G. Tanzini

Adjuvant epirubicin with or without Ifosfamide for adult soft-tissue sarcoma.

This randomized study compared the efficacy of epirubicin-based adjuvant chemotherapy on the disease-free interval (DFI) and overall survival of patients with high-risk soft-tissue sarcomas. After curative surgery, 43 of the 88 enrolled patients were assigned to surgery with or without radiotherapy and 45 to surgery plus chemotherapy (26 epirubicin, 19 epirubicin + ifosfamide) with or without radiotherapy. The trial closed prematurely because of poor patient accrual. There was a statistical significant difference in the 5-year disease-free survival of the patients receiving adjuvant chemotherapy with or without radiotherapy (69%) and that of those treated with surgery with or without radiotherapy (44%) (p = 0.01). The 5-year survival of the patients treated with adjuvant chemotherapy with or without radiotherapy was 72% as against 47% of those treated with surgery with or without radiotherapy (p = 0.06). The power of the study was 0.65 for both the DFI and overall survival. The results of the study suggest a possible advantage of epirubicin-based adjuvant chemotherapy in patients with soft-tissue sarcoma at high risk of relapse.

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.

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 β -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.

FOLFOX-4 Stop and Go and Capecitabine Maintenance Chemotherapy in the Treatment of Metastatic Colorectal Cancer

Objective: Patients with metastatic colorectal cancer (MCC) usually receive FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of progressive disease, with an increase in the incidence of neurotoxicity which is correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated with a low incidence of severe neurotoxicity in the treatment of MCC patients. Methods: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m2 day 1, leucovorin 200 mg/m2, 5-fluorouracil bolus 400 mg/m2 and 22 h 600 mg/m2 days 1 and 2, every 2 weeks). Patients who achieved objective response (OR) or stable disease (SD) then received oral capecitabine 2,500 mg/m2 days 1–14 every 3 weeks; L-HOP was reintroduced as soon as progression occurred. Results: Twenty-eight of the 29 patients who achieved OR or SD then received capecitabine. FOLFOX-4 was reintroduced in 18 patients (56.2%). The median response duration (RD) was 9.2 months and median progression-free survival (PFS) was 8.6 months. Twenty-eight patients (87.5%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.1%). Conclusions: FOLFOX-4 stop and go and capecitabine maintenance chemotherapy was associated with a very low incidence of grade 3 neurotoxicity. Although the number of patients enrolled was far too low for a definite conclusion, RD and PFS were comparable to those usually reported in the treatment of MCC patients.

TREATMENT OF ADVANCED COLORECTAL CANCER WITH HIGH-DOSE INTENSITY FOLINIC ACID AND 5-FLUOROURACIL PLUS SUPPORTIVE CARE

This randomised clinical trial, involving patients with advanced colorectal cancer, was carried out to compare the effectiveness of accelerated folinic acid (FA) plus 5-fluorouracil (5-FU) with that of the conventional regimen of 5-FU alone. Both regimens were administered with simulataneous supportive care. 185 patients were eligible: 94 were randomly allocated to receive FA 200 mg/m2 i.v. plus 5-FU 400 mg/m2 i.v. on days 1-5 every 3 weeks; and 91 to receive 5-FU 400 mg/m2 i.v. on days 1-5 every 4 weeks. The response rate was 33.3% in the accelerated FA/5-FU and 18.6% in the 5-FU arm (P = 0.045). Median survival was 13.5 months in the FA/5-FU arm and 7.5 months in the 5-FU arm (P = 0.039). Toxicity was mild and slightly more pronounced in the FA/5-FU arm (P = 0.078). This study indicates that, in patients with advanced colorectal cancer, accelerated chemotherapy with FA and 5-FU and simultaneous supportive care is capable of achieving a higher response rate and longer survival than conventional 5-FU alone, without severe toxicity.

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.

Continuous oral capecitabine at fixed dose in patients older than 75 years with metastatic colorectal and gastric cancer: a study of the Multidisciplinary Oncology Group on Gastrointestinal Tumors

The aim of this study was to investigate the safety profile of continuous oral capecitabine at fixed dose in patients older than 75 years, having metastatic colorectal and gastric cancer. Capecitabine was administered at a fixed dose of 2000 mg daily without interruptions. Thirty-four patients were considered evaluable for toxicity and efficacy. The median age was 81 years (range 76–85). The median duration of treatment was 113 days (range 24–238 days). No grade 4 toxicity was observed. One patient had grade 3 nausea and vomiting, and one had grade 3 diarrhea. Partial responses were observed in six patients with colorectal cancer, and in one patient with gastric cancer. This study suggests that continuous oral capecitabine at a fixed daily dose of 2000 mg is well tolerated, and that it allows for the simplification and ease of dosing in elderly patients with metastatic colorectal and gastric cancer.

Double rectal perforation after stapled haemorrhoidectomy

Dear Editor: In the last 10 years, in addition to the conventional haemorrhoid-resection techniques (Milligan & Morgan, Ferguson, Parks, etc.) the technique described by Longo rapidly spread into surgical practice, thanks to the reported advantages of less postoperative pain, reduced need of analgesics, earlier return to work or normal activity, shorter recovery and operative time and earlier pain-free first defecation. This treatment is based on the concept that haemorrhoidal prolapse is not just a venous disease but a disease of the whole haemorrhoidal complex, including the connective tissue, the rectal wall, the Treitz muscle and all other muscles involved in the structure, very important for anal continence. Many studies have compared Longo’s stapled anopexy with conventional methods and some complications were reported. The most common described early complication was bleeding (5–8%), followed by severe anal pain, thrombosis, urinary retention (anaesthesia could be involved) and suture dehiscence. After 1 week from the intervention, later complications noted were: recurrence of haemorrhoids, residual prolapse or persistence of symptoms(the most common), occurring in about 5% of the patients, chronic anal pain (2%), stenosis, anal fissure, faecal urgency, incontinence and anal sepsis (fistulas and abscesses). Rectal perforation was rarely reported. We treated a female patient, 27 years old, who came to our attention from a local hospital with an acute abdomen condition and a CT diagnosis of a rectal perforation. She had been previously treated for third-degree prolapsed haemorrhoids in the same hospital, where she received a Longo’s stapled haemorrhoidopexy using the Ethicon Endo Surgery PPH set. She was discharged on the second day after intervention, and she complained of diffused abdominal pain, she has no passed gas and mild temperature. Before the discharge, an enema was performed. The woman had a negative general and gynaecological anamnesis. She was nulliparous and never previously operated or hospitalised. She performed a colonoscopy before the intervention that was negative. No defecography or other diagnostic exams were performed before the intervention. On a fifth postoperative day, she was readmitted; a CT was performed and she was transferred to the emergency room of our hospital. CT examination showed a double rectal perforation, the first at the staple line level and the second further up in the rectum, with a faecal peritonitis and pneumoperitoneum. She presented tachycardia, high temperature (>38°C) and 100/60 of blood pressure. At physical examination, a severe diffuse abdominal pain was found. At rectal digital exploration a small dehiscence of the staple line was noted, about 5 cm above the anal verge, with no external signs of abscess. The exploration caused intense pain, but no stenosis of faecal impact was detected. No other endoanal procedures were performed. Laboratory data showed a white blood cell count of 20,300/mm. An emergency intervention was performed. At laparotomy, generalised faecal peritonitis was found and a rectal posterior perforation at the rectal–sigmoid junction was noted. The hole was closed with a discontinue suture and a left colostomy was performed. Her recto-sigmoid tract was not redundant and there were no diverticula or something else notable. Two suction drains were put in place. No specimens were sent to pathology. The patient was Int J Colorectal Dis (2009) 24:1113–1114 DOI 10.1007/s00384-009-0665-7

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.

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.