Accuracy of transrectal ultrasound after preoperative radiochemotherapy compared to computed tomography and magnetic resonance in locally advanced rectal cancer.

INTRODUCTION: The aim of the present study was to compare the restaging results obtained by transrectal ultrasound (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) performed after preoperative chemoradiation with pathologic staging of the operative specimen. METHODS: From January 2008 to December 2009, all the consecutive patients with locally advanced rectal cancer that underwent neoadjuvant therapy at our department were evaluated. The results of diagnostic examinations and the definitive pathological examination were considered and compared. RESULTS: Thirty-seven patients were included in the study (27 males, 73%), mean age was 65.5 years (range 45­82 years). In all the patients TRUS and CT and in 20 patients MRI were performed before and after the treatment. Concerning the depth of invasion after treatment TRUS agreed with histopathology in 25/37 patients (67.5%), CT agreed in 22/ 37 cases (59.5%), and MRI in 12/20 cases (60%). Considering only neoplasia with stage T3, TRUS agreed in 23/24 cases (96%), CT in 19 cases (79%), and MRI in 10/12 cases (83.5%). Considering the tumors that did not exceed the rectal wall (T0, T1, and T2), TRUS agreed with histology in 2/13 cases (15.5%),CTin 3/13 cases (23%), andMRI 2/8 cases (25%). Concerning the presence of positive lymph nodes TRUS agreed with histology in 28/37 cases (75.5%), while CT agreed in 21/37 cases (56.5%) and MRI in 11/20 cases (55%). The concordance between the techniques was found to be low. CONCLUSIONS: Transrectal ultrasonography resulted as the most accurate method to determine neoplastic wall infiltration and lymph node involvement even after radiochemotherapy. In most cases, considering the poor correlation between the diagnostic procedures and the disagreement of the results, a restaging performed only with TRUS could be proposed, limiting the use of the other imaging methods to selected cases.

Familial colorectal cancer: a concept revisited.

OBJECTIVE: The family history of patients with colorectal cancer (CRC) shows an increased risk of disease although evident inherited syndromes are demonstrable in only a small percentage of patients. The purpose of this study was to identify factors that might suggest an inherited component in the transmission of CRC. METHOD: The study monitored 880 consecutive patients between 1980 and 2005 treated for CRC. RESULTS: Familial adenomatous polyposis (FAP) was found in only one patient, and a classical mutation of hereditary nonpolyposis colon cancer was found in only two patients. The risk assessment was possible mainly because of factors such as early onset CRC, the presence of multiple primary tumours and a high risk family history. Considering these 36 more patients were suspected to be high risk and referred for further genetic testing. At least one first-degree relative with CRC was reported in 140 patients. In 49 patients, CRC was diagnosed before 50 years of age. Multiple primary tumours, colonic or extra colonic, synchronous or metachronous were found in 136 patients. CONCLUSION: Our study suggests that if only patients with identified mutations are taken into consideration, then the percentage of evident hereditary colon cancer is very low, but this percentage quickly increases if we make marginal adjustments to the identifying criteria. It seems that it is the physician's clinical suspicion, more than the fulfillment of rigid criteria, which plays a fundamental role in the timely identification and a subsequent focused treatment of patients with hereditary CRC.

Adenosine kinase gene expression in human colorectal cancer.

Real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of adenosine kinase, a key enzyme in adenosine metabolism, in human intestinal biopsy specimens of 10 colorectal cancer patients. Quantitative mRNA expression levels were normalized against the reference gene beta-actin. The results showed that adenosine kinase gene expression was significantly higher in cancer than in normal-appearing tissue, in line with our previous measurements of adenosine kinase enzyme activities in colorectal tumor samples.

Biweekly triple combination chemotherapy with gemcitabine, oxaliplatin, levofolinic acid and 5-fluorouracil (GOLF) is a safe and active treatment for patients with inoperable pancreatic cancer.

GOLF is a triple translational combination chemotherapy regimen with gemcitabine, oxaliplatin, and 5-fluorouracil (5-FU) (plus levofolinic acid), cytotoxic drugs currently used in the treatment of pancreatic carcinoma. Considering its promising anti-tumor effects in patients with gastroenteric malignancies, we carried out the present study to investigate its toxicity and anti-tumor activity in patients with advanced pancreatic carcinoma. Twenty-seven patients were enrolled in the study, 15 males and 12 females with an average age of 61 years and a performance status (ECOG)

Metabolism of adenosine in human colorectal tumour.

The aim of this work is to analyse the activities of the enzymes metabolising adenosine in fragments of neoplastic and normal-appearing mucosa, surrounding the tumour in 20 patients affected by colorectal cancer. The results show that the activities of the enzymes are markedly higher in tumour in comparison to normal mucosa to coope with the accelerated purine metabolism in cancerous tissues.

Enzyme activities controlling adenosine levels in normal and neoplastic tissues.

Adenosine is known to be associated with effects such as inhibition of immune response, coronary vasodilation, stimulation of angiogenesis, and inhibition of inflammatory reactions. Some authors suggest that adenosine may also have similar functions in tumor tissues. Tissue levels of adenosine are under close regulation by different enzymes acting at different levels. Adenosine is produced from AMP by the action of 5'-nucleotidase (5'-NT) and is converted back into AMP by adenosine kinase (AK) or into inosine by adenosine deaminase (ADA). Inosine is converted into purine catabolites by purine nucleoside phosphorylase (PNP), whereas AMP is converted into ADP and ATP by adenylate kinase (MK). The aim of this study was to analyze the activities of the above enzymes in fragments of neoplastic and apparently normal mucosa, obtained less than 5 cm and at least 10 cm from tumors, in 40 patients with colorectal cancer. The results showed much higher activities of ADA, AK, 5'-NT, and PNP in tumor tissue than in neighboring mucosa (p > 0.01 for ADA, AK, and PNP; p > 0.05 for 5'-NT), suggesting that the activities of purine metabolizing enzymes increase to cope with accelerated purine metabolism in cancerous tissue. The simultaneous increase in ADA and 5'-NT activities might be a physiological attempt by cancer cells to provide more substrate to accelerate salvage pathway activity.

UFT/leucovorin and oxaliplatin alternated with UFT/leucovorin and irinotecan in metastatic colorectal cancer.

A total of 41 metastatic colorectal cancer (CRC) patients received tegafur/uracil (UFT)+leucovorin (LV)+oxaliplatin alternated with UFT/LV+irinotecan. The overall response rate was 58.5% (95% confidence interval, 42.2-73.3%), and the median progression-free survival was 8.8 months. There were no grade 4 toxicities; 12 patients (29%) experienced grade 3 diarrhoea. There were no cases of hand-foot syndrome. This alternating regimen seems to be effective and well tolerated in the first-line treatment of patients with metastatic CRC.

Melting temperature analysis as quantitative method for detection of point mutations.

Different methods have been devised to detect point mutations. Some are very sensitive, detecting mutations even in a background of normal tissue, but none provide information about the percentage of cells with mutant DNA. Here we describe an easy, fast and reliable method, melting temperature analysis, which not only detects point mutations but also provides quantitative information on the percentage of cells with mutant DNA. By this method we detected a G-A transition in codon 12 of the K-ras gene in DNA of subjects with colorectal cancer. The K-ras mutation was found in 9/10 bowel cancers and 8/10 normal adjacent samples. It was also detected in 4/7 stool samples from the same patients. In colorectal cancers, the proportion of K-ras mutant cells was variable: in two the mutant/wild-type DNA ratio was 30/70, in three 50/50, and in four 70/30. Melting temperature analysis was sensitive for the detection of point mutations in bowel cancer and also in apparently normal tissue, providing quantitative information about the percentage of cells with mutant DNA.

[Total gastrectomy and quality of life]. / Gastrectomia totale e qualità della vita.

We have evaluated quality of life after surgery in 24 patients (9 males and 15 females mean age 64.23 years, range 47-83 years) who underwent total gastrectomy for cancer (23 carcinomas and 1 lymphoma) in the last three years at the Department of Clinical Surgery, University of Siena. Intestinal continuity was re-established with Y jejunal loup according to Roux. All patients were studied prospectively: after the operation every six months they were interviewed using Korenaga's questionnaire. Group performance status scale was used to determine the level of activity of each patients. Comparing symptoms of patients after six months and 18 months there was a significant difference (p = 0.005) in terms of number of meals throughout the day, food tolerance and abdominal pain. Postoperative performance status revealed a complete recovery in 11 of 24 patients (45.8%) after 18 months. According to our experience patients who have undergone total gastrectomy enjoy a good quality of life and most of them return to the preoperative lifestyle in 18 months.

[Total gastrectomy and malnutrition]. / Gastrectomia totale e malnutrizione.

BACKGROUND: The operation more frequently performed for gastric malignancy is total gastrectomy. METHODS: Our reconstructive technique is Roux en Y esophago-jejunostomy, jejunal interposition after gastrectomy. In the next weeks after operation there is always an important, sometimes pathologic, slimming in gastrectomized patients. But is this slimming due to malnutrition or malabsorption? This is the real question. In our Institute a quarterly perspective clinical and instrumental follow-up for these patients has been prepared. RESULTS: We started with 41 patients, but we conducted the complete study only on 23. Of these patients, 56% have lost 10 kg weight, 25% 5 kg and 18% have not lost weight after 2 weeks from discharge dimission. But after 5 weeks, all patients had stabilized their own weight, and 18 months later the first two groups regained weight again, 1-2 kg. With our follow-up, we had educated patients to a correct personal natural diet necessary to normal social and working life. With our program in 3-4 weeks the weight of each patient was stable and we were able to control the malabsorption. CONCLUSIONS: Moreover, according to personal experience, it is important to plan a follow-up to rehabilitate patients to usual social life. This program allows to evaluate malnutrition and the possible iron or vit. B12 deficiency.

[Short bowel syndrome. Still a current problem]. / La sindrome da intestino corto. Un problema sempre attuale.

In the last year the Authors operated two patients presenting with a clinical feature of intestinal infarct. A wide intestinal resection was performed and patients had a residual tract of 40 cm and 50 cm of bowel respectively, later manifesting as short bowel syndrome. It was not possible during the operation to preserve the Baubin valve in one case, in the other one the value had been sacrificed during a previous operation for right colonic malignancy. In the postoperative period, patients were temporarily transferred to the intensive care unit, returning in the surgery ward after few days, and counting total parenteral nutrition with progressive decreasing mixture in calories. Contemporarly enteral nutrition was started slowly increasing the quantity of water, calories and azote administration. In a second time oral diet was started up to completely weaning parenteral and enteral nutrition. At the present patients are enlisted in quarterly follow-up, completely stabilized, and independent from artificial nutrition with a good quality of life. Furthermore a saving of sanitary costs was obtained.

[Family anamnesis, cholecystectomy and gastric resection in patients with colorectal carcinoma: a case-control study]. / Anamnesi familiare, colecistectomia e gastroresezione in pazienti con carcinoma colorettale: studio caso-controllo.

An increased risk of colorectal cancer has been reported in first-degree relatives of affected patients, and following cholecystectomy or partial gastrectomy for benign peptic ulcer disease. The aim of this study was to examine the incidence of these potential risk factors in 197 patients (127 males, 70 females, mean age 70 years +/- 10.9, range 22-94 years) with cancer of the large bowel and 202 controls (91 males, 111 females, mean age 68 years +/- 14.06, range 17-93 years) who underwent a total colonoscopy, that revealed no colorectal neoplasms. No significant differences were found between the case and control group for a past history of cholecystectomy or gastric surgery, respectively reported by 14 and 12 patients of group 1 and 18 and 8 patients of group 2. Patients with large bowel cancer show a significant excess of both colorectal (21.31% vs 11.9%) and extracolonic malignancies (46.19% vs 26.73) in first degree relatives (p < 0.05). In approximately 7% of them the aggregation of two or more colorectal cancers among relatives is suggestive for a hereditary form of large bowel cancer.

Papillary thyroid carcinoma in three siblings with familial adenomatous polyposis.

The authors report three siblings (two sisters and their aunt, aged 20, 22 and 36, respectively) with familial adenomatous polyposis (FAP) and papillary thyroid carcinoma. After diagnosis of FAP, a single, non palpable nodule was revealed in each patient by routine screening ultrasonography of the gland. The diagnosis of papillary carcinoma was made by fine-needle-aspiration biopsy of the nodules and confirmed by histologic examination of surgical specimens. A review of the literature reveals about 40 reports of such an association, that is considered not fortuitous. Nevertheless, in this family the association seems to be a distinctive, clinical feature of the syndrome, affecting three out of five members intensively screened for extracolonic lesions.

Levels of folic acid in plasma and in red blood cells of colorectal cancer patients.

The levels of folic acid have been determined by radioimmunological method in the plasma and in the red blood cells of normal subjects and colorectal cancer patients. A decrease was evident both in the plasma and erythrocytes of cancer patients. The possible reasons and applications of this observation are discussed.

[Heredity and colorectal cancer]. / Ereditarietà e cancro colorettale.

Colorectal cancer is the second leading cause of death from malignancies in Western Countries. In spite of advances in treatment, little change in survival has been accomplished in last decades and this mandates greater importance to prevention and early detection. Although dietary factors have received primary attention familial clustering suggests that susceptibility to KCR is inherited. Hereditary colorectal cancer can arise on Familial Adenomatous Polyposis (HCC) or not on polyposis (HNPCC) and members of these families are at high risk of such neoplasias. Anyway, even in "sporadic" forms of KCR first-degree relatives have a 2 to 3-fold increased risk of the same cancer. The most desirable screening protocol would be a simple procedure involving only a blood test to identify gene defect by molecular biology techniques. Unfortunately, this is not practically possible, for lack of specific genetic alterations, out of FAP, and only the study of family history can enable targeted surveillance and cost-effective management strategies.

[Update on epidemiology and risk factors of colorectal carcinoma]. / Attualità in tema di epidemiologia e fattori di rischio del carcinoma colo-rettale.

Etiology of colorectal cancer is not completely clear. Epidemiologic studies, especially those on migrant populations, demonstrate the importance of environmental factors, particularly dietary, in cancerogenesis. Anyway, familial aggregation within a given population shows that genetic factors play an important role. General risk factors are represented by age, sex, physical activity... while some pathologies increased the risk of developing KCR or are frankly precancerous (adenomas, ulcerative colitis, Crohn's disease...).

[Blood gastrin and colorectal neoplasms]. / Gastrinemia e neoplasie colorettali.

Gastrin has a trophic effect on the mucosa of the gastrointestinal tract and seems to have the potential for promoting colonic cancerogenesis through a chronic stimulation of the epithelial proliferation. Plasma gastrin has been reported to be elevated in patients with colorectal neoplasms. The aim of the present study was to verify this observation. Presurgical serum levels of gastrin were compared between 49 patients with colorectal neoplasms and 47 controls hospitalized for other surgical lesions. Results show significantly higher gastrin levels of case group than controls: 72.72 + 85.41 vs. 46.79 + 24.09 pg/ml (p < 0.05), and provide support for the hypothesis of a gastrin-stimulated neoplastic growth enhancing at the same time the potential therapeutic role of reducing gastrin secretion.

Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer.

BACKGROUND/AIMS: Colon cancer is one of the major health problems in industrialized countries, and its incidence appears to be increasing. Surgical resectability is the most important prognostic determinant, although despite apparently curative surgery, recurrent tumors are common. Metastatic disease cannot be cured, and thus, there is a need for better adjuvant therapies. METHODS: Two hundred and thirty-nine patients with surgically resected colon cancer in Dukes' stage B2 or C were randomly assigned to chemotherapy or observation alone to determine whether adjuvant chemotherapy could effectively reduce the rate of cancer recurrence. One hundred and twenty-one patients in stage B2 and 118 patients in stage C were enrolled in the study. Adjuvant treatment consisted of folinic acid 200 mg/m2, intravenously, plus 5-fluorouracil 400 mg/m2, intravenously, on days 1-5 every 4 weeks for 12 cycles. RESULTS: In stage B2, no significant difference between the adjuvant arm and the observation arm was noted. In stage C, adjuvant chemotherapy produced an advantage over observation in terms of a reduction in cancer recurrence rate with prolongation of a disease-free interval (P = 0.0016) and an improvement in overall survival (P = 0.0025). CONCLUSIONS: This study shows that folinic acid plus 5-fluorouracil adjuvant chemotherapy is effective in patients with surgically resected Dukes' stage C colon carcinoma.