Carlo Pignatelli

Hemodynamic and pulmonary changes during open, carbon dioxide pneumoperitoneum and abdominal wall-lifting cholecystectomy. A prospective, randomized study.

BackgroundCarbon dioxide (CO2) pneumoperitoneum effects are still controversial. The aim of this study was to investigate cardiopulmonary changes in patients subjected to different surgical procedures for cholecystectomy.MethodsIn this study, 15 patients were assigned randomly to three groups according to the surgical procedure to be used: open cholecystectomy (OC), CO2 pneumoperitoneum cholecystectomy (PP), and laparoscopic gasless cholecystectomy (abdominal wall lifting [AWL]), respectively. A pulmonary artery catheter was used for hemodynamic monitoring in all patients. A subcutaneous multiplanar device (Laparo Tenser) was used for abdominal wall lifting. To avoid misinterpretation of results, conventional anesthesia was performed with all parameters, and the position of the patients held fixed thoroughout surgery. The following parameters were analyzed: men arterial pressure (MAP), heart rate (HR), cardiac output (CO), cardiac index (CI), stroke volume index (SVI), central venous pressure (CVP), systemic vascular resistances index (SVRI), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), pulmonary vascular resistances index (PVRI), peak inspiratory pressure (PIP), end-tidal CO2 pressure (ETCO)2, CO2 arterial pressure (PaCO2), and arterial pH.ResultsAll the operations were completed successfully. The Laparo Tenser allowed good exposition of the surgical field. A slight impairment of the cardiopulmonary functions, with reduction of SVRI, MAP, and CI and elevation of pulmonary pressures and vascular resistance, followed induction of anesthesia. However, these effects tended to normalize in the OC and AWL groups over time. In contrast, CO2 insufflation produced a complex hemodynamic and pulmonary syndrome resulting in increased right- and left side filling pressures, significant cardiac index reduction, derangement of the respiratory mechanics, and respiratory acidosis. All of these effects normalized after desufflation.ConclusionsCardiopulmonary adverse effects of general anesthesia were significant but transitory and normalized during surgery. Carbon dioxide pneumoperitoneum caused a significant impairment in cardiopulmonary functions. In high-risk patients, gasless laparoscopy may be preferred for reliability and absence of cardiopulmonary alterations.

DETERMINATION OF MOLECULAR MARKER EXPRESSION CAN PREDICT CLINICAL OUTCOME IN COLON CARCINOMAS

Purpose: Conventional staging procedures are often unable to precisely predict prognosis in colorectal cancer (CRC). In this study, we set out to investigate the possible role of molecular/structural indicators involved in cell cycle regulation (p27 and p53), apoptosis (p53 and p27), and tumor neoangiogenesis [p53, vascular endothelial growth factor (VEGF), and microvessel count] in predicting tumor behavior and clinical outcome in CRC patients Experimental Design: Analysis of the above indicators was performed by immunohistochemistry on 104 CRC patient samples and 25 normal colon mucosa specimens. Results: Intense p27 nuclear staining was found in normal colon mucosa, with p53 nuclear staining and VEGF cytoplasmic accumulation <10%, and low microvessel count. In contrast, in CRC samples, p27 was down-regulated in 53.8%, p53 protein was overexpressed in 52%, and VEGF stained positive in 67.3% of the cases, respectively. Multiple regression analysis showed that molecular markers were strongly correlated. In patients treated with curative surgery, a significant relationship was seen between p27 down-regulation and Dukes’ stage, nodal status, and the presence of distant metastases. VEGF overexpression correlated significantly with Dukes’ stage, tumor (t) and metastasis (m) parameters, and left site. Stepwise regression selected p27, p53, VEGF, and Dukes’ stage as the best combination of variables capable of predicting both disease-specific and disease-free survival. Conclusions: The investigated indicators may be useful for the prediction of outcome and recurrence rate in curatively treated CRC patients. In conjunction with clinical and pathological staging, they may provide a stronger indication of clinical outcome than staging alone and help better select therapeutic options in CRC patients.

Prognostic Significance of Epidermal Growth Factor Receptor Expression in Colon Cancer Patients Undergoing Curative Surgery

BackgroundTo investigate the role of epidermal growth factor receptor (EGFR) expression as a prognostic marker for prediction of cancer behavior and clinical outcomes in colon cancer patients undergoing potentially curative surgery.MethodsEGFR determination using a commercially available immunohistochemistry kit was performed in tissues from 149 colon cancer patients receiving primary surgical treatment and in 25 normal colon mucosa specimens from noncancer patients. EGFR positivity was correlated in univariate and multivariate analyses with disease recurrence and survival. In addition, p27, p53, and vascular endothelial growth factor expression were assessed by immunohistochemistry in 104 patients and correlated with EGFR tumor expression and clinical outcome.ResultsEGFR expression was detected in approximately one third of colon cancer patients (53 of 149; 35.6%). In 126 curatively treated patients, EGFR expression was correlated with disease recurrence and worse survival in both univariate and multivariate analyses. In a multivariate model for predicting recurrence and survival, Dukes’ staging, p27, and EGFR expression were the only independent covariates. In particular, in Dukes’ A and B patients the 5-year survival probability was 96% for EGFR-negative and high p27 expression cases and was 30.7% for EGFR-positive and low p27 expression cases.ConclusionsEGFR expression was an independent prognostic indicator of disease recurrence and poor survival in colon cancer patients undergoing curative surgery. In the context of novel therapeutic options such as molecularly targeted therapies, these findings suggest that anti-EGFR drugs could be evaluated in the adjuvant treatment of EGFR-positive colon cancer patients.

Elevated Serum Levels of Interleukin-8 in Advanced Non-Small Cell Lung Cancer Patients: Relationship with Prognosis

Interleukin-8 (IL-8) is a pleiotropic cytokine that has also been shown to exert effects relevant to cancer growth and progression. Cancer progression is believed to be contributed to by the ability of this cytokine to promote angiogenesis and mitogenic effects. As IL-8 production at the tumor site may determine elevated serum levels of this cytokine because of hematogenous leakage, it is conceivable that patients with high IL-8 serum levels may have tumors actively producing this cytokine. The aim of this study was, therefore, to assess IL-8 serum levels in 60 non-small cell lung cancer (NSCLC) patients undergoing chemotherapy and to correlate them with prognosis. IL-8 serum levels were found to be significantly elevated in cancer patients with respect to controls. Moreover, IL-8 serum levels were shown to be significantly increased in stage IV patients compared with stage III patients. When basal IL-8 serum levels in cancer patients were analyzed according to response to chemotherapy, responders were shown to have significantly lower IL-8 serum levels than nonresponders. On univariate analysis, the IL-8 serum level was included among the variables capable of affecting both overall survival (OS) and time to treatment failure (TTF). However, multivariate analysis failed to demonstrate an independent prognostic significance for IL-8 serum levels. In conclusion, this study showed that IL-8 serum levels were elevated in advanced NSCLC patients and correlated with both OS and TTF, but they were shown not to be an independent prognostic factor.

Circulating levels of interleukin-10 and interleukin-6 in gastric and colon cancer patients before and after surgery: relationship with radicality and outcome

Elevated interleukin-10 (IL-10) and IL-6 serum levels in advanced gastrointestinal cancer patients have been shown previously. To investigate the behavior and the prognostic role of IL-10 and IL-6 serum levels in gastric and colon cancer patients undergoing surgery, we studied the relationship between these cytokine levels and surgical radicality and outcome. Seventy-eight patients with gastric or colon cancer were admitted to the study, and 50 underwent radical surgery. Cytokine serum levels were measured by ELISA the day before surgery and 16 days after surgery. Circulating levels of IL-10 and IL-6 were found to be higher in cancer patients than in controls. Both IL-10 and IL-6 serum levels were demonstrated to be able to predict likelihood to perform radical surgery. IL-10 serum levels returned to normal in all but 8 radically resected patients. These 8 patients had tumor recurrence. In contrast, IL-6 serum levels were shown to significantly decrease in all patients but not to normalize regardless of the radicality of the operation. On multivariate analysis, basal IL-10 serum levels were found to be among the variables significantly affecting the disease-free survival rate. Stepwise regression selected tumor stage, number of metastatic resected nodes, and basal IL-10 serum level as the best combination of variables for prediction of likelihood of tumor recurrence. Preoperative IL-10 serum levels may be a useful marker to predict likelihood of performing radical surgery. Abnormally high postoperative IL-10 values negatively affected disease-free survival and tumor recurrence. IL-6 serum levels were found to have a more limited prognostic role.

Combined CD133/CD44 expression as a prognostic indicator of disease-free survival in patients with colorectal cancer.

HYPOTHESIS Because of some inconsistencies in the traditional model of human colorectal carcinogenesis, the cancer stem cell (CSC) model was recently proposed, in which tumor results from neoplastic transformation of stem cells, which become CSCs. Identification of CSCs by expression of surface antigens remains a critical issue because no biomarker has been shown to be completely reliable. CD133 and CD44 are commonly used as CSC markers, and correlation of their expression with colorectal cancer (CRC) clinicopathological features and outcomes may be useful. DESIGN Pilot study. SETTING University hospital. PATIENTS Thirty-six consecutive patients with CRC. CD133 and CD44 expression (alone or combined) was determined in nontumor cells and in tumor cells by flow cytometry, which identified viable cells only. MAIN OUTCOME MEASURES Correlation of CD133 and CD44 expression with each other, with other prognostic indicators, and with disease-free survival. RESULTS CD133 and CD44 expression was significantly higher in tumor cells than in nontumor cells, and expression of one did not necessarily correlate with expression of the other. CD133 or CD44 expression alone was variable, while combined CD133/CD44 expression identified a small subset of cells positive for CRC. CD133 or CD44 overexpression was not associated with CRC recurrence; only high frequencies of CD133(+)/CD44(+) cells were a strong indicator of worse disease-free survival and an independent risk factor for CRC recurrence. CONCLUSION Evaluation of combined CD133/CD44 expression could be useful to identify putative colorectal CSCs and tumors with a poor prognosis.

Lateral internal sphincterotomy together with haemorrhoidectomy for treatment of haemorrhoids: a randomised prospective study.

OBJECTIVE To investigate anorectal manometric findings in patients with haemorrhoids and to evaluate the clinical effects and physiological consequences of adding a lateral internal sphincterotomy (LIS) to haemorrhoidectomy. DESIGN Randomised prospective study. SETTING Teaching hospital, Naples. PATIENTS 48 consecutive patients with prolapsed piles who had anorectal manometry; 10 healthy volunteers served as controls. INTERVENTIONS Resting and squeeze pressures, sphincter length and rectoanal inhibitory reflex were recorded. 6 patients were excluded because anal pressures were not raised, so 42 patients were randomised. 22 patients had haemorrhoidectomy plus LIS; and 20 had haemorrhoidectomy alone. MAIN OUTCOME MEASURES Morbidity, continence, and anorectal manometry. RESULTS Sphincter anomalies were found in 87.5% (n = 42) of patients. Haemorrhoidectomy alone did not affect anal pressures, which returned to the normal ranges after sphincterotomy. Those who had LIS did better postoperatively than those who had did not. 4 patients who did not have a sphincterotomy developed anal strictures. No patient who had LIS developed incontinence of faeces. CONCLUSIONS High anal pressures are common in patients with haemorrhoids suggesting that they may have a pathogenetic role; anorectal manometry is useful in the investigation of anal pressure patterns; and when indicated, lateral sphincterotomy avoids pain, urinary retention, and stenosis, and is safe.

Prognostic Value of p27, p53, and Vascular Endothelial Growth Factor in Dukes A and B Colon Cancer Patients Undergoing Potentially Curative Surgery

PURPOSEEarly-stage colon cancer patients (Dukes A or B; pT1–T3 pNO pMO) are excluded from adjuvant chemotherapy following potentially curative surgery because they are expected to have good long-term survival. However, 20 percent to 30 percent of these patients ultimately succumb from recurrent disease. This indicates that the conventional staging procedures may be unable to precisely predict cancer prognosis.METHODSIn 65 early-stage colon cancers, we investigated by immunohistochemistry the role of molecular markers such as p27, p53, and vascular endothelial growth factor in identifying high-risk patients who may benefit from adjuvant treatments.RESULTSNo clinicopathologic factor, namely Dukes stage, t parameter, number of resected nodes, and vascular or lymphatic invasion, was found be an independent significant predictor of disease-specific and disease-free survival. In contrast, each molecular marker predicted survival and recurrence rates much better than the conventional Dukes staging system. The best combination of variables for prediction of long-term outcome and recurrence rate included p27, p53, and vascular endothelial growth factor. Interestingly, the greater the number of molecular alterations, the lower the five-year estimated survival function. Nearly all cancer-related deaths were observed among patients whose colon cancers expressed all three molecular alterations. Regardless of Dukes stage, the recurrence rate was found to increase with the increase in the number of molecular alterations. Early-stage colon cancers expressing p27 down-regulation and high p53 and vascular endothelial growth factor immunoreactivity showed a 100 percent actuarial four-year recurrence rate.CONCLUSIONSAssessment of molecular alterations may be useful to identify a higher-risk group of early-stage colon cancer patients who may benefit from adjuvant chemotherapy.

The Lymph Node Ratio Is a Powerful Prognostic Factor of Node-Positive Colon Cancers Undergoing Potentially Curative Surgery

BackgroundThe number of harvested (LNs) and metastatic nodes (LNs+) represents the most significant factor to define postoperative treatment and prognosis in colon cancer. However, its assessment may be inadequate causing an incorrect cancer staging. The lymph node ratio (LNR: the ratio between metastatic and resected nodes) has shown prognostic significance in many tumors; however, its role in colon cancer is not clearly elucidated. This study investigated LNR as a prognostic factor in node-positive colon cancers.MethodsA total of 145 consecutive patients with node-positive colon cancer who underwent curative surgery and adjuvant chemotherapy in a single oncologic unit entered this study.ResultsLNR ranged from 0.0416 to 0.9; it was clearly lower in pN1 than pN2 patients, and increased as tumor stage worsened. ROC analysis selected 0.1818 as the best LNR cutoff value. Low LNR patients did significantly better than high LNR patients; this difference was not dependent on the number of LNs and stronger than differences observed by grouping patients according to LNs or LNs+. When stratified by low and high LNR value, pN1 and pN2 patients, as well as stage III subgroups were shown to display substantially different outcomes. LNR was an independent prognostic factor for disease-specific survival, and the only covariate related to disease-free survival.ConclusionsLNR was a robust prognostic indicator for node-positive colon cancers undergoing curative surgery. Because this ratio-based staging was demonstrated to reduce stage migration and to aid in identifying high-risk patients, it should be proposed as a standard tool for colon cancer staging.

Comparison between the biofragmentable anastomosis ring and stapled anastomoses in the extraperitoneal rectum: a prospective, randomized study.

Abstract Serious complications can be carried by intestinal anastomoses, particularly in the distal and proximal part of the gastrointestinal tract. The biofragmentable anastomosis ring (BAR) has been shown to be a safe anastomotic technique, but its clinical applicability in the extraperitoneal rectum has not yet been completely established. This study compared BAR anastomoses and stapled anastomoses in the middle rectum. Thirty-six consecutive patients initially suitable for elective colorectal anastomosis in the middle rectum were enrolled into this study. All patients had intraperitoneal rectum carcinoma, and 31 underwent a colorectal anastomosis in the middle extraperitoneal rectum. They were randomly allocated to a stapled technique or BAR anastomosis. Intraoperative findings and technical drawbacks, tumor behavior, and postoperative course were recorded. All patients were followed up, and late stenosis rate was investigated by endoscopy. The procedure was carried out in each of the 15 patients randomized to receiving a BAR anastomosis. No major difficulties were encountered, and the time needed was even less than that required for a stapled anastomosis. One patient in the stapled group had an early bleeding that required a further laparotomy. No significant differences in postoperative complications were noted between the two groups, although one patient with stapled anastomosis experienced a clinical leakage that needed loop colostomy. Biofragmentability was regular; buttons were eliminated in 3weeks without any bowel disturbance. BAR ring insertion in the deep pelvis did not produce a shorter colonic resection. The late stenosis rate was similar between the groups. This study shows that in extraperitoneal middle rectum BAR anastomosis is as feasible and safe as the stapled method. The latter is more expensive, and manual suture is more difficult. Therefore the BAR is now the method of choice for this anastomosis in the authors’ unit.