Small bowel dose parameters predicting grade ≥ 3 acute toxicity in rectal cancer patients treated with neoadjuvant chemoradiation: an independent validation study comparing peritoneal space versus small bowel loop contouring techniques.

PURPOSE: To determine whether volumes based on contours of the peritoneal space can be used instead of individual small bowel loops to predict for grade ≥3 acute small bowel toxicity in patients with rectal cancer treated with neoadjuvant chemoradiation therapy. METHODS AND MATERIALS: A standardized contouring method was developed for the peritoneal space and retrospectively applied to the radiation treatment plans of 67 patients treated with neoadjuvant chemoradiation therapy for rectal cancer. Dose-volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. RESULTS: Grade ≥3 small bowel toxicity occurred in 16% (11/67) of patients in the study. A highly significant dose-volume relationship between small bowel irradiation and acute small bowel toxicity was supported by the use of both small bowel loop and peritoneal space contouring techniques. Receiver operating characteristic analysis demonstrated that, for both contouring methods, the greatest sensitivity for predicting toxicity was associated with the volume receiving between 15 and 25 Gy. CONCLUSION: DVH analysis of peritoneal space volumes accurately predicts grade ≥3 small bowel toxicity in patients with rectal cancer receiving neoadjuvant chemoradiation therapy, suggesting that the contours of the peritoneal space provide a reasonable surrogate for the contours of individual small bowel loops. The study finds that a small bowel V15 less than 275 cc and a peritoneal space V15 less than 830 cc are associated with a less than 10% risk of grade ≥3 acute toxicity.

Dose-volume histogram predictors of chronic gastrointestinal complications after radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer.

PURPOSE: The purpose of this study was to evaluate dose-volume histogram (DVH) predictors for the development of chronic gastrointestinal (GI) complications in cervical cancer patients who underwent radical hysterectomy and postoperative concurrent nedaplatin-based chemoradiation therapy. METHODS AND MATERIALS: This study analyzed 97 patients who underwent postoperative concurrent chemoradiation therapy. The organs at risk that were contoured were the small bowel loops, large bowel loop, and peritoneal cavity. DVH parameters subjected to analysis included the volumes of these organs receiving more than 15, 30, 40, and 45 Gy (V15-V45) and their mean dose. Associations between DVH parameters or clinical factors and the incidence of grade 2 or higher chronic GI complications were evaluated. RESULTS: Of the clinical factors, smoking and low body mass index (BMI) (<22) were significantly associated with grade 2 or higher chronic GI complications. Also, patients with chronic GI complications had significantly greater V15-V45 volumes and higher mean dose of the small bowel loops compared with those without GI complications. In contrast, no parameters for the large bowel loop or peritoneal cavity were significantly associated with GI complications. Results of the receiver operating characteristics (ROC) curve analysis led to the conclusion that V15-V45 of the small bowel loops has high accuracy for prediction of GI complications. Among these parameters, V40 gave the highest area under the ROC curve. Finally, multivariate analysis was performed with V40 of the small bowel loops and 2 other clinical parameters that were judged to be potential risk factors for chronic GI complications: BMI and smoking. Of these 3 parameters, V40 of the small bowel loops and smoking emerged as independent predictors of chronic GI complications. CONCLUSIONS: DVH parameters of the small bowel loops may serve as predictors of grade 2 or higher chronic GI complications after postoperative concurrent nedaplatin-based chemoradiation therapy for early-stage cervical cancer.

Resident peritoneal inflammatory cells are pivotal in the development of experimental atherosclerosis.

AIM: Based on evidence that ionizing radiation can ameliorate chronic and autoimmune diseases in patients and experimental animals, we investigated the effects of radiation on the induction and development of experimental atherogenesis. METHODS: Male New Zealand rabbits were divided into 5 groups and given an atherogenic diet for 90 days. Peritoneal and thoracic areas (9 Gy) were irradiated on the 1st and 45th days for groups 1 and 2, the 45th day for groups 3 and 4, and not at all for group 5. Prior to irradiation, the peritoneal cavity of animals from groups 1 and 3 was washed with buffered saline. Cells collected by peritoneal washing were reinfused into the peritoneal cavity of the same animal after irradiation. Animals from groups 2 and 4 were intraperitoneally injected with saline as a control. RESULTS: Despite similar lipid profiles among the experimental groups, the percentage of aortas covered by plaques was remarkably reduced (p<0.001) among animals submitted to irradiation (groups 2 and 4). These differences were completely abolished in irradiated animals reconstituted with their own peritoneal cells. CONCLUSIONS: These findings point to an important role of resident inflammatory peritoneal cells in experimental atherogenesis.

Functional phenotype of macrophages depends on assay procedures.

Macrophages display different phenotypes that can switch in response to their micro-environment. In our earlier study (Chiang, C. S., Liu, W. C. and Jung, S. M., 2005. Compartmental responses after thoracic irradiation of mice: strain differences. Int. J. Radiat. Oncol. Biol. Phys. 62:862) on radiation-induced cytokine expression in lung lavage samples, there was a suggestion that the procedures used to harvest lung macrophages affected the profiles they expressed. To further explore this issue, we examined gene expression by cell populations, mainly macrophages, isolated by lavage from lung and peritoneal cavity following either in vivo or in vitro stimulation with LPS, IFN-gamma or irradiation. We found that expression of mRNA for tumor necrosis factor-alpha, IL-1 alpha/beta and IL-6 varied several fold depending on whether the assay was performed on cells immediately after isolation or after in vitro manipulation. The relative level of inducible nitric oxide synthase (iNOS) to arginase I (Arg I), which is frequently used as index of the M1 versus M2 functional macrophage phenotype, also varied. LPS stimulation in vivo was able to change the profile from Arg I expression to one where the iNOS pathway became dominant, but was unable to do this in vitro. This contrasts with the ability of IFN-gamma to generate an iNOS-dominant pathway in vitro, but not in vivo. This study cautions that the expression of inflammatory cytokines and the iNOS to Arg I ratio, which is often used as an index of their functional capacity, varies with the experimental conditions.

Cutting edge: inherent and acquired resistance to radiation-induced apoptosis in B cells: a pivotal role for STAT3.

Radiation-induced apoptosis (RiA) is used therapeutically for tumor cell ablation as well as a tool to characterize hemopoietic cell lineages. We report that the peritoneal B-1 B cell subset is selectively resistant to RiA. Inherent radioresistance is not shared by splenic B-2 or B-1 cells. However, it is conferred upon B-2 cells by BCR crosslinking in the presence of IL-6 or IL-10. In vivo experiments with gene-targeted mice confirm that IL-6 and, to a lesser extent, IL-10 are the relevant stimuli that combine with BCR ligands to promote B-1 cell radioresistance. STAT3 promotes cell survival in response to selected growth factors, and is activated by combined BCR crosslinking and IL-6 (IL-10). Importantly, STAT3(-/-) B-1 cells become susceptible to irradiation, indicating that STAT3 activation by the BCR in the presence of IL costimuli account for the inherent radioresistance of peritoneal B-1 B cells.

White-light toxicity, resulting from systemically administered 5-aminolevulinic acid, under normal operating conditions.

This study has investigated damage to the intraperitoneal organs of the rat after systemic (intraperitoneal and intravenous) administration of low doses of 5-aminolevulinic acid (ALA) and illumination with a standard white-light operating-room (o.r.) lamp. The study has been done within the framework of a larger study in which the possibility of using ALA for localization of small-volume macroscopically nonvisible peritoneal metastasis of ovarian tumors is being investigated. Fluorescence diagnostics are done in addition to the standard staging and localization procedures, either through a laparoscope or during laparotomy. In these circumstances, fluorescence diagnostics involve some risk of photosensitization of critical organs since a broad-band (o.r.) light source is used during the surgical procedures for illumination of the operating area. The drug dose and the time interval between administration of ALA and illumination are varied and normal tissues are examined both macroscopically and microscopically for damage. A relationship is demonstrated between the maximum tolerable dose (MTD) of ALA (defined as the dose that does not cause any tissue damage) and the time interval between administration and illumination. The white light that is used for illumination of the operating area is sufficient to induce damage to the peritoneal organs at relatively low ALA doses. The MDTs for 2, 6 and 16 h intervals are found to be respectively 1, 10 and 100 mg kg-1. The results are similar for both intraperitoneal and intravenous administration.

Intraperitoneal photodynamic therapy: comparison of red and green light distribution and toxicity.

The aim of this study was to compare red (652 nm) and green (514 nm) light for photodynamic therapy (PDT) of the peritoneal cavity with emphasis on light distribution and toxicity. Red-light PDT was limited by intestinal toxicity and it was hypothesized that less penetrating green light would allow higher light doses to be used in the peritoneal cavity. Female non-tumor-bearing rats were photosensitized with mTHPC (meta-tetrahydroxyphenylchlorin, Foscan) intravenously or intraperitoneally and the peritoneum was illuminated using a minimally invasive technique. For both red and green light, the time of illumination was varied to give the required dose. Light fluence rate was measured in situ at multiple sites within the abdominal cavity. The toxicity experiments were carried out with a total of 160 J incident red or 640 J incident green light and a drug dose of 0.15 mg/kg Foscan. For red light a mean fluence rate of 55.2 +/- 38.5 mW cm-2 was measured, with a peak fluence rate of 128 mW cm-2 on the intestines. For green light the mean and peak fluence rates were 8.2 +/- 9.0 (i.e. including zero fluence rate measurements) and 28 mW cm-2, respectively. Intestines were most vulnerable to red light illumination. The intravenous injection route resulted in increased toxicity for red light, but for green light there were no major differences between intravenous and intraperitoneal routes. The 4 h interval between drug and illumination resulted in very little toxicity for both wavelengths. We conclude that for intraperitoneal PDT green light allows higher light doses than red light, but the light distribution over the peritoneum is much less favorable and may not be suitable for whole peritoneal illumination using a minimal-access technique.

Complications associated with intraperitoneal 32P.

The charts of all patients having received intraperitoneal 32P in the Indiana University Department of Radiation Oncology were retrospectively reviewed for complications and potentially related factors. Ninety-five patients had received this therapy, with a mean follow-up of 43.6 months. The majority of patients (81) had ovarian cancer. Complications were defined as mild if no intervention was required, moderate if medical intervention was required, and severe if the event was life-threatening or required surgical correction. Twenty patients (21%) had acute side effects recorded, with 15 of them (16%) being mild. The moderate complications (five patients) consisted of three cases of bowel obstruction, and two cases of abdominal pain requiring narcotics. There were no severe acute side effects. Chronic complications were found in 15 patients (20% actuarial 5-year incidence). Seven cases were mild (12% 5-year incidence), one was moderate (1%), and seven cases were classified as severe (7.4% 5-year incidence). All moderate and severe cases were bowel obstructions. Acute side effects were found to be related only to the volume of instillate (P = 0.049). Chronic complications were found to be related only to adjunctive pelvic/abdominal radiotherapy, with a 44% 5-year rate in patients receiving the combination having complications vs 17% (P = 0.04) (or 4.7% if mild complaints are excluded, P = 0.002) of those with 32P only. Comparison is made to other reports in the literature.

[Low-intensity laser irradiation in the combined treatment of suppurative peritonitis]. / Nizkointensivnoe lazernoe izluchenie v kompleksnom lechenii gnoinogo peritonita.

The results of treatment of 32 patients with diffuse forms of purulent peritonitis are analyzed. Prolonged laparoscopic sanitation of the peritoneal cavity, combined with He-Ne laser irradiation of the peritoneum and parenchymatous organs, were effectively used in the complex of therapeutic measures. For immunity stimulation intravascular laser irradiation of the blood was carried out. The terms of normalization of local inflammatory shifts in the peritoneum shortened and the number of lethal outcomes decreased. Prospects for the use of this method are outlined.

An autopsy case of peritoneal malignant mesothelioma in a radiation technologist.

A case of peritoneal malignant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, well developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane-bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mesothelioma.

Radiation therapy in the management of ovarian cancer.

The present review of selected clinical trials of the use of radiotherapy in ovarian cancer indicates that this modality has a curative role in postoperative treatment. Techniques which encompass the entire peritoneal cavity produce superior survival rates and better control of occult upper abdominal metastasis than the techniques which treat only part of the peritoneum. The volume of residual tumour, its pathology subtype and grade, and the presenting stage each independently influence the outcome of therapy. An approach to planning treatment which considers all of these variables is presented. No long-term survival data exist to permit a comparison of the relative efficacies of abdominopelvic irradiation and cisplatin-based combination chemotherapy regimes, but a rational strategy for choice of treatment can be devised. Combined modality therapy is an important area for future study.