Micrometastases in esophagogastric cancer: High detection rate in resected rib segments

doi:10.1016/S0016-5085(99)70175-7

Gastroenterology

Volume 116, Issue 3, March 1999, Pages 543-548

Presented in part as an oral presentation, American Gastro-enterological Association, Digestive Disease Week, New Orleans, Louisiana, May 1998.

https://doi.org/10.1016/S0016-5085(99)70175-7 Get rights and content

Abstract

Background & Aims: Micrometastases within bone marrow indicate a poor prognosis. We prospectively examined micrometastases in patients undergoing resection of esophagogastric cancers for (1) prevalence in rib marrow; (2) comparative detection rates in rib and iliac crest marrow; (3) responsiveness to neoadjuvant therapy; and (4) viability and tumorigenicity. Methods: In 50 consecutive patients, marrow was obtained before manipulation of the primary tumor. Micrometastatic cells were detected by staining contaminant cytokeratin-18–positive cells. Viability and tumorigenicity were determined by culture and xenograft. Results: Micrometastases were detected in rib marrow from 88% of patients (44 of 50). When bilateral iliac crest marrow was also obtained, micrometastases were found in 15% (4 of 27) compared with 89% (24 of 27) for ribs (P < 0.001). Detection rates were independent of histological type or nodal status and were similar in patients with and without neoadjuvant therapy. Metastatic cells were cultured from rib marrow of 5 of 7 patients and were tumorigenic in nude mice. Conclusions: Most patients undergoing resection of esophagogastric malignancies have micrometastases in rib marrow. Detection rates based on iliac crest marrow are underestimates. Hematogenous spread of metastatic cells is independent of histological type or nodal status. The metastatic cells are viable, tumorigenic, and resistant to neoadjuvant therapy.

GASTROENTEROLOGY 1999;116:543-548

Section snippets

Patients

Fifty consecutive patients undergoing potentially curative surgical resection of an esophageal or esophagogastric junction malignancy were included in the study, which began prospectively in August 1996. The histological types included 19 squamous and 31 adenocarcinomas. All tumors were classified according to the TNM system after histological examination of the resected tissue. Patients with known metastases demonstrable by conventional or nonsurgical means were excluded; there were no other

Results

Micrometastases were detected in rib marrow in 88% (44 of 50) of consecutive patients. Rib marrow processed for histochemical staining was available for 36 patients, 33 of which were positive for micrometastases. In all of these cases, it was possible to provide direct immunohistochemical confirmation of the flow cytometric result (Figure 1).

. Cytokeratin-positive cells within bone marrow that are morphologically abnormal and easily distinguished from the indigenous marrow cells (original

Discussion

Bone marrow is an optimal site to look for micrometastases because of its large blood supply, rich cellular repository, and mesenchymal nature, within which cytokeratin-positive epithelial deposits are easily identifiable.¹⁵ Bone marrow should probably be regarded as a window on the metastatic process because other tissues such as liver and lung almost certainly also harbor dormant microdeposits of residual disease that may be more clinically relevant. These organs are less accessible, and

Acknowledgements

The authors thank Bernie Crowley and Jim O'Callaghan for technical assistance and the staff of the Mercy Hospital, Cork, for kindness and cooperation.

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Citation Excerpt :
These include delayed clinical presentation, or the presence of micro metastases spreading via longitudinal lymphatic drainage within the submucosal plexus at time of resection.16 The theory of micro metastasis is further supported by O’Sullivan et al. who identified the presence of rib marrow metastasis in patients undergoing curative resection of oesophago-gastric malignancies.17 Local and regional metastases often occur within one year of surgery, indicating that both must have been present at the time of operation.
The outcome of the treatment of oesophageal cancer remains poor despite improved treatment modalities and recurrence remains a major problem despite improved staging and treatment. The aim was to identify the independent risk factors responsible in the recurrence of oesophageal cancer.
The patients who had elective oesophagectomy (n = 244) with curative intent were studied. One hundred and eighty four patients had surgery alone, 44 patients had neo-adjuvant chemotherapy and surgery while 16 patients had neo-adjuvant chemotherapy, surgery and adjuvant chemotherapy. We have analyzed patients who had surgery alone (n = 184). Data was collected for demography, type of operation, histology, staging (TNM), vascular invasion (VI), differentiation of tumour, type of chemotherapy and recurrence of tumour.
The median age was 67 years (IQR 60, 71). The T1, T2, T3 distribution was 10%, 24% and 66% respectively. Forty percent had no nodal involvement (N0) and 60% had N1 stage disease. Twenty three percent of patients had vascular invasion. Univariate analysis of histo-pathological factors identified lymph node yield (p = 0.06), curative resection R0 (p = 0.004) and vascular invasion (VI) (P = 0.69) as prognostic indicators of recurrence. Multivariate analysis showed that number of lymph nodes yielded (p = 0.01) and R0 resection remain independent indicators of recurrence of tumour. However, VI (p = 0.2) and age at disease onset (p = 0.8) were not indicators of recurrence in oesophageal cancer patients.
R0 and lymph node yield may help to predict the recurrence of oesophageal cancer. However the presence of VI may not be a significant risk factor in disease recurrence.

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^☆: Address requests for reprints to: Fergus Shanahan, M.D., Department of Medicine, Cork University Hospital, Cork, Ireland. e-mail: [email protected]; fax: (353) 21-345300.

^☆☆: Supported by the Cork Cancer Research Centre, the Health Research Board of Ireland, and the Cancer Research Appeal Mercy Hospital (CRAM).

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Alimentary TractMicrometastases in esophagogastric cancer: High detection rate in resected rib segments☆,☆☆

Abstract

Section snippets

Patients

Results

Discussion

Acknowledgements

Lancet

Lancet

Gastroenterology

Lancet

Gastroenterology

Micrometastases in bone marrow in patients with primary breast cancer: evaluation as an early predictor of bone metastases

Br Med J

Prediction of early relapse in patients with operable breast cancer by detection of occult bone marrow micrometastases

J Clin Oncol

Detection of occult bone marrow micrometastases in patients with operable lung carcinoma

Ann Surg

Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization, and prognostic significance

J Clin Oncol

Micrometastases: marker of metastatic potential or evidence of residual disease?

Gut

A comparison of multimodal therapy and surgery for esophageal adenocarcinoma

N Engl J Med

Alimentary Tract
Micrometastases in esophagogastric cancer: High detection rate in resected rib segments☆,☆☆