A cohort study of local excision followed by adjuvant therapy incorporating a contact X-ray brachytherapy boost instead of radical resection in 180 patients with rectal cancer.

AIM: Recent data have suggested near-equivalent oncological results when treating early rectal cancer by local excision followed by radio- ± chemotherapy rather than salvage radical surgery. The aim of this retrospective study was to assess the use of contact X-ray brachytherapy within this paradigm. METHOD: All patients had undergone local excision and were referred to our radiotherapy centre for treatment with contact X-ray brachytherapy. Postoperative (chemo)radiotherapy was also given in their local hospital in most cases. Variables assessed were local excision method, postoperative therapy received, follow-up duration, disease-free survival, salvage surgery and stoma-free survival. RESULTS: In total, 180 patients with a median age of 70 (range 36-99) years were assessed. Following local excision, pT stages were pT1 = 131 (72%), pT2 = 44 (26%), pT3 = 5 (2%). All patients received contact X-ray brachytherapy boosting at our centre and, in addition, 110 received chemoradiotherapy and 60 received radiotherapy alone. After a median follow-up of 36 months (range 6-48), 169 patients (94%) remained free of local recurrence. Of the 11 patients with local recurrence (three isolated nodal), five underwent salvage abdominoperineal excision. Eight patients developed distant disease, of whom five underwent metastasis surgery. At last included follow-up 173 (96%) patients were free of all disease and 170 (94%) were stoma free. CONCLUSIONS: Contact therapy can be offered in addition to external beam radio (±chemo) therapy instead of radical surgery as follow-on treatment after local excision of early rectal cancer. This combination can provide equivalent outcomes to radical surgery. The added value of contact therapy should be formally assessed in a clinical trial.

Salvage surgery after inadequate combined local treatment for early rectal cancer.

The outcome of salvage surgery after failed local treatment of early rectal cancer is crucial because it determines the overall survival and therefore influences the initial choice of local therapy. The published results of salvage surgery are controversial and unclear. We treated 220 patients with early rectal cancer between 1992 and 2007 and report our experience of salvage surgery. There was an overall salvage rate of 68% (30/44) and a salvage cure rate of 87% (26/30). Immediate surgical salvage was carried out for incompletely eradicated local disease no longer than 6 months after the completion of treatment and had an 87.5% (21/24) salvage rate with a 90% (19/21) cure rate. Delayed salvage was carried out when local recurrence occurred after an apparent cure was sustained for at least 3 months and was undertaken in nine of 11 (82%) patients with local recurrence alone with an 86% (6/7) cure rate for salvage surgery. These data suggest that salvage surgery is effective management after failed local treatment. These high cure rates may reflect the fact that local recurrence is usually intraluminal after multimodality treatment, as initially involved lymph nodes are often sterilised. Follow-up after initial local treatment must be thorough and intensive, particularly during the first 3 years, in order to identify patients who are suitable for salvage and to enable prompt surgery.

Combined modality treatment of early rectal cancer: the UK experience.

With the introduction of colorectal screening in the UK, more patients will probably be diagnosed with early rectal cancer. The UK has an increasingly elderly population and not all patients diagnosed with early rectal cancer will be suitable for radical surgery. Therefore, a national plan is needed to develop the provision of alternative local treatment with equity of access across the country. Here we review the Clatterbridge Centre for Oncology multimodality treatment policy, which has been in clinical practice since 1993 and we discuss its rationale. Clatterbridge is the only centre in the UK offering Papillon-style contact radiotherapy. In total, 220 patients have been treated over 14 years, most of whom were referred from other centres. One hundred and twenty-four patients received Papillon (contact radiotherapy) as part of their multimodality management. The guidelines of the Association of Coloproctology of Great Britain and Ireland recommend local treatment for T1 tumours<3 cm in diameter, but this refers to treatment by surgery alone. There are no published national guidelines for radiotherapy. We plan each treatment in stages and achieve excellent local control (93% at 3 years) with low morbidity. We conclude that radical local treatment for cure can be offered safely to carefully selected elderly patients. Close follow-up is necessary so that effective salvage treatment can be offered. Because of a lack of randomised trial evidence, at present local radiotherapy is not yet accepted as an alternative option to the gold standard surgical treatment. Even with international collaboration, a randomised trial will be difficult to complete as the number of cases requiring local radiotherapy is small due to the highly selective nature of the treatment involved. However, an observational phase II trial is planned. In addition, the Transanal Endoscopic Microsurgery Users Group is also planning a phase II trial using preoperative radiotherapy. These studies will provide evidence to help establish the true role of radiotherapy in early rectal cancer.

A training programme for operating theatre personnel in transanal endoscopic operation procedures for local excision of rectal tumours.

The transanal endoscopic operation (TEO) is a minimal access surgical procedure for the removal of benign and early malignant rectal tumours (Nieuwenhuis et al 2009). This surgery involves specialist equipment, set up and positioning by the perioperative team. We report on and evaluate the first ever TEO course designed specifically for theatre practitioners.

The natural history of murine intra-abdominal abscess formation.

We determined the natural history of experimental abscess formation and had a secondary interest in the effect of muramyl dipeptide. Swiss-Webster mice were injected intraperitoneally with autoclaved mouse fecal suspension and either Bacteroides fragilis (10(8) colony-forming units [cfu]/mL) alone or Escherichia coli (10(4) cfu/mL), enterococcus (10(3) cfu/mL), and B fragilis (10(5) cfu/mL) after pretreatment with muramyl dipeptide or saline solution. All deaths occurred within 48 hours of injection and surviving mice, including those bearing abscesses, appeared to be healthy throughout the study. The number of mice with abscesses and the number of abscesses per group were at their maximum at two to four weeks. Groups with live bacteria had a substantial reduction in the number of abscesses between eight and 26 weeks, compared with two- and four-week values. Manual rupture of palpably large eight-week-old abscesses in 21 mice produced only one death and at autopsy two weeks later, all of the mice showed multiple smaller abscesses. Abscess formation appeared to be beneficial and the natural history of such may include spontaneous resolution without mortality.

Comparison of antibody response with delayed hypersensitivity in severely injured patients.

Twenty-seven severely injured patients had antibody response to gram-negative organisms measured of whom 25 also had skin testing. Twenty-three patients (92%) were anergic at admission. Injury Severity Scores were greater in patients who remained anergic for three weeks compared with patients whose skin tests became positive. Patients with major infection had longer anergy duration than uninfected patients. Twenty-two (81%) of 27 anergic patients mounted antibody responses. Initial bacterial contamination determined the clinical outcome and antibody response. Six of eight patients with moderate contamination mounted IgM responses to all organisms and/or an IgG response to Escherichia coli, and they remained uninfected. Of the other two patients, one died, and the other developed chronic infection. Seven of eight patients with heavy contamination developed major sepsis despite mounting several antibody responses. Six patients without contamination mounted no antibody responses and remained uninfected.

Cystic dysplasia in ectopic kidney associated with absent vas deferens and congenital inguinal hernia.

We report a case of congenital cystic dysplasia of a kidney associated with an absent vas deferens and congenital inguinal hernia on the same side. The findings are explained in embryologic terms. Congenital abnormalities of the kidney are often associated with other abnormalities of the urogenital system and should be looked for when managing children with this condition.

Alpha 2 interferon in the prevention of N-nitroso-methyl urea induced breast cancer in rats.

Human interferons have been shown to be effective treatment for hairy cell leukaemia and are now commercially available. Their role in treatment of solid tumours has yet to be established. This study assessed the value of alpha 2 interferon (IFN) in an experimental breast cancer model. Four groups of female Sprague-Dawley rats were studied. The first received three intravenous injections (7 mg/kg) of N-nitroso-methyl urea (NMU) at weeks 0, 3 and 7. The second received the same NMU dosage regime plus IFN (100,000 IU, twice weekly for 3 weeks). A third received IFN alone and the fourth was a control group receiving three intravenous injections of normal saline. At week 16, 19 of 20 rats in the NMU alone group had developed tumours significantly more than four of 15 rats with tumour in the NMU plus IFN group (P less than 0.001). Both the mean tumour number/rat and the mean tumour weight/rat was significantly more in the NMU group than the NMU plus IFN group P less than 0.05). No rats in the IFN alone or control group developed tumour. These data suggest that IFN prevents carcinogen induced breast cancer in rats. It may have a role in the prevention and treatment of human breast cancer.

Clinical experience with CA-50 in the serum of carcinoma patients.

A radioimmunoassay was used for the detection of the human carcinoma-associated antigen CA-50 in the serum of 60 normal subjects, 236 patients with benign disease and 482 patients with carcinomas of different type. Serum levels in all normal subjects and 220 of 236 patients (93%) with benign disease were below 17 units/ml, while 269 of 482 patients (56%) with carcinoma had CA-50 levels above 17 units/ml. This tumour marker may prove useful in the diagnosis and monitoring of patients with various carcinomas.

The management of retroperitoneal soft tissue sarcoma: a single institution experience with a review of the literature.

AIM: Ten percent of soft tissue sarcomas (STS) arise in the retroperitoneal tissues. The prognosis for patients with retroperitoneal sarcoma is poor with a 5-year survival rate between 12% and 70%. Stage at presentation, high histological grade, unresectable primary tumour and incomplete resection are associated with a less favourable outcome. METHODS: Complete follow-up data were available on 22 patients who underwent surgery for retroperitoneal STS in our institution between 1990 and 2000. Patient, tumour and treatment variables were analysed including use of adjuvant therapy and survival status. RESULTS: Eighteen patients underwent surgery for primary disease, four patients were treated for recurrent disease or metastases. Ten patients presented with pain, seven with an abdominal mass, other presentation included weight loss and haematuria. Thirteen patients presented with tumours larger than 10 cm. The tumours were seven liposarcomas, six leiomyosarcomas, three malignant fibrous histiocytomas, two rhabdomyosarcomas, two malignant schwannomas and two undifferentiated sarcomas. Six primary tumours were completely excised, five patients received radiotherapy and five received chemotherapy. Local recurrence rate was 45% and recurrence-free interval for 10 patients with recurrence was 11 months. Five patients received radiotherapy and five received chemotherapy. The median survival for patients with primary tumours was 36 months, and 5-year survival was 44%. Adjuvant therapy was not associated with higher survival rates. CONCLUSION: This study re-emphasizes the poor outcome of patients with retroperitoneal STS. Adjuvant radiotherapy and chemotherapy do not appear to be any proven benefit and the single most important prognostic factor is aggressive successful en bloc resection of the primary tumour. Our resection rate and 5-year survival rates are comparable with previous reported UK series although lower than large reports from North American centres. This might partly be explained by difficulty in data collection in a retrospective analysis, but may reflect inadequate subspecialization in UK centres.

The use of CA-50 radioimmunoassay inhibition test in the differential diagnosis of benign and malignant breast disease.

The role of the tumour marker CA-50 has been studied in the differential diagnosis of benign and malignant breast disease. Serum levels of CA-50 were determined by radioimmunoassay using a level of 17 units/ml as a cut-off. All 50 normal subjects and 22 of 24 patients (92%) with benign breast disease had CA-50 levels below 17 units/ml. By contrast, 15 of 36 patients (42%) with breast carcinoma had serum CA-50 levels above 17 units/ml (P less than 0.001). There was no clear correlation with tumour stage. The data suggest that CA-50 levels may help to differentiate benign and malignant diseases of the breast.

HLA-DR antigen expression on peripheral blood monocytes correlates with surgical infection.

Monocyte human leukocyte antigen-DR (HLA-DR) expression has correlated closely with clinical outcome in severely injured patients at high risk for infection. Monocytes from 77 asymptomatic volunteers expressed HLA-DR antigen with minimal variability in respect to age, gender, race, time of day or year, or serum alcohol level. Patients who developed infection after elective laparotomy had a significantly lower mean percentage of monocytes expressing HLA-DR antigen and a lower mean fluorescent intensity than uninfected patients (p less than 0.05). Severely infected nonsurgical patients had significantly lower values than normal volunteers (p less than 0.01), and the mean fluorescent intensity of those who died from infection was significantly lower than that of those who survived (p less than 0.05). Patients on immunosuppressive regimens after renal transplantation had levels of HLA-DR expression similar to those of the volunteers. Monocyte HLA-DR expression was found to be a reliable marker of clinical infection and showed remarkable reproducibility within the normal uninfected study population.

Association of cytomegalovirus infection with increased morbidity is independent of transfusion.

Forty-three consecutive trauma patients with an injury severity score greater than 20 were studied prospectively for evidence of cytomegalovirus (CMV) infection. Twenty-one patients had serologic conversion: 3 with primary CMV infections, 18 with reactivation of CMV infection (CMV group). Twenty-two patients had no serologic conversion (no CMV group). To differentiate the effects of CMV and transfusion, the CMV group and the no CMV group were each divided into high (more than 10 units) and low (less than 10 units) transfusion subgroups. Similar fever peaks, leukocyte counts, lymphocyte counts, and incidence of major bacterial sepsis were recorded for the four subgroups. Several factors were significantly associated with CMV infection independent of transfusion, including increased duration of major bacterial sepsis and number of septic episodes per patient; prolonged duration of anergy; increased duration of intensive care unit and hospital stay; increased duration of ventilatory assistance and rate of tracheostomy; and increased suppressor cells, decreased helper: suppressor ratios, increased functional suppressor cells, and increased natural killer cells. Although mortality was not increased with CMV infection, our data suggest that such infection after trauma may delay recovery from major bacterial infection, often resulting in a major increase in morbidity.

Endorectal magnetic resonance imaging of a rectal duplication cyst.

A case of a duplication cyst of the rectum is presented. This case highlights the potential role of endoluminal magnetic resonance imaging in the diagnosis of this uncommon condition. Alternative imaging modalities and differential diagnoses are discussed.

The use of CA-50 radioimmunoassay test in diagnosis of urologic malignancy. Tie for second place Jobst award.

Circulating levels of the oncofetal antigen, CA-50, have been used to differentiate benign and malignant disease of the prostate, bladder, and kidney, taking 17 units/ml as the upper limit of normal. All 60 normal subjects and 59 of 61 (97%) patients with benign prostatic hypertrophy had levels below 17 units/ml. The test was positive in 29 of 68 (43%) patients with prostatic carcinoma, including 24 of 34 (75%) with metastases, but only five of 34 (15%) patients without metastases (P less than 0.01). Positivity also correlated with histologic grade: 0 per cent with well-differentiated tumors (n = 8), 33 per cent with moderately differentiated (n = 11), and 66 per cent with poorly differentiated tumors (n = 27). All 14 patients with benign bladder disease had negative values, whereas 13 of 21 (62%) patients with bladder carcinoma had positive. Noninvasive tumors were less likely to give a positive value than invasive tumors (42 vs 89%; P less than 0.05). One of 11 (9%) patients with benign renal conditions was positive as opposed to seven of 15 (47%) patients with renal carcinoma. The overall sensitivity of the CA-50 test for urologic malignancy was 47 per cent and specificity was 97 per cent; moreover, serum levels correlated with stage and grade of disease.

The response of immunoglobulins to infection after thermal and nonthermal injury.

Traumatic and thermal injuries are leading causes of mortality and morbidity due to their high incidence of infection. Host defense is vital to recovery in these patients yet incompletely understood. On days 1, 7, and 14, serum immunoglobulins of the IgA, IgG, and IgM classes were measured in 46 consecutive patients who sustained severe trauma with an injury severity score of at least 20. The patients were divided into four groups: 1) an uneventful recovery group (n = 11) of nonthermal trauma patients who did not become infected; 2) an infected nonthermal group without splenectomy; 3) an infected group of burn patients; and 4) 12 patients who underwent splenectomy of which nine became infected following nonthermal trauma. In each patient group, IgA, IgG, and IgM were all reduced, and group 1 had a steady return to normal range. Group 2 patients exhibited supranormal responses in all 3 classes at one week and supranormal IgA and IgG responses at two weeks. In contrast, both infected burn and splenectomized patients had markedly reduced IgG and IgM levels compared with the group 2 patients (P less than 0.05). Splenectomy sharply reduced IgM response to infection at 7 and 14 days compared with nonsplenectomized infected posttraumatic patients. Immunoglobulin response after trauma depended on the type of injury, presence of infection, splenic function, and type of immunoglobulin. Recognition of immunoglobulin deficiencies in both the burn and splenectomized patient may permit focused therapy, such as specific replacement of these proteins.

Evaluation of copovithane as a nonspecific immunomodulator in surgically simulated sepsis.

Copovithane (CPV), a synthetic polymer, has been shown to have antitumor activity and also to reduce mortality in experimental murine peritonitis. The purpose of this study was to compare CPV with muramyl dipeptide (MDP), an immunomodulator of proven efficacy in simulated surgical infection. Six groups of CBA/J mice were compared; they received intramuscular injections of normal saline (controls), MDP (100 micrograms), or CPV (100, 200, and 400 mg/kg) 24 h prior to bacterial challenge. The challenge consisted of a Klebsiella-impregnated thigh suture. The first experiment assessed survival after bacterial challenge. The MDP and the CPV groups both had median survival times of 3 days, significantly longer than the control group (1 day, p less than .05). In the second experiment, animals were sacrificed at 6, 24, and 48 h following bacterial challenge, and blood and infected muscle were taken for quantitative bacteriology. At 6 h, there was no difference between groups. Both the MDP and CPV groups had significantly (p less than .05) lower blood bacterial counts than the control group at 24 and 48 h. Both the MDP and CVP groups had significantly lower local bacterial recovery than controls at 48 h (p less than .05), and local bacterial recovery of the MDP group was significantly lower than the control group at 24 h (p less than .05). CPV improved survival and reduced local and systemic bacterial recovery compared with controls. Although the effect of CPV was similar to MDP in this model, it consistently was of lower magnitude and had a narrow dose range.

Laparoscopic laser cholecystectomy: our first 200 patients.

A series of 200 consecutive patients were considered for laparoscopic laser cholecystectomy. Laparoscopic laser cholecystectomy was attempted in 195 cases and was performed in 192 cases. Laparoscopy was performed in five patients, but laparoscopic cholecystectomy was not attempted owing to dense adhesions (3), cholangiocarcinoma (1) and an absent gallbladder (1). The indications for operation were symptomatic gallstones which included biliary colic (142), acute cholecystitis (49) and gallstone pancreatitis (9). The median duration of operation was 75 min. Operative cholangiography was attempted in 151 (77%) of cases, and was successful in 85% of attempts. Laparoscopic common bile duct visualisation was performed three times with successful stone extraction twice. The other common bile duct was normal. The median duration of postoperative hospital stay was 2 days, for return to normal activity 6 days, and for return to work 10 days. Mean analgesic and antiemetic requirements were approximately one-third of those for open cholecystectomy. Of the patients, 94% reported good or excellent overall satisfaction and 96% reported excellent cosmetic results. Seven complications occurred (4%). Three patients had immediate conversion to laparotomy owing to haemorrhage (2) and gallbladder rupture (1). Four patients required laparotomy for postoperative complications (common bile duct damage, slipped clips from cystic duct, perforated duodenum and leaking accessory hepatic duct). No complications occurred in the last 140 cases. These data suggest that laparoscopic laser cholecystectomy reduces the discomfort of laparotomy and allows a shorter postoperative recovery. The operation has a learning curve, but will ultimately be applicable to the majority of patients with symptomatic gallstones.

Angiomyolipoma of the kidney: a clinical enigma in diagnosis and management.

Renal angiomyolipomas are uncommon benign tumours which clinically mimic renal cell carcinoma. They have characteristic features on ultrasound and CT scanning which may enable their diagnosis preoperatively. We review our experience of six cases of renal angiomyolipoma. These cases highlight the difficulties in making a preoperative diagnosis despite the use of modern scanning. We advocate conservative resection when the diagnosis is made preoperatively and when technically possible, but radical nephrectomy should be performed if there is a possibility of a carcinoma.

Inspecting the colon from inside and out to solve pyrexia of unknown origin.

A man with longstanding intermittent symptoms of abdominal pain, diarrhoea and pyrexia of unknown origin was diagnosed with the novel technique of laparoscopic-assisted colonoscopy. At subsequent laparotomy, a longstanding perforation of sigmoid diverticular disease was resected, with resolution of his symptoms.