Randomized controlled trial of 8 weeks' vs 12 weeks' interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.

AIM: The aim was to compare the pathological complete response (pCR) rate at 8 compared to 12 weeks' interval between completion of neoadjuvant chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. METHOD: This was a randomized trial which included a total of 330 patients from two institutions. Patients with locally advanced (T3-4N0M0, TxN+M0) rectal cancer were randomized into 8- and 12-week interval groups. All the patients received long-course CRT (45 Gy in 1.8 Gy fractions and concomitant oral capecitabine or 5-fluorouracil infusion). Surgery was performed at either 8 or 12 weeks after CRT. The primary end-point was pCR. Secondary end-points were sphincter preservation, postoperative morbidity and mortality. RESULTS: Two-hundred and fifty-two patients (n = 125 in the 8-week group, n = 127 in the 12-week group) were included. Demographic and clinical characteristics were similar between groups. The overall pCR rate was 17.9% (n = 45): 12% (n = 15) in the 8-week group and 23.6% (n = 30) in the 12-week group (P = 0.021). Sphincter-preserving surgery was performed in 107 (85.6%) patients which was significantly higher than the 94 (74%) patients in the 12-week group (P = 0.016). Postoperative mortality was seen in three (1.2%) patients overall and was not different between groups (1.6% in 8 weeks vs 0.8% in 12 weeks, P = 0.494). Groups were similar in anastomotic leak (10.8% in 8 weeks vs 4.5% in 12 weeks, P = 0.088) and morbidity (30.4% in 8 weeks and 20.1% in 12 weeks, P = 0.083). CONCLUSION: Extending the interval between CRT and surgery from 8 to 12 weeks resulted in a 2-fold increase in pCR rate without any difference in mortality and morbidity.

Preventing parastomal hernia with modified stapled mesh stoma reinforcement technique (SMART) in patients who underwent surgery for rectal cancer: a case-control study.

PURPOSE: Parastomal hernia is a frequent complication of an abdominal wall stoma. Surgical repairs have high complication and recurrence rates. Several different techniques have been suggested to prevent parastomal hernia during stoma creation. The aim of the present case-control study was to evaluate the efficacy of modified Stapled Mesh stomA Reinforcement Technique (SMART) for prevention of parastomal hernia compared with conventional colostomy formation in patients who underwent open or laparoscopic rectal resection and end colostomy for cancer. METHODS AND MATERIALS: Between January 2014 and May 2016, all consecutive patients who underwent open or laparoscopic resection and end colostomy for primary or recurrent rectal cancer were identified from a prospectively collected database. Since January 2014, one surgeon in our team has routinely offered modified SMART procedure to all patients who are candidates for permanent terminal colostomy. In the SMART group patients, while creating an end colostomy, we placed a standard polypropylene mesh in the retromuscular position, fixed and cut the mesh by firing a 31- or 33-mm-diameter circular stapler and constructed the stoma. In the control group, a stoma was created conventionally by a longitudinal or transverse incision of the rectus abdominis sheath sufficiently large for the colon to pass through. RESULTS: Twenty-nine patients underwent parastomal hernia prophylaxis with modified SMART and 38 patients underwent end-colostomy formation without prophylaxis (control group). Groups were similar in terms of age, sex and underlying conditions predisposing to herniation. Median follow-up time is 27 (range 12-41) months. Nineteen patients (28.4%) developed parastomal herniation. In the SMART group, 4 patients (13.8%) developed parastomal herniation which is significantly lower than the control group in which 15 patients (39.5%) developed parastomal herniation (p = 0.029). We did not observe mesh infection, stenosis, erosion or fistulation in the SMART group. One patient in the control group underwent surgical correction of stoma stricture, another patient underwent surgery for stoma prolapse and four patients underwent surgery for parastomal herniation. CONCLUSION: New systemic reviews and meta-analysis support parastomal hernia prevention with the use of a prophylactic mesh. Until more evidence is available, prophylactic mesh should be routinely offered to all patients undergoing permanent stoma formation. SMART is easy to use, safe and effective for paracolostomy hernia prophylaxis.

The prognostic impact of the log odds of positive lymph nodes in colon cancer.

AIM: This study aimed to investigate the prognostic impact of the log odds of positive lymph nodes (LODDS) in colon cancer. METHOD: Four hundred and forty patients with colon cancer were divided into three each groups according to their lymph node ratio (LNR) and LODDS. Survival analysis was performed. RESULTS: The 5-year overall survival (OS) rate was 70.2%. In univariate analysis age, pT and pN stage, tumour grade, lymphatic, venous and perineural invasion, surgical margin clearance, LNR and LODDS were significantly associated with OS. In multivariate analysis age, surgical margins, perineural invasion and LODDS were found to be independent prognostic factors. In subgroup analysis of patients with an inadequate number of examined lymph nodes (NELN) (n = 76) and node-negative patients (n = 210), LODDS retained its prognostic value, whereas the impact of LNR was not statistically significant (P = 0.063). The overall survival rates of node-negative patients in the LODDS groups 0, 1 and 2 were 81%, 74.2% and 50%, respectively (P = 0.020). LNR and LODDS classifications were both significantly associated with survival in Stage III colon cancer, but only LODDS was an independent prognostic factor. CONCLUSION: Conventional TNM staging for nodes (pN) and LNR status cannot reliably classify node-negative patients into homogeneous groups. LODDS provides more valuable information than LNR independently of the NELN.

Insulin production and resistance in cystic fibrosis: effect of age, disease activity, and genotype.

AIM: To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD). SUBJECTS AND METHODS: One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic ß-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR). RESULTS: The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes. CONCLUSIONS: IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, ß-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.

Role of gelatinases (matrix metalloproteinases 2 and 9), vascular endothelial growth factor and endostatin on clinicopathological behaviour of rectal cancer.

AIM: The aim of this study was to evaluate the role of matrix metalloproteinases (MMPs), their tissue inhibitors [tissue inhibitors of metalloproteinases (TIMPs)] and activators [membrane-type MMPs (MT1-MMPs)], vascular endothelial growth factor (VEGF) and endostatin on clinicopathological variables and prognosis in patients with rectal cancer. METHOD: Paired samples of tumour tissue and normal tissue were obtained from patients with rectal cancer who underwent curative surgery (n = 34). Gelatin zymography for MMP-2 and MMP-9, an activity assay for MT1-MMP and enzyme-linked immunoassays for TIMP-2, VEGF and endostatin were performed using extracts from the paired tissue samples. RESULTS: Active MMP-9 showed statistically significant relationships with metastatic disease and perineural invasion (P = 0.002 and P = 0.042). A significant relationship was observed between the levels of tumoral pro-MMP-2 and pro-MMP-9 and the presence of lymph node metastasis (P = 0.012 and P = 0.021, respectively). Tumoral TIMP-2 levels showed a significant relationship with tumour recurrence (P = 0.011). A significant relationship was also observed between tumour VEGF levels and the presence of perineural invasion (P = 0.044), and VEGF levels were correlated with the size of the tumour (P = 0.009, r = 0.454). CONCLUSION: These results might contribute to further investigation of a possible prognostic significance in rectal cancer.

Antimicrobial prophylaxis in clean surgery with special focus on inguinal hernia repair with mesh.

Until recently, antimicrobial prophylaxis was thought to be unnecessary for clean surgery except when a foreign body is implanted or the presence of infection poses a significant risk to patients. However, the results of several trials support extending the administration of antimicrobial prophylaxis to other types of clean surgery such as inguinal hernia repair or breast surgery. A recent Cochrane meta-analysis concluded that antimicrobial prophylaxis for inguinal hernia repair with or without mesh cannot be recommended or discarded. Resolution of this problem is important because inguinal hernia repair with mesh is one of the most common procedures in general surgery, and antibiotic consumption for preventive purposes is becoming a serious problem due to the risk of contribution to development of bacterial resistance and the significant increase in healthcare costs. This review will document clinical trials and meta-analyses on clean surgery, and will focus on inguinal hernia repair with mesh.

Single-dose oral ciprofloxacin compared with single-dose intravenous cefazolin for prophylaxis in inguinal hernia repair: a controlled randomized clinical study.

The aim of this study was to compare the efficacy of single-dose intravenous cefazolin prophylaxis with single-dose oral ciprofloxacin prophylaxis in patients undergoing tension-free inguinal hernia repair with polypropylene mesh. In a prospective and randomized setting, 395 patients received either a single dose of 500 mg of ciprofloxacin orally, 1--2h before the operation, or a single dose of 1g cefazolin intravenously on induction of anaesthesia. The primary outcome was to determine the wound infection rate within one year. The overall infection among the entire study population was 2% (eight of 395) including 2% (four of 199) of those receiving intravenous cefazolin and 2% (four of 196) of those treated with oral ciprofloxacin. There was no statistically significant difference between groups (P=0.59). All the infections were superficial incisional surgical site infections, and none progressed to a deep infection. Escherichia coli was the most commonly isolated bacterium. None of the infected patients developed recurrence of hernia. The rate of recurrence was 1.3% (five of 395) at one year including 2% (four of 199) of those receiving cefazolin and 0.5% (one of 196) of those receiving ciprofloxacin. Oral ciprofloxacin prophylaxis was found to be an attractive option with its wide antibacterial spectrum, low cost and ease of administration in patients undergoing tension-free inguinal hernia repair with polypropylene mesh.

Chemical necrotizing fasciitis due to household insecticide injection: is immediate radical surgical debridement necessary?

We describe two cases of chemical necrotizing fasciitis in the upper extremities, anterior chest wall and epigastric region of the abdominal wall caused by household insecticide injection. We suggest that surgical debridement can be successfully performed in the subacute period under close observation in hemodynamically stable patients.

Prevention of deleterious effects of reperfusion injury using one-week high-dose allopurinol.

Allopurinol has been widely used to reduce the severity of the reperfusion injury. However, conflicting data have been reported regarding the dosage, the duration of the timing, and the administrative regimen of the drug. The aim of this study was, therefore, to evaluate the effects of short versus long periods of allopurinol pretreatment on the anastomotic healing of intestines, directly after being subjected to ischemia-reperfusion (IR) stress. Furthermore, the effects of an allopurinol pretreatment on the survival rate following IR stress, was also assessed. One hundred thirty-seven male Wistar rats with a median weight of 235 (range, 180-275) g used in the study. In group I (control group, N = 20) superior mesenteric artery (SMA) and collateral vessels were isolated but not occluded. In group II, the profound IR group (PIR, N = 42), the SMA was occluded immediately distal to the aorta with collateral interruption using an atraumatic arterial clip for 30 min. In group III [two days of allopurinol (ALL) pretreatment group, 2ALL, N = 38], allopurinol (100 mg/kg body wt) was given intraperitoneally on a daily basis for two days prior to the experiment. In group IV (seven days of allopurinol pretreatment group, 7ALL, N = 37), the same pretreatment and the allopurinol schedule was performed for seven days before surgery. All animals underwent 3 cm of ileal resection and primary anastomosis, 10 cm proximal to ileocecal valve. Within each group, animals were anesthetized either on the third or seventh postoperative days. Abdominal wound healing, intraabdominal adhesions, anastomotic complications, anastomotic bursting pressure measurements, and bursting site were recorded as were the histopathologic evaluation. No rats in group I, 20 rats in group II, 18 rats in group III, and 7 rats in group IV died (P = 0.0003). Anastomotic dehiscence was found in one of 20 group I, in 11 of 22 in group II, in 9 of 20 in group III, and in 3 of 30 in group IV (P = 0.0003). On the third and seventh days, the median bursting pressures of the anastomosis were determined: 42 and 235 mm Hg in group I, 17 and 105 mm in Hg in group II, 22 and 183 mm Hg in group III, and 36 and 214 mm Hg in group IV (P < 0.0001). The burst occurred at the anastomoses in all animals tested on the third postoperative day, one in group I, six in group II, four in group III and one in group IV on the seventh postoperative day (P < 0.01). All deleterious effects of reperfusion injury on intestinal anastomosis healing, including survival rates and the histopathological parameters, were significantly prevented by seven days, but not two days, of high-dose allopurinol pretreatment.

Relationship of angiogenesis and p53 protein expression in colorectal carcinomas.

OBJECTIVE: Recently, new functions have been attributed to the p53 protein, particularly a prominent role in the regulation of angiogenesis. Tumours expressing mutant forms of p53 protein may be associated with increased angiogenesis. The aim of this study is to investigate the relationship between p53 protein expression and the quantitative expression of tumour angiogenesis in colorectal carcinomas. PATIENTS AND METHODS: Sections from paraffin-embedded blocks from 46 patients with primary colorectal carcinomas that had been completely removed were analysed. p53 protein expression and all vascular structures were evaluated by immunohistochemistry. The vessel parameters of angiogenesis including vascular surface density (VSD), number of vessels per mm2 (NVES) and number of vessels in unit area (n) were assessed by morphometry. Mann-Whitney U-test was used for comparing the extent of neovascularization in p53-positive and -negative cases. RESULTS: Twenty-four (52%) cases were p53+ and 22 (48%) were p53-. Mean VSD, NVES and n values for p53 protein-positive and -negative groups were as follows: VSD 96.7 +/- 65.4/mm vs 79.6 +/- 45.24/mm; NVES 104.8 +/- 97.5/mm2 vs 62.2 +/- 44.3/mm2; n 79.7 +/- 74.2 vs 52 +/- 35.7, respectively. There was no association between the angiogenesis parameters and p53-positive and -negative cases, when VSD (P=0.226) or n (P=0.176) were considered, but a statistically significant difference was obtained for NVES values (P=0.035). CONCLUSION: The authors concluded that tumoural angiogenesis assayed by morphometric investigation in colorectal carcinomas might be related to p53 protein expression when NVES is considered. This finding supports the possible role of p53 protein in increased angiogenesis in colorectal tumours.

Isolated mesosigmoidal hydatid cyst as an unusual cause of colonic obstruction: report of a case.

We report herein an unusual case of primary mesosigmoidal hydatid cyst that presented as acute left colonic obstruction mimicking sigmoid colon cancer. A 61-year-old man with a 3-day history of abdominal pain, distention, obstipation, vomiting, and fever was admitted to the emergency department of our hospital. Surgery was performed under a presumptive diagnosis of acute left colonic obstruction. The intraoperative findings were highly suggestive of sigmoid colonic carcinoma and Hartmann's procedure was performed. Histopathological examination of the pathological specimen revealed an isolated hydatid cyst embedded in mesosigmoid which had caused mechanical sigmoidal obstruction. Primary extrahepatic, intra-abdominal localization of a hydatid cyst is not unusual. Therefore, as a hydatid cyst may cause a wide variety of clinical syndromes, it should be kept in mind in the differential diagnosis of mechanical bowel obstruction, especially in endemic regions.

Prognostic significance of angiogenesis in rectal cancer: a morphometric investigation.

BACKGROUND: Neo-angiogenesis is crucial for tumor growth and metastasis and has been proposed as an independent prognostic factor for survival in patients with solid tumors. In this study the quantitative expression of angiogenesis was investigated by direct stereologic assessment of the vascular surface density in rectal carcinoma to determine the possible correlation of angiogenesis with clinicopathological factors and prognosis. PATIENTS AND METHODS: Sections from formalin-fixed paraffin-embedded tissue blocks of 29 primary rectal carcinomas were resected and immunostained for endothelial cell factor-VIII-related antigen. The vascular surface density (VSD), number of vessels per square mm (NVES), maximum NVES (NVESmax) according to the three maximum values of NVES and number of vessels in the unit area (N) were assessed by means of morphometry. The results were related to the main prognostic variables and the survival of patients. RESULTS: There were no significant differences between survivors and non-survivors in terms of the angiogenesis parameters that were investigated. The overall survival rate was not significantly different for sex, age, tumor size and differentiation, extrahepatic metastasis, depth of invasion and the mode of adjuvant therapy. However, a significantly lower overall survival rate was observed in patients with liver metastatic disease (p<0.001), lymph node involvement (p=0.04) and incomplete resection (p<0.001). Multivariate analysis indicated that only the number of vessels in the unit area (HR = 1. 028, p = 0. 04), hepatic metastases (HR=14.94, p=0.007) and type of resection (HR=23.81, p=0.004) predicted overall survival. CONCLUSION: These findings suggest that increased tumoral vascularity, consistent with previous studies, adversely affects survival in rectal cancer patients. Liver metastatic status and completeness of the surgical resection were the most powerful criteria to predict the final outcome of these patients. Thus, neo-angiogenesis is indeed an important and key step in tumorigenesis, but it may not be the single overwhelming factor that determines recurrence and metastasis in rectal carcinoma.

Prognostic value of CD44 expression in colorectal carcinomas.

BACKGROUND: CD44 has diverse functions in cell-cell and cell-matrix interactions and its expression appears to be an indicator of invasive and metastatic behaviour in carcinomas. However, contradictory data have been reported about the correlation between CD44 expression and prognosis in colorectal carcinomas. We aimed (i) to establish whether immunohistochemically detectable CD44 expression is related to tumor aggressiveness, (ii) to correlate CD44 expression with the degree of tumor differentiation and (iii) to determine the relationship between CD44 expression and patient survival and other conventional clinicopathological features. PATIENTS AND METHODS: The immunohistochemical expression of CD44 in a series of 111 colorectal carcinomas was examined using the monoclonal mouse anti-human phagocytic glycoprotein-1, CD44 (clone DF 1485) in correlation with clinicopathological variables. To achieve a reliable semi-quantitative evaluation, not only the staining intensity but also the distribution of positive tumor cells were analyzed. RESULTS: CD44 staining was high-grade positive in 42 and low-grade positive/negative in 69 tumor tissues. There was no association between CD44 expression and tumor size, histological differentiation, depth of invasion, lymph node involvement, clinical stage of the disease, or the radicality of surgical resection. CD44 expression was not correlated significantly with recurrence and distant metastases. Multivariate analysis showed that only the modified Astler-Coller (MAC) staging system was an independent prognostic factor of recurrence (HR=15.267; 15.267-6.808, 95% CI; p=0.001) and survival (HR=37.064; 13.309-103.220, 95% CI; p=0.001). Kaplan-Meier curves showed that there was no significant association between CD44 expression and recurrence and overall survival in either MAC B or C colorectal cancer. CONCLUSION: Expression of CD44 was not associated with any conventional clinicopathological features. CD44 cannot be considered as a prognostic predictor of recurrence, metastasis and overall survival.

Neurofibromatosis type 1 and precocious puberty.

Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP, the association with optic pathway tumors (OPT), and other clinical, auxological and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%), and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients with PP involved the chiasm in four patients, and the optic nerves alone in three patients. The age at the onset of puberty (or better at diagnosis) ranged from 5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist therapy was used in only three children because in the others the predicted height at diagnosis was good, treatment was refused or the patients were referred to us too late. The three treated patients attained a final height within the familial range. In the untreated patients the progression of puberty was not too rapid and final height was slightly below the genetic target in four patients; however, three patients had a final height markedly below the familial range. In conclusion, the prevalence of PP is increased in children with NF1, and frequently but not exclusively is associated with OPT. Moreover, sexual precocity does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be useful in the children with younger age at the onset of puberty or with a progressive decline in predicted final height.

Polypoid lesions of the gallbladder: report of 100 cases with special reference to operative indications.

BACKGROUND: The nature of polypoid lesions of the gallbladder is difficult to define before operation, and surgical indications still remain controversial. The aim of this study was to identify characteristics of each type of polypoid lesion of the gallbladder and indications for surgery. METHODS: Clinical data were retrospectively correlated with the histopathologic characteristics of polypoid lesions in 100 patients who had cholecystectomy. RESULTS: There were 74 benign polypoid lesions, including 39 cholesterol polyps, 20 adenomas, and 15 with adenomyomatous hyperplasia and 26 malignant polypoid lesions. Twenty-seven percent of patients with benign polyps and 73 percent of patients with malignant polyps were over 60 years of age. Polypoid lesions of the gallbladder were diagnosed by preoperative ultrasonography in only 36 patients (36%). All types of polypoid lesions of the gallbladder, whether benign or malignant, were frequently solitary, and gallstones coexisted in the majority of patients with all polypoid lesions of the gallbladder except cholesterol polyps. The lesions were > 10 mm in 88% of the malignant polyps and in only 15% of the benign polyps. CONCLUSIONS: The risk factors for malignancy were the age of the patient ( >60 years), the coexistence of gallstones, and the size of the polypoid lesions (>10 mm in diameter). In asymptomatic patients, cholecystectomy can be justified if there are risk factors for malignancy.

Effect of ischemia/reperfusion as a systemic phenomenon on anastomotic healing in the left colon.

Intestinal ischemia/reperfusion provokes a local inflammatory response leading to a systemic inflammatory state. In this study we aimed to assess the effects of intestinal ischemia/reperfusion injury on anastomotic healing in the left colon with an intact vascular supply. A total of 94 Wistar albino rats were divided into three groups: sham-operated control (group I, n = 25), 30 minutes of intestinal ischemia/reperfusion (group II, n = 40), and 7-day allopurinol pretreatment and intestinal ischemia/reperfusion (group III, n = 29). After the reperfusion experiment, a segmental left colon resection and anastomosis were done. On postoperative days 3 and 7 anastomotic bursting pressure, anastomotic and operative complications, and intraabdominal adhesions were assessed. Mortality rates were 1/25, 16/40, and 4/29 for groups I, II, and III, respectively (p = 0.001). There was no difference among the groups for wound and anastomotic healing parameters evaluated by macroscopic criteria. On postoperative day 7 the mean bursting pressures were 220.3 +/- 18.5, 162.0 +/- 21.0, and 213.9 +/- 24.7 for groups I, II, and II, respectively (p = 0.000). Significantly dense adhesions were found in group II (p = 0.000). Allopurinol pretreatment prevented the effects of ischemia/reperfusion on anastomotic healing of the left colon. Intestinal/ischemia reperfusion causes impairment of anastomotic healing of the left colon. In addition to remote organ effects, reperfusion injury may affect anastomotic healing in the viscera with an intact vascular supply.

Tumor angiogenesis as a prognostic predictor in pancreatic cancer.

The purpose of this study was to evaluate the role of angiogenesis, proliferative activity (assessed by Ki-67 expression), p53 and ras-oncogene (H-ras) expression, and conventional clinicopathologic factors in predicting overall survival rates in patients with pancreatic ductal adenocarcinoma. We followed-up 22 patients with ductal adenocarcinoma of the pancreas for a median of 19 months (range, 2 to 44 months). Angiogenesis was quantitated as vascular surface density (VSD) and the number of vessels per mm2 stroma (NVES) after microvessels were immunostained, using factor VIII-related antigen. p53, H-ras, and Ki-67 proteins were also determined immunohistochemically. VSD and NVES showed significant correlations with increased proliferative activity, poor tumor differentiation, and tumor size of 3 cm or more (P = 0.001, P = 0.013, and P = 0.047, respectively). The overall 2-year survival rate of 33.3% in patients with high VSD and NVES values was significantly worse than that of 66.6% estimated in patients with low microvessel count (log rank, 3.97; P = 0.046). In multivariate analysis using the Cox model, VSD was found to be an independent prognostic factor of survival (P = 0.039). H-ras and p53 expressions were not correlated with angiogenesis parameters. We conclude that, in pancreatic ductal adenocarcinoma, angiogenesis is closely related to tumor growth and patient survival.

[The pediatrician and the child in a multiethnic society]. / Il pediatra ed il bambino nella società multietnica.

The increasing immigration from developing countries has determined new health problems. Italian Pediatricians must become acquainted with these health concerns such as the excessive use of public pediatric structures, especially hospitals, specific diseases unusual among Italian children (malaria, tuberculosis, tropical parassitosis, sickle cell anemia, rickets and others), control of previous immunizations and repetition when one is not sure of their efficacy. Moreover, immigrated children seem to be more susceptible to common pediatric diseases (mostly infections) than Italian children. Finally, children adopted from developing countries deserve special attention because they arrive from a very poor social context with frequent history of important infectious diseases, congenital diseases, malnutrition and abuse. Central precocious puberty is a frequent evolution in some of the adopted girls.