Screening for Squamous Cell Anal Cancer in HIV Positive Patients: A Five-Year Experience.

AIM: Potential screening modalities for early diagnosis of squamous cell anal cancer (SCC) in HIV patients include digital anorectal examination (DARE), anal Papanicolaou testing (Pap test), human papilloma virus (HPV) co-testing, and high-resolution anoscopy. The aim of this study was to demonstrate the results of a five-year screening program for SCC in HIV patients. MATERIALS AND METHODS: We conducted a retrospective study on 204 HIV patients who underwent a screening program for SCC from October 2010 to January 2015. All patients were screened by DARE, anal Pap test, including HPV test and cytology, and high-resolution video-proctoscopy (HR-VPS) with and without acetic acid 3%. Depending on macroscopic appearance and biopsies, patients underwent observation or treatment. Median follow-up was 36 months. RESULTS: Cytologic abnormalities (Cyt+) for high-risk HPV genotypes were recorded in 34% of patients. HR-VPS was positive in 59 patients (29%), of whom 13 patients (22%) were positive for warts; the rest have typical features of anal intraepithelial neoplasia (AIN). Sixteen (8%) patients had AIN (AIN I-III) and underwent wide local excision, ablation, or imiquimod. Absence of progression was recorded. Fourteen patients (7%) had SCC: eight (57%) with no evidence of recurrence, two (14%) had recurrence, and four (29%) died from metastatic disease. CONCLUSIONS: Our data demonstrated a successful screening program in preventing SCC in HIV patients. We demonstrate the advantages of progression towards SCC. Moreover, we used a new screening tool, the HR-VPS, a low-cost and manageable instrument to collect patients' long-term data.

Indications for the laparoscopic approach to acute small bowel obstruction: A retrospective review of 50 cases, a literature review, and a single hospital's preliminary experience.

Small bowel obstruction (SBO) is mainly caused by postoperative adhesions, but a broad spectrum of diseases may cause this pathogenetic condition. Laparoscopic treatment represents an efficient approach to SBO. The aim of this paper was to review a single center's experience with a minimally invasive approach to multiple pathologic scenarios causing SBO. From January 2010 to December 2012, 50 consecutive patients underwent laparoscopic surgery for mechanical SBO. In 90% of patients, the surgical procedure was totally laparoscopic, while 10% required conversion to midline laparotomy. In-hospital morbidity was 15% among totally laparoscopic patients and 40% among those who underwent conversion to midline laparotomy. Thirty-day mortality was zero. One patient died 4 months postoperatively from neoplastic disease progression; the remaining patients were free from occlusive symptoms at follow-up. The minimally invasive technique applies to a broad spectrum of cases. A larger cohort of patients seems necessary to reproduce our results and confirm the effectiveness of a laparoscopic approach to SBO.

Simultaneous Delorme's procedure and inter-sphinteric prosthetic implant for the treatment of rectal prolapse and faecal incontinence: preliminary experience and literature review.

AIM: Rectal prolapse is a distressing condition affecting mostly elderly patients and females. Delorme's procedure is frequently performed since it offers good results and is burdened by a particularly low morbidity. Faecal Incontinence is associated with prolapse in a large percentage of patients, due to the sphincter damage caused by the prolapsed rectum through the anal canal. Prolapse resection is often ineffective in treating incontinence, and further specific procedures are frequently required. At present, no data are available on combined Delorme's procedure with the implant of Bulking Agents for the simultaneous treatment of rectal prolapse and faecal incontinence. METHOD: Three patients affected by complete external rectal prolapse underwent simultaneous Delorme's procedure with application of six polyacrylonitrile prosthetic cylinders in the inter-sphinteric space (Gate Keeper™, THD, Correggio Italy). Follow up was at 3,6 and 12 months. RESULTS: Gate Keeper procedure required a short operative time; no morbidity or complications were experienced. Prolapse was successfully treated in all patients and the mean Vaizey's incontinence score value dropped from pre-operative 19.3 to 9.3 after 3 months. All patients experienced a reduction of incontinence episodes and an improvement in daily activities and lifestyle. CONCLUSION: Gate Keeper implant is feasible and safe when associated to surgical procedures like Delorme's prolapse resection. Preliminary results are positive even if a study with a larger numbers of patients is needed to confirm the efficacy. A simultaneous treatment of faecal incontinence should be always considered when performing surgery for rectal prolapse. SHORT STATEMENT: The present manuscript describes a simultaneous combination of two surgical techniques to treat rectal prolapse and faecal incontinence. To date, there are no published data on a similar approach. The paper underlies the importance of treating faecal incontinence when performing surgery for rectal prolapse.

Prognostic value of preoperative neutrophils to lymphocytes ratio in patients resected for gastric cancer.

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.

Recurrence of retroperitoneal Merkel cell carcinoma. A case report.

BACKGROUND: 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. CASE PRESENTATION: 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. DISCUSSION: 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+, synaptophysin +, TTF-1-, neurofilaments +, CK 7-, chromogranin, Ki67 90%. In the patient's medical history no skin localizations were mentioned. CONCLUSION: The hypothesis of a MCC with a primary retroperitoneal localization has been strength by the histopathological and immunoistochemistry analysis of two intra-operative samples from two different surgical procedure and from the absence of either a primary skin location or of secondary recurrences. Is therefore reinforced the theory that from a cell into a retroperitoneal lymph node can arise a retroperitoneal mass originating a Merkel cell tumour.

Analysis of operative morbidity in a single center initial experience with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis has been traditionally considered a rapidly lethal disease and consequently managed by merely palliative options. In the last decade, the clinical interest in the condition has increased because encouraging results have been reported in association with a new treatment strategy that combines cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Relatively high rates of severe complications are generally associated to this complex procedure. Our aim was to analyze treatment-related morbidity in our institutional initial experience. MATERIALS AND METHODS: Since October 2006, 36 hyperthermic intraperitoneal chemotherapy plus cytoreductive surgery procedures have been carried out in our Department. Patients treated showed abdominal malignancies and ovarian cancer with peritoneal carcinomatosis. Only 9 patients were treated with prophylactic treatment for gastric cancer at high risk to develop peritoneal carcinomatosis. RESULTS: In 27 patients, a macroscopically complete cytoreduction was done. The overall morbidity was 75%. Grades IV and V represented only 11.1%. CONCLUSIONS: Rigorous preoperative workup and strict selection criteria allowed a successful safe start of a new program of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a general surgery unit.

Preliminary results of prophylactic HIPEC in patients with locally advanced gastric cancer.

BACKGROUND: The prognosis of locally advanced Gastric Cancer following surgical therapy alone is poor. Peritoneum represents a preferential site of dissemination in such neoplasm. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in association with cytoreductive surgery (CRS) in the treatment of GC peritoneal carcinomatosis (PC). Aim of our preliminary experience is reporting our data on prophylactic HIPEC (P-HIPEC) in patients with GC at high risk of developing PC. METHODS: Eleven patients underwent P-HIPEC at our General and Emergency Surgery Department. All the patients were affected of high risk GC: serosa invasive tumors (T4), conventional cytology-positive or quantitative PCR detection of CEA mRNA on peritoneal lavage. Seven subtotal and four total gastrectomies with D2 or D2+ were performed. All the anastomoses were made before HIPEC. The procedure was carried out for 60 minutes with Mytomicin C and Cisplatin in all patients. Post-operative monitoring in Intensive Care Unit least for 24-48 hours. Oral nutrition was started precociously (day 5) also according with bowel movements and stool/gas passage. Follow-up took place in all patients at 1 month from surgery then every 6 months for 2 years and every 12 months for the following years. RESULTS: In four patients a neoadjuvant treatment was scheduled due to T or N stage at pre-operative evaluation. Gastric resection was guided on tumor location while the choice of performing a D2 or D2 + lymphadenectomy was up to preoperative imaging and intra-operative nodal status. No intra-operative complications were recorded. Median operation time was 398 minutes. In our series we recorded 20 adverse events. Median number for each patient was 1 adverse effect (range 0-2). Eight patients experienced a surgical adverse effect (G2-G3) that did not require any surgical treatment. Only one patient with duodenal stump dehiscence and intra-abdominal sepsis (G4-G5) underwent re-operation and died for severe hemorrhagic pancreatitis. Another patient died for ARDS. Per-operative mortality was 18%. Both patients were older then 70 years old. Median hospital stay was 14 days. Median follow-up was 15.9 months. Median survival was 29.6 months and median DFS was 20 months. Only one patient developed a peritoneal recurrence at 12 months and died for disease progression. Seven patients are still alive and disease free at last follow-up. One patient affected of variable immunodeficiency died at 9 months for pulmonary sepsis without any sign of local recurrence. CONCLUSIONS: Peritoneal dissemination appears to be a strong determinant in defining GC patients prognosis. Even after curative resection, peritoneal recurrence develops in about 60% of the patients with T3 and T4 tumors, and up to 40% of resected gastric cancer patients die as a direct result of peritoneal dissemination. Clinical trials showed that surgery plus HIPEC was associated with a significant improvement in survival compared to surgery alone in patients affected of GC with resectable PC. At present day there are not studies evaluating the role of P-HIPEC in patients at high risk of developing PC. The rationale of P-HIPEC is based on the concept that positive peritoneal lavage is considered an M1 (stage IV) similarly to macroscopic PC by the 7th TNM classification. Also analogous is the median survival of this 2 groups of patients. Detection of peritoneal micrometastases with cytologic examination has been considered a major method to predict peritoneal recurrences; the sensitivity of this assay is low. Recently, molecular approaches using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique has made possible the increase in the sensitivity. We can conclude, although the preliminary experience, that prophylactic HIPEC in locally advanced gastric cancer is feasible, increasing median survival compared to surgery alone. For sure this procedure need to be performed in the highly specialized centres strongly respecting the eligibility criteria.

Prognostic value of the seventh AJCC/UICC TNM classification of non-cardia gastric cancer.

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.

Malignant ascites: pathophysiology and treatment.

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.

Epigenetic modulation by methionine deficiency attenuates the potential for gastric cancer cell dissemination.

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.

Gene expression changes induced by HIPEC in a murine model of gastric cancer.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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 mesenteric nodules (p<0,05) and the HIPEC procedure increased median survival significantly. By gene array analysis, HIPEC was found to effectively modulate the expression of a subset of genes involved in formation of peritoneal metastasis, including adenomatous polyposis coli; beta (3) subunit of the integrin gene; chemokine stromal cell-derived factor-1 receptor; spleen tyrosine kinase; vascular endothelial growth factor receptor 3; collagen, type IV, alpha 2 and Carbossi-terminal binding proteins 1. CONCLUSION: In the present study we have provided evidence that HIPEC protects against peritoneal dissemination in a mouse model of peritoneal gastric carcinogenesis and brings about specific changes in gene expression wich may be related to this protection.

Mechanistic role of p38 MAPK in gastric cancer dissemination in a rodent model peritoneal metastasis.

Peritoneal dissemination is a highly frequent complication of poorly differentiated gastric cancers for which no effective therapies are available. Constitutive activation of mitogen-activated protein kinases (MAPKs) signaling cascades is recognized as a causative factor in the malignant transformation of several carcinoma cell types. In the present study we provide evidence that p38 MAPK inhibition protects against gastric cancer cells dissemination in a mouse model of peritoneal carcinomatosis. Administering mice with ML3403 and SB203580, potent and selective p38 MAPK inhibitors, attenuate the formation of neoplastic foci induced by intraperitoneal inoculation of gastric cancer cells. By gene array analysis we found that such a protective effect correlates with a robust downregulation in the expression of CXC chemokine receptor-4, Fms-related tyrosine kinase 4 (FLT4), the non-receptor spleen tyrosine kinase (SYK) and the collagen α2(IV) (COL4A2) in neoplasic foci. Inhibition of p38 MAPK in vivo increased the sensitivity of tumor cells to cisplatin and associated with a robust downregulation in the expression of the multidrug resistance (MDR)-1, a well defined marker of resistance to chemotherapy. In summary, p38 MAPK inhibition by a small molecule is beneficial in preventing the peritoneal dissemination of poorly differentiated gastric cancer cells by acting at multiple check-points in the process of attachment and diffusion of tumor cells in the peritoneum.

Do perioperative blood transfusions influence prognosis of gastric cancer patients? Analysis of 927 patients and interactions with splenectomy.

BACKGROUND: This study was to assess the influence of perioperative blood transfusions on the prognosis of patients undergoing a potentially curative resection for gastric cancer and to investigate the interaction between transfusions and splenectomy. MATERIALS AND METHODS: Between January 1990 and December 2005, 927 patients from 6 Italian tertiary referral centers underwent curative resections for gastric cancer. Clinical and pathologic variables were prospectively collected. The influence of perioperative blood transfusions on survival were evaluated by univariate and multivariate analysis. Moreover, the influence of splenectomy both in transfused and nontransfused patients undergoing total gastrectomy was also evaluated. RESULTS: The overall 5-year survival was 54.6%. The 5-year survival rate in transfused patients (n = 327) was 50.6% compared with 56.6% in nontransfused patients (n = 600) (P = .094). In the subgroup of patients who underwent total gastrectomy with spleen preservation (n = 209), 5-year survival rate was 46% and 51.4% in transfused and nontransfused patients, respectively (P = .418); those who underwent total gastrectomy with splenectomy (n = 199) presented a 5-year survival rate of 45% in transfused group compared with 39.1% in nontransfused patients (P = .571). CONCLUSIONS: Our study indicates a slightly, but not significantly, negative effect of allogeneic blood transfusion on prognosis of gastric cancer patients. In the subgroup of patients who underwent total gastrectomy, splenectomy seems to invert this mild effect, with a positive influence on overall survival.

Successful palliation of malignant ascites from peritoneal mesothelioma by laparoscopic intraperitoneal hyperthermic chemotherapy.

A variety of options have been proposed to treat malignant ascites but most of them have failed to reach a significant impact in terms of palliation. Laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC) could represent a good therapeutic tool for patients in whom medical therapies have failed and peritoneovenous shunting is contraindicated. Here we present a case of a 49-year-old woman with malignant ascites secondary to peritoneal spreading of a right pleural mesothelioma. After failure of medical therapy, the patient underwent LHIPEC with Cisplatin 25 mg/m/L and Doxorubicin 7 mg/m/L. A dramatic reduction of ascites was documented in the postoperative period and the patient experienced complete abdominal symptom relief. Ascites did not recur during a follow-up period of 6 months. LHIPEC could be a good therapeutic option to palliate malignant ascites from mesothelioma in cases not eligible for a radical treatment. Further studies are needed to standardize dosage and perfusion parameters.

A diagnosis of pneumococcal peritonitis secondary to pyo-salpinx in a young healthy female by culturing peritoneal pus.

Pneumococcal intra-abdominal infections of female genital tract origin are rare. A 33-year-old woman with peritonitis due to Streptococcus pneumoniae serotype 3 was reported. The patient did not have any of the known predisposing conditions for intra-abdominal pneumococcal infection. The clinical presentation included signs of multiorgan failure. Peritoneal toilette, bilateral salpingectomy and antibiotic treatment were promptly administered. The patient remained febrile, developed respiratory failure and required a repeated laparotomy and a prolonged antimicrobial treatment. Penicillin susceptible S. pneumoniae was isolated from the pus collected at surgery. Thus, culturing of intra-operative specimens should never be neglected to establish the correct microbiologic diagnosis.

Emerging role of transplantation for primary liver cancers.

Liver transplantation (LT) has been utilized in the treatment of primary hepatic malignancy for decades. Hepatocellular cancer (HCC) remains the most common malignant condition treated with LT, with almost 400 such transplants performed annually 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 reported following LT for select patients with epithelioid hemangioendothelioma and hepatoblastoma. Patients with cholangiocarcinoma treated with LT have generally faired poorly, with survival rates far below that of LT for nonmalignant conditions. Improved survival has recently been reported following LT for cholangiocarcinoma in highly select patients treated with aggressive neoadjuvant therapy. The future utility of LT in the treatment of malignancy will be influenced by several factors, including a profound organ donor shortage faced worldwide; increasing prevalence of hepatitis C, HCC and cirrhosis; and the evolution of live donor liver transplantation.