Minichromosome maintenance protein 2 (MCM2) is a stronger discriminator of increased proliferation in mucosa adjacent to colorectal cancer than Ki-67.

BACKGROUND: Loss of control of mucosal crypt cell proliferation resulting in a hyperproliferative field change occurs early in the adenoma-carcinoma sequence. Ki-67, the current gold-standard marker of cellular proliferation, is a cell cycle protein that may lack sensitivity in demonstrating altered mucosal crypt cell dynamics. Minichromosome maintenance protein 2 (MCM2) has a specific role in DNA replication and has been proposed as a new marker for screening for colorectal cancer. AIM: To compare the expression of Ki-67 with that of MCM2 in colorectal mucosa associated with colorectal cancer. METHODS: Ki-67 and MCM2 immunostaining was performed on serial sections taken from formalin-fixed, paraffin-embedded specimens. Labelling indices were calculated by counting the proportion of positively stained nuclei in representative areas of adenocarcinoma, and in equivalent superficial, middle and basal crypt compartments of mucosa sampled 1 cm from tumour (Ca1) and 10 cm from tumour (Ca10). RESULTS: Specimens were obtained from 43 patients (27 adenocarcinoma, 16 no-cancer controls). Most nuclei in specimens of adenocarcinoma stained positively for MCM2 and Ki-67. In Ca1 and Ca10 samples, significantly greater staining of MCM2 than Ki-67 was seen in all crypt compartments. Receiver operator characteristic curve analysis suggested that proliferation changes (assessed by either MCM2 or Ki-67 staining) in Ca10, but not in Ca1, mucosa significantly predicted origin from a carcinoma-associated colon. CONCLUSIONS: MCM2 was more sensitive than Ki-67 in identifying colorectal mucosal proliferation. Increased proliferation (assessed by either MCM2 or Ki-67 staining) in mucosa at 10 cm, but not at 1 cm, from carcinoma significantly predicted origin from a carcinoma-associated colon.

A "field change" of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma.

BACKGROUND: Colorectal cancer is associated with a "field change" of increased proliferation throughout the colonic and rectal mucosa. Both proliferation and apoptosis are disrupted during carcinogenesis. Whether altered apoptosis contributes to this field change of microscopic abnormality is, however, unclear. Bcl-xL is an anti-apoptotic protein that inhibits apoptosis by preventing release of cytochrome c, a recognised pathway to cell death. AIM: To determine whether Bcl-xL inhibition of apoptosis is increased in colorectal mucosa adjacent to colorectal adenocarcinoma over that in normal non-neoplastic colorectal mucosa. PATIENTS: PATIENTS undergoing surgical resection for neoplastic (adenocarcinoma) or non-neoplastic disease of the colorectum (rectal prolapse, diverticular disease or volvulus). METHODS: Formalin-fixed, paraffin-wax-embedded surgical colorectal resection specimens were immunostained for Bcl-xL protein. Labelling indices were determined by counting the proportion of positively stained cells in mucosal crypts. RESULTS: 85 patients were studied. Bcl-xL immunostaining was most marked in the upper third of mucosal crypts. It occurred in a minority of samples from non-neoplastic colorectal mucosa, but was seen in most mucosal samples adjacent to colorectal adenocarcinoma. Significant increases (p<0.001) were observed in Bcl-xL labelling indices in the mucosa at 1 cm (n = 46, median labelling index 31.8%, interquartile range 8.3-43.9%) and at 10 cm (n = 52, median labelling index 22.0%, interquartile range 0.0-36.3%) from colorectal carcinoma, compared with normal, non-neoplastic colorectal mucosa (n = 22, median labelling index 0.0%, interquartile range 0.0-0.0%). CONCLUSIONS: The findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma.

Topical phenylephrine in the treatment of radiation-induced faecal incontinence.

AIMS: Acute bowel toxicity after pelvic radiotherapy is defined as occurring within 3 months of the start of treatment; chronic gastrointestinal toxicity may continue after the acute phase or start after a latent period. One in five patients develop chronic faecal incontinence affecting quality of life; how best to treat these patients is not known. This retrospective study aimed to determine the effects of a new agent, phenylephrine gel, in the treatment of chronic radiation-induced faecal incontinence. MATERIALS AND METHODS: Patients prescribed phenylephrine gel for new-onset faecal incontinence after radiotherapy were identified from our database of patients treated in a specialist radiation-induced bowel damage clinic since 2000. Changes in the level of faecal incontinence were assessed using the Vaizey faecal incontinence scoring system before and after treatment. RESULTS: Fifteen patients (nine men and six women) of mean age 70.5 years (standard deviation 8.2, age range 56-82 years) were treated with phenylephrine gel a median of 43 months after completing radiotherapy. The median Vaizey score before treatment with phenylephrine gel was 17 (interquartile range [IQR] 14-20) and after treatment was 14 (IQR 11-18) (P = 0.005). The median length of treatment with phenylephrine gel was 28 days (IQR 28-365). Scores improved in 11 out of 15 patients; four out of 15 patients showed substantial improvements of 7 or more points; and seven patients considered the gel helpful. CONCLUSION: Topical phenylephrine gel for the treatment of radiation-induced faecal incontinence has not been previously reported. This small, retrospective study suggests that it may help most patients and, in some, the improvement may be substantial. However, larger placebo-controlled prospective studies are required.

Epidural analgesia in gastrointestinal surgery.

BACKGROUND: The ideal perioperative analgesia should provide effective pain relief, avoid the detrimental effects of the stress response, be simple to administer without the need for intensive monitoring, and have a low risk of complications. METHODS: This review defines the physiological effects of epidural analgesia and assesses whether the available evidence supports its preferential use in gastrointestinal surgery. All papers studied were identified from a Medline search or selected by cross-referencing. RESULTS: Epidural analgesia is associated with a shorter duration of postoperative ileus, attenuation of the stress response, fewer pulmonary complications, and improved postoperative pain control and recovery. It does not reduce anastomotic leakage, intraoperative blood loss, transfusion requirement, risk of thromboembolism or cardiac morbidity, or hospital stay compared with that after conventional analgesia in unselected patients undergoing gastrointestinal surgery. Thoracic epidural analgesia reduces hospital costs and stay in patients at high risk of cardiac or pulmonary complications. CONCLUSIONS: Epidural analgesia enhances recovery after gastrointestinal surgery. The results support the development of structured regimens of early postoperative feeding and mobilization to exploit the potential for thoracic epidural analgesia to reduce hospital stay after gastrointestinal surgery.

Hepatocellular carcinoma.

Primary hepatocellular carcinoma is one of the 10 most common tumours, and the most common primary liver malignancy, in the world. In the majority of cases, it occurs against a background of hepatitis B or C viral infection and/or liver cirrhosis, and is associated with a dismal prognosis of a few months. Current treatments in routine clinical practice are surgical resection and liver transplantation, but these therapies are applicable to only a small proportion of patients and prolongation of survival is restricted. Other treatment options include intra-arterial chemotherapy, transcatheter arterial chemoembolisation, percutaneous ethanol injection, cryotherapy, thermotherapy, proton therapy, or a wide range of their possible combinations. The current lack of definitive data, however, limits the use of these therapies. Another option is gene therapy, which although in its infancy at the present time, may have a significant role to play in the future management of hepatocellular carcinoma.