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Clinical Analysis of Malignant Chest and Abdominal Cavity Hyperthermic Intraperitoneal Chemotherapy
Malignant pleural and abdominal effusion is one of the common clinical manifestations and serious complications of malignant tumors. Any malignant tumor can cause malignant pleural and abdominal effusion when it invades the thoracic or abdominal cavity. The treatment of malignant pleural and abdominal effusion can be divided into systemic and local treatment methods. For malignant tumors that are sensitive or relatively sensitive to chemotherapy, systemic chemotherapy can lead to malignant pleural effusion.
Release time:
2022-08-26
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Malignant pleural and abdominal effusion is one of the common clinical manifestations and serious complications of malignant tumors. Any malignant tumor can cause malignant pleural and abdominal effusion when it invades the thoracic or abdominal cavity. The treatment of malignant pleural and abdominal effusion can be divided into systemic and local treatment methods. For malignant tumors that are sensitive or relatively sensitive to chemotherapy, systemic chemotherapy may control malignant pleural and abdominal effusion. These systemic treatments are only suitable for patients with mild malignant pleural and abdominal effusion, while most cases with large amounts of pleural and abdominal effusion still require effective local treatment to achieve satisfactory control. Our department compared the efficacy of hyperthermic perfusion chemotherapy and simple intraluminal chemotherapy in hospitalized cases of malignant pleural and abdominal effusion from March 2000 to July 2003, and the clinical data is summarized as follows.
1. Clinical Data
1.1 General Information: Group A: 28 cases, including 14 males and 14 females; age range 38-75 years, average age 57 years; 13 cases of malignant pleural effusion, 11 cases of malignant abdominal effusion, and 4 cases with both pleural and abdominal effusion, all treated with hyperthermic perfusion chemotherapy. Group B: 28 cases of late-stage tumors with malignant pleural or abdominal effusion hospitalized at the same time, treated with simple local intraluminal chemotherapy. The malignant tumors included breast cancer, ovarian cancer, esophageal cancer, gastric cancer, lung cancer, intestinal cancer, renal cancer, liver cancer, pancreatic cancer, malignant lymphoma, and other metastatic cancers of unknown primary origin, all pathologically confirmed as malignant tumors.
1.2 Required Conditions: Closed catheter drainage must be implemented, and an ultrasound examination must be performed before catheter drainage: to check for adhesions and partitions in the thoracic or abdominal cavity, as significant adhesions or partitions are relative contraindications for catheter drainage; to determine the volume of pleural and abdominal effusion; to measure the depth of fluid accumulation at a specific site or puncture point using ultrasound, to assist in selecting the puncture point and the depth of the puncture needle, ensuring smooth puncture and avoiding accidents. Liver and kidney function tests, blood routine tests should be performed before hyperthermic perfusion chemotherapy, and medications such as metoclopramide or ondansetron, dexamethasone, etc., should be used to prevent or alleviate adverse reactions.
1.3 Catheter and Hyperthermic Perfusion Materials: One thoracic or abdominal puncture pack; one silicone tube (20-25 cm long) and a matching puncture cannula, guide wire, and skin expansion needle set; injection needles, syringes, local anesthetics, adhesive tape, etc.; plastic urine retention bag, connecting tube between silicone tube and urine bag; medical thermometer (upper limit at 100℃), 500ml/bottle of saline (3-4 bottles), chemotherapy drugs, 100℃ hot water, containers (such as basins).
1.4 Operating Method: Selection of puncture point: for thoracentesis, select the scapular line or posterior axillary line at the highest level of pleural effusion below the rib; for abdominal effusion, the puncture point is at the junction of the outer middle third of the line connecting the umbilicus and the iliac crest. At the puncture point, lidocaine is used for subcutaneous infiltration anesthesia from shallow to deep layers to the thoracic or abdominal cavity. The puncture cannula is slowly advanced perpendicularly to the skin at the anesthesia point until it penetrates the thoracic or abdominal cavity, stopping when pleural or abdominal effusion flows out smoothly. An elastic stainless steel guide wire is then inserted along the cannula, and the cannula is removed. The skin expansion needle is used to expand the skin to facilitate the insertion of the silicone tube. The expansion needle is removed, and the silicone tube is sent into the thoracic or abdominal cavity. When the length of the silicone tube left in the thoracic or abdominal cavity is about 10 cm, the tube insertion is stopped, the guide wire is removed, leaving the silicone tube in the thoracic or abdominal cavity, and the silicone tube is securely adhered to the skin with sterile dressings and adhesive tape to prevent slippage. Once secured, the silicone tube is connected to the urine bag using a connector, and when fluid is seen flowing smoothly from the silicone tube to the urine bag, the urine bag can be fixed to the bedside with a fine rope, completing the closed thoracic and abdominal drainage procedure.
After the effusion is completely drained, perform hyperthermic perfusion chemotherapy: immerse 500ml/bottle of saline, a total of 3-4 bottles (one bottle reserved for temperature measurement, approximately 1000ml for thoracic perfusion, and approximately 1500ml for abdominal perfusion) in a basin of about 100℃ hot water for about 5 minutes. Open one bottle and use a thermometer to test the temperature. When the temperature reaches about 45-46℃ (to achieve a temperature of 42-43℃ in the thoracic and abdominal cavities, which is the optimal temperature for hyperthermia), hang the other 2-3 bottles of saline on the infusion stand, connect them to a disposable infusion set, remove the needle and soft tube from the infusion set, and connect the thick tube to the silicone tube. Open the infusion set to the maximum speed, and raise the infusion stand, allowing the saline at 45-46℃ to flow rapidly into the thoracic or abdominal cavity in a straight line. Since the infusion process takes about 10-12 minutes for every 500ml, the temperature of the saline will not drop too quickly (indoor temperature has a certain effect), allowing the temperature in the thoracic and abdominal cavities to approach 42-43℃. When about 50-100ml of liquid remains, close the saline infusion, inject the pre-dissolved chemotherapy drug from the silicone tube connection, and then connect the infusion set to infuse the remaining 50-100ml of saline into the thoracic or abdominal cavity, preventing the chemotherapy drug from leaking out and causing skin damage. Finally, clamp the silicone tube and seal the connection with sterile gauze, instructing the patient to change positions frequently to retain the chemotherapy drug for more than 24 hours before releasing it. Once a week, for 3-4 consecutive times, observe the efficacy.
1.5 Efficacy Evaluation Criteria: Currently, the National Health Commission has not established a unified standard for the efficacy of pleural and abdominal effusion. This article refers to and improves upon the Millar scheme, with specific standards as follows: Patients with pleural effusion are divided into three levels: large, medium, and small based on the volume of pleural effusion. Pleural effusion above the level of the second anterior rib is classified as large; from the level of the second anterior rib to the level of the fifth anterior rib is classified as medium; below the level of the fifth anterior rib is classified as small. Patients with abdominal effusion are classified into large, medium, and small based on the measurement of liquid dark areas in centimeters using abdominal ultrasound. Liquid present in the entire abdominal cavity and around the liver is classified as large; liquid present in the abdominal cavity and pelvic cavity (with no effusion in the upper abdominal cavity) is classified as medium; liquid limited to the posterior wall of the bladder and surrounding areas in the pelvic cavity, with a liquid dark area not exceeding 5cm, is classified as small. The efficacy evaluation of pleural and abdominal effusion is as follows: (1) Complete Response (CR): Complete disappearance of pleural and abdominal effusion for more than 1 month. (2) Partial Response (PR): Reduction of pleural and abdominal effusion by one level, such as from large to medium or from medium to small, lasting more than 1 month. (3) Improvement (MR): Reduction of pleural and abdominal effusion within the same level, lasting more than 1 month. (4) Stable Disease (SD): Maintenance of pleural and abdominal effusion at the same level, lasting more than 1 month. (5) Progressive Disease (PD): Increase in pleural and abdominal effusion compared to the original level.
2. Results
Among 28 patients, none experienced adverse reactions related to hyperthermic perfusion chemotherapy. The effective rate (CR+PR) in group A was 82.1%, while in group B it was 57.1%, as shown in Table 1. The difference between the two groups was significant (P<0.05), indicating that hyperthermic perfusion chemotherapy has a significant effect on reducing pleural and abdominal effusion and alleviating clinical symptoms. Table 1 Comparison of efficacy between the hyperthermic perfusion chemotherapy group and the simple intraluminal chemotherapy group (omitted).
3. Discussion
Some biologists have observed that degeneration and necrosis are no longer the only manifestations of thermal injury; both heating alone and heating combined with chemotherapy drugs can induce programmed cell death. The biological rationale for heating tumors has two aspects: the vascular structure and microcirculation of tumors are inherently poor compared to normal tissues, and after heating, the heat dissipates more slowly within the tumor than in normal tissues, thus the temperature in severely heated tumors may be higher than that of surrounding normal tissues; the proportion of hypoxic cells in human solid tumors is very high, and hypoxic cells are relatively heat-sensitive, so the effect of hyperthermia increases with the proportion of hypoxic cells. There are some experimental studies on the mechanism of the cytotoxic effect of thermochemotherapy, generally believed that the net increase in DNA damage due to the interaction of heating and drugs has the following mechanisms: heating disrupts the stability of the cell membrane, increasing membrane permeability, facilitating drug penetration and absorption; heating alters the intracellular distribution of drugs; heating changes the metabolism of drugs or increases the rate of drug action on DNA; heating inhibits the repair of DNA damage caused by drugs. For any drug, there may be more than one of the above mechanisms simultaneously during heating.
Local hyperthermia combined with systemic chemotherapy is a promising field in the clinical application of tumor hyperthermia and chemotherapy, currently representing the most active area of research in this domain. Local hyperthermia typically utilizes three primary methods: ultrasound, radiofrequency, and microwave. From September 1990 to September 1991, Issel et al. treated 23 adult high-risk (non-metastatic) sarcoma patients with local hyperthermia combined with systemic chemotherapy, successfully controlling local tumors. Nagata et al. reported a survival rate of 31.7% at 1 year and 0% at 5 years for 173 liver cancer cases treated with RF (radiofrequency) capacitive heating. In China, Huang Jiaolin and Hu Zisheng achieved notable results using hepatic artery embolization hyperthermia combined with chemotherapy for advanced hepatocellular carcinoma. Since 1984, Li Dingjiu et al. from the Henan Provincial Tumor Hospital have employed an esophageal microwave radiator for intraluminal hyperthermia in 33 esophageal cancer cases while administering BLM (bleomycin), DDP (cisplatin), and CTX (cyclophosphamide) for chemotherapy, which significantly extended survival for advanced patients. In 1984, Kubota et al. reported favorable outcomes in treating bladder tumors at various stages using 42-43°C hot water combined with BLM (30μg/ml) for intravesical perfusion alongside radiotherapy (40Gy).
Closed drainage of the thoracic and abdominal cavities can alleviate compression symptoms and is also the basis for intrathoracic and intra-abdominal chemotherapy. Clinically, there are many examples of using intrathoracic and intra-abdominal chemotherapy to control pleural and abdominal effusion, but reports on hyperthermic perfusion chemotherapy in these cavities are rare. The author has found that the combined treatment of hyperthermia and chemotherapy for tumors has developed rapidly in recent years, thus adopting local hyperthermic perfusion chemotherapy to control pleural and abdominal effusion, and indeed found that it achieved better efficacy than using local perfusion chemotherapy alone. However, due to the small number of cases, further clinical validation is needed.
References
Zhou Jichang. Practical Oncology, Beijing: People's Health Publishing House, 2000, 133;135;138-142.
Author's affiliation: 056404 Hebei Shexian Tianjin Iron Factory Employee Hospital Oncology Department
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