Survival benefit of surgical resection after first-line triplet chemotherapy and bevacizumab in patients with initially unresectable metastatic colorectal cancer.

BACKGROUND: Surgical resection of metastatic disease in patients with initially non-resectable colorectal cancer (CRC) has improved overall survival. Intensified chemotherapy regimens have increased the probability of converting unresectable metastasis to resectable. Here, we report the result of combining intensive chemotherapy (triplet) and surgical resection of metastatic lesions in patients with metastatic CRC. PATIENTS AND METHODS: Patients with unresectable metastatic CRC were enrolled in phase I/II trial of triplet chemotherapy consisting of capecitabine, oxaliplatin, irinotecan, and bevacizumab. Patients were given 5-8 cycles induction chemotherapy of the above regimen followed by maintenance capecitabine and bevacizumab until disease progression, unacceptable toxicity, or patient request. All patients were assessed at a multidisciplinary conference for possible surgical resection of their metastatic disease at the time of inclusion in the trial and 2 monthly intervals thereafter. Patients who underwent R0 resection of their metastatic disease received adjuvant oxaliplatin and capecitabine to complete a total of 6 months of chemotherapy. RESULTS: Fifty-three patients were enrolled. The median age was 52 years (range 23-74), 29 (55%) were males, ECOG PS 0-1 was 13 (66%), 11 (42%) had a right-sided tumor, 29 (55%) had resection of their primary tumor, 22 (42%) had a single metastatic site, and 8 (15.1%) had a liver-limited disease. Thirteen patients (24.5%) underwent surgical resection of residual metastatic disease +/- the primary tumor with 10 (18.9%) of them were R0. The surgical group had a higher incidence of males compared to the non-surgical group (69.3% vs 47.2%, p = 0.2), equal performance status, lower median number of metastatic sites (1 vs 2, p = 0.09), higher mutant Kras (53.8% vs 34.2%, p = 0.3), and higher response rate (84.6% vs 56.2%, p = 0.3). With a median follow-up duration of 89 months, the median PFS for the whole group was 16.1 months [95% confidence interval (CI) 9.1-20] and the median OS was 28.2 months (95% CI 22.5-53.3). The median PFS for the surgery group was 18.9 months (95% CI 12.6-not reached) compared to 9.6 months (95% CI 7.0-18.3) for the non-surgical group, log-rank p = 0.0165. The median OS for both groups was not reached (95% CI 53.3-not reached) and 23.2 months (95% CI 17.0-28.4) respectively, log-rank p = 0.0006. Five-year PFS and OS for the surgery group were 46.2% and 67.6% respectively. CONCLUSIONS: Patients with unresectable metastatic CRC and fit for triplet chemotherapy should have the benefit of combining this intensified regimen and surgical resection of their metastatic disease if possible. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01311050 , registered March 6, 2011, retrospectively registered.

Incidence of leukopenia and thrombocytopenia with cisplatin plus mitomycin-c versus melphalan in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

INTRODUCTION: Cytopenia after hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported in non-comparative studies with various chemotherapeutic regimens. This study compared the incidence of leukopenia and thrombocytopenia in patients who underwent CRS/HIPEC and received melphalan or cisplatin plus mitomycin-c (CIS + MMC). METHODS: This retrospective study included patients who underwent CRS/HIPEC at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from March 2011 to March 2017 and received melphalan 60 mg/m2 or CIS 100 mg/m2 combined with MMC 30 mg/m2. Incidences and severity of leukopenia, neutropenia, thrombocytopenia, and anemia were compared between groups. RESULTS: This study included 46 patients who received CIS + MMC and 35 patients who received melphalan. The leukopenia incidence was 25.7% in the melphalan group and 17.3% in the CIS + MMC group (P = 0.362), with one patient (2.8%) in the melphalan group developed grade V leukopenia. The number of days to leukocyte nadir was 32.8 days for CIS + MMC group compared to 9.8 days for melphalan group(P = 0.035). Thrombocytopenia occurred at a similar rate in the melphalan (60%) and CIS + MMC (68.8%) groups (P = 0.4). Grade III thrombocytopenia developed in 3.2% and 5% of patients in the melphalan and the CIS + MMC groups, respectively. Neutropenia did not occur in any patient. In multivariate analysis, leukopenia predictors were female gender (P = 0.047) and baseline leukocyte counts (P = 0.029). Baseline platelet count predicted thrombocytopenia (P < 0.001). CONCLUSIONS: Melphalan and CIS + MMC regimens were associated with comparable incidences of leukopenia and thrombocytopenia. Severe leukopenia and severe thrombocytopenia were rare following CRS/HIPEC using both chemotherapy regimens.

Knowledge, attitude, and belief regarding burn first aid among caregivers attending pediatric emergency medicine departments.

BACKGROUND AND OBJECTIVES: Emergency departments witness many cases of burns that can be prevented with various first-aid measures. Immediate and effective burn first aid reduces morbidity and determines the outcome. Thus, it is imperative that measures of primary burn prevention and first-aid knowledge be improved. This descriptive study determines the current level of knowledge, attitude, and belief regarding burn first aid among caregivers. MATERIALS AND METHODS: Caregivers attending four pediatric emergency departments answered a structured questionnaire for demographic information, knowledge, and the burn first aid they provide including two case scenarios. Applying cold water for 15-20min, smothering burning clothes, and covering the pot of oil on fire with a wet cloth were considered appropriate responses. The main outcome measure was the proportion of caregivers who were aware of burn first aid and did not use inappropriate remedies. Additional questions regarding the best means of educating the public on burn first aid were included. Individual chi-squared tests and univariate logistic regressions were performed to correlate knowledge with demographic features, history of burns, and first-aid training. RESULTS: The 408 interviewed caregivers (55% women) reflected a wide range of age, occupation, and educational level. Sixty percent (60%) of respondents had a large family, with 52% reporting a history of burns. Overall, 41% treated burns with cool or cold water, although 97% had inappropriate or no knowledge of the duration. Further, 32% treated burns with nonscientific remedies alone or in combination, including honey, egg white, toothpaste, white flour, tomato paste, yogurt, tea, sliced potato, butter, or ice. Only 15% had first-aid training. While 65% of caregivers covered a pot of oil on fire with a wet cloth, only 24% reported smothering burning clothes. Participants preferred learning more of first aid for burns via social media (41%), hospital visits (30%), and television (TV) (16%). No significant correlation was found between age, family size, language, history of burns, or training and knowledge; however, female gender and higher educational level were associated with increased awareness, although this was not statistically significant (p=0.05 and p=0.17, respectively). The logistic regression accounting for all significant variables showed that the history of burns had the greatest effect on knowledge of first aid (p<0.03). CONCLUSION: Knowledge of burn first aid among caregivers is limited, with many resorting to non-scientific remedies. Use of social media, hospital visits, and TV for first-aid education might improve caregivers' awareness. A nationwide educational program emphasizing first-aid application of only cold water and reduced use of inappropriate home remedies for burns is recommended.

Glucocorticoids do not protect against the lethal effects of experimental heatstroke in baboons.

The mortality and neurological morbidity in heatstroke have been attributed to the host's inflammatory responses to heat stress, suggesting that anti-inflammatory therapy may improve outcome. We tested the hypothesis that a high dose of dexamethasone protects baboons against the lethal effects of heatstroke. Ten anesthetized baboons (Papio hamadryas) were assigned randomly to dexamethasone (n = 5) or control group (n = 5). Dexamethasone (2 mg/kg i.v.) was administered in four divided doses every 6 h starting immediately before heat stress and continuing during cooling. All animals were heat-stressed in a prewarmed neonatal incubator at 44 degrees C to 47 degrees C until systolic blood pressure fell less than 90 mmHg and then cooled passively at the ambient temperature. Mortality and neurological morbidity were noted, and biochemical markers of tissue injury/organ dysfunction were determined. Circulating interleukin (IL) 6 and complement components (C3 and C4) were measured sequentially. All heat-stressed animals had systemic inflammation indicated by increased plasma IL-6 and decreased C3 and C4 levels. Dexamethasone attenuated the complement system activation and maintained a higher plasma concentration of IL-6, with a significant augmentation of arterial blood pressure. Dexamethasone did not prevent the occurrence of severe heatstroke but unexpectedly aggravated significantly the tissue injury and multiorgan system dysfunction. Two animals (40%) in the control group and one in the steroid group survived (P > 0.05). Dexamethasone failed to protect the baboons from the lethal effects of heatstroke. These results do not support clinical testing of corticosteroids as beneficial in preventive or therapeutic strategies for the treatment of heatstroke in humans.