novel or combinatory therapies targeting the tumor microenvironment have shown some promising results in clinical trials, with the aim to disarm this resistance, reverse the tumor microenvironment, and to promote immune effector cell infiltration. This review covers current major advances in the field of cancer immunotherapy, and also discusses the immunotherapeutic strategies used in current trials and those under development for pancreatic cancer.

Impact of neoadjuvant chemoradiation on perioperative outcomes in patients with rectal cancer

Neoadjuvant chemoradiation for rectal cancer is associated with lower local recurrence rates. The objective of this study is to assess the impact of neoadjuvant therapy on perioperative complications in patients with rectal cancer.

Anaplastic Pancreatic Carcinoma Arising Within a Mucinous Cystic Neoplasm of the Pancreas: A Case Report and a Brief Review of the Literature

Abstract Background: Anaplastic pancreatic carcinomas (APCs) are among the least frequently encountered pancreatic malignancies, ranging from 0.5% to 7% of all nonendocrine pancreatic malignancies. Furthermore, few cases of APCs have been described arising within a pancreatic mucinous cystic neoplasm (MCN). Case Presentation: A 36-year-old female presented with left upper quadrant pain and a 10 × 8 cm complex cystic mass in the pancreatic tail. Fine needle aspiration of the cyst showed papillary clusters of cells with mild cytological atypia, cyst fluid carcinoembryonic antigen >4000 ng/mL, and amylase of 25 U/L. After an open distal pancreatectomy and splenectomy, the specimen revealed an MCN with multifocal microscopic foci of invasive well-differentiated adenocarcinoma. After additional sampling, foci of undifferentiated malignancy—morphologically resembling sarcomas but with immunohistochemical staining consistent with anaplastic carcinoma—were identified. The patient had an uneventful recovery and is currently undergoing a regimen of gemcitabine-based adjuvant chemotherapy; she remains disease-free at 5 months after initial diagnosis. Conclusions: In this study, we describe a rare case of APC originating from a large pancreatic MCN lesion. This case underlines the importance of scrupulous pathological evaluation of the entire MCN epithelium and adds to the limited world literature of APC originating from pancreatic MCN lesions.