A4.3 Drug resistance without mutation

Topic

Beyond standard resection, oncological surgery has incorporated special modalities that combine mechanical tumor removal with an additional physical effect—heat, cold, or microwaves—or with the administration of chemotherapy directly into the peritoneal cavity.

These special modalities aim to overcome three distinct limitations of standard resection, depending on the situation: when the tumor has spread as multiple implants across the peritoneum, standard resection alone is insufficient to eliminate them all; when there are multiple metastases within the liver, resecting each one individually would deprive the patient of too much healthy liver tissue; and when the tumor is located where direct surgery would carry an unacceptable mortality rate, standard resection ceases to be a safe option.

The additional physical effect employed by these special modalities can be heat or cold, both of which kill tumor cells via different mechanisms: in hyperthermia ablation, heat causes tumor cell proteins to denature as soon as the temperature exceeds sixty degrees Celsius; in cryosurgery, cold kills the tumor cell because, at temperatures below minus forty degrees, ice crystals form within the cell itself.

Radiofrequency is one method used to generate the heat required for hyperthermia ablation: a high-frequency alternating electric current heats the tumor tissue to a temperature between ninety and one hundred and ten degrees Celsius—well above the threshold at which tumor cell proteins denature.

The fourth special modality combines heat with chemotherapy rather than using it to kill tumor cells directly: in hyperthermic intraperitoneal chemotherapy, the chemotherapy agent is administered hot directly into the peritoneal cavity, and this hyperthermia enhances the drug's penetration into residual tumor implants on the peritoneum—a challenge that standard resection alone cannot address. Taken together, all these special modalities—hyperthermic ablation, cryosurgery, radiofrequency, and hyperthermic intraperitoneal chemotherapy—share the same purpose: to add an extra physical or pharmacological effect to oncological surgery that standard resection alone cannot achieve, particularly in situations where the tumor is disseminated, multifocal, or located in an area where direct surgery would be too risky.

ID:2312