Corrado Pedrazzani

CA19-9 serum levels in obstructive jaundice: clinical value in benign and malignant conditions

BACKGROUND Obstructive jaundice is frequently associated with false CA19-9 elevation in benign conditions. The diagnostic accuracy of this tumor marker was evaluated in the present longitudinal study. METHODS In 128 patients admitted for obstructive jaundice (87 with pancreato-biliary malignancy and 41 benign disease) serum CA19-9 was measured. Statistical analysis of marker levels obtained before and after endoscopic biliary drainage was performed in 60 patients. RESULTS Elevated CA19-9 levels (>37 U/mL) were found in 61% of benign cases and 86% of malignancies. After biliary drainage, decrease of serum CA19-9 was observed in 19 of 38 malignant cases and in almost all benign cases (Wilcoxon matched pairs test: P = .207 and P <.001, respectively). Receiver operating characteristic (ROC) analysis identified a cut-off value of 90 U/mL to be associated with improved diagnostic accuracy after biliary drainage (sensitivity 61%, specificity 95%). CONCLUSIONS In the presence of successfully drained obstructive jaundice, CA19-9 serum levels that remain unchanged or measure more than 90 U/mL are strongly indicative of a malignant cause of obstruction. However, the real clinical utility of this marker remains controversial.

Treatment of peritoneal carcinomatosis with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: State of the art and future developments

Peritoneal carcinomatosis (PC) had long been regarded as a terminal disease, characterized by a very poor survival and worth treating with palliative therapy. A new strategy combining maximal surgery (cytoreductive surgery, CRS), with maximal regional chemotherapy (hyperthermic intraperitoneal chemotherapy, HIPEC), has been proposed to treat PC, resulting in long-term survival rates in selected patients. The emerging trend is to view localised peritoneal carcinomatosis, in the absence of other metastases, as a regional metastatic disease that is amenable to locoregional therapy. In spite of the need for more high quality studies, many international experts now agree that the use of this new strategy is a gold standard for treating selected patients with PC with the intent of curing. The best results are achieved in patients with limited disease who have completed macroscopic tumor removal. To offer a comprehensive review, we summarized the present status and possible future progress of this treatment modality, in particular outlining its rationale, current practice and general outcome.

Complications after Extended (D2) and Superextended (D3) Lymphadenectomy for Gastric Cancer: Analysis of Potential Risk Factors

BackgroundVery few studies from Western centers have compared D2 and D3 dissection in the surgical treatment of gastric cancer. The aim of the prospective observational study reported here was to analyze the postoperative outcome and potential risk factors for complications following D2 and D3 lymphadenectomy.MethodsA total of 330 consecutive patients, of which 251 submitted to D2 lymphadenectomy and 79 were treated by D3 lymphadenectomy, were enrolled in the study. Twenty potential risk factors for morbidity and mortality were studied by means of univariate and multivariate analysis.ResultsOverall morbidity and mortality rates were 34% (111 patients) and 4% (14 patients), respectively. Abdominal abscess, anastomotic leakage, pleuropulmonary diseases and pancreatitis were the most commonly observed complications. No differences in morbidity, surgical morbidity, mortality rates and mean hospital stay between D2 and D3 lymphadenectomy were found. Multivariate analysis revealed that American Society of Anesthesiologists’ (ASA) class II/III versus class I, perioperative blood transfusions, and low albumin serum levels were independent predictors of postoperative complications. Age, surgical radicality (R1/R2 vs. R0) and low albumin serum levels independently predicted mortality. Mortality rate was .5% in the 203 patients aged 75 years or younger who underwent curative surgery. Most of deaths were observed in patients older than 75 years with low albumin serum levels or treated by non-curative surgery.ConclusionsD2 lymphadenectomy represents a feasible procedure associated to acceptable morbidity and mortality rates. In specialized centers, D3 lymphadenectomy may be performed without increasing the risk of postoperative complications and associated deaths in carefully selected patients. These techniques should be avoided in subgroups of patients with a high risk of postoperative mortality.

Safety and Potential Benefit of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Peritoneal Carcinomatosis From Primary or Recurrent Ovarian Cancer

To analyze the outcomes of cytoreductive surgery and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer.

Treatment of Peritoneal Carcinomatosis by Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemoperfusion (IHCP): Postoperative Outcome and Risk Factors for Morbidity

BackgroundCytoreductive surgery with limited or extended peritonectomy associated with intraperitoneal hyperthermic chemoperfusion (IHCP) has been proposed for treatment of peritoneal carcinomatosis (PC) from abdominal neoplasms.MethodsFifty-nine patients with PC from abdominal neoplasms underwent 61 treatments using this technique from January 2000 to August 2005. Surgical debulking, completed by partial or total peritonectomy, was performed in most cases. In 16 patients with positive peritoneal cytology without macroscopic peritoneal disease, IHCP was performed in order to prevent peritoneal recurrence. IHCP was carried out throughout the abdominopelvic cavity for 60 minutes using a closed abdomen technique. Intra-abdominal temperature ranged between 41°C and 43°C; mitomycin C (25 mg/mq) and cisplatin (100 mg/mq) were the anticancer drugs generally used, and they were administered with a flow rate of 700–800 ml/minute.ResultsMean hospital stay was 13 ± 7 (range 7–49) days. Postoperative complications occurred in 27 patients (44.3%); of these, major morbidity was observed in 17 (27.9%). The most frequent complications were wound infection (9 cases), grade 2 or greater hematological toxicity (5 cases), intestinal fistula (5 cases), and pleural effusion requiring drainage (5 cases). Reoperation was necessary in 5 patients (8.2%). One patient with multiorgan failure died in the postoperative period (mortality rate: 1.6%). Multivariate analysis of several variables identified completeness of cancer resection (CCR-2/3 vs. CCR-0/1, relative risk: 9.27) and age (relative risk: 1.06 per year) as independent predictors of postoperative morbidity. Preliminary follow-up data indicate that survival probability may be high in patients with ovarian or colorectal cancer and low in patients with gastric cancer.ConclusionsIHCP combined with cytoreductive surgery involves a high risk of morbidity, but postoperative complications could be resolved favorably in most cases with correct patient selection and adequate postoperative care. Tumor residual and advanced age significantly increase the risk of morbidity after this procedure.

Perforated gastric carcinoma: a report of 10 cases and review of the literature.

BackgroundPerforation is a rare complication of gastric carcinoma, accounting for less than 1% of all gastric cancer cases. The aim of the present study is to evaluate the prognostic value of perforation and to point out the surgical treatment options.MethodsA total of 10 patients with perforated gastric carcinoma were retrospectively reviewed among 2564 consecutive cases of gastric cancer operated in three Centers belonging to the Italian Research Group for Gastric Cancer. The clinicopathological features including tumor stage and survival were analyzed and compared to literature data.ResultsIncidence rate was 0.39%. All patients underwent emergency surgery, being performed gastrectomy in 6 patients (mortality 17%) and repair surgery in 4 patients (mortality 75%). The survival of patients was related to the stage of the disease, with 2 long-survival cases.ConclusionPerforation usually occurs in advanced stages of gastric cancer; nevertheless surgeons should not be always discouraged from a radical treatment of perforated gastric cancer, since perforation even occurs in early stages and seems not to be a negative prognostic factor itself. When possible, emergency gastrectomy should be performed, leaving repair surgery for unresectable tumors. A two-stage treatment is a good treatment option for frail patients with resectable tumors.

Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction.

AIMS This study reports mode, timing and predictive factors of recurrence after curative surgery for cardia cancer. METHODS A prospective study in a series of 92 curatively (R0) resected patients from 1988 to 2002. RESULTS The 5-year recurrence rate was 71%. Lymph node involvement was the only predictor of recurrence. No patients with more than 6 metastatic nodes were free from relapse 2 years after surgery. Locoregional, peritoneal and haematogenous relapses showed a similar median recurrence time (12, 10 and 12 months, respectively), 80% occurred within 24 months. CONCLUSIONS Few patients can be cured by surgery, lymph nodal involvement is the only predictor of recurrence.

Results of surgical treatment of adenocarcinoma of the gastric cardia

BACKGROUND Comparison among different studies regarding adenocarcinoma of the cardia has been difficult since the Siewert classification was introduced. This study analyzed the experience of a single institution in the treatment of gastric cardia cancer with the aim of assessing principal prognostic factors and long-term outcome. METHODS The results of 96 patients who underwent resection with curative intent for gastric cardia cancer at the First Division of General Surgery, University of Verona, from January 1988 to February 2000, were analyzed statistically with special reference to Siewert type. RESULTS Despite a high number of curative resections (85.4%), the 5-year survival rate was poor (24%) for all Siewert types (p = 0.8), and for early tumors (51%) also. Chance of cure was limited to pN0 and pN1 patients. Multivariate analysis showed that microscopic or macroscopic residual tumor and pN-positive categories had a significantly higher risk of death (risk ratio, 2.18 and 2.68, respectively) and the pN2 and pN3 category had the most negative prognostic factor (risk ratio, 7.6). CONCLUSIONS The long-term prognosis for gastric cardia cancer remains poor and is independent of Siewert type, with cure limited to pN0 and pN1 patients.

Super-extended (D3) lymphadenectomy in advanced gastric cancer

PURPOSE To analyze our experience with D3 lymphadenectomy in the treatment of advanced GC with specific reference to post-operative morbidity and mortality, incidence of para-aortic node (PAN) metastases, and long-term prognosis. METHODS Short- and long-term results of D3 lymphadenectomy were analyzed in 286 patients with advanced GC. RESULTS PAN metastases were demonstrated in 37 patients. PAN involvement was significantly higher in upper third tumours (29%) compared to middle and lower third (7%; P < 0.001). Eighty patients developed post-operative complications, being pulmonary disorders (6%), abdominal abscesses (4.5%) and pancreatic fistulas (3%) the most frequently observed. In-hospital mortality was 2%. Overall 5-year survival rate for R0 pT2-4 patients was 52%. When considering survival in relation to nodal involvement, both pN3 and non-regional lymph node metastases (M1a) patients showed a chance of long-term survival: 5-year survival was 31% for pN3 and 17% for M1a cases. Furthermore, the 5-year survival rate was remarkably high (about 60%) even in pN2 and pN3 subsets when no serosal invasion (pT2) was demonstrated. CONCLUSIONS D3 lymphadenectomy could be further explored in specialized centers for curative surgery of advanced GC, especially for upper third tumours, providing that an acceptable morbidity and no increase in mortality can be offered.

E-cadherin genetic screening and clinico-pathologic characteristics of early onset gastric cancer

AIM CDH1 germline alterations occur in about 40% of hereditary diffuse gastric cancer (HDGC) families. CDH1 germline mutations are also documented in few early onset diffuse gastric cancer patients (EODGC) without family history, but the real frequency in this setting in unknown. In these patients, the advanced stage at the time of diagnosis remains a clinical burden due to the poor long term survival. METHODS The entire coding region and exon flanking sequences of the CDH1 gene was analysed by direct sequencing in 21 EODGC patients aged ≤50 years. The potential deleterious nature for a new CDH1 missense variant was assessed by cell-cell aggregation and invasion assays. Somatic CDH1 mutation, loss of heterozygosity (LOH) and promoter hypermethylation was explored in the tumour from one CDH1 germline mutation carrier. RESULTS Two novel CDH1 germline variants were identified in 21 EODGC cases, c.670C>T and -63C>A. Functional analysis of the c.670C>T missense variant classified this mutation as non-pathogenic. The analysis of CDH1 somatic second hits failed to demonstrate E-cadherin structural and epigenetic alterations in the tumour sample. CONCLUSION Data from the present work and a systematic review of the literature revealed that CDH1 germline mutations occurred in 7.2% of EOGC patients invariably with diffuse of mixed histology. From these, proved CDH1 mutation pathogenicity has been assigned only to 2.3% of the cases who were recurrently diagnosed before 35 years old. Germline CDH1 mutation remain the only germline genetic defect described in this type of patients and CDH1 mutation screening should be recommended for patients with these characteristics.