Prevention by methylprednisolone of increased circulating tumor necrosis factor-alpha levels and lung injury associated with systemic inflammatory response syndrome due to intraperitoneal hyperthermia.

UNLABELLED: We previously demonstrated that intraperitoneal hyperthermic perfusion (IPHP), which is performed clinically as a treatment for patients with advanced gastrointestinal cancer, can lead to increased serum tumor necrosis factor-alpha (TNF-alpha), systemic inflammatory response syndrome (SIRS), and acute lung injury. Glucocorticoids inhibit the production and actions of TNF-alpha. We investigated whether pretreatment with methylprednisolone (MPS) may modulate serum TNF-alpha and lung injury in patients subjected to IPHP. Serum TNF-alpha was not detected in the patients pretreated with MPS, whereas serum TNF-alpha increased in the control patients (45.7 +/- 8.3 pg/mL, mean +/- SEM) after IPHP. Postoperative lung injury scores were significantly lower in patients pretreated with MPS than in the control patients (P < 0.001). IMPLICATIONS: Pretreatment with methylprednisolone attenuates the increase in circulating tumor necrosis factor-alpha and prevents lung injury in this systemic inflammatory syndrome due to intraperitoneal hyperthermic perfusion.

Improved mortality rate of gastric carcinoma patients with peritoneal carcinomatosis treated with intraperitoneal hyperthermic chemoperfusion combined with surgery.

BACKGROUND: Peritoneal carcinomatosis from gastric carcinoma has a very poor prognosis. The purpose of this study was to evaluate the efficacy of intraperitoneal hyperthermic chemoperfusion (IHCP) in advanced gastric carcinoma patients with peritoneal carcinomatosis. METHODS: IHCP combined with aggressive surgery was performed in 48 gastric carcinoma patients with peritoneal carcinomatosis; 18 gastric carcinoma patients with peritoneal carcinomatosis serving as controls were treated with surgery alone. RESULTS: The survival period was extended for the 48 patients who underwent surgery plus IHCP compared with the control patients (P = 0.00167). Of the 29 patients with peritoneal carcinomatosis in the upper abdominal cavity, the 21 patients treated with IHCP and surgery had survival periods superior to those of the 8 patients treated by surgery alone (P = 0.000817). The 5-year survival rate of the 18 IHCP patients with countable metastases in the entire cavity was 41.6%, whereas the 50% survival duration of the control group was 110 days. Nineteen patients with numerous metastases in the entire cavity died within 673 days, regardless of whether or not IHCP was used. CONCLUSIONS: Peritoneal carcinomatosis is not a disease beyond treatment. IHCP treatment combined with extensive surgery provides an effective and practical method of treating this disease entity.

TNF-alpha and endotoxin serum levels in cancer patients undergoing intraperitoneal hyperthermic perfusion.

Intraperitoneal hyperthermic perfusion (IPHP) is performed as one treatment for patients with advanced gastrointestinal cancer complicated by peritoneal dissemination or carcinomatous peritonitis. However, the anticancer mechanism of IPHP and its safety have not yet been fully elucidated. It has been experimentally known that endotoxinemia occurs by high body temperature, and that endotoxin stimulates the macrophage, monocyte and endothelial cell to induce the production of TNF-alpha. TNF-alpha is one of cytokines to be induced at the initial phase as a host immune response and play an important role to initiate the systemic inflammatory response syndrome (SIRS). We have tested whether the serum concentrations of TNF-alpha and endotoxin are elevated following IPHP. Eleven patients with gastro-intestinal cancer underwent surgery combined with IPHP. Mixed venous blood obtained from pulmonary artery (PA-blood) was collected at four sampling points. TNF-alpha and endotoxin levels in the PA-blood were measured by ELISA and a limulus amoebocyte lysate assay respectively. In all patients the serum TNF-alpha levels in PA-blood were temporarily elevated following IPHP from less than 10 pg/ml before IPHP to 42.8 +/- 26.6 pg/ml; endotoxin levels were not altered. This study shows that IPHP has the ability to induce endogenous TNF-alpha not mediated by endotoxin.

[Comparison of temperatures from 7 points in the patients under intraperitoneal hyperthermic perfusion].

We measured the temperatures from 7 points in the patients under intraperitoneal hyperthermic perfusion (IPHP), associated with induced hypothermia. The temperatures from the 7 points were as follows, pulmonary artery blood temperature (PAT), bladder temperature (BT), sole deep body temperature (ST), forehead deep body temperature (FT), external aural cannal temperature (EAT), esophageal temperature (ET), and rectal temperature (RT). We studied the relationship between PAT and the other 6 temperatures. During IPHP, DT rose up to nearly 40 degrees C, and we considered it very useful to judge the temperatures of the other intra-abdominal organs, which were in contact with the perfusate of IPHP. Judging from the difference of PAT and ST, ST was found useful to estimate the degree of insufficiency of the peripheral circulation. We calculated the correlation coefficients with PAT among the four points, and the order of the correlation coefficients was EAT > ET > FT > RT. EAT showed the highest correlation coefficient with PAT (r = 0.981), and we considered EAT can be a substitute for PAT during IPHP. ET also showed a high correlation with PAT (r = 0.959), but it showed an unusual rise in a case of hydrothorax with hot perfusate for IPHP. Therefore, ET cannot be used solely as a substitute for PAT, but ET can be used as a marker to find a complication of IPHP, hydrothorax.

[The hemodynamic changes during the intraperitoneal hyperthermic perfusion under induced hypothermia].

We investigated the whole body oxygen consumption (VO2) and the hemodynamic changes during the intraperitoneal hyperthermic perfusion (IPHP), which was coupled with induced hypothermia to prevent the cerebral disorder. IPHP was carried out for 90-120 min with 45-47 degrees C perfusate after the operation. We induced hypothermia using the surface cooling method and the infusion of triflupromazin. In no patient, the pulmonary artery temperature (PAT) rose above 40 degrees C. In the IPHP, there was a significant correlation between VO2 and PAT. If PAT reached 42 degrees C during the IPHP, VO2 would increase to 130-140% of the value at 37-38 degrees C. This rise is smaller than that during the total body hyperthermia (TBH), in which VO2 at 42 degrees C reached 130-190% of the value at 38 degrees C. Heart rate increased in proportion to the rising rate of body temperature. During the IPHP, PAT sometimes rose remarkably about 8 degrees C (from 32 degrees C to 40 degrees C) with a marked rise in heart rate. This rising rate of PAT is greater than that of TBH, in which PAT rose about 4-5 degrees C (from 37-38 degrees C to 42 degrees C). We consider that IPHP is not applicable to the patients with ischemic heart disease. During the rise of PAT, other circulatory parameters related to IPHP, changed in the same direction as those related to TBH. The rate of change of these parameters related to IPHP was smaller than that of the TBH, because during the IPHP the highest PAT was lower than that during TBH.