- Email: [email protected]
Local recurrence after colorectal surgery
The results of treatment with respect to (infectious) complications have not been as bad as Jensen’s interpretation of data suggests. It is only in the subgroup of multitransfused patients who had died without evidence of cancer recurrence (n=32) that, mainly shortly after surgery, 31% (n=10, 5% of the 198 patients transfused with >3 units) died from infection and 9% (n=3, 1-5%) died because of blood loss. As
explain and in accordance with Jensen and Heiss, we consistently showed-also after correction for other risk factors and for differences between hospitals-only blood transfusion and tumour location to be an independent risk factor of infection. One of the reasons for the high overall percentage of infections is the inclusion of urinary and respiratory tract infections (16% and 9%, respectively). The we
percentage of wound infections/abscesses we recorded is in the same order as that shown by Jensen and Heiss (9-5%, 8-1%, and 6-7%, respectively). Whether survival or cancer recurrence is the most valid index for measurement of cancer prognosis, we detected no beneficial effect of leucocyte depletion; nor did we show an association between blood transfusion and outlook in the overall study population. The observed correlation between transfusion of greater than 3 units with survival is restricted to a patient subpopulation that is rather prone to selection for risk factors or bad outlook. The lack of an association between blood transfusion and cancer prognosis in our large prospective study is in agreement with most retrospective studies’ and the conclusion of a recent meta-analysis,2 and provides no evidence for the cause-and-effect relation that Gantt postulated. J G A Houbiers, L M G van de C J H van de Velde, A Brand
Watering,
and Blood Bank, P0 Box 9600, 2300 RC Leiden, Netherlands
Department of Immunohaematology
PJ M
Verwey,
University Hospital Leiden,
1 Francis DMA. Relationship between blood transfusion and tumour behaviour. Br J Surg 1991; 78: 1420-428. 2 Vamvakas EC, Moore SB. Perioperative blood transfusion and colorectal cancer recurrence: a qualitative statistical overview and meta-analysis. Transfusion 1993; 33: 754-65.
Local
recurrence
after colorectal surgery
SiR-Adam and colleagues (Sept 10, p 707) report the relation between involvement of the circumferential tumour margin and local recurrence of rectal cancer. They show that the circumferential margin was involved in 25% of biopsy specimens that surgeons thought were potentially curative, compared with 6-5% of specimens in a previous study.’ In part, this difference can be explained by variations in laboratory technique of examining the specimens. However, it is far more likely that this difference is attributable to failure to excise the mesorectum completely with the tumour. Adam and colleagues’ paper reports the poor outcome after 190 procedures done by 23 different surgeons. It is hardly surprising that incomplete excision of carcinoma results in local recurrence. Surely this makes a compelling case for the treatment of these patients by
Dimethylsulphoxide-induced serum hyperosmolality after cryopreserved stem-cell graft SIR-Haemopoietic stem cells used for marrow transplantation are commonly cryopreserved in 10% v/v dimethylsulphoxide (DMSO) which is a 1-4 molar solution of DMSO. This solution is very hypertonic with a total tonicity of about 1700 mosmol/L, more than fivefold that of human plasma. There is little information on the human toxicity of intravenous DMSO, as highlighted in a previous case report.’ We describe a case with pre-existing central diabetes insipidus and symptomatic plasma hyperosmolarity after infusion of haemopoietic stem cells cryopreserved in DMSO. A 16-year-old boy was treated for second relapse of a malignant intracranial germ-cell tumour with chemotherapy and peripheral blood stem-cell rescue. Hypothalamic infiltration by tumour had caused pituitary failure and central diabetes insipidus requiring full hormone replacement. He maintained fluid balance on intranasal desmopressin 5 µg twice daily. Anorexia was the principal symptom of relapse, the patient weighing only 27 kg. Stem cells harvested after priming chemotherapy and granulocyte colony-stimulating factor were cryopreserved in 700 mL 10% v/v DMSO and reinfused rapidly two days after highdose cyclophosphamide. One hour after the infusion (35 mmol DMSO per kg) he was extremely unwell with severe headache, confusion, and abdominal pain. Physical examination revealed sunken eyes and poor tissue turgor. Measurement of plasma osmolality and electrolytes confirmed severe hyperosmolality (396 mosmol/L) with a positive osmolal gap (50 mosmol/L) and hypernatraemia (sodium 170 mmol/L) (figure). He was vigorously rehydrated with 3 LJm2 half-normal saline and clinically returned to normal the following day. Four weeks later a second cryopreserved stem-cell graft was infused in 187 mL 10% v/v DMSO (8 mmoL DMSO per kg). Care was taken to ensure adequate hydration with hypotonic fluids. He remained clinically well. No significant hypernatraemia occurred; plasma osmolality increased to 340 mosmol/L with an osmolal gap of 48 mosmol/L. In both instances measured serum osmolalities up to ten hours after DMSO infusion grossly exceeded the osmolality expected from serum electrolytes and DMSO load. This strongly argues against the widely assumed rapid distribution attributed to DMSO and would explain significant transient fluid shifts. A linear relation between serum DMSO and serum osmolarity has been shown by Runckel and Swanson.2
specialist surgeons? C G Marks Royal Surrey County Hospital, Guildford, Surrey GU2 5XX, 1
2
-
UK
-J
V
J
Time to stem-cell
LV
graft (h)
Cawthorn SJ, Parums DV, Gibbs NM, et al. Extent of mesorectal spread and involvement of lateral resection margin as prognostic
Figure: Increased osmolality after infusion cryopreserved with DMSO
factors after surgery for rectal cancer. Lancet 1990; 335: 1055-59. Heald RJ. The Holy Plane of rectal suyrgery. J R Soc Med 1988; 81: 503-08.
Calculated osmolality was approximated by doubling values for serum sodium since glucose and urea concentrations remained constant
of stem-cell
graft
throughout. 1431
explain and in accordance with Jensen and Heiss, we consistently showed-also after correction for other risk factors and for differences between hospitals-only blood transfusion and tumour location to be an independent risk factor of infection. One of the reasons for the high overall percentage of infections is the inclusion of urinary and respiratory tract infections (16% and 9%, respectively). The we
percentage of wound infections/abscesses we recorded is in the same order as that shown by Jensen and Heiss (9-5%, 8-1%, and 6-7%, respectively). Whether survival or cancer recurrence is the most valid index for measurement of cancer prognosis, we detected no beneficial effect of leucocyte depletion; nor did we show an association between blood transfusion and outlook in the overall study population. The observed correlation between transfusion of greater than 3 units with survival is restricted to a patient subpopulation that is rather prone to selection for risk factors or bad outlook. The lack of an association between blood transfusion and cancer prognosis in our large prospective study is in agreement with most retrospective studies’ and the conclusion of a recent meta-analysis,2 and provides no evidence for the cause-and-effect relation that Gantt postulated. J G A Houbiers, L M G van de C J H van de Velde, A Brand
Watering,
and Blood Bank, P0 Box 9600, 2300 RC Leiden, Netherlands
Department of Immunohaematology
PJ M
Verwey,
University Hospital Leiden,
1 Francis DMA. Relationship between blood transfusion and tumour behaviour. Br J Surg 1991; 78: 1420-428. 2 Vamvakas EC, Moore SB. Perioperative blood transfusion and colorectal cancer recurrence: a qualitative statistical overview and meta-analysis. Transfusion 1993; 33: 754-65.
Local
recurrence
after colorectal surgery
SiR-Adam and colleagues (Sept 10, p 707) report the relation between involvement of the circumferential tumour margin and local recurrence of rectal cancer. They show that the circumferential margin was involved in 25% of biopsy specimens that surgeons thought were potentially curative, compared with 6-5% of specimens in a previous study.’ In part, this difference can be explained by variations in laboratory technique of examining the specimens. However, it is far more likely that this difference is attributable to failure to excise the mesorectum completely with the tumour. Adam and colleagues’ paper reports the poor outcome after 190 procedures done by 23 different surgeons. It is hardly surprising that incomplete excision of carcinoma results in local recurrence. Surely this makes a compelling case for the treatment of these patients by
Dimethylsulphoxide-induced serum hyperosmolality after cryopreserved stem-cell graft SIR-Haemopoietic stem cells used for marrow transplantation are commonly cryopreserved in 10% v/v dimethylsulphoxide (DMSO) which is a 1-4 molar solution of DMSO. This solution is very hypertonic with a total tonicity of about 1700 mosmol/L, more than fivefold that of human plasma. There is little information on the human toxicity of intravenous DMSO, as highlighted in a previous case report.’ We describe a case with pre-existing central diabetes insipidus and symptomatic plasma hyperosmolarity after infusion of haemopoietic stem cells cryopreserved in DMSO. A 16-year-old boy was treated for second relapse of a malignant intracranial germ-cell tumour with chemotherapy and peripheral blood stem-cell rescue. Hypothalamic infiltration by tumour had caused pituitary failure and central diabetes insipidus requiring full hormone replacement. He maintained fluid balance on intranasal desmopressin 5 µg twice daily. Anorexia was the principal symptom of relapse, the patient weighing only 27 kg. Stem cells harvested after priming chemotherapy and granulocyte colony-stimulating factor were cryopreserved in 700 mL 10% v/v DMSO and reinfused rapidly two days after highdose cyclophosphamide. One hour after the infusion (35 mmol DMSO per kg) he was extremely unwell with severe headache, confusion, and abdominal pain. Physical examination revealed sunken eyes and poor tissue turgor. Measurement of plasma osmolality and electrolytes confirmed severe hyperosmolality (396 mosmol/L) with a positive osmolal gap (50 mosmol/L) and hypernatraemia (sodium 170 mmol/L) (figure). He was vigorously rehydrated with 3 LJm2 half-normal saline and clinically returned to normal the following day. Four weeks later a second cryopreserved stem-cell graft was infused in 187 mL 10% v/v DMSO (8 mmoL DMSO per kg). Care was taken to ensure adequate hydration with hypotonic fluids. He remained clinically well. No significant hypernatraemia occurred; plasma osmolality increased to 340 mosmol/L with an osmolal gap of 48 mosmol/L. In both instances measured serum osmolalities up to ten hours after DMSO infusion grossly exceeded the osmolality expected from serum electrolytes and DMSO load. This strongly argues against the widely assumed rapid distribution attributed to DMSO and would explain significant transient fluid shifts. A linear relation between serum DMSO and serum osmolarity has been shown by Runckel and Swanson.2
specialist surgeons? C G Marks Royal Surrey County Hospital, Guildford, Surrey GU2 5XX, 1
2
-
UK
-J
V
J
Time to stem-cell
LV
graft (h)
Cawthorn SJ, Parums DV, Gibbs NM, et al. Extent of mesorectal spread and involvement of lateral resection margin as prognostic
Figure: Increased osmolality after infusion cryopreserved with DMSO
factors after surgery for rectal cancer. Lancet 1990; 335: 1055-59. Heald RJ. The Holy Plane of rectal suyrgery. J R Soc Med 1988; 81: 503-08.
Calculated osmolality was approximated by doubling values for serum sodium since glucose and urea concentrations remained constant
of stem-cell
graft
throughout. 1431