Francesco Giovinazzo

Laparoscopic hepatic resection

BackgroundAlthough laparoscopy in general surgery is increasingly being performed, only recently has liver surgery been performed with laparoscopy. We critically review our experience with laparoscopic liver resections.MethodsFrom January 2000 to April 2004, we performed laparoscopic hepatic resection in 16 patients with 18 hepatic lesions. Nine lesions were benign in seven patients (five hydatid cysts, three hemangiomas, and one simple cyst), five were malignant in five patients (five hepatocarcinoma), and four patients had an uncertain preoperative diagnosis (one suspected hemangioma and three suspected adenomas). The mean lesion size was 5.2 cm (range, 1–12). Twelve lesions were located in the left lobe, three were in segment VI, one was in segment V, one was in segment IV, and one was in the subcapsular part of segment VIII.ResultsThe conversion rate was 6.2%; intraoperative bleeding requiring blood transfusions occurred in two patients. Mean operative time was 120 min. Mean hospital stay was 4 days (range, 2–7). There were no major postoperative complications and no mortality.ConclusionsHepatic resection with laparoscopy is feasible in malignant and benign hepatic lesions located in the left lobe and anterior inferior right lobe segments (IV, V, and VI). Results are similar to those of the open surgical technique in carefully selected cases, although studies with large numbers of patients are necessary to drawn definite conclusions.

Effects of Dietary Components on Cancer of the Digestive System

Cancer is the second leading cause of death in developed countries and poor diet and physical inactivity are major risk factors in cancer-related deaths. Therefore, interventions to reduce levels of smoking, improve diet, and increase physical activity must become much higher priorities in the general populations health and health care systems. The consumption of fruit and vegetables exerts a preventive effect towards cancer and in recent years natural dietary agents have attracted great attention in the scientific community and among the general public. Foods, such as tomatoes, olive oil, broccoli, garlic, onions, berries, soy bean, honey, tea, aloe vera, grapes, rosemary, basil, chili peppers, carrots, pomegranate, and curcuma contain active components that can influence the initiation and the progression of carcinogenesis, acting on pathways implied in cell proliferation, apoptosis and metastasis. The present review illustrates the main foods and their active components, including their antioxidant, cytotoxic, and pro-apoptotic properties, with a particular focus on the evidence related to cancers of the digestive system.

Concomitant pulmonary carcinoma and abdominal aortic aneurysm: Therapeutic strategies

PurposeA diagnosis of concomitant pulmonary carcinoma and abdominal aortic aneurysm is rare (<1% of treated cases). However, such an association makes the therapeutic decisions critical, especially regarding the priority and timing of treatment. This article reports on our experience of 14 cases of concomitant pulmonary carcinoma and abdominal aortic aneurysm.MethodsFrom April 1987 to June 2006 we observed 14 cases of concomitant pulmonary carcinoma and abdominal aortic aneurysm. In patients for whom simultaneous treatment was not indicated due to a poor general condition, priority was given to lung cancer except for cases in which the aneurysm needed an urgent approach. Patients observed after 2000 and scheduled for a two-stage treatment were treated with endovascular procedures whenever possible.ResultsOnly one patient was treated by a simultaneous aneurysmectomy and a left lower lobectomy, while in the other 13 patients two-stage treatment was performed. Lung carcinoma was operated on first in 7 cases but one patient underwent an urgent aneurysmectomy after chest surgery due to a rupture of the aneurysm. Priority was given to an aneurysmectomy in 2 patients. An endovascular approach was performed in 4 patients, thus allowing a pulmonary resection during the same period of hospitalization, 2 days after 2 uneventful endovascular procedures and on the 6th and 7th postoperative days in 2 cases due to an intraoperative rupture of right iliac artery and type I postoperative endoleak, respectively.ConclusionAn endovascular exclusion of the aneurysm may therefore be proposed in order to achieve a concomitant treatment of both diseases. Such an approach excludes complications due to a postoperative rupture of the aneurysm when a pulmonary resection would be first performed; moreover, it does not delay the performance of a pulmonary resection when treatment of the aneurysm is considered to have priority.

Intra-thoracic desmoid tumour in a patient with a previous aortocoronary bypass.

BackgroundIntra-thoracic desmoid tumours with mediastinal invasion are very rare. Although rare they have to be taken into account in the differential diagnosis of a thoracic mass and therapeutic options have to be weighted since surgical treatment may require wide excision.Case presentationA 48-year-old male diabetic, dyslipidaemic, former heavy smoker with psychiatric illness was operated by sternotomy for a triple aorto-coronary bypass 4 years before, presented with complains of recent onset such as constant and oppressive chest pain. At surgery a mass extending from the aortic arch into the entire anterior mediastinum and to most of the right pleural cavity was found. The mass was separated from sternal periosteum and vessels of aorto-coronary by pass were isolated starting from the aortic arch up to the pericardium. The histological examination revealed aggressive fibromatosis.ConclusionAlthough technically demanding, radical surgical excision is actually the most indicated therapeutic approach for intra-thoracic desmoid tumours.

Ectopic expression of the heterotrimeric G15 protein in pancreatic carcinoma and its potential in cancer signal transduction

G15 is a heterotrimeric G protein selectively expressed in immature cell lineages in adult tissues that feature higher cell renewal potential. It promiscuously couples a wide variety of G protein-coupled receptors (GPCRs) to phospholipase C. Intriguingly, G15 is poorly affected by GPCR desensitization. We show here that G15 α-subunit (Gα15) supports sustained stimulation of PKD1 by a constitutively desensitized GPCR co-transfected over a negative cell background. Based on the fact that PKD1 is a multifunctional protein kinase activated by PKC and known for promoting oncogenic signaling, we hypothesized that, if expressed out of its natural cell context, G15 might promote tumor growth. A screening for Gα15 mRNA expression pointed to pancreatic carcinoma among different human cancer cell types and revealed significant expression in human tumor biopsies xenografted in mice. In addition, G15 ectopic presence could functionally contribute to the transformation process since siRNA-induced depletion of Gα15 in pancreatic carcinoma cell lines dramatically inhibited anchorage-independent growth and resistance to the lack of nutrients. Altogether, our findings suggest that G15 supports tumorigenic signaling in pancreas and hence it may be considered as a novel potential target for the therapy of this form of cancer.

Monosegment ALPPS hepatectomy preserving segment 4 for colorectal liver metastases: literature review and our experience

Monosegment 4±1 Associating Liver Partition and Portal Vein ligation for Staged hepatectomy (ALPPS) for bilateral colorectal liver metastases decreases the risk of drop-out of two stage hepatectomy, triggering a rapid and significant increase in future liver remnant (FLR) with promising oncological outcomes. We report two cases of segment 4+1 monosegment ALPPS for multiple colorectal liver metastases performed at our institution. In the literature, seven similar cases have been reported. Short and long term outcomes of our two patients were reported along with a review of data from the literature. Our patients showed a FLR increase from 13% to 37% and from 14% to 41% of total liver volume, respectively. This was compared to a median growth from 19% at baseline to 34% before stage 2, in the literature. After 20 and 27 months since resection both patients are alive and disease-free. In the literature, median overall survival and disease free survival were 13 months (range, 5-24 months) and 5 months (range, 3-23 months), respectively. Segment 4±1 ALPPS is associated with promising oncological outcomes and a significant FLR growth. It may be safely performed in selected patients as a salvage procedure, reducing the risk of the dropout of two-stage hepatectomy.

Basic science, translational research and surgery: an unresolved controversy

During the centuries, surgeons have contributed to the advance of the medicine improving the surgical outcomes in daily clinical practice and participating to the progress of the basic research science. In 1909, Dr. Teododor Koker was the first surgeon to win the Nobel Prize, and in 1990, Dr. Joseph Murray was the seventh and the last surgeon to reach the award [1]. Therefore, together with other academic figures traditionally more oriented towards basic science, the surgeon always had an irreplaceable role in the development of medical science from both points of view, practical and intellectual through a process of gradual awareness and participation in the development of the research projects [2]. In recent years, the explosion of molecular biology has shown that this discipline, often confined to basic research, occupies an important place in surgical research. The impact on clinical practice varies from the analysis of molecular biomarkers and genetic risk of cancer to the application of transgenic technologies in xenografts [3]. Playing in this scenario, the question about the role of the surgeon in translational research and basic science becomes every day more urgent to plane the future of the Academic Departments of Surgery, whose central mission is to produce new knowledge and validate the laboratory results in the clinical practice. Therefore, looking at this radical change of perspective, the academic surgical community is called to answer several questions. Is it sufficient for us to be a good surgeon focused only on the quality of care or worth equipping and accepting the challenge, playing a game in an integrated research system? Could the strong practical experience of the surgical disciplines improve the theoretical approaches of basic sciences? Could the privileged relationship with the patient help to humanize the research interpreting the deepest need of the human being? Could the surgeon contribute to drive the results of basic science towards clinical applications in the era of genomics and proteomics? All these questions converge towards the conclusions that in the future academic surgeons will have a key role in the development of translational research program, and the surgical community needs to re-address our own vision of the research [4].

The Biological Effects of Preconditioning Hyperbaric Oxygen Therapy in Pancreaticoduodenectomy: Results of a Randomized, Double-Blind Trial in Humans

Context Hyperbaric oxygen (HBO) therapy involves the intermittent inhalation of 100% oxygen in chambers pressurized between 1.5 and 3.0 atmosphere absolute (ATA). HBO attenuates the production of pro-inflammatory cytokines in response to the inflammatory stimulus such surgery and the subsequent modulation of immune response. The positive role of HBO in human surgery was demonstrated only in cardiovascular and orthopedic surgery and after liver transplantation. Pancreaticoduodenectomy (PD) represents one of the most important surgical procedures burdened by a considerable number of local and systemic complication, ranging between 30 and 60%. Objective The main objective of this study was to identify the possible presence of major differences between the concentration of inflammatory cytokines in two study groups depending on the receiving or not HBO before PD procedure. Secondary objective was the comparison of the complication rate and hospital stay between the two study groups. Materials and methods The study was a prospective, randomized double-blind study lasting 6 months. Ethics approval was obtained from local ethics committee (2176/2012). Thirty-two patients were recruited to this study. Twenty-four hours before PD, atients of group “A” were submitted to HBO session while patients of group “B” breathed air in an hyperbaric chamber pressurized to 1.15 ATA (placebo procedure). In all patients, blood was taken before (T0) and at the end HBO session or placebo procedure (T1), in the first post-operative day (T2) and in the seventh post-operative day (T3). It was used to measured IL-1, IL-6, IL-8, IL-10, IL-12p70 and TNF-α. For the evaluation of the post-operative outcome we considered the presence of postoperative pancreatic fistula (POPF), biliary fistula, fever, intra-abdominal collections, bleeding, pulmonary complications, delay gastric empty and the use of postoperative antibiotics. Result Significant differences in favor of HBO group were found regarding the pulmonary complications (none in HBO group versus 6 in the placebo group; P=0.023). The maximum concentration of cytokines is in T2 and HBO exposure can modulated the concentration of IL-6 and IL-10 (P=0.009 and P=0.030 HBO vs . placebo). Conclusions Preliminary data suggest that preconditioning hyperbaric oxygen therapy is safe and can be applied to all patients after careful clinical evaluation and identification of absolute contraindications with a potential role in decreasing the pulmonary complications.

Gα15 Potential as a Biomarker for Pancreatic Carcinoma

Context Pancreatic carcinoma still lacks specific markers. Earlier diagnosis could benefit many patients anticipating resection or other potential cures that today have palliative effects. In addition, differential diagnosis of suspect lesions obtained by imaging could spare resections of benign tumors. Here, we analyzed Gα15 as a potential diagnostic marker. Gα15 is an intracellular signaling protein that we previously found to be ectopically expressed in the pancreas upon transformation. Objective To establish a correlation between the presence of malignant cells in human pancreas and Gα15 mRNA expression in biopsies and in the blood. Methods Microarray studies available in Oncomine analyzing pancreatic cancer were selected; all data sets including human pancreatic cancer cases paired to adjacent healthy tissue were taken in consideration, for a total of 54 pairs of samples. Furthermore, free RNA was extracted from serum of patients affected by pancreatic cancer. First-strand cDNA was generated retrotranscribing with random hexamers. RT PCR was performed using TaqMan gene-specific primers and probe specific for Gα15 sequence. Results All three microarrays datasets, normalized to compare neoplastic to normal tissues, report Gα15 overexpression in neoplastic tissue with higher Gα15 mRNA levels in 49/54 patients. The presence of circulating Gα15 mRNA was assessed in the serum of 8 adenocarcinoma patients showing a significant increase over samples obtained from 8 healthy donors. Conclusions Gα15 mRNA appearance in neoplastic pancreas or in the blood stream should be explored to assess its potential as an indicator of the presence of malignant cells.