675
Stapled anastomoses and colon
cancer
recurrence 1 editorial about
large bowel of colorectal cancer. We would emphasise that the reduced incidence of tumour recurrence associated with stapled anastomoses in our randomised clinical trial’ exceeded any improvement on the results of surgical treatment previously reported by the use of topical cytotoxic agents, notouch operative techniques, or any adjuvant radiotherapy or chemotherapy trials. As you discuss, experimental studies have suggested several potential explanations for this finding, and on the basis of these results, the investigators have proposed that sutureless anastomotic techniques may be even safer than staples. However, we believe that you omitted an important clinical observation that may have bearing on this conclusion. Our experience suggests that the integrity of the anastomosis is a major factor in determining the recurrence risk. In a subgroup of 167 patients (78 sutured, 89 stapled) who survived curative operations for left-sided colorectal cancer, the local recurrence rates for patients with clinically apparent and symptomless radiological anastomotic leaks were 46-7% and 35-3%, respectively, compared with 12.6% for patients with clinically and radiologically secure anastomosesSutured and stapled groups were well matched preoperatively, and this apparent influence of anastomotic integrity on outcome was independent of tumour stage. Clinical leak rates were similar in the sutured and stapled groups, but the incidence of symptomless radiological leaks was significantly lower in association with stapling (7-2% vs 17-6%). To explain these fmdings, we might postulate that the high recurrence rate associated with impaired anastomotic integrity reflects leakage of viable intraluminal tumour cells and their implantation in the "fertile soil" of injured perianastomotic tissue. Altematively, an anastomotic leak (clinical or subclinical) may, by increasing the perianastomotic inflammatory and healing responses, create a more favourable environment for otherwise clinically insignificant microscopic tumour deposits to adhere and proliferate. However, definitive conclusions cannot be drawn from these data and current clinical and experimental studies in our institution are being directed towards the investigation of this relation beween anastomotic technique, anastomotic security, and tumour recurrence. Nevertheless, until proven otherwise we would suggest that clinical and radiological integrity of the anastomosis may be critical to prognosis after large-bowel cancer surgery and we believe that this should be considered when introducing alternative anastomotic techniques such as sutureless compression devices. SIR,-We
welcome your
anastomotic techniques and
Department of Surgery, Western Infirmary, Glasgow G11 6NT, UK
Aug
recurrence
JOHN R. MCGREGOR JAMES G. DOCHERTY A. MURAT AKYOL
1 Akyoll AM, McGregor JR, Galloway DJ, Murray GD, George WD. Recurrence of colorectal cancer after sutured and stapled large bowel anastomoses. Br J Surg 1991, 78: 1297-300 2 Akyol AM, McGregor JR, Galloway DJ, Murray GD, George WD. Anastomotic leaks in colorectal cancer surgery: a risk factor for recurrence? Int J Colorect Dis 1991; 6: 179-83.
Respiratory arrest after N-acetylcysteine for paracetamol overdose SIR,—Intravenous N-acetylcysteine (Parvolex) is regarded as the treatment of choice in paracetamol poisoning. Severe adverse effects
although early reports of bronchospasm or anaphylactoid reaction led the manufacturers to include a caution in the data sheet about use in asthmatic patients. Between February, 1977, (when N-acetylcysteine was introduced) and August, 1991, the UK Committee on Safety of Medicines had received only sixteen reports of asthma or bronchospasm, none of which was lifethreatening. We report a case of severe asthma and respiratory arrest after intravenous administration of N-acetylcysteine. A 17-year-old girl presented 16 h after self-poisoning with 20 g paracetamol with 2 pints (about 1’ 1 litres) of cider. She had a history of mild asthma controlled with inhaled steroids and had never required inpatient or outpatient care. On admission she was well are rare,
with a mild wheeze. Blood paracetamol at 16 h was 32 µg/ml and, in accordance with local policy to treat up to 24 h, she was given intravenous N-acetylcysteine. Before completion of the first infusion she had respiratory arrest with no preceding worsening of asthma. There was no respiratory effort or palpable pulse, and mask ventilation and cardiac massage were started immediately. Intubation was difficult but adequate ventilation was achieved 3 min after the arrest. Treatment included intravenous salbutamol and hydrocortisone followed by a salbutamol infusion. She had extensor posturing with small, equal pupils reactive to light. After sedation she was paralysed and transferred to intensive care, where she was hyperventilated for 36 h before weaning off the ventilator. She was treated throughout with intravenous salbutamol and steroids. She was discharged 10 days after admission. 15-20% of patients taking paracetamol in overdose have plasma concentrations above the "treatment line" and are thus defined as being at risk of developing severe liver damage.1.2 However, the good safety record and efficacy of N-acetylcysteine led to the suggestion that it should be used in all cases.3 Certainly, fears that use more than 15 h after injestion would not only be ineffective but may also prove harmful are unfounded.’ There is a view that when a large amount (over 7.5g) is suspected of having been taken more than 8 h previously,s or time of ingestion is uncertainNacetylcysteine should be given immediately without waiting for plasma concentrations. Staff who delay treatment have been criticised.7 Thus there is a tendency towards more liberal use of N-acetylcysteine, largely because of the absence of severe complications. While further studies may justify this conclusion, our case suggests a cautionary approach before redefining treatment with N-acetylcysteine. KEVIN REYNARD ANNE RILEY St James’s University Hospital, Leeds LS9 7TF, UK BARRY E. WALKER 1. Prescott LF. Paracetamol
overdosage: pharmacological consideration and clinical management. Drugs 1983; 25: 290-314. 2. Smilkstein MD, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. N Engl J Med 1988; 319: 1557-62 3. Roberts WO Acetylcysteine in paracetamol poisoning. Lancet 1990; 336: 948. 4. Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991; 303: 1026-29. 5. Prescott LF, Illingworth RN, Critchley JAJH, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. BMJ 1979; ii: 1097-100. 6 Anon 24 hour overdose care urged. Hospital Doctor 1992, April 2: 39. 7. Brahams D. Paracetamol overdose: timing the antidote. Lancet 1989; i: 567-68.
Transmission of hepatitis C with pasteurised factor VIII SIR,-For those concerned with the safety of blood and blood products, Dr Schulman and colleagues’ (Aug 1, p 305) report should have been of considerable interest. Their claim that "our demonstrates that a factor VIII concentrate, which has undergone viral inactivation through pasteurisation (60°C for 10 h in solution), may still occasionally transmit HCV" should be viewed with caution. They failed to reveal evidence of transmission of HCV in other recipients of the two batches of factor VIII that were PCR positive and they were unable to rule out the possibility that the acquisition of infection arose as it does most commonly in the community-through mechanisms not associated with blood transfusion.1-3 It would be interesting to know the prevalence of HCV in that remote part of Sweden and the HCV type in factor VIII concentrate and the patient. case
Scottish National Blood Transfusion Service Headquarters, Ellen’s Glen Road, Edinburgh EH17 7QT, UK 1. Katkov
JOHN D. CASH
WM, Friedman LS, Cody H, et al Elevated serum alanine aminotransferase
levels in blood donors; the contribution of hepatitis C virus Ann Intern Med 1991; 115: 882-84. 2 Alter MJ, Coleman PJ, Alexander J, et al. Importance of heterosexual activity in the transmission of hepatitis B and non A non B hepatitis JAMA 1989, 262: 1201-05. 3 Alter MJ, Hadler SC, Judson FN, et al. Risk factors for acute non A non B hepatitis in the United States and association with hepatitis C virus infection. JAMA 1990; 264: 2231-35
Stapled anastomoses and colon
cancer
recurrence 1 editorial about
large bowel of colorectal cancer. We would emphasise that the reduced incidence of tumour recurrence associated with stapled anastomoses in our randomised clinical trial’ exceeded any improvement on the results of surgical treatment previously reported by the use of topical cytotoxic agents, notouch operative techniques, or any adjuvant radiotherapy or chemotherapy trials. As you discuss, experimental studies have suggested several potential explanations for this finding, and on the basis of these results, the investigators have proposed that sutureless anastomotic techniques may be even safer than staples. However, we believe that you omitted an important clinical observation that may have bearing on this conclusion. Our experience suggests that the integrity of the anastomosis is a major factor in determining the recurrence risk. In a subgroup of 167 patients (78 sutured, 89 stapled) who survived curative operations for left-sided colorectal cancer, the local recurrence rates for patients with clinically apparent and symptomless radiological anastomotic leaks were 46-7% and 35-3%, respectively, compared with 12.6% for patients with clinically and radiologically secure anastomosesSutured and stapled groups were well matched preoperatively, and this apparent influence of anastomotic integrity on outcome was independent of tumour stage. Clinical leak rates were similar in the sutured and stapled groups, but the incidence of symptomless radiological leaks was significantly lower in association with stapling (7-2% vs 17-6%). To explain these fmdings, we might postulate that the high recurrence rate associated with impaired anastomotic integrity reflects leakage of viable intraluminal tumour cells and their implantation in the "fertile soil" of injured perianastomotic tissue. Altematively, an anastomotic leak (clinical or subclinical) may, by increasing the perianastomotic inflammatory and healing responses, create a more favourable environment for otherwise clinically insignificant microscopic tumour deposits to adhere and proliferate. However, definitive conclusions cannot be drawn from these data and current clinical and experimental studies in our institution are being directed towards the investigation of this relation beween anastomotic technique, anastomotic security, and tumour recurrence. Nevertheless, until proven otherwise we would suggest that clinical and radiological integrity of the anastomosis may be critical to prognosis after large-bowel cancer surgery and we believe that this should be considered when introducing alternative anastomotic techniques such as sutureless compression devices. SIR,-We
welcome your
anastomotic techniques and
Department of Surgery, Western Infirmary, Glasgow G11 6NT, UK
Aug
recurrence
JOHN R. MCGREGOR JAMES G. DOCHERTY A. MURAT AKYOL
1 Akyoll AM, McGregor JR, Galloway DJ, Murray GD, George WD. Recurrence of colorectal cancer after sutured and stapled large bowel anastomoses. Br J Surg 1991, 78: 1297-300 2 Akyol AM, McGregor JR, Galloway DJ, Murray GD, George WD. Anastomotic leaks in colorectal cancer surgery: a risk factor for recurrence? Int J Colorect Dis 1991; 6: 179-83.
Respiratory arrest after N-acetylcysteine for paracetamol overdose SIR,—Intravenous N-acetylcysteine (Parvolex) is regarded as the treatment of choice in paracetamol poisoning. Severe adverse effects
although early reports of bronchospasm or anaphylactoid reaction led the manufacturers to include a caution in the data sheet about use in asthmatic patients. Between February, 1977, (when N-acetylcysteine was introduced) and August, 1991, the UK Committee on Safety of Medicines had received only sixteen reports of asthma or bronchospasm, none of which was lifethreatening. We report a case of severe asthma and respiratory arrest after intravenous administration of N-acetylcysteine. A 17-year-old girl presented 16 h after self-poisoning with 20 g paracetamol with 2 pints (about 1’ 1 litres) of cider. She had a history of mild asthma controlled with inhaled steroids and had never required inpatient or outpatient care. On admission she was well are rare,
with a mild wheeze. Blood paracetamol at 16 h was 32 µg/ml and, in accordance with local policy to treat up to 24 h, she was given intravenous N-acetylcysteine. Before completion of the first infusion she had respiratory arrest with no preceding worsening of asthma. There was no respiratory effort or palpable pulse, and mask ventilation and cardiac massage were started immediately. Intubation was difficult but adequate ventilation was achieved 3 min after the arrest. Treatment included intravenous salbutamol and hydrocortisone followed by a salbutamol infusion. She had extensor posturing with small, equal pupils reactive to light. After sedation she was paralysed and transferred to intensive care, where she was hyperventilated for 36 h before weaning off the ventilator. She was treated throughout with intravenous salbutamol and steroids. She was discharged 10 days after admission. 15-20% of patients taking paracetamol in overdose have plasma concentrations above the "treatment line" and are thus defined as being at risk of developing severe liver damage.1.2 However, the good safety record and efficacy of N-acetylcysteine led to the suggestion that it should be used in all cases.3 Certainly, fears that use more than 15 h after injestion would not only be ineffective but may also prove harmful are unfounded.’ There is a view that when a large amount (over 7.5g) is suspected of having been taken more than 8 h previously,s or time of ingestion is uncertainNacetylcysteine should be given immediately without waiting for plasma concentrations. Staff who delay treatment have been criticised.7 Thus there is a tendency towards more liberal use of N-acetylcysteine, largely because of the absence of severe complications. While further studies may justify this conclusion, our case suggests a cautionary approach before redefining treatment with N-acetylcysteine. KEVIN REYNARD ANNE RILEY St James’s University Hospital, Leeds LS9 7TF, UK BARRY E. WALKER 1. Prescott LF. Paracetamol
overdosage: pharmacological consideration and clinical management. Drugs 1983; 25: 290-314. 2. Smilkstein MD, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. N Engl J Med 1988; 319: 1557-62 3. Roberts WO Acetylcysteine in paracetamol poisoning. Lancet 1990; 336: 948. 4. Keays R, Harrison PM, Wendon JA, et al. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. BMJ 1991; 303: 1026-29. 5. Prescott LF, Illingworth RN, Critchley JAJH, Stewart MJ, Adam RD, Proudfoot AT. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. BMJ 1979; ii: 1097-100. 6 Anon 24 hour overdose care urged. Hospital Doctor 1992, April 2: 39. 7. Brahams D. Paracetamol overdose: timing the antidote. Lancet 1989; i: 567-68.
Transmission of hepatitis C with pasteurised factor VIII SIR,-For those concerned with the safety of blood and blood products, Dr Schulman and colleagues’ (Aug 1, p 305) report should have been of considerable interest. Their claim that "our demonstrates that a factor VIII concentrate, which has undergone viral inactivation through pasteurisation (60°C for 10 h in solution), may still occasionally transmit HCV" should be viewed with caution. They failed to reveal evidence of transmission of HCV in other recipients of the two batches of factor VIII that were PCR positive and they were unable to rule out the possibility that the acquisition of infection arose as it does most commonly in the community-through mechanisms not associated with blood transfusion.1-3 It would be interesting to know the prevalence of HCV in that remote part of Sweden and the HCV type in factor VIII concentrate and the patient. case
Scottish National Blood Transfusion Service Headquarters, Ellen’s Glen Road, Edinburgh EH17 7QT, UK 1. Katkov
JOHN D. CASH
WM, Friedman LS, Cody H, et al Elevated serum alanine aminotransferase
levels in blood donors; the contribution of hepatitis C virus Ann Intern Med 1991; 115: 882-84. 2 Alter MJ, Coleman PJ, Alexander J, et al. Importance of heterosexual activity in the transmission of hepatitis B and non A non B hepatitis JAMA 1989, 262: 1201-05. 3 Alter MJ, Hadler SC, Judson FN, et al. Risk factors for acute non A non B hepatitis in the United States and association with hepatitis C virus infection. JAMA 1990; 264: 2231-35
