Maurizio Cervellera

Superoxide dismutase in gastric adenocarcinoma: is it a clinical biomarker in the development of cancer?

Abstract Gastric cancer is the second most common cancer worldwide. The involvement of reactive oxygen species (ROS) in the pathogenesis of gastric malignancies is well known. Many human tumours have shown significant changes in the activity and expression of superoxide dismutase (SOD), which might be correlated with clinical–pathological parameters for the prognosis of human carcinoma. The aim of this study is the detection of MnSOD and CuZnSOD activity and their expression in gastric adenocarcinoma and healthy tissues. Gastric samples (adenocarcinoma and healthy tissues) harvested during endoscopy or resected during surgery were used to determine MnSOD and CuZnSOD activity and expression by spectrophotometric and Western blotting assays. The total SOD activity was significantly higher (p<0.05) in healthy mucosa with respect to gastric adenocarcinomas. No differences were found in MnSOD activity and, on the contrary, CuZnSOD activity was significantly lower (p<0.001) in cancer samples with respect to normal mucosa. The rate of MnSOD/CuZnSOD activity in adenocarcinoma was over ninefold higher than that registered in healthy tissues (p<0.05). Moreover, in adenocarcinoma MnSOD activity represented the 83% of total SOD with respect to healthy tissues where the ratio was 52% (p<0.001). On the contrary, in cancer tissues, CuZnSOD activity accounted for only 17% of the total SOD (p<0.001 if compared with the values recorded in normal mucosa). After immunoblotting, MnSOD was more expressed in adenocarcinoma with respect to normal mucosa (p<0.001), while CuZnSOD was similarly expressed in adenocarcinoma and healthy tissues. The SOD activity assay might provide a specific and sensitive method of analysis that allows the differentiation of healthy tissue from tumour tissue. The MnSOD to CuZnSOD activity ratio, and the ratio between these two isoforms and total SOD, presented in this preliminary study might be considered in the identification of cancerous from healthy control tissue.

Biochemical Alterations from Normal Mucosa to Gastric Cancer by Ex vivo Magnetic Resonance Spectroscopy

Background and Aims: The metabolic profile and morphologic aspects of normal and pathologic human gastric mucosa were studied. The aim of the present research was the application of ex vivo high-resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS MRS) to the human gastric tissue to get information on the molecular steps involved in gastric carcinogenesis and the identification of biochemical markers useful for the development of in vivo MRS methodologies to diagnose gastric pathologies in clinical situations. Methods: Twelve normal subjects, five with autoimmune atrophic gastritis, five with Helicobacter pylori infection, and five with adenocarcinoma were examined. Ten biopsies were taken during endoscopy from each patient. Specimens from carcinoma were also obtained during gastrectomy. Of the 10 biopsies, 4 were used for histologic evaluation, 4 were fixed in glutaraldehyde and processed for transmission and scanning electron microscopy, and 2 were immersed in liquid nitrogen and stored at −85°C for monodimensional and bidimensional ex vivo HR-MAS MRS analysis. Results: Ex vivo HR-MAS MRS identified glycine, alanine, free choline, and triglycerides as possible molecular markers related to the human gastric mucosa differentiation toward preneoplastic and neoplastic conditions. Ultrastructural studies of autoimmune atrophic gastritis and gastric adenocarcinoma revealed lipid accumulations intracellularly and extracellularly associated with a severe prenecrotic hypoxia and mitochondria degeneration. Conclusions: This is the first report of synergic applications of ex vivo HR-MAS MRS and electron microscopy in studying the human gastric mucosa differentiation. This research provides useful information about some molecular steps involved in gastric carcinogenesis. The biochemical data obtained on gastric pathologic tissue could represent the basis for clinical applications of in vivo MRS. (Cancer Epidemiol Biomarkers Prev 2008;17(6):1386–95)

Laparoscopic appendectomy: Which factors are predictors of conversion? A high-volume prospective cohort study

UNLABELLED Appendicitis represents one of the most frequent condition requiring surgery. In Italy almost 0.2% of the population will be affected by acute appendicitis every year. Laparoscopic appendectomy (LA) has gained acceptance over the past years and despite several meta-analyses, randomized studies and retrospective studies have been conducted, the indications and results are still conflicting especially in cases of complicated appendicitis. The aim of our study is to evaluate which factors are related to conversion to open appendectomy (OA) during laparoscopic appendectomy (LA). MATHERIALS AND METHODS From September 2011 to May 2013, appendectomy for acute appendicitis was performed on 434 patients in our Surgical Unit at S. Orsola-Malpighi Hospital, Bologna, Italy. Of these, 369 patients (85%) underwent LA. The clinical, demographic, surgical and pathological data of these patients were included in a prospective database. To note, only laparoscopic appendectomies were considered to be included in the analysis. The following factors were analyzed in order to identify which were associated with the conversion: age, sex, body mass index (BMI), previous abdominal surgery, comorbidities, clinical and laboratory parameters including Alvarado score, PCR, intraoperative findings such as anatomy and degree of inflammation. During our study period, laparoscopic appendectomies were performed by different surgeons both residents and attending surgeons. The decision to convert the intervention in an open procedure was taken by the individual surgeon. Regarding the postoperative period, were considered the time of hospitalization and related costs, time of oral intake of liquid and solid, time of passage of stool, readmissions and reoperations. RESULTS At univariate analysis, the factors significantly related to the conversion were the presence of comorbidities (p < 0.001) and, among these, the presence of arterial hypertension (p = 0.006) or other cardiovascular diseases (p = 0.031) and the history of previous abdominal surgery (p = 0.023). Patients with higher mean age (33.9 ± 15.4 vs. 46.0 ± 19.3, p = 0.001) and higher body mass index (BMI) (23.5 ± 4.3 vs 25.8 ± 4.9 kg/m(2), p = 0.006) had a higher risk of conversion. Multivariate analysis finally showed that factors significantly related to the conversion were the presence of comorbidities (p = 0.029), the presence of an appendiceal perforation (p = 0.003), a retrocecal appendix (p = 0.004), the presence of appendicular abscess (p = 0.023) and the presence of diffuse peritonitis (p = 0.008). CONCLUSION The majority of patients with acute appendicitis can be successfully managed with laparoscopy. We found that the only preoperative independent factor related to conversion during laparoscopic appendectomy is the presence of comorbidities. Nevertheless surgeons should take into account that presence of peri-appendicular abscess and diffuse peritonitis are both independently related not only to higher rate of conversion but also to higher risk of postoperative complication.

The Multidisciplinary Management of Acute Complicated Diverticulitis

Background: Acute complicated diverticulitis (ACD) is an important and increasing issue in Western countries that leads to a significant impact and burden for patients, but also for the society due to its effects on hospital costs. In recent years, essential progression has been made regarding the research and implementation of novel or improved treatment strategies for the various disease entities of ACD. Much debated topics in the multidisciplinary approach of patients with ACD, such as the choice for nonoperative treatment options, the role of percutaneous drainage for diverticular abscesses, the role of laparoscopic lavage for perforated diverticulitis with purulent peritonitis, and the role of sigmoidectomy with primary anastomosis for patients with perforated diverticulitis, require clinicians to attentively follow and participate in these discussions. Summary: The aim of this review article is to provide clinicians with a structured overview of the recent literature on the multidisciplinary management of complicated diverticulitis by a panel of experts on the topic. By performing an extensive literature search in the online medical databases MEDLINE (Ovid) and Embase, insights into nonoperative treatment, percutaneous drainage, minimally invasive and open surgical treatment of ACD are provided. Furthermore, a comprehensive algorithm for the treatment of ACD has been developed. Key Messages: Accurate patient evaluation and selection based on patient and disease characteristics is of paramount importance to determine the appropriate treatment strategy for patients with complicated diverticulitis. The presence of an experienced surgeon with advanced skills in laparoscopic emergency colorectal surgery is crucial for the treatment of patients with perforated diverticulitis in order to properly evaluate, select and treat patients suitable for nonoperative or operative treatment with an open or laparoscopic approach.

Giant abdominal metastasis from cardiac liposarcoma

The patient was a 58-year-old man. His history began 6 years before the admission to our hospital because of a syncopal episode. MRI showed a 2 cm lesion at the confluence of the left pulmonary veins. It was surgically removed and the histopathological diagnosis was of ‘pleomorphic liposarcoma’. The postoperative course was regular. Since the patient lived in a rural area, he was not treated in a high-volume reference centre for sarcoma and follow-up was not managed by a dedicated multidisciplinary team. Three years later, for the onset of an intestinal occlusion, he underwent emergency laparotomy. An ileo-ileal invagination due to a little ileal lesion was treated with a 30 cm intestinal resection. The histopathological response was again of liposarcoma. Chemotherapy was not performed. One year later, a thoracoabdominal CT scan showed a heart recurrence and an enormous abdominal mass involving many ileal loops with intestinal subocclusion. The patient was evaluated in a reference centre for sarcoma and he was deemed inoperable. Because the symptomatology progressively worsened with continuous episodes of melena and severe anaemia, he showed up at our emergency department in extremely critical condition. Thoracoabdominal CT scan confirmed both abdominal and cardiac recurrences (figure 1). An emergency life-saving surgery …

A Rare Case of Intraductal Papillary Mucinous Carcinoma of the Pancreas

Context Intraductal papillary mucinous neoplasms (IPMN) of the pancreas represent an evolving pancreatic disease. Case report A 68-year-old asymptomatic woman, mild smoker, with clinical history of gallstones, arterial hypertension and surgical treatment for breast carcinoma, was admitted to our surgical unit in January 2012. An ultrasound examination, performed as a follow-up for gallstones, showed a cystic lesion of the pancreatic head. Laboratory tests revealed an increase of pancreatic amylases (114 U/L; reference range: 8-52 U/L) and lipases (89 U/L; reference range: 8-78 U/L), while tumor markers were within reference range. A contrast-enhanced CT scan showed the presence of a 22 mm diameter, multilocular, cystic lesion of the pancreatic head, with contrast-enhanced mural nodules. An endoscopic ultrasonography confirmed the lesion, the mural nodules and showed no dilatation of the main pancreatic duct (MPD); a fine needle aspiration (FNA) revealed an increase of CEA (416.6 ng/mL; reference range: 0-192 ng/mL) in the cystic fluid and cytological analysis showed mild to high grade dysplasia. The CEA levels were suggestive of a mucinous cystic neoplasm, while the presence of mural nodules suggested a malignant type II IPMN. Thus, a pancreaticoduodenectomy was performed. The postoperative course was uneventful and the patient was discharged in postoperative day 18 th . The pathological specimen macroscopically showed a solid 14 mm diameter microcystic lesion with endoluminal micropapillae. Microscopically, the lesion was characterized by a carcinoma with tubulo-papillary pattern of growth, atypical cube-shaped cells without cytoplasmatic mucin and intralesional necrotic foci. Moreover, in the pathological specimen, clusters of IPMN gastric-subtype, with low to moderate dysplasia, were detected. These findings suggested the diagnosis of a well differentiated tubulo-papillary carcinoma associated to a mild dysplasia type II IPMN. All lymph nodes were negative. The patient is well and alive at 6 months from surgery. Conclusion To our knowledge, in literature only ten cases of ITPN were reported and its peculiar characteristic seems to be a more aggressive natural history.