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Micrometastatic tumour cells in bone marrow in colorectal cancer
501
cause of chronic perineal pain and that MRI appears to be better than CTM in demonstrating them. This evidence suggests that MRI of the lumbosacral spine should be one of the early investigations in a patient with chronic perineal pain. A follow-up of 18 months after surgery, which consisted of occlusion or resection of the sacral meningeal cysts in 12 patients, demonstrated moderate to excellent results. All but 2 patients were free of signs and symptoms and remain as such. In 2 patients there was no significant improvement. We noted no complications. Since 75% of all investigated patients showed one or more sacral meningeal cysts, we hope the tide will turn in favour of more frequent investigation by MRI of patients with chronic perineal pain. Treatment of meningeal cysts by excision or occlusion should be generally accepted as the treatment of choice.
Department of Neurosurgery,
E. VAN DE KELFT M. VAN VYVE
Antwerp University Hospital, 2560 Edegem, Belgium
1. Van de Kelft E, Van Vyve M. Chronic perineal pain related to sacral
meningeal cysts. Neurosurgery 1991; 29: 223-26. 2. Tarlov IM. Perineural cysts of the spinal nerve roots. Arch Neurol Psychiatry 1938; 40: 1067-74. 3. Nabors MW, Pait TG, Byrd EB, et al.
of spinal
Updated assessment and current classification meningeal cysts. J Neurosurgery 1988; 68: 366-77.
Acute colonic
pseudo-obstruction
SIR,-Part of the title of
your Jan 16 commentary is acute but it is apparent that Professor Vantrappen knows little or nothing about the problem that confronts the surgeon after midnight on an orthopaedic ward with a patient who has recently undergone treatment for a fractured femoral neck and now presents with features of acute large-bowel obstruction. In this context Vantrappen does not draw an adequate distinction between chronic pseudo-obstruction which relates to autonomic dysfunction, as many studies have shown, and the emergency patient who may well have one of many causes for the problem.1 Furthermore, there is, in his discussion, confounding of cause with post-operative paralytic ileus which is not necessarily related to pseudo-obstruction. Finally, the statement that "... at one time decompression by tube caecostomy was the surgical treatment of choice..." is nonsense and denies the thought that surgeons have put into this difficult problem over the past forty odd years. There are better up-to-date accounts of the syndrome and its management in surgical publications with which Vantrappen is clearly not familiar.
pseudo-obstruction,
Broombrae, Glenbuchat, Strathdon,
HUGH DUDLEY
Aberdeenshire AB36 8UA, UK
1. Dudley HAF, Sinclair ISR, McLaren IF, McNair TJ, pseudo-obstruction. J R Coll Surg Edin 1958; 3: 206-17.
Newsam JE. Intestinal
PHENOTYPIC CHARACTERISTICS OF MICROMETASTATIC TUMOUR CELLS IN BONE MARROW*
*No of
patients with tumour cells expressing respective molecule per total no of patients analysed, tumour cells were defined by monoclonal antibody CK2 to cytokeratln no 18 in double-labelling procedures tMonoclonal antibody used for detection of indicated molecule. tp-00 02, §p0.001 vs colorectal cancer (x2-test). tumour cells in the bone marrow microenvironment, we have applied immunocytochemical double-labelling techniques.3.’ The expression of proliferation-associated nuclear markers, such as Ki-67 or pl20, was only recorded in 7 of 38 (18%) patients, independent of the histogenetic origin of the tumour, which is consistent with the notion of dormancy, by which disseminated tumour cells can hibernate for many years until metastatic disease becomes apparent by clinical diagnosis. Similarly, expression of the epidermal growth factor receptor (erb-Bl) was only noted in 1 of 16 patients with breast or colorectal cancer, whereas its structural homologue, the erb-B2 oncogene was in particular frequently detected in breast cancer (table). In view of the stimulatory role of erb-B2 on epithelial tumour cell growth,sour findings suggest that breast-cancer cells in marrow inherit a greater proliferative potential than do colon carcinoma cells. Moreover, breast tumour cells also showed more frequently a deficient expression of MHC class I antigens, which may allow them to escape from T-lymphocytemediated cytotoxicity3 (table). Colon carcinoma cells are able to seed to the bone marrow but they may lack factors supporting their survival and outgrowth in this peculiar "soil". Yet their presence must be taken, as Silly et al say, "as evidence of the general disseminative capability of an individual tumour". In general, double-labelling might be helpful to define further the oncogenic potential of disseminated epithelial tumour cells in individual patients.
KLAUS PANTEL STEPHAN BRAUN GÜNTER SCHLIMOK GERT RIETHMÜLLER
Institute of Immunology, University of Munich, D-8000 Munich 2, Germany
1. Schlimok G, Funke I, Bock B, Schweiberer B, Witte J, Riethmuller G. Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance. J Clin Oncol 1990; 8: 831-37. 2. Schlimok G, Funke I, Holzmann B, et al. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc Natl Acad Sci USA 1987; 84: 8672-76. 3. Pantel K, Schlimok G, Kutter D, et al. Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells. Cancer Res 1991; 51: 4712-15. 4. Riesenberg R, Oberneder R, Kriegmair M, et al. Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumor cells. Histochemistry (in press). 5. Slamon JD, Godolphin W, Jones LA, et al Studies of the HER-2/neu proto-oncogene in human breast cancer and ovarian cancer. Science 1989; 244: 707-12.
Micrometastatic tumour cells in bone marrow in colorectal cancer SIR,-Dr Silly and colleagues (Nov 21, p 1288) apply our immunocytochemical technique (Sept 19, p 685) to assess bone marrow cancer
micrometastasis in 12
patients
with metastatic colorectal
(T 1-4’ N1, M1). Surprisingly, cytokeratin-positive tumour
cells in bone marrow were only detected in 17% (2) of these patients which seems lower than the corresponding frequency (39%, 13 of 33 patients) we reported.l This discrepancy can be explained by variables that affect the outcome of the assay, such as the dilution of marrow aspirates by sinusoidal blood, and the total number of nucleated cells analysed, as well as the number and site of marrow
aspirations. Nevertheless,
the occurrence of bone-marrow micrometastases in advanced colorectal cancer (Dukes stage D) seems to be less frequent than that in metastatic breast cancer.1,2 To evaluate whether this difference can be explained by a differential expression of molecules relevant to the survival and outgrowth of disseminated
Doppler ultrasound screening during pregnancy SIR,-Dr colleagues’ report (Nov 28, p 1299) draws attention to two major difficulties in the analysis of randomised controlled trialS.l,2 The first is the interpretation of a non-significant Davies and
difference
on
the main
outcome
criterion; the second is the
interpretation of an unexpected significant difference. With respect to the first, readers might be tempted to conclude that doppler ultrasonography is ineffective. However, to accept this conclusion, two points should be mentioned besides those addressed by Davies et al.
First, the objective of a screening test is generally to detect anomalies; therefore it could increase antenatal care and antenatal admission for high-risk pregnancies detected as a result of screening. And this increase might even be necessary to improve the health of these
women
and their babies. Therefore evaluation of
cause of chronic perineal pain and that MRI appears to be better than CTM in demonstrating them. This evidence suggests that MRI of the lumbosacral spine should be one of the early investigations in a patient with chronic perineal pain. A follow-up of 18 months after surgery, which consisted of occlusion or resection of the sacral meningeal cysts in 12 patients, demonstrated moderate to excellent results. All but 2 patients were free of signs and symptoms and remain as such. In 2 patients there was no significant improvement. We noted no complications. Since 75% of all investigated patients showed one or more sacral meningeal cysts, we hope the tide will turn in favour of more frequent investigation by MRI of patients with chronic perineal pain. Treatment of meningeal cysts by excision or occlusion should be generally accepted as the treatment of choice.
Department of Neurosurgery,
E. VAN DE KELFT M. VAN VYVE
Antwerp University Hospital, 2560 Edegem, Belgium
1. Van de Kelft E, Van Vyve M. Chronic perineal pain related to sacral
meningeal cysts. Neurosurgery 1991; 29: 223-26. 2. Tarlov IM. Perineural cysts of the spinal nerve roots. Arch Neurol Psychiatry 1938; 40: 1067-74. 3. Nabors MW, Pait TG, Byrd EB, et al.
of spinal
Updated assessment and current classification meningeal cysts. J Neurosurgery 1988; 68: 366-77.
Acute colonic
pseudo-obstruction
SIR,-Part of the title of
your Jan 16 commentary is acute but it is apparent that Professor Vantrappen knows little or nothing about the problem that confronts the surgeon after midnight on an orthopaedic ward with a patient who has recently undergone treatment for a fractured femoral neck and now presents with features of acute large-bowel obstruction. In this context Vantrappen does not draw an adequate distinction between chronic pseudo-obstruction which relates to autonomic dysfunction, as many studies have shown, and the emergency patient who may well have one of many causes for the problem.1 Furthermore, there is, in his discussion, confounding of cause with post-operative paralytic ileus which is not necessarily related to pseudo-obstruction. Finally, the statement that "... at one time decompression by tube caecostomy was the surgical treatment of choice..." is nonsense and denies the thought that surgeons have put into this difficult problem over the past forty odd years. There are better up-to-date accounts of the syndrome and its management in surgical publications with which Vantrappen is clearly not familiar.
pseudo-obstruction,
Broombrae, Glenbuchat, Strathdon,
HUGH DUDLEY
Aberdeenshire AB36 8UA, UK
1. Dudley HAF, Sinclair ISR, McLaren IF, McNair TJ, pseudo-obstruction. J R Coll Surg Edin 1958; 3: 206-17.
Newsam JE. Intestinal
PHENOTYPIC CHARACTERISTICS OF MICROMETASTATIC TUMOUR CELLS IN BONE MARROW*
*No of
patients with tumour cells expressing respective molecule per total no of patients analysed, tumour cells were defined by monoclonal antibody CK2 to cytokeratln no 18 in double-labelling procedures tMonoclonal antibody used for detection of indicated molecule. tp-00 02, §p0.001 vs colorectal cancer (x2-test). tumour cells in the bone marrow microenvironment, we have applied immunocytochemical double-labelling techniques.3.’ The expression of proliferation-associated nuclear markers, such as Ki-67 or pl20, was only recorded in 7 of 38 (18%) patients, independent of the histogenetic origin of the tumour, which is consistent with the notion of dormancy, by which disseminated tumour cells can hibernate for many years until metastatic disease becomes apparent by clinical diagnosis. Similarly, expression of the epidermal growth factor receptor (erb-Bl) was only noted in 1 of 16 patients with breast or colorectal cancer, whereas its structural homologue, the erb-B2 oncogene was in particular frequently detected in breast cancer (table). In view of the stimulatory role of erb-B2 on epithelial tumour cell growth,sour findings suggest that breast-cancer cells in marrow inherit a greater proliferative potential than do colon carcinoma cells. Moreover, breast tumour cells also showed more frequently a deficient expression of MHC class I antigens, which may allow them to escape from T-lymphocytemediated cytotoxicity3 (table). Colon carcinoma cells are able to seed to the bone marrow but they may lack factors supporting their survival and outgrowth in this peculiar "soil". Yet their presence must be taken, as Silly et al say, "as evidence of the general disseminative capability of an individual tumour". In general, double-labelling might be helpful to define further the oncogenic potential of disseminated epithelial tumour cells in individual patients.
KLAUS PANTEL STEPHAN BRAUN GÜNTER SCHLIMOK GERT RIETHMÜLLER
Institute of Immunology, University of Munich, D-8000 Munich 2, Germany
1. Schlimok G, Funke I, Bock B, Schweiberer B, Witte J, Riethmuller G. Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance. J Clin Oncol 1990; 8: 831-37. 2. Schlimok G, Funke I, Holzmann B, et al. Micrometastatic cancer cells in bone marrow: in vitro detection with anti-cytokeratin and in vivo labeling with anti-17-1A monoclonal antibodies. Proc Natl Acad Sci USA 1987; 84: 8672-76. 3. Pantel K, Schlimok G, Kutter D, et al. Frequent down-regulation of major histocompatibility class I antigen expression on individual micrometastatic carcinoma cells. Cancer Res 1991; 51: 4712-15. 4. Riesenberg R, Oberneder R, Kriegmair M, et al. Immunocytochemical double staining of cytokeratin and prostate specific antigen in individual prostatic tumor cells. Histochemistry (in press). 5. Slamon JD, Godolphin W, Jones LA, et al Studies of the HER-2/neu proto-oncogene in human breast cancer and ovarian cancer. Science 1989; 244: 707-12.
Micrometastatic tumour cells in bone marrow in colorectal cancer SIR,-Dr Silly and colleagues (Nov 21, p 1288) apply our immunocytochemical technique (Sept 19, p 685) to assess bone marrow cancer
micrometastasis in 12
patients
with metastatic colorectal
(T 1-4’ N1, M1). Surprisingly, cytokeratin-positive tumour
cells in bone marrow were only detected in 17% (2) of these patients which seems lower than the corresponding frequency (39%, 13 of 33 patients) we reported.l This discrepancy can be explained by variables that affect the outcome of the assay, such as the dilution of marrow aspirates by sinusoidal blood, and the total number of nucleated cells analysed, as well as the number and site of marrow
aspirations. Nevertheless,
the occurrence of bone-marrow micrometastases in advanced colorectal cancer (Dukes stage D) seems to be less frequent than that in metastatic breast cancer.1,2 To evaluate whether this difference can be explained by a differential expression of molecules relevant to the survival and outgrowth of disseminated
Doppler ultrasound screening during pregnancy SIR,-Dr colleagues’ report (Nov 28, p 1299) draws attention to two major difficulties in the analysis of randomised controlled trialS.l,2 The first is the interpretation of a non-significant Davies and
difference
on
the main
outcome
criterion; the second is the
interpretation of an unexpected significant difference. With respect to the first, readers might be tempted to conclude that doppler ultrasonography is ineffective. However, to accept this conclusion, two points should be mentioned besides those addressed by Davies et al.
First, the objective of a screening test is generally to detect anomalies; therefore it could increase antenatal care and antenatal admission for high-risk pregnancies detected as a result of screening. And this increase might even be necessary to improve the health of these
women
and their babies. Therefore evaluation of