Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer.

The recent successful development of monoclonal antibodies that target key components of biological pathways has expanded the armamentarium of treatment options for patients with colorectal cancer (CRC). In particular, the epidermal growth factor receptor (EGFR), a tyrosine kinase growth factor receptor involved in CRC development and progression, is exploited by the newest monoclonal antibody that is available for use in CRC patients. Cetuximab, the first chimeric monoclonal antibody, which has been generated against the EGFR, is currently registered in USA, Europe and worldwide, in combination with irinotecan in the treatment of metastatic CRC patients who have progressed on irinotecan containing chemotherapy. Cetuximab is well tolerated and does not exacerbate the toxicity of concomitant chemotherapy. Furthermore, a series of phase III clinical trials are currently evaluating the combination of cetuximab with standard chemotherapy regimens in the first-line treatment chemotherapy-naïve patients with metastatic CRC.

Effects of alpha1-blockers on urodynamic parameters of bladder outlet obstruction in patients with lower urinary tract symptoms suggestive of benign prostatic enlargement: a review.

α1-adrenergic receptors blockers (ABs) are recommended as first-line medical therapy in men with Lower Urinary Tract Symptoms suggestive of Benign Prostatic Enlargement (LUTS/BPE). Available ABs include: terazosin, doxazosin, tamsulosin, naftopidil, alfuzosin and silodosin. These agents have different profiles of selectivity for α1-adrenergic receptors subtypes. All these agents are efficacious in improving both storage and voiding LUTS. In recent years the efficacy of ABs in improving urodynamic parameters of bladder outlet obstruction (BOO) has been questioned. We reviewed literature evidences about the effects of available ABs on invasive urodynamic parameters of BOO in men with LUTS/BPE. The impact of ABs therapy on urodynamic parameters indicative of BOO has been evaluated for all currently approved drugs. Available data demonstrate improvements in terms of both free uroflowmetry and pressure-flow parameters. While the impact of ABs on maximum urinary flow is clinically modest, the improvement of detrusor pressure at maximum urinary flow is more robust. Only few studies exist that directly compare the urodynamic effects of a small number of ABs. According to these studies there are no differences among ABs in terms of urodynamic efficacy. Indirect comparison of ABs suggests greater effectiveness of silodosin in terms of detrusor pressure at maximum urinary flow reduction. Studies that stratified populations based upon the degree of obstruction at baseline demonstrated greater urodynamic changes in patients with baseline BOO with respect to the unobstructed patients. Globally, the quality of studies available is low and there is considerable heterogeneity among studies.

DNA ploidy as a significant prognostic factor after radical resection for large bowel carcinoma: a prospective study.

It is controversial whether cell DNA measurement is a reliable method to predict prognosis in radically resected large bowel carcinomas. A study using strict rules was undertaken on 54 consecutive patients to clarify the usefulness of DNA ploidy by image cytometric analysis as a prognostic indicator. The tumors were 39% diploid and 61% aneuploid. DNA ploidy was not related to more advanced stages and it, with histological grade and Dukes' stage, was an independent covariate and influenced both disease-free and overall survival. Aneuploid tumors showed the worse prognosis in all Dukes' stages. This prospective study shows that DNA ploidy is an important independent prognostic indicator of clinical outcome and recurrence rate, and it should be used to both select high-risk patients and guide postoperative treatments, particularly in early-stage large bowel carcinomas.

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

BACKGROUND: Carbon 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. METHODS: In 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 throughout surgery. The following parameters were analyzed: mean 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. RESULTS: All 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. CONCLUSIONS: Cardiopulmonary 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.

Retroperitoneal abscess after retained stones during laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is associated with a significant risk of gallbladder perforations with bile and stone spillage. The retrieval of dropped stones is sometimes impossible, and intraperitoneally retained stones can be the source of serious complications, such as inflammatory masses or abscesses. The authors describe a patient in whom a large retroperitoneal abscess developed as a result of missed stone fragments during cholecystectomy. Although several cases of intraperitoneal abscess have been reported in the literature, retroperitoneal collection is very uncommon. Crushed and infected stones seem to be the essential prerequisite for abscess formation. Therefore, every attempt should be made to avoid stone spillage and intra-abdominally retained stones. Conversion to open surgery has to be considered in the presence of adverse factors, such as primary acute cholecystitis or cholecystitis induced by previous sphincterotomy, or bilirubinate stones believed to be infected. Abdominal abscess treatment requires removal of missed stones by surgical incision or new laparoscopic procedure because simple percutaneous drainage is usually unsuccessful.

[Hereditary colonic cancer. Analysis of 3 families at risk]. / Il cancro del colon eredo-familiare. Analisi di tre famiglie a rischio.

Hereditary colorectal cancer is a clearly identified entity today; it is transmitted as a dominant autosomal heritage, and represents about 25% of large bowel malignancies. The poor prognosis of this tumor, one of the most frequent in Western Countries, despite the improvements in therapeutic field, is due to a delated diagnosis that affects an advanced stage of disease in which the results of treatment are significantly worse, whereas cumulative 5-year survival rate is 35% vs 95% in early stage tumors. Existence of an inherited cancer, even in the absence, at present, of specific biomarkers, allows to identify a high risk population in which early diagnosis of colorectal cancer is possible, on the basis of anamnestic and clinical features. Only in this way, with the extension of the results to general population, prognosis of colorectal cancer will be improved.

[Multidisciplinary treatment of hepatocarcinoma]. / Il trattamento multidisciplinare dell'epatocarcinoma.

Radical treatment of the hepatocellular carcinoma (HCC) is complete surgical removal; it may be done by resection or total hepatectomy. Although multicentric carcinogenesis predicts that liver transplantation is likely adequate to treat both the hepatoma and the underlying cirrhosis, it doesn't seem justified in the advanced stages or in absence of end-stage liver disease and therefore liver resection remains the treatment of choice for radical cure of HCC. However, low resectability and high recurrence rate make surgery alone ineffective. Unresectable HCC may be converted to resectable by multimodality radiation/chemotherapy, and embolization of portal branch feeding tumour, improving the function of the nonembolized liver, can extend the surgical indications for HCC. Adjuvant chemoembolization has already shown to reduce recurrence rate after radical resection and it should be widely applied. In unresectable or not converted HCCs as well as in postoperative recurrence, alternative therapies, particularly as multimodality treatment, can improve survival rate. To date, multidisciplinary treatment of hepatocellular carcinoma, waiting for further studies on newer modalities (prevention and gene therapy, especially), represents the best way to improve long-term results.

[Biliary ileus: a review of the literature and report of a clinical case treated by minilaparotomy]. / Ileo biliare: revisione della letteratura e presentazione di un caso clinico trattato con minilaparotomia.

OBJECTIVE: To evaluate the diagnostic and therapeutic approach to gallstone ileus. MATERIAL AND METHODS: A gallstone ileus report, diagnosed by integrated radiological approach, treated by minilaparotomy plus enterolithotomy and followed up for two years. RESULTS: Traditional radiologic findings, ultrasonography and computed tomography showed both the stone in the bowel lumen and the cholecystoduodenal fistula with air in the biliary tract. The enterolithotomy alone worked out the obstruction and no complication was observed. DISCUSSION: Integrated radiologic examinations are indicated in defining nature, site and seriousness of gallstone ileus. In most cases surgical treatment is mandatory to work out both the bowel occlusion and bilioenteric illness even though it is often wiser to perform an operation of enterolithotomy alone owing to the general and local conditions of the patient. After this surgical approach, bilioenteric fistula disappears in most cases with no residual lithiasis; in the cases in which fistula and/or lithiasis persist, a decisive surgical operation can be performed in a second step.

[The usefulness of lateral internal sphincterotomy combined with hemorrhoidectomy in the treatment of hemorrhoids: a randomized prospective study]. / Utilità della sfinterotomia laterale interna associata alla emorroidectomia nel trattamento delle emorroidi: studio prospettico randomizzato.

The aim of this prospective randomized study was to investigate anorectal manometric findings in hemorrhoid patients and to evaluate the clinical benefits and physiological consequences of additioning a lateral internal sphincterotomy (LIS) to haemorrhoidectomy. Anorectal manometry was preoperatively performed in forty-eight consecutive patients with prolapsed piles; resting and squeeze pressures, sphincter length and rectoanal inhibitory reflex were recorded. Ten healthy volunteers served as controls. Six patients were excluded because no raised and pressures were found. Forty-two patients were randomised: Group 1 (n = 22) patients underwent haemorrhoidectomy plus LIS; Group 2 (n = 20) patients underwent haemorrhoidectomy alone. Postoperative course was carefully evaluated; all patients were questioned about continence and anorectal manometry was repeated twice. Sphincter anomalies were found in 87.5% of patients. Haemorrhoidectomy alone did not affect anal pressures, which returned into the normal ranges after sphincterotomy. Postoperative course was better in LIS group. Anal stricture was seen in four patients without sphincterotomy; no patients with LIS experienced and incontinence. This study shows that high and pressures are very frequent in hemorrhoid patients; they are not due to hypertensive and cushions and might have a pathogenetic role. Anorectal manometry is very useful to identify patients with raised anal pressures; in these cases additioning a lateral internal sphincterotomy to haemorrhoidectomy seems justified; it significantly improves postoperative course and can be safely performed.

[Ectopic thyroid: report of a case]. / Tiroide ectopica: a proposito di un caso clinico.

The development of thyroid tissue can occur in any moment of the migration of the thyroid along the thyroglossal duct from the tongue, resulting in lingual (at tongue base), sublingual (below the tongue), prelaryngeal (in front of the larynx), and substernal (in the mediastinum) ectopy. Thyroglossal duct cyst is the most common type of clinical abnormality related to thyroid ectopy. Surgical removal of such ectopic tissue is justified since some Authors describe thyroid cancer arising from aberrant thyroid tissue. The Authors report a case of thyroid ectopy in a patient who underwent 20 years before a left thyroid resection with isthmectomy; during the operation the surgeon described a hypertrophic pyramidal lobe which was left in situ and the patients did not receive any hormone suppressing therapy.

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.

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

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 3 weeks 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.

Bladder neoplasms after nephroureterectomy: does the surgery of the lower ureter, transurethral resection or open surgery, influence the evolution?

OBJECTIVE: Nephroureterectomy is the treatment of choice for tumors of the upper urinary tract (UUTT). In 1952, a modified version of this technique was described, involving endoscopic detachment of the ureter followed by nephroureterectomy with a single lumbar incision. We reviewed a retrospective survey to assess whether UUTT patients treated with nephroureterectomy with no prior history of bladder tumor had different rates of incidence or different sites of bladder recurrence according to the specific technique employed. METHODS: Patients were divided into group A, 87 patients who underwent a double incision nephroureterectomy and group B with 58 patients with prior detachment of the ureter. In both groups, incidence was calculated for two variables (bladder tumor recurrences and homolaterality of such recurrences) and chi-square tested. RESULTS: Bladder tumor was diagnosed at follow-up in 39% of patients in group A and 34.5% in group B, with no statistically significant difference (N.S.). Bladder tumor recurrences were homolateral to UUTT in 50% of group A cases and 55% of group B cases (N.S.). CONCLUSIONS: Although this is a retrospective survey of two asynchronous groups, given the similar nature of the UUTT cases in both groups and the fact that no statistically significant differences have been found, it is reasonable to conclude that nephroureterectomy with prior endoscopic detachment of the ureter is a safe and radical procedure.