COMMENTARY

Does surgery disseminate or accelerate cancer?

Los cambios generados en los últimos años en el tratamiento de pacientes con tumores primarios del SNC nos obligan a considerar seriamente el «timing» o «los tiempos» en los que estos tratamientos son instaurados. A su vez, es aceptado el concepto que, para maximizar la efectividad del tratamiento de los pacientes con cáncer, este debiera ser comenzado lo antes posible. Entre los factores que intervienen en la determinación de este «tiempo» se menciona la complejidad que tiene la evaluación de estos pacientes antes de iniciar los tratamientos. El objetivo del siguiente trabajo, a partir de una revisión sistemática de la literatura, es desarrollar recomendaciones en cuanto a la distribución de los tiempos desde la primera evaluación del paciente hasta la instauración del tratamiento. Este trabajo está dirigido a los profesionales comprometidos en la evaluación y tratamiento de los pacientes con tumores primarios del SNC.

The changes generated in recent years concerning the treatment of patients with primary CNS tumors require us to seriously consider the timing in which these treatments are administered. In turn, it is accepted the concept which holds that in order to maximize effectiveness in the treatment of cancer patients, such treatment should be started as soon as possible. Among the factors involved in determining this «timing», it is mentioned the complexity implied in the evaluation of these patients prior to the beginning of a treatment. From a systematic review of the literature, the purpose of the following paper is to develop recommendations regarding timing since the patient's first evaluation to the administration of a treatment. This paper is aimed at those professionals involved in the evaluation and treatment of patients with primary CNS tumors.

Surgical removal remains the principal treatment modality in the management of lung cancer. Our aim is to characterize the effects of tumor removal on subsequent tumor recurrence at both local and systemic levels.

C57/BL6 mice [10/group] underwent a mammary fat pad inoculation of 3LL cells [5 × 10⁵/animal] and were divided into two groups. Group 1 served as control while mice in group 2 were further subdivided into groups 2A and 2B. After 2 weeks, all mice in 2A were killed, and primary tumors and lungs were excised. At 2 weeks, primary tumors were excised completely for all mice in group 2B. These mice were then recovered and recurrent tumor growth evaluated for a further 2 weeks. Four weeks from the onset of the study, all remaining primary tumors and lungs were excised from groups 1 and 2.

After 4 weeks undisturbed growth, primary tumors in group 1 reached a mean size of 2.85 ± 0.33 cm. After 2 weeks growth, primary tumors in groups 2A and 2B were comparable at 1.36 ± 0.44 m and 1.53 ± 0.29 cm, respectively. Two weeks after primary tumor excision, recurrent tumors in group 2B had reached a mean size of 2.65 ± 0.74 cm. Moreover, for several animals, recurrent tumors rapidly reached similar volumes to that of primary tumors in group 1. Primary tumors were typically encapsulated and nonadherent. In contrast, recurrent tumors were locally invasive and adherent to chest wall and wound. Interestingly, pulmonary metastatic burden was increased in group 2B relative to group 1. Histologic examination revealed increased mitosis in recurrent tumors when compared with primary tumors.

Tumor removal is followed by accelerated growth of locally recurrent tumors and metastases. Moreover, recurrent tumors are more locally invasive than primary tumors. These findings strongly indicate that resection may be followed by tumor progression in residual disease.

Even after apparently curative resection, lung cancer recurrence continues to lead to high mortality levels. The aim of this study was to assess the effects of cyclooxygenase-2 (COX-2) inhibitor on local and systemic recurrent tumor growth.

C57BL/6 mice underwent mammary fat pad inoculation with 3LL cells. After two weeks growth, flank tumors were resected completely and followed for recurrent tumor growth. Postresection mice were randomized to receive placebo alone (group 1) or the selective COX-2 inhibitor, rofecoxib (group 2), daily for two weeks by tube feeding. Recurrent tumor growth kinetics were compared for both groups. Two weeks following primary tumor excision animals were sacrificed, after which lungs were resected and pulmonary metastatic burden was assessed using the lung-body weight ratio. Apoptotic and mitotic indices were established for recurrent tumors and lungs, using hematoxylin and eosin histology.

Two weeks postexcision of the primary tumor, recurrent tumors in the placebo group were significantly greater than the treatment group (p = 0.002). While primary tumors were typically encapsulated and not adherent, recurrent tumors in the placebo group were invasive, adherent to the chest wall and the overlying wound. In contrast, recurrent tumors in the treatment group were nonadherent to the chest wall. Moreover, postoperative pulmonary metastatic burden was significantly reduced in treated animals. Histologic examination revealed increased apoptosis as well as an increase in the apoptosis-mitosis ratio in treated animals.

Primary tumor excision was associated with accelerated local and systemic tumor recurrence. However, these effects were significantly attenuated using selective COX-2 inhibition. The COX-2-inhibition was associated with increased levels of apoptosis. These findings endorse a role for COX-2 inhibition in the secondary prevention of lung cancer recurrence at both local and systemic levels.

Excisional surgery is one of the primary treatment modalities for cancer. Minimal residual disease (MRD) is the occult neoplastic disease that remains in situ after curative surgery. There is increasing evidence that tumour removal alters the growth of MRD, leading to perioperative tumour growth. Because neoplasia is a systemic disease, this phenomenon may be relevant to all patients undergoing surgery for cancer. In this review we discuss the published work that addresses the effects of tumour removal on subsequent tumour growth and the mechanisms by which tumour excision may alter residual tumour growth. In addition, we describe therapeutic approaches that may protect patients against any oncologically adverse effects of tumour removal. On the basis of the evidence presented, we propose a novel therapeutic paradigm; that the postoperative period represents a window of opportunity during which the patient may be further protected against the oncological effects of tumour removal.

α-fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a marker of hepatocellular carcinoma (HCC) cells disseminated into the circulation, but its clinical significance remains controversial. We prospectively assessed the prognostic value of AFP mRNA in patients undergoing curative hepatic resection for HCC. Peripheral blood samples were taken from 87 patients before and after surgery to determine the presence of AFP mRNA by use of a reverse-transcription polymerase chain reaction. A primary endpoint was recurrence-free interval. AFP mRNA was detectable preoperatively in 31 patients (36%) and postoperatively in 30 patients (34%). With a median follow-up period of 28 months (range, 3-41 months), HCC recurred in 46 patients (53%). Among 4 groups separated according to preoperative and postoperative AFP mRNA status, patients with consistent positivity of AFP mRNA showed the highest recurrence rate (85%) and trend to distant or multiple recurrence. The recurrence-free interval was significantly shorter in patients with postoperative positivity of AFP mRNA than in those without (53% [95% CI, 36-71] vs. 88% [95% CI, 79-96] at 1 year, 37% [95% CI, 17-57] vs. 60% [95% CI, 46-75] at 2 years; P = .014), whereas the preoperative positivity of AFP mRNA provided no significance (P = .100). Cox's proportional-hazards model identified the postoperative positivity of AFP mRNA as an independent prognostic factor for HCC recurrence (relative risk, 2.33; 95% CI, 1.26-4.34; P = .007). In conclusion, postsurgical recurrence of HCC can be predicted by detecting AFP mRNA–expressing cells in peripheral blood. (HEPATOLOGY 2002;35:853-860.)