Adaptive capability as indicated by behavioral and physiological responses, plasma HSP70 level, and PBMC HSP70 mRNA expression in Osmanabadi goats subjected to combined (heat and nutritional) stressors.

A study was conducted to assess the impact of heat and nutritional stress simultaneously on the adaptive capability as indicated by behavioral and physiological responses, plasma heat shock protein 70 (HSP70) level, and peripheral blood mononuclear cells (PBMC) HSP70 gene expression in goats. Twenty-four adult Osmanabadi bucks (average body weight (BW) 16.0 kg) were used in the present study. The bucks were divided into four groups viz., C (n = 6; control), HS (n = 6; heat stress), NS (n = 6; nutritional stress), and CS (n = 6; combined stress). The study was conducted for a period of 45 days. C and HS bucks had ad libitum access to their feed while NS and CS bucks were under restricted feed (30 % intake of C bucks) to induce nutritional stress. The HS and CS bucks were exposed to solar radiation for 6 h a day between 10:00 a.m. and 4:00 p.m. to induce heat stress. The data was analyzed using repeated measures analysis of variance. The standing time differed significantly (P < 0.01) between ad libitum fed groups (C and HS) and restricted feeding groups (NS and CS). The highest (P < 0.01) lying time was recorded in the CS group while the lowest in the C and HS groups. The highest (P < 0.01) drinking frequency was also recorded in the CS group. Water intake recorded was significantly (P < 0.01) higher in both the HS and CS groups. The highest respiration rate (RR), pulse rate (PR), and rectal temperature (RT) during the afternoon were also recorded in the CS group. Further, skin temperature of the head, flank, and scrotum during the afternoon was also higher (P < 0.01) in the CS group. In addition, both plasma HSP70 concentration and PBMC HSP70 messenger RNA (mRNA) transcript expression were also significantly (P < 0.01) higher in the CS group. It can be concluded from this study that when two stressors occur simultaneously, they may have severe impact on adaptive capabilities of Osmanabadi bucks as compared to that would occur individually. Further, the study indicated that lying time, drinking frequency, RR, RT, plasma HSP70, and PBMC HSP70 gene expression may act as ideal biological markers for assessing the impact of CS on adaptive capabilities in bucks.

Preoperative chemoradiation and flap reconstruction provide high local control and low wound complication rates for patients undergoing limb salvage surgery for upper extremity tumors.

BACKGROUND AND OBJECTIVES: Neoadjuvant protocols in the management of upper extremity sarcoma have improved local control rates but have been associated with high complication rates. We present a refinement of the Eilber protocol using judicious preoperative chemoradiation, limb salvage surgery, and flap coverage to achieve high local control rates with acceptable wound healing complications. METHODS: Patients presenting with upper extremity neoplasms from 1986 to 2002 were treated with a modified Eilber protocol, consisting of 3 days of adriamycin (30 mg/day) and sequential radiotherapy (300 cGy/day for 10 days). Limb salvage surgery with flap coverage where needed was performed 4-8 weeks later. Patients were followed prospectively for recurrence. RESULTS: Fifty-three consecutive patients with upper extremity tumors were treated and followed for a mean of 6.1 years. This cohort included 44 sarcomas and nine non-metastasizing, locally aggressive tumors. There were two local recurrences (3.8%). Limb salvage was achieved in all patients. Flaps were required in 43.4% of patients. Major complications occurred in 11%, were all flap related (partial flap loss, venous congestion), and went on to heal promptly with treatment. CONCLUSION: This modified Eilber protocol achieved 96% local control for upper extremity tumors with a wound complication rate of 11%. The liberal use of flaps of resulted in healed, stable wounds in all patients.

Use of tissue expanders and pre-operative external beam radiotherapy in the treatment of retroperitoneal sarcoma.

INTRODUCTION: We report our experience of treating retroperitoneal sarcoma (RPS) using pre-operative external beam radiotherapy (EBRT) in combination with radical resectional surgery from 1990 to 2005. METHODS: Twenty-eight primary and 10 recurrent tumors were identified from a prospective database. RESULTS: The resection rate was 71% overall; 82% in primary (23/28) and 40% (4/10) in recurrent cases. EBRT was administered preoperatively in 25 patients, postoperatively in 1, and palliatively in 11. In 33 patients a saline-filled tissue expander was inserted into the abdomen before radiotherapy to displace small bowel from the radiation field. 4,500-5,000 cGy was administered in fractions of 180-200 cGy over a 5-week period; surgery followed 6-8 weeks later. Expander insertion was associated with minimal morbidity; 31/37 patients received a dose of 4,000 cGy or more (median 4,650 cGy). Median resected tumor diameter was 13 cm, and a median of three adjacent organs was resected per patient. Complete macroscopic resection was achieved in 25/27 patients (93%); R0 in 9 (33%) and R1 in 13 (48%) (microscopic margins unclear in 5). There was no postoperative mortality. Tumors were high-grade in 20 patients, low-grade in 14 and ungraded in 4. Actuarial 5- and 10-year survival for all patients was 74 and 60%. For operable primary tumors, the 5-year survival and disease-free rates were 90 and 80%. In four patients with operable recurrent tumors, median disease-free interval was 91 months (27-160). In the 11 inoperable cases, median survival after radiotherapy was 48 months (9-77). CONCLUSIONS: We conclude that a combination of pre-operative tissue expander placement, high-dose EBRT and radical resectional surgery can achieve acceptable morbidity, extended survival and low long-term recurrence in patients with RPS. STATISTICS: Median (interquartile range).

Implications of radiation dosimetry of the mandible in patients with carcinomas of the oral cavity and nasopharynx treated with intensity modulated radiation therapy.

Intensity modulated radiation therapy (IMRT) is a newer method of delivering highly conformal, salivary gland sparing radiation treatment that is finding increasing applications in head and neck malignancies. However, the radiation dose distribution to the mandible is rarely considered with IMRT, and the potential risks of osteoradionecrosis or osseointegrated implant failure are not well characterized for this modality. In a series of 10 patients with oral cavity and nasopharyngeal cancers who previously underwent IMRT, examination of the three-dimensional mandibular dose distribution was undertaken. The findings indicate a modest potential risk of osteoradionecrosis and osseointegrated implant failure in cases where IMRT optimization constraints are not specifically aimed at sparing the mandibular bone. Significantly higher mandibular doses (P < 0.04) were received in cases of oral cavity as opposed to nasopharyngeal cancers with IMRT. Efforts to optimize IMRT to further reduce doses to the mandible should be considered, and development of software tools to integrate three-dimensional dose distributions into planning of post-radiotherapy osseointegration would be beneficial.

Groin soft tissue tumors--a challenge for local control and reconstruction: a prospective cohort analysis.

BACKGROUND AND OBJECTIVES: Groin soft tissue tumors are associated with high local recurrence rates of 16-48% and postoperative complications in 40-68%. Neoadjuvant chemoradiation and aggressive reconstructive techniques were utilized to improve local control and complication rates in this challenging area. METHODS: Nine patients in this prospective series were treated with neoadjuvant chemoradiation (30 mg IV doxorubicin x 3d followed by 300 cGy/d x 10d) followed by surgery and two patients received radiation (5,000 cGy with tissue spacer) followed by surgery for tumors with a pelvic/retroperitoneal component. Surgery included resection plus reconstruction of the abdominal wall, myocutaneous flaps for large defects, and vascular reconstruction as necessary. RESULTS: The 11 consecutive patients presented with Stage I (30%), II (40%), or III (30%) disease. Four patients (36%) were operated on for possible incarcerated hernia prior to referral and two (18%) presented with recurrent tumors. Pathology included 10 sarcomas and 1 desmoid tumor; tumor grade was low (30%), moderate (40%), or high (30%). Local control (mean follow-up 55 months; minimum follow-up 36 months) and limb salvage rate was 100%. Minor wound complications not requiring re-operation occurred in three patients, lymphedema in two, and there were no postoperative hernias. CONCLUSIONS: Preoperative therapy provides excellent local control of groin soft tissue tumors. Current surgical techniques allow extensive resection with limb salvage, dependable primary wound healing and long-term integrity of the abdominal wall.

Heat shock protein immunoreactivity in CSF: correlation with oligoclonal banding and demyelinating disease.

The detection of raised immunoglobulin and the presence of oligoclonal bands (OCBs) on electrophoresis of multiple sclerosis (MS) CSF has been a useful diagnostic test, but a universal antigen to which these MS antibodies are directed has yet to be found. Potentially immunogenic heat shock proteins (HSPs) are preferential expressed in vitro in human oligodendrocytes compared with other glia, and in situ in oligodendrocytes found within the plaques of MS. Immunoreactivity directed against HSPs might therefore contribute to the immune-mediated demyelinating process found in MS. We examined this possibility by quantitatively (ELISA) measuring antibodies directed against a recombinant human HSP (HSP60) in CSF from 18 MS patients, and compared them with eight patients with acute disseminated encephalomyelitis, 12 with demyelinating peripheral neuropathies, and 59 with other neurologic diseases. Immunoblotting was used to confirm the specificity of the antibodies for binding to HSP60. We found a statistically significant correlation between antibody titers to HSP60 and the presence of OCBs in CSF. These results support the notion that HSP expression in the CNS, such as that observed in MS, may be immunogenic, leading to localized HSP antibody secretion. Such HSP-directed immunoreactivity could play a role in the pathogenesis of MS and other immune-mediated disorders of the nervous system.