Papers by Emanuel Cavazzoni
Molecular Determinants of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in a Model of Peritoneal Gastric Cancer Carcinogenesis
Gastroenterology, 2011

Colorectal Disease, 2020
Aim Anorectal physiology tests provide a functional assessment of the anal canal. The aim of this... more Aim Anorectal physiology tests provide a functional assessment of the anal canal. The aim of this study was to compare the results generated by standard high-resolution water-perfused manometry (WPM) with the newer THD â Anopress manometry system. Method This was a prospective observational study. Conventional manometry was carried out using a water-perfused catheter with high-resolution manometry and compared with the Anopress system with air-filled catheters. All patients underwent the two procedures successively in a randomized order. Time to arrive at the resting pressure plateau, resting, squeeze, straining pressure and visual analogue scale (VAS) scores for pain were recorded. A qualitative analysis of the two devices was performed. Results Between 2016 and 2017, 60 patients were recruited. The time from insertion of the catheter to arriving at the resting pressure plateau was significantly lower with the Anopress compared with WPM: 12 s [interquartile range (IQR) 10-17 s] versus 100 s (IQR 67-121 s) (P < 0.001). A strong correlation between the manometric values of WPM and the Anopress was observed. Both procedures were well tolerated, although the VAS score for insertion of the WPM catheter was significantly higher. The Anopress was easier to use and more time-efficient than the WPM. Conclusion The pressure values obtained with Anopress correlated well with those of conventional manometry. The Anopress has the advantage of being less time-consuming, user-friendly and better tolerated by patients.

Journal of neurogastroenterology and motility, Jan 30, 2018
The Anopress device is a new portable manometry system. The aim of this study is to formulate nor... more The Anopress device is a new portable manometry system. The aim of this study is to formulate normative data using this new device by recording the anorectal function of asymptomatic subjects. Patient comfort was also assessed. Anorectal function was assessed in asymptomatic volunteers using the Anopress. All volunteers were examined in a standardized way in accordance with the study protocol. Normative values for the Anopress were obtained from the recorded data and patient comfort was assessed using a visual analogue scale. We recruited 153 healthy volunteers. Eighty were female (23 parous; median age 39.5 [interquartile range {IQR}, 28.75-53.00]) and 73 were male (median age 40.5 [IQR, 29.00-52.25]). For the female cohort, the following normal range (2.5-97.5 percentile) values were recorded across the whole anal canal: resting pressure 40.0-103.0 mmHg; squeeze increment 35.0-140.6 mmHg; endurance 1.3-9.0 seconds; involuntary squeeze 41.1-120.8 mmHg; and strain pressure 22.1-77.9...
International Journal of Gastroenterology Research and Practice, 2016

International Journal of Gastroenterology Research and Practice, 2015
Objective: Primary Malignant Melanoma (PMM) arising from the digestive, respiratory or genitourin... more Objective: Primary Malignant Melanoma (PMM) arising from the digestive, respiratory or genitourinary tract is extremely rare. Rectal PMM accounts for less than 1% of all melanomas; it is often advanced at initial presentation with a poor prognosis with a 5-year survival below 20%. Treatment of this particular disease is still debated with weak evidence that aggressive surgery may lead to a better outcome. The objective of the present paper is to descibe a case of PMM and review the published literature on the treatment of such extremely rare condition. Methods: A 78 years old man presenting mild anal bleeding underwent a colonoscopy which showed a centimetric mass in the posterior wall of the rectum, less than 1 cm above the pectinea line. Biopsy revealed amelanotic malignant melanoma infiltrating the submucosa. Preoperative assessment revealed no distant metastases and no nodal involvement. Abdominoperineal resection (APR) with total mesorectal excision and iliac nodes sampling was performed. Results: the patient is alive and disease-free after 48 months from diagnosis. According to a literature review, APR with or without intra abdominal pelvic lymph node dissection represents a more radical approach in patients seeking curative options. However, some series suggest that wide local excision (WLE) may have similar survival outcomes but seems to be burdened with a higher rate of local recurrences. Conclusions: Our experience confirms that treatment recommendations are not standardized and tend to be individualized. An aggressive surgical approach may be justified in patient with a long life expectancy accepting a demolitive surgery and a definitive colonostomy.
Su1985 The CCR5 Antagonist Maraviroc Reduces the Potential for Gastric Cancer Dissemination in Rodent Models of Peritoneal Metastasis
Gastroenterology, 2013
Journal of surgical case reports, 2011
A patient with ulcerated gastric cancer causing mild anaemia and simultaneous three-vessel corona... more A patient with ulcerated gastric cancer causing mild anaemia and simultaneous three-vessel coronary artery disease (CAD) underwent "off pump" coronary artery bypass grafting (OP-CABG) and total D2 gastrectomy.
Il Giornale di chirurgia
Extrapleural Solitary Fibrous Tumors (SFT), in particular small bowel mesentery SFTs, are extreme... more Extrapleural Solitary Fibrous Tumors (SFT), in particular small bowel mesentery SFTs, are extremely rare neoplasms. We describe the case of a young male hospitalized for unspecific abdominal symptoms and evidence of a well-circumscribed mass arising from the small bowel mesentery. Histopathological and immunohistochemical analysis on the surgical specimen confirmed the diagnosis of SFT. A Pubmed search revealed only another case of small bowel mesentery SFT, confirming the extremely rarity of this tumor.

In vivo (Athens, Greece)
Peritoneal carcinogenesis (PC) is the most frequent pattern of metastasis in patients with locall... more Peritoneal carcinogenesis (PC) is the most frequent pattern of metastasis in patients with locally advanced gastric cancer. Despite this, there is a consensus on the use of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of PC from gastric cancer. The molecular mechanisms involved in beneficial effects of HIPEC remain unexplored. Human gastric cancer MKN45 cells were injected into the peritoneal cavity of immune-deficient NOD-SCID mice. After induction of PC, the animals were randomized into five groups: HIPEC with mitomycin and cisplatin; normothermic intraperitoneal chemotherapy (NIPEC); normothermic intraperitoneal saline; hyperthermic intraperitoneal saline alone; no treatment. After 10 days of treatment, the mice were sacrificed and the extent of PC was assessed. Compared with the other groups of treatment, HIPEC reduced the extent and severity of peritoneal dissemination as measured by assessing the total number of peritoneal and m...

Il Giornale di chirurgia, 2011
Lung cancer represents the leading cause of tumor death in the world with 50% of patients present... more Lung cancer represents the leading cause of tumor death in the world with 50% of patients presenting metastatic disease at the time of diagnosis. Gastrointestinal (GI) lung cancer metastasis were thought to be extremely rare, but a much higher incidence has been noted in several autoptic reports. Clinical relevance of GI metastasis is low, but can increase with the higher number of newly diagnosed patients and with the efficacy of systemic chemotherapy in advanced stages. Prognosis of complicated GI lung cancer metastasis seems to be worse than the natural course of the disease and acute bleeding or perforation of metastatic site can be accelerated by chemotherapy. We describe the clinical case of a patient presenting with acute abdomen due to small bowel perforation from GI lung cancer metastasis. A review of the most recent published literature on GI lung cancer metastasis was performed. GI metastasis from lung cancer may occur within the clinical course of the disease and require...

Recurrence of retroperitoneal Merkel cell carcinoma. A case report
Annali italiani di chirurgia
Merkel cell carcinoma (MCC) is a neuroendocrine malignant neoplasm that usually has its primary l... more Merkel cell carcinoma (MCC) is a neuroendocrine malignant neoplasm that usually has its primary location on the skin. It often metastasizes to lymph nodes, liver, lungs, bones and brain. Actually there have been few cases of MCC of the retroperitoneal region without a primary skin lesion. Our case is a male of 55 year old who initially underwent a partial resection (R1) of a bulky pelvic mass; the histopathological analysis and the immunoistochemistry showed the presence of neuroendocrine Merkel cells. The patient underwent 6 cycles of postoperative chemotherapy (carbon platinum and etoposide) and adjuvant radiotherapy. Afterwards the patient underwent surgery again with the complete resection of the tumour. The histopatological and immunoistochemistry analysis of the first and the second surgical samples confirmed the diagnosis of a retroperitoneal high-grade neuroendocrine carcinoma with a high mitosis index. The immunoistochemistry profile showed neoplastic cell with: CD 20+, syn...

The American Journal of Surgery, 2015
BACKGROUND: The neutrophil/lymphocyte ratio (NLR) in the peripheral blood is considered an easily... more BACKGROUND: The neutrophil/lymphocyte ratio (NLR) in the peripheral blood is considered an easily assessable prognostic factor in cancer patients. We evaluated the predictive significance of the NLR in patients affected by gastric cancer that underwent gastric resection. METHODS: From July 2003 to March 2012, 156 patients who had undergone gastrectomy with curative intent for gastric adenocarcinoma were included. Data were retrieved from a prospective collected database. NLR was calculated from lymphocyte and neutrophil counts on routine blood tests taken before surgery. Survival analyses were generated according to the Kaplan-Meier method. Univariate and multivariate analyses were carried out by the Cox proportional hazard model. RESULTS: The median follow-up time for surviving patients was 38 months (range 1 to 108 months) and median preoperative NLR was 2.3 (range .47 to 19.73). Subjects were dichotomized at the N/L value of 2.3. Median survival of patients with NLR below the median was around 60 months compared with the 36 months of patients with an NLR above the median. A multivariate analysis established a significant and independent relationship between the NLR and the overall survival with a P value of less than .05. CONCLUSIONS: The results suggest that the elevated preoperative NLR predicts poor overall survival following resection for gastric adenocarcinoma. It may be used as a simple, reliable prognostic factor for risk stratification.

World Journal of Surgical Oncology, 2013
Background: The TNM staging criteria for gastric carcinoma have seen numerous revisions, the most... more Background: The TNM staging criteria for gastric carcinoma have seen numerous revisions, the most recent of which are reflected in the seventh edition AJCC TNM cancer staging manual. Methods: A retrospective evaluation of the sixth and seventh TNM classification of gastric cancer on a prospective database, regarding patients operated on for primary gastric cancer, was conducted. The end point of the study was prognosis evaluation in terms of overall survival. Patients operated on for primary gastric cancer between September 2003 and March 2012 at our Department of Emergency and General Surgery, were consecutively retrieved in this study; a total of 114 patients were considered. Cardia gastric cancers, gastric lymphomas and gastrointestinal stromal tumors (GIST) were excluded. Median and mean follow-up periods were 22.5 and 27.7 months (range 15 days to 5 years). Both TNM6 and TNM7 were used to evaluate our patients. Overall survival and survival rates at different stages were analyzed using the Kaplan-Meier method and differences were determined using a log-rank test. Cox's proportional hazard model was used to identify significant factors related to prognosis in a multivariate analysis. Results: Overall survival between the sixth and seventh TNM classification was not significantly different. Both the Kaplan-Meier analysis and the multivariate analysis showed that the major negative prognostic factor was lymphovascular invasion (P < 0.001 in the univariate analysis and P = 0.035 to 0.048 in the multivariate analysis). Stage distribution and stage-related survival changed from the sixth to the seventh edition, especially in T3 stage where median survival for the sixth edition was 720 days versus 1,200 days for the seventh edition. Moreover, differences were shown in the survival rate of N1 versus N2 stages within the seventh TNM. Conclusions: Even though further studies are needed in order to increase the number of patients studied, the seventh edition seems to provide a more accurate prognosis, especially regarding N1 and N2 tumors, showing that the most important prognostic factor is lymphovascular invasion.
The Cancer Journal, 2004
This chapter reviews the role of LT in the treatment of primary hepatic malignancies and provides... more This chapter reviews the role of LT in the treatment of primary hepatic malignancies and provides Liver transplantation (LT) has been utilized in the treatment of a brief description of the issues surrounding LT organ primary hepatic malignancy for decades. Hepatocellular cancer allocation policies. With the exception of metastatic neu-(HCC) remains the most common malignant condition treated roendocrine tumors, secondary hepatic malignancies do with LT, with almost 400 such transplants per formed annually poorly with LT and are not discussed here. in the US. Refinement in the selection criteria for LT in patients with HCC has led to survival rates similar to those for LT in nonmalignant conditions. Excellent results have also been

Journal of Gastrointestinal Surgery, 2012
Introduction Methionine dependency occurs frequently in tumor cells. Here we have investigated th... more Introduction Methionine dependency occurs frequently in tumor cells. Here we have investigated the effect of methionine deficiency on metastatic potential of gastric cancer cells in vitro and in vivo. Materials and Methods Model of peritoneal carcinomatosis and xenograft was generated by intraperitoneal or subcutaneous implantation of gastric cancer cells in NOD-SCID mice. In comparison to control medium, 3-day culture of MKN45, MKN74, and KATOIII cells in a methionine-deficient medium inhibited cell proliferation, increased the rate of cell apoptosis, and reduced cell adhesion and migration. In the xenograft model induced by implantation of MNK45 and MNK74 cells, two cycles of methionine-deficient diet reduced the tumor growth. Further on, a 10-day cycle of methionine-deficient diet reduced the number of peritoneal nodules in the model of peritoneal carcinomatosis induced by MKN45 cells injection. Finally, a microarray analysis of the methylation of promoter CpG islets demonstrated that methionine deficiency reduced the promoter methylation of E-cadherin whose expression was markedly increased in vivo and in vitro. Results In summary, we have provided evidence that a methionine-deficient diet modulates the growth of gastric tumor cells and in vitro deficiency of methionine increased apoptosis and decreased cellular adhesion and migration associated to epigenetic change of E-cadherin gene, in vivo and in vitro.

International Journal of Clinical Oncology, 2012
Malignant ascites (MA) accompanies a variety of abdominal and extra-abdominal tumors. It is a pri... more Malignant ascites (MA) accompanies a variety of abdominal and extra-abdominal tumors. It is a primary cause of morbidity and raises several treatment challenges. MA has several symptoms, producing a significant reduction in the patient's quality of life: loss of proteins and electrolyte disorders cause diffuse oedema, while the accumulation of abdominal fluid facilitates sepsis. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk. A Pubmed, Medline, Embase, and Cochrane Library review of medical, interventional and surgical treatments of MA has been performed. Medical therapy, primarily paracentesis and diuretics, are first-line treatments in managing MA. Paracentesis is widely adopted but it is associated with significant patient discomfort and several risks. Diuretic therapy is effective at the very beginning of the disease but efficacy declines with tumor progression. Intraperitoneal chemotherapy, targeted therapy, immunotherapy and radioisotopes are promising medical options but their clinical application is not yet completely elucidated, and further investigations and trials are necessary. Peritoneal-venous shunts are rarely used due to high rates of early mortality and complications. Laparoscopy and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed as palliative therapy. Literature on the use of laparoscopic HIPEC in MA includes only reports with small numbers of patients, all showing successful control of ascites. To date, none of the different options has been subjected to evidence-based clinical trials and there are no accepted guidelines for the management of MA.

Hepatology, 2003
Serum levels of CEA and CA 19.9 are occasionally elevated in cases of cholangiocarcinoma (CC). Th... more Serum levels of CEA and CA 19.9 are occasionally elevated in cases of cholangiocarcinoma (CC). They, however, have low sensitivity and specificity, which makes the diagnosis of CC difficult, and better tumor markers are needed. CYFRA 21-1 is a cytokeratin fragment that is being evaluated as a tumor marker with diagnostic potential for small cell lung carcinoma. This study aimed at evaluating the role of measuring serum and bile CYFRA 21-1 as a tumor marker in patients with CC, comparing it to CEA and CA19.9. Patients and Methods: Twenty consenting patients (15 males, mean age 55.7 years) with histologically proven CC (7 patients were Bismuth stage I, 4 patients stage II, 3 patients stage III, and 6 patients stage W) were included. Patients were studied preoperatively using ultrasound, helical CT, ERCP and brush cytology, and percutaneous transhepatic biliary drainage (PTD) if ERCP failed. Serum and bile samples were obtained at time of biliary drainage and stent placement (18 during ERCP and 2 during Pro). The diagnosis of CC was confirmed by histopathology in 11 patients who underwent surgery, by bile cytology in 8 patients and by fine needle biopsy in one patient. In addition, 20 consenting patients with calcular obstructive jaundice had serum and bile samples obtained during endoscopic removal of stones to control for the effect of biliary obstruction on CYFRA 21-1 levels. CEA and CA 19.9 were measured using enzyme immunoassay (EIA), and CYFRA 21-1 level was measured using electrochemiluminescece immunoassay (ECLIA) in serum and bile of the CC patients and the gall stone controls. Results: Patients with CC had significantly higher serum levels of CEA (24.5 ± 6 vs 4.3 ± 1.3 ng/ml, p<0.01), CA 19.9 (118.9 ± 25.4 vs 31.2 ± 8.4 U/ml, p< 0.01) and CYFRA 21-1 (8.3 ± 2.7 vs 2.1 ± 0.5 ng/ml, p<0.01) than patients with benign biliary obstruction. Bile levels of the 3 markers were significantly higher in CC than benign obstruction (CEA: 376 ± 82 vs 7.6 ± 1.9 ng/ml p<0.001; CA 19.9:169 ± 30.5 vs 56.3 ± 12.6 U/ml, p< 0.01; CYFRA 21-1:29.3 ± 7.8 vs 5.9 ± 1.6 ng/ml, p<0.001). All bile concentrations were significantly higher than serum concentrations of all 3 markers in both benign and malignant obstruction. A serum cut off value for CYFRA 21-1 of 4.5 ng/ml had a 73% sensitivity and a 96% specificity for diagnosing CC, and the sensitivity, specificity and diagnostic accuracy of serum and bile CYFRA 21-1 were all higher than those for CEA and CA 19-9. Patients with Bismuth stages III and IV CC had significantly higher levels of the 3 markers than stage I and II patients. Conclusion: CYFRA 21-1, CEA, and CA 19.9 levels increase in serum and bile of CC patients, and the level is related to the tumor stage. Their measurement in bile is important for the supplementary diagnosis of CC, especially when brush cytologies are negative. Serum and bile concentrations of CYFRA 21-1 appear superior as tumor markers than CEA and CA 19-9 in diagnosis of CC, and their clinical validity requires further studies.
European Journal of Surgical Oncology (EJSO), 2013
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Papers by Emanuel Cavazzoni