Locally advanced rectal cancer: a multivariate analysis of outcome risk factors.

BACKGROUND AND OBJECTIVES: Stages II and III rectal tumors are known as locally advanced rectal cancer (LARC) because they are characterized by a high incidence of local and distant relapses and a low probability of long-term survival. Adjuvant treatments have been advocated to ameliorate overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) without a univocal beneficial trend. The aim of this study was to identify the independent predictive factors of OS, LRFS, and MFS which could best select patients for adjuvant treatment of LARC. METHODS: Of 153 rectal cancer cases seen consecutively from 1991 to 1998, we studied the main clinical and pathological parameters of 73 LARCs. Clinical and pathological variables were studied by univariate analysis, and independent predictive factors were identified by multivariate analysis. RESULTS: Stages II and III rectal cancer have shown not statistically different rates of OS, LRFS, and MFS. Factors independently associated with increasing OS and MFS were low preoperative carcinoembryonic antigen level (CEA), low number of metastatic lymph nodes, low percentage of metastatic lymph nodes out of the total number of lymph nodes excised, and adjuvant treatment. Increased staging and distal resection margins < or =1 cm were shown to be independent detrimental risk factors regarding OS and MFS, respectively. Independent prognostic factors associated with a reduction in LRFS were advanced age, Hartman's resection, distal resection margins < or =1 cm, and fewer than 14 resected nodes. CONCLUSIONS: Whereas stage I rectal cancer can be treated with a good probability of cure by surgery alone, avoiding adverse effects of adjuvant regimens, the outcome of LARC appears to be positively influenced by adjuvant therapies. In LARC, an accurate study of risk factors would be useful to identify which subset of patients could be favorably influenced by postoperative radiochemotherapy.

Biological prognostic factors for early stage completely resected non-small cell lung cancer.

BACKGROUND AND OBJECTIVES: The different and unpredictable outcomes in early-stage non-small cell lung cancer patients requires urgent research concerning the biological pathway of this neoplasm. Our study investigated the frequency of expression and the clinicopathologic and prognostic significance of a series of biological markers in stage I and II resected non-small cell lung cancer. METHODS: A total of 99 cases of pathologic stage I and II were analyzed. The mean follow-up of surviving patients was 41 months. The expressions of the following biological markers were tested: bcl-2, p53, Ki-67, angiogenesis, and tumor vessel invasion. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical variables and biological markers using Cox's model for multivariate analysis. RESULTS: Tumoral vessel invasion was present in 22 (22%) pathologic samples, the angiogenesis mean value was 37 +/- 13, and median was 35; 13 (13%) patients showed positive immunostaining for bcl-2 oncoprotein. P53 oncoprotein expression was present in 48 patients (48.5%). All samples presented Ki-67 expression (mean value = 25.3 +/- 19.3, median = 20). The pathologic staging of the tumor was the most important independent prognostic factor for survival (P = 0.037) and for recurrence of disease (P = 0.040). Tumoral vessel invasion was the only marker with an independent predictive factor for survival and recurrence of disease in the group of patients without lymph node involvement (P = 0.02). CONCLUSION: Our data do not support a relevant prognostic role for p53, bcl-2, or Ki-67 immunohistochemical markers in non-small cell cancer. Tumor vessel invasion was an independent predictive factor of poor outcome in the group of patients without lymph node involvement. Pathological stage was confirmed as the most important independent prognostic factor.

[Perioperative changes in the plasma levels of fibrinogen and D-dimer during laparoscopic cholecystectomy: the preliminary results of a prospective randomized clinical study]. / Modificazioni perioperatorie dei tassi plasmatici di fibrinogeno e D-dimero in corso di colecistectomia laparoscopica: risultati preliminari di uno studio clinico prospettico randomizzato.

AIM: Considering that laparoscopic procedure is associated with increased resistance to lower-limb venous return and subsequent stasis, with possible implications in terms of thromboembolic complications, the aim of our study was to investigate prospectively the coagulative-fibrinolytic profile, in laparoscopic and open cholecystectomy, in patients randomly alloted to receive or not preoperative heparin. METHODS: We prospectively analyzed 36 patients (20 laparoscopic and 16 open) and we randomly divided the patients in two groups: Group-A (28 patients--16 laparoscopic and 12 open) didn't take any preoperative thromboprophylaxis, Group-B (8 patients--4 laparoscopic and 4 open) took preoperative subcutaneous heparin. We took blood venous samples before surgery, at time 0 and + 30 min., at the end and 1 and 24 hours postoperatively. The following parameters were assessed: prothrombin time, partial thromboplastin time, fibrinogen and D-dimer. We statistically analyzed the differences by ANOVA test. RESULTS: In Group A, fibrinogen and D-dimer were significantly higher (p < 0.0001 and p = 0.0266) in open group as compared with laparoscopic one and we observed significant time-depending changes of fibrinogen's concentration (p = 0.0168). In Group B we obtained a higher fibrinogen's value in laparoscopic group than in conventional one, with a significant difference (p = 0.0283); also, the sampling-time affected the result in a very significant meaning (p = 0.0041). Comparing fibrinogen levels between Groups A and B, we observed lower values in heparin-treated group than in the other one (p < 0.0001), while in laparoscopic surgery there was not a significant difference between two groups of treatment. CONCLUSIONS: Our preliminary data suggest that, perioperatively (besides a smaller laparoscopic acute-phase response) the coagulative-fibrinolytic changes are lower in laparoscopic cholecystectomy than in open one and heparin treatment significantly reduces these changes in open surgery but doesn't seem to affect laparoscopic group. Our results seem to show another possible advantage of the laparoscopic surgical procedures over the traditional ones.

Pancreatic regeneration after subtotal distal resection in rats. Effects of bombesin and octreotide by the in vivo bromodeoxyuridine uptake technique.

Forty male Wistar rats were randomly allocated to four treatment groups after 90% distal pancreatectomy: group A (control) received saline (0.5 ml subcutaneously); group B received bombesin (BBS; 10 microg/kg intraperitoneally); group C received octreotide (2.5 microg/kg subcutaneously), and group D received BBS and octreotide. All substances were injected three times a day until sacrifice after 28 days. BBS increased pancreas weight (p = 0.003) and DNA synthesis (p < 0.001), as measured by a bromodeoxyuridine nuclear-labeling index (BrdU LI). The simultaneous administration of octreotide significantly decreases the remnant pancreas weight (p = 0.016) as compared to group B rats; however the BrdU LI is not significantly reduced in group D as compared to group B. BBS administration promotes regeneration of the remnant pancreas in terms of hypertrophy and hyperplasia. Although octreotide appears to significantly reduce the pancreatic weight increase induced by BBS, it does not reduce DNA synthesis and cell proliferation.

[Effect of octreotide on the hepatic metastasis of human colorectal cancer: an experimental model in athymic mice]. / Effetti dell'octreotide sulle metastasi epatiche da cancro del colonretto umano: modello sperimentale su topo atimico.

The aim of this randomized study was to determine the effects of octreotide therapy on the growth and development of experimental liver metastases from a human colonic cancer cell line (HT 29) in nude mice model. No important and significant difference could be found between mice, lungs and liver weights of both groups as well as lung metastatization; indeed, significant was the difference between groups concerning liver, metastases (the majority of them were in treated group): in spite of the small number of data collected, which does not allow to draw any conclusion on the efficacy of this drug on liver metastases, we believe that octreotide therapy does not affect dramatically the growth and development of liver metastases from a human colon cancer.

Hepatoid carcinoma of the stomach: is it still an unusual anatomo-clinical entity? Six cases-report.

Hepatoid carcinoma of the stomach is a rare neoplasm (especially in western countries) characterized by high levels of serum alpha-fetoprotein (AFP), the presence of "hepatoid foci" inside the gastric tumor and poor prognosis, due to the earlier onset of liver metastases. We treated six patients for hepatoid carcinoma of the stomach between 1990 and 1997. The female to male ratio was 1:1, the average age was 71 (54-81) and the average AFP-level was 1160 ng/ml (603-1531). We performed 2 total gastrectomies, 2 subtotal gastrectomies and 2 gastro-jejunostomies (due to presence of liver metastases): in one case, the patient underwent a splenectomy as well. All the tumors showed the presence of "hepatoid foci" (the morphological feature is close to the hepatocellular carcinoma) and a positive immunoreactivity to AFP. The mean survival was 3 months: only one patient is still alive and disease-free (with a 52 months follow-up). After radical surgery, she underwent a chemotherapic treatment with cisplatin, epirubicin, 5-fluorouracil and l-leucovorin. We conclude that our series (the widest in Italy and one of most impressive in Europe) confirm the poor prognosis of this neoplasm, but we also want to underline that this tumor is not so "unusual" any more and it requires new types of treatment, like postoperative chemotherapy, besides surgery, to be fighted properly.

Adenocarcinoma arising from a recurrent fistula-in-ano.

Anal fistulas are frequent events which often recur after an inadequate surgical treatment. Nevertheless their evolution into malignant diseases is infrequently observed. The authors report one case of mucinous adenocarcinoma arising out of a recurrent, long-lasting fistula-in-ano. As reported, abdomino-perineal resection combined with radiotherapy can be the choice treatment. The difficulty is to obtain a reliable differential diagnosis. No imaging technique nor histologic examination can establish a definitive reliable diagnosis; nevertheless, as the risk of adenocarcinoma developing from a long-lasting recurrent fistula-in-ano, although small, is real, authors believe that operative exploration and biopsy of recurrent abscesses and fistulas should be recommended.

Bombesin-induced pancreatic regeneration in pigs is mediated by p46Shc/p52Shc and p42/p44 mitogen-activated protein kinase upregulation.

BACKGROUND: In several animal species the pancreas has the capacity to partially regenerate in a self regulating process. A complex network of growth factors modulates this process. There is evidence that bombesin stimulates pancreatic regeneration in rodents. Whether bombesin stimulates pancreas regrowth in large mammals is unknown. Shc proteins, the target of tyrosine kinase-coupled receptors, activate p42 and p44 mitogen-activated protein (MAP) kinase and induce the transcriptional upregulation of genes involved in cell proliferation. The aims of our study were to determine whether bombesin stimulates pancreatic growth in large mammals and whether this event requires Shc-MAP kinase pathway upregulation. METHODS: Three groups of pigs were submitted to sham operation (group 1); to subtotal (70%) distal pancreatectomy (group 2), and to subtotal pancreatectomy followed by bombesin (5 mg three times daily) for 4 weeks (group 3). After a 4-week follow-up a second laparotomy was performed, and the residual pancreas removed. p46Shc, p52Shc and p66Shc, Grb2, and p42/p44 MAP kinase expression and phosphorylation were measured either in freshly isolated pancreatic acinar cells or whole pancreatic extracts. RESULTS: In vivo bombesin administration resulted in: 1) approximately 100% growth of pancreatic duodenal lobe; 2) rapid recovery from exocrine pancreatic failure; and 3) a threefold increase in the rate of pancreatic acinar cell proliferation. Incubating freshly isolated pancreatic acinar cells with bombesin resulted in time- and concentration-dependent stimulation of p46Shc/p52Shc phosphorylation, Shc-Grb2 complex formation, and p42/p44 MAP kinase activation. In vivo bombesin administration significantly upregulated p46Shc/p52Shc and MAP kinase expression and/or activity in whole pancreatic extracts. CONCLUSIONS: In vivo chronic bombesin administration stimulates pancreatic regeneration after pancreatectomy in large mammals. Bombesin-stimulated pancreatic growth is associated with upregulation of the Shc-Grb2-SOS-Ras-MAP kinase pathway.

Eversion versus conventional carotid endarterectomy: a prospective study.

OBJECTIVES: To analyse comparatively eversion and conventional CEA for later association with restenosis, perioperative stroke/death and ipsilateral cerebrovascular events (early, late, disabling and non-disabling). DESIGN: Prospective non-randomised clinical study. MATERIALS AND METHODS: A total of 469 patients underwent 514 procedures; 274 (53%) eversion CEA and 240 (47%) conventional CEA. Perioperative monitoring was carried out by clinical evaluation under local anaesthesia or by transcranial Doppler under general anaesthesia. Follow-up was carried out by clinical evaluation and Duplex scanning. RESULTS: Clamping time was significantly shorter in the eversion group (25.5 +/- 7.4 vs. 28.3 +/- 10.1 min; p = 0.0001; CI delta 4.40/1.12). The perioperative disabling stroke/death rate was 0.7% for eversion vs. 1.2% for conventional CEA, p = 0.6; odds ratio (OR), 0.58. There were two early carotid occlusions (within 30 days) in both groups. According to life-table analysis, after 3 years the probability of > 50% carotid restenosis was significantly lower in the eversion group (2.2% vs. 6.9%, p = 0.03; relative risk reduction 67%). There were no significant differences between the two groups relative to new cerebrovascular events (92% in both groups, p = 0.6). Using multivariate analysis (Cox regression), eversion CEA, and to a lesser extent standard CEA with patch, appeared to protect the vessel from restenosis. CONCLUSIONS: The eversion technique was associated with reduced clamping time and probability of restenosis. However, because of the nature of a non-randomised study, the present analysis should be confirmed by a multicentre randomised trial.

["Hepatoid" gastric tumor]. / Il tumore gastrico "epatoide".

In this study the Authors describe two cases of hepatoid adenocarcinoma of the stomach: one is characterized by the presence of alpha-fetoprotein (AFP) high levels of the serum both pre and post-operating and by the very positive response to the adjuvant chemotherapy (how the return to the normality of such values demonstrates). The other is instead characterized by the presence of post operating hepatic metastasis, event which is very frequent in this kind of neoplasm, but presents many problems concerning the differential histological diagnostics with the primitive hepatocarcinoma (problems which are nowadays not completely solved). Moreover the Authors relate to this study the revision of the international literature of the main characteristics and of prognosis of this particular and rare neoplasm.

Transcranial Doppler monitoring during carotid endarterectomy: is it appropriate for selecting patients in need of a shunt?

PURPOSE: This report summarizes our experience in evaluating a series of 168 patients who underwent a total of 175 carotid endarterectomy procedures under local anesthesia. Patients were monitored by stump pressure (SP) measurement and transcranial Doppler scanning (TCD). The need for shunting was compared between SP/TCD flow velocity reduction and the awake response (gold standard). METHODS: The study cohort represented 56% of all the carotid patients treated during the study period. Clamping ischemia was defined as the appearance of focal deficit (focal ischemia) or unconsciousness (global deficit) on carotid clamping. In the case of clamping ischemia, a shunt was inserted. To define the optimal value of SP and TCD flow velocity that is able to discriminate patients with clamping ischemia, a receiver operator characteristic (ROC) curve was constructed. Sensitivity and specificity tests, together with negative and positive predictive values (NPV and PPV), were calculated. Cutoff values were defined as the ROC curve values that correlated the highest sensitivity with the highest specificity for both SP and TCD. RESULTS: Clamping ischemia was present in 18 procedures (10%) in which a shunt was used. No perioperative deaths were recorded. Major perioperative morbidity occurred in one patient (0.6%). Two nondisabling strokes were also recorded (1.8% overall rate of neurologic morbidity). Cutoff values for both SP and TCD, using the ROC curve, were < or = 50 mm Hg and > or = 70% flow velocity reduction from baseline, respectively. SP values of < or = 50 mm Hg or less showed a sensitivity of 100%, a specificity of 83%, a PPV of 40%, and an NPV of 100%. TCD flow monitoring (> or = 70% flow reduction) revealed a lower sensitivity (83%) but a greater ability to avoid false positive results (96% specificity), resulting in increased PPV (71%) and NPV (98%). Combining SP and TCD failed to provide better results in terms of specificity (81%) and PPV (38%). CONCLUSIONS: SP measurement using a 50 mm Hg cutoff appears to be a reliable predictor of clamping ischemia but requires the use of a shunt in 17% of the patients who would otherwise not require this procedure. In contrast, TCD has greater specificity but is associated with a lower sensitivity, with 17% false negative results. In our experience, both SP and TCD show limitations, as they overestimate or underestimate carotid endarterectomy procedures in need of a shunt. We believe that sensitivity is more important than specificity in carotid endarterectomy, and thus conclude that TCD flow velocity measurement is not an optimal method for detecting clamping ischemia.

Surgical care in octogenarians.

The general surgical profile of octogenarians compared with that of younger patients, and risk factors predictive of operative mortality and morbidity, were determined retrospectively using a computer database for all patients admitted between 1989 and 1993. There were 934 admissions of octogenarians and surgery was performed in 447 cases (47.9 percent). The admission rate of patients over 80 years of age increased during the 5-year period from 4.6 to 9.0 per cent, and was significantly higher than that of geriatric patients aged 65-79 years (P < 0.01). Emergency admissions (63.6 percent) and operations (42.3 percent) were more frequent in patients aged over 80 years (P < 0.01); emergency operations increased during the 5 years from 38 to 59 percent. Altogether, 83 deaths and 171 complications were recorded. The mortality rate of octogenarians was greater than that of younger patients (P < 0.01). Postoperative mortality and morbidity rates were 10.1 and 32.2 percent respectively. After multiple logistic regression analysis with stepwise backward elimination, an American Society of Anesthesiologists score of II-V (P < 0.01), the presence of two associated diseases (P < 0.01) and laparotomy procedures (P < 0.03) appeared to be independent risk factors for postoperative mortality and morbidity.

Postoperative intraabdominal abscesses: percutaneous versus surgical treatment.

The optimal treatment of postoperative intraabdominal abscesses has not yet been defined and mortality and morbidity remain high. In this retrospective study 2.310 laparotomies were reviewed. The records of 39 patients with postoperative intraabdominal abscesses (1.6%) are reported and the results obtained in percutaneous drainage (PD, n = 27) versus surgical drainage (SD, n = 10) are compared. The choice of drainage was made after consultation with the interventional radiologist, and PD was preferred in single, well-defined abscesses. Two patients had prompt spontaneous resolution of the abscess. The two groups were homogeneous for age, sex and postoperative day of abscess diagnosis. There was no difference in severity of illness assessed by Acute Physiologic Score (APS) between PD and SD groups (7.9 vs 9.3). No significant difference was found in mortality (11% vs 20%), morbidity (11% vs 40%) and duration of drain tube (14 vs 15 days) between PD group and SD group. This study confirms the data of recent retrospective stratified series: PD and SD are equally efficacious to cure postoperative intraabdominal abscesses. However, PD should be the treatment of choice because of its lower invasiveness and cost.

Computerised tomography findings as a risk factor in carotid endarterectomy: early and late results.

OBJECTIVES: To evaluate whether preoperative CT evidence of brain infarction is associated with an increased risk of early and late stroke and death in patients undergoing CEA. DESIGN: Retrospective clinical study. MATERIALS AND METHODS: We evaluated 844 CT scanning records from 893 patients undergoing CEA from 1986-1994: 43% (367) CT positive for cerebral infarction and 57% (477) negative. Univariate and multivariate analysis was performed for risk factors and preoperative symptoms in patients with positive and negative CT scans, and Kaplan Meier survival curves for late events. RESULTS: A positive CT was significantly more frequent in males vs. females (p < 0.0001; O.R. 2.52; C.I. 1.73-3.73), diabetics vs. non-diabetics (p = 0.03; O.R. 1.52; C.I. 1.03-2.26), symptomatics vs. asymptomatics (p < 0.001; O.R. 2; C.I. 1.93-3.53) and contralateral occlusion vs. patency (p < 0.001; O.R. 2; C.I. 1.30-3.10). The perioperative disabling stroke/ death rate was higher in patients with a positive CT (p = 0.002; O.R. 6.27; C.I. 1.73-34.20); in asymptomatic patients this difference was striking (5 patients vs. O, p = 0.0002). Multiple logistic regression analysis for risk factors, CT findings, symptoms preceding surgery, and congruity of brain infarction confirmed a significantly higher incidence of perioperative stroke/death rate (p = 0.003; O.R. 6.37; C.I. 5.12-7.63) and early and late stroke (p = 0.02; O.R. 1.95; C.I. 1.38-2.53) and death (p = 0.0005; O.R. 2.38; C.I. 1.89-2.88) in patients with brain lesions. After 7 years, the survival rate (p = 0.0009) and stroke-free interval (p = 0.003) were lower in patients with a positive CT. After 5 years, in asymptomatic patients the survival rate (p = 0.003) and stroke-free interval (p = 0.01) were lower in the positive CT group. CONCLUSIONS: A positive CT finding, regardless of congruity of the lesion, should be regarded as an indicator of an increased risk of stroke and death in patients scheduled for carotid surgery, especially in those with asymptomatic stenosis.

Ultrasonography in the management of acute appendicitis.

BACKGROUND: Ultrasonography (US) shows promise in the diagnosis of acute appendicitis. METHODS: The authors present their own experience in ultrasonography (US) employed in the diagnosis of appendicitis, based on 40 patients admitted to the Department of Surgery of the University of Perugia. RESULTS: US was found to be easily obtainable and reliable; it had good specificity and sensitivity, was not very time consuming, and had a good cost/benefit ratio. CONCLUSIONS: The authors believe US is an important diagnostic tool that can reduce useless laparotomies for false acute appendicitis, particularly in cases presenting with unclear clinical findings.

Carotid endarterectomy contralateral to an occluded carotid artery: a retrospective case-control study.

OBJECTIVES: To analyse whether contralateral occlusion represents an additional perioperative risk factor in carotid endarterectomy (CEA), and whether long-term survival after surgery in patients with contralateral occlusion differs from that of patients without. DESIGN: Retrospective clinical study. SETTING: Vascular Surgery Unit, Department of Surgery, University of Perugia, Perugia, Italy. MATERIALS: Fifty-five patients with carotid stenosis and contralateral occlusion undergoing CEA (Group 1) were compared with 110 patients (Group II), without contralateral occlusion selected from a cohort of 367 patients with a patent contralateral artery, matched for gender, age and ipsilateral symptoms. CHIEF OUTCOME MEASURES: Perioperative stroke/death rate at 30 days and minor complications in Group I vs. Group II over a mean follow-up of 38 months. MAIN RESULTS: The perioperative stroke/death rate at 30 days was 0% in Group I and 2.7% in Group II (p = 0.6) while minor complications amounted to 11% in Group I and 5% in Group II (p = 0.2). Survival rates of patients free from stroke, using Kaplan Meier curves, were 79.4% in Group I and 83.3% in Group II (p = 0.4); stroke free rates were 92.8% and 94.3% in Groups I and II, respectively. The incidence of late stroke, fatal or not, in patients who had undergone CEA with contralateral obstruction was the same as in similarly operated patients without contralateral obstruction (7% vs. 6%). However, the incidence of late vascular death, exemplified by a crude rate of 14% vs. 6% (p = 0.1; O.R. = 2.50; C.I. = 0.77-8.25) was greater in patients with contralateral occlusion. CONCLUSIONS: In this study, CEA in patients with contralateral occlusion was not associated with an increased perioperative morbidity/mortality rate. The higher incidence of vascular death in the late follow-up of patients with contralateral carotid occlusion, although not statistically significant, could indicate the presence of more severe systemic vascular disease.