Trends in colorectal cancer survival following the 2-week rule.

OBJECTIVE: The 2-week rule has reduced waiting times for a specialist opinion among patients with a suspected malignancy. We aimed at assessing the effect of this rule on colorectal cancer survival. METHOD: Patients diagnosed with colorectal cancer before (group 1) and after (group 2) the introduction of the 2-week rule were identified from a prospective database. Emergency patients were excluded. Overall 2-year survival for each group was calculated using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Waiting times fell from 26 to 21 days (P =0.22). There was no significant difference in 2-year survival between the groups (hazard ratio 1.1; P = 0.56). There was a slight divergence between the survival curves at 2 years. CONCLUSION: There has been no improvement in 2-year survival from colorectal cancer following the introduction of the 2-week rule.

A single common urgent pathway for all colorectal referrals reduces time to diagnosis and treatment.

OBJECTIVE: Guidelines for the urgent referral of patients with suspected colorectal cancer were introduced in 2000. They aimed to facilitate the prompt diagnosis and treatment of patients with symptoms suggestive of malignant disease. Recent assessment of these guidelines has suggested that although they identify 9-14% of patients with colorectal cancer, they may be used inappropriately and may lead to delays in treatment for those patients with cancers whose symptoms do not fit the guidelines. We aimed to assess the effect of introducing a single pathway for all referrals irrespective of indicated urgency. METHOD: All referral letters to a single consultant colorectal surgeon over a 6-month period were coded 'urgent' irrespective of the indicated urgency on the original referral letter. Data was collected prospectively on 47 patients diagnosed with colorectal cancer identified over the trial period. Patient demographics, the mode of presentation, urgency of referral and waiting times were documented. RESULTS: Following the introduction of the common urgent referral pathway, no patient waited longer than 62 days from referral to treatment or 31 days from the decision to treat to first treatment, thus meeting government targets introduced in 2005. CONCLUSION: The introduction of the urgent referral guidelines has accelerated the referral pathway for patients with symptoms suggestive of colorectal cancer, although this is at the expense of the majority of patients who present via conventional pathways. The introduction of a common urgent pathway allows prompt diagnosis and treatment and is of particular benefit for the majority of patients not referred via the 2-week standard. Until a more accurate method of identifying the highest risk patients is implemented, we suggest that all patients are seen on an urgent basis.

The clinical significance of the circumferential resection margin following preoperative pelvic chemo-radiotherapy in rectal cancer: why we need a common language.

OBJECTIVE: The presence of microscopic tumour cells within 1 mm of the circumferential surgical resection margin (CRM) is the endpoint most strongly associated with local recurrence in rectal cancer and doubles the risk of developing distant metastases. Reporting on the CRM can monitor surgical quality assurance and over the past two decades has driven advances in surgical technique with the increasing use of total mesorectal excision. The aim of this review was to use the evidence from both phase II and phase III randomized trials of preoperative radiotherapy and chemoradiation in rectal cancer, to assess how often CRM involvement is currently documented and examine its utility as an early predictor of both disease-free and overall survival. METHOD: A literature search identified both randomized and nonrandomized trials of preoperative radiation therapy and chemoradiation therapy in rectal cancer since 1993. The aim was to find those studies, which documented the distance from the periphery of the tumour and the CRM. Small trials treating < 20 patients were excluded. RESULTS: One hundred and eighty-seven phase II and 28 phase III trials of preoperative radiotherapy or chemoradiation were identified. Most trials documented the degree of response but only 10 of 187 phase II/retrospective studies and four of 28 phase III trials presented data on the achievement of a negative CRM. Few defined this early pathological endpoint prospectively with accurate measurements. However, the majority of studies did use the definition of

Can pathological complete response in the primary tumour following pre-operative pelvic chemoradiotherapy for T3-T4 rectal cancer predict for sterilisation of pelvic lymph nodes, a low risk of local recurrence and the appropriateness of local excision?

INTRODUCTION: Local excision is considered inappropriate treatment for T3-T4 rectal adenocarcinomas, as it cannot provide prognostic information regarding lymph node involvement and has a high risk of pelvic recurrence. Preoperative chemoradiation (CRT) studies in rectal cancer suggest that a pathological complete response (pCR) in the primary tumour provides an excellent long-term outcome. If downstaging to stage pT0 predicts a tumour response within the perirectal and pelvic lymph nodes, this may allow local excision to be performed without increased risk of pelvic recurrence. This retrospective study aimed to determine the incidence of involved lymph nodes following pCR (ypT0) after preoperative CRT and total mesorectal excision. METHOD: The outcome and treatment details of 211 patients undergoing preoperative CRT for clinically staged T3-T4 unresectable rectal adenocarcinomas between 1993 and 2003 at Mount Vernon Hospital were reviewed. RESULTS: Data were recorded from the 143 patients who completed treatment with a median follow-up of 25 months. Twenty-three patients (18%) were found to have had a pCR. Four out of 23 patients (17%) had involved lymph nodes. No pelvic recurrences developed after a ypCR. Overall survival was similar for patients with ypT0 or residual tumour. CONCLUSION: Pathological complete response in the primary tumour failed to predict a response in the perirectal lymph nodes (p=0.08). The degree of response predicted a lymph node response (p=0.02). The detection of ypCR identified patients with a low rate of pelvic recurrence. This may in the future allow selection of patients for whom local excision can be performed without a higher risk of local relapse.

Conservative management of tension pneumoperitoneum.

Tension pneumoperitoneum is characterized by a rapidly increasing intra-abdominal pressure, the haemodynamic and respiratory consequences of which are potentially fatal. Prompt laparotomy, surgical drainage and identification of possible sites of perforation is usually advocated in spite of previous reports of negative laparotomies in the literature. We report the successful non-surgical management of two cases of tension pneumoperitoneum.

Side-to-side stapled anastomosis may delay recurrence in Crohn's disease.

PURPOSE: Perianastomotic recurrence after resection in Crohn's disease may be related to ischemia and subacute obstruction at the anastomosis. A technique designed to minimize these factors currently is being evaluated. METHODS: From 1984 to 1997 69 patients underwent resection and primary anastomosis for symptomatic Crohn's disease (17 jejunal or ileal, 72 ileocolic, and 7 colocolic resections). Of these, 42 patients underwent functional end-to-end anastomoses with the use of linear cutting staplers (Proximate 75 mm or GIA 228 80 mm) and 27 patients underwent end-to-end sutured anastomoses. RESULTS: In the stapled anastomosis group one (2 percent) patient required reoperation for recurrent symptoms at 46 months. Complications occurred in four (8 percent) patients (one enterocutaneous fistula, one wound infection, one abscess, and one ileus). There were no anastomotic leaks. The median postoperative stay was seven (range, 5-26) days. In the sutured anastomosis group 14 (43 percent) patients required 15 further resections for symptomatic recurrence at a median of 46 (range, 4-91) months. Complications occurred in six (17 percent) patients (two anastomotic leaks, two fistulas, one stricture, and one pulmonary embolus). The median postoperative stay was 10 (range, 6-28) days. CONCLUSIONS: Functional end-to-end stapled anastomoses after resection for Crohn's disease may be associated with fewer complications than sutured anastomoses and may delay reoperation for symptomatic recurrence. Further evaluation of the technique is indicated.

Epirubicin-Lipiodol chemotherapy versus 131iodine-Lipiodol radiotherapy in the treatment of unresectable hepatocellular carcinoma.

BACKGROUND: Arterially administered iodized oil (Lipiodol) is selectively retained by hepatocellular carcinomas (HCCs), and has been used as a vehicle for delivery of therapeutic agents to these tumors. This study compared the efficacy of Lipiodol-targeted epirubicin chemotherapy with Lipiodol-131I radiotherapy. METHODS: Ninety-five patients with unresectable HCC confined to the liver were administered either Lipiodol-epirubicin emulsion (n = 69; 61 cirrhotics; Okuda tumor Stage I, 14; II, 37; III, 18; epirubicin dose, 75 mg/m2) or Lipiodol-131I (131I) (n = 26; 18 cirrhotics; Okuda tumor Stage I, 6; II, 19; III, 1; dose 750-1050 MBq). The last 28 patients (17 epirubicin, 11 131I) were treated within a prospective randomized trial. Bolus drug or isotope was injected into the hepatic artery by transfemoral cannulation. Lipiodol and 131I uptake were gauged by 10th day computed tomography and 48-hour scintiscan. Treatments were repeated two-monthly when indicated. RESULTS: Tumor size at 2 months remained static or diminished partially in 21 of 38 epirubicin recipients (55%) and 15/22 131I recipients (68%). Actuarial survival at 6, 12, and 24 months was 40%, 25%, and 6% with epirubicin, and 58%, 25%, and 0% with 131I; 30-day mortality was 11% and 15%, respectively. Comparison with historic controls indicated survival benefit in Stages I and II. Similar findings were recorded in the 28 patients in the randomized trial. CONCLUSIONS: Patients with unresectable HCC receiving Lipiodol-epirubicin or Lipiodol-131I show good tumor localization, acceptable toxicity, and comparable survival benefit at 6 and 12 months with either modality.

Iodized oil in the treatment of hepatocellular carcinoma.

When injected into the hepatic artery the contrast agent Lipiodol (iodized poppy seed oil) is selectively retained by hepatocellular carcinoma (HCC) for a prolonged period of time. Liver computed tomography (CT) performed after Lipiodol angiography is more sensitive than ordinary CT at imaging HCC. Arterial administration of cytotoxic drugs and radioisotopes conjugated to Lipiodol has been shown to be reasonably safe in patients with irresectable HCC. These therapies, often combined with embolization, provide effective palliation, better tumour response and improved survival compared with other available treatments. Their use as a preoperative adjunct to surgical resection of HCC is controversial.

Prospective randomized trial of Ivalon sponge versus sutured rectopexy for full-thickness rectal prolapse.

Ivalon sponge rectopexy is a safe reliable procedure in the management of rectal prolapse. Sutured rectopexy is simpler and avoids the use of foreign material. Sutured rectopexy is mandatory if synchronous resection is to be considered. Sixty-three patients (62 women) with full-thickness rectal prolapse were entered into a prospective randomized trial of Ivalon sponge rectopexy (31 patients) versus sutured rectopexy (32). Twenty patients (32 per cent) had coexistent incontinence (ten in each group). The operation was performed in the standard manner with a sutured rectangle of sponge or sutures alone placed along the length of the sacrum. Postoperative morbidity occurred in nine patients (14 per cent) of whom three underwent a sutured procedure and six Ivalon rectopexy: wound infection in three, chest infection in two, urinary tract infection in two and thromboembolism in two. There were no deaths within 30 days. At a median follow-up of 47 months prolapse had recurred in two patients (3 per cent), one in each group, 14 (22 per cent) suffered from incontinence (of whom five had undergone a sutured procedure), while 25 (40 per cent) had developed constipation (of whom 15 had received Ivalon rectopexy). The medium-term results of rectopexy by suture alone are equivalent to those obtained following the conventional Ivalon procedure. These data suggest that Ivalon rectopexy could now be abandoned.

Selective radionuclide localisation in primary liver tumours (pilot study).

The therapeutic potential of 131I-Lipiodol was investigated in 8 patients with cholangiocarcinoma (CCA) and 15 patients with hepatocellular carcinoma (HCC). Patients received one or two doses of 131I-Lipiodol via hepatic arterial injection. The mean total administered activity was 668 (SD 325) MBq in CCA and 953 (SD 477) MBq in HCC. One patient with CCA retained 131I-Lipiodol. The cumulative radiation dose was 9.6 Gy to tumour, 6.4 Gy to liver and 1.5 Gy to lung. The patient remained asymptomatic with no evidence of tumour 30 months from the start of treatment, whereas the remaining 7 patients exhibited tumour progression. The mean survival in CCA was 11.6 (SD 14.5) months. All 15 patients with HCC retained 131I with tumour: liver ratios of up to 30:1. The mean cumulative radiation dose was 34.7 (SD 32.4) Gy to tumour, 3.3 (SD 1.5) Gy to liver and 4.4 (SD 2.3) Gy to lung. The mean dose per administered activity was 3.8 (SD 4.1) cGy/MBq. Partial response (reduction in tumour size > 50%) was observed in 6 patients (40%). The mean survival was 7.1 (SD 6.0) months. 131I-Lipiodol can deliver highly selective internal irradiation to foci of HCC with evidence of objective response and may be the treatment of choice for patients with cirrhosis and a small tumour.

Long-term results of large-dose, single-session phenol injection sclerotherapy for hemorrhoids.

PURPOSE: The aim of our study was to assess the medium to long-term outcome following single session large dose injection sclerotherapy for symptomatic hemorrhoids. METHODS: One hundred eighty-nine patients (male = 106, female = 83, median age, 51; range, 20-85 years) were assessed following single-session, large-dose (3 x 5 ml) phenol injection therapy. The most frequent complaint was bleeding (100 percent). RESULTS: At four-year follow-up, 53 patients (28.0 percent) were cured, 26 (13.7 percent) were improved, 35 (18.5 percent) remained unchanged, 59 (31.2 percent) deteriorated, and 16 (8.5 percent) required surgical intervention. Among the patients who were not cured, symptoms were minimal in 50 percent. Sclerotherapy was associated with a reduced incidence of bleeding (P < 0.05) but an increase in difficulty in perineal cleaning was observed (P < 0.05). CONCLUSION: Large-dose, single-session sclerotherapy provides only short-term benefits in the majority of patients with symptomatic hemorrhoids.

Mycotic aneurysm of the cervical carotid artery due to Salmonella enteritidis.

A case of mycotic carotid aneurysm due to Salmonella enteritidis infection is reported. The features of the condition and the principles of treatment are described.

Selective regional chemotherapy of unresectable hepatic tumours using lipiodol.

Over a 30 month period from 1987 to 1990, selective hepatic cannulation under fluoroscopic control was performed in 57 consecutive patients with primary and secondary malignancies of the liver. Fifty-three patients were subsequently treated using intra-arterial Lipiodol emulsified with epirubicin. The tumours treated were hepatocellular carcinoma (n = 35), metastatic adenocarcinoma (n = 14), intrahepatic cholangiocarcinoma (n = 3) and leiomyosarcoma (n = 1). For hepatocellular carcinoma the cumulative survival was 38% at one year; the median survival was 12.2 months for Stage I, 6.3 months for Stage II and 0.9 months for Stage III tumours. In metastatic disease the cumulative survival was 63% at one year. These data suggest that targeted intra-arterial chemotherapy with Lipiodol-epirubicin is a useful palliative therapy for patients with Stage I and II HCC, and that a controlled trial of this treatment should be undertaken.

Therapeutic aspects of radio-isotopes in hepatobiliary malignancy.

Liver tumours frequently present at a late stage and only a minority of patients are likely to benefit from resection or transplantation. Inoperable tumours carry a grave prognosis. External beam irradiation of the liver is dose-limited by the radiosensitivity of hepatocytes, particularly in the presence of cirrhosis, but internal radiation using radio-isotope sources can achieve more selective irradiation of the chosen field. Sealed sources are dose-limited by their effects on surrounding tissues, whereas with unsealed sources the dose of radio-isotope administered is limited by bone marrow suppression. Iridium-192 wires are most frequently employed as a sealed intracavitary source. They may be inserted surgically, transhepatically or endoscopically. Doses of up to 60 Gy can be delivered to a malignant biliary stricture without damage to the surrounding parenchyma. The incidence of cholangitis is low if treatment is administered after insertion of an endoprosthesis. Unsealed radio-isotope sources may be injected directly into the tumour, administered embolically via the hepatic artery in the form of microspheres or lipid droplets, or given via parenteral infusion attached to tumour-specific antibodies. Of these vehicles, the lipid agent Lipiodol appears to be the most effective and can deliver a potentially lethal dose of radiation to small tumours. Host reaction to the injected antibody remains a major drawback to the use of monoclonal antibodies as targeting agents. Iodine-131 is a beta- and gamma-emitter, producing a local tumoricidal effect and allowing accurate dosimetry by means of external scintigraphy. Yttrium-90 is a pure beta-emitter with a greater maximum beta energy and cytotoxic range; however, it is retained in bony tissues, resulting in a dose-related risk of marrow suppression. Bone absorption cannot be measured by external imaging owing to the absence of gamma emission. This lack of accurate dosimetry, coupled with the toxic side-effects of yttrium treatment, make iodine-131 the current isotope of choice.