Vitamin E succinate inhibits colon cancer liver metastases

BACKGROUND: Vitamin E succinate (VES) is a promising anti-cancer micronutrient. In this study, we tested the hypothesis that VES will promote colon cancer tumor dormancy and inhibit liver metastases in colon cancer. METHODS: CT-26 colon cancer cells were treated with VES in vitro and in an in vivo model of liver metastases. The impact of VES on cellular proliferation and apoptosis was measured in vitro by MTS assay and sandwich ELISA and in vivo by PCNA staining and TUNEL assay, respectively. Correlation coefficients and independent t tests were used for statistical analysis. RESULTS: VES significantly and specifically inhibited cell proliferation (P = 0.011) and promoted apoptosis (P < 0.0074) of cancer cells in vitro. VES produced a 40% reduction of liver metastases (P = 0.037). Five of the eight mice had an excellent response to VES. Subsequent analysis of these five mice revealed a 75% reduction in the number of liver metastases (P < 0.05). VES significantly promoted tumor cell apoptosis (P < 0.0003) and inhibited cell proliferation (P = 0.0069) in vivo. CONCLUSIONS: VES inhibits the growth of colon cancer cells in vitro and in vivo. This is the first report of VES inhibition of colon cancer tumor metastases. The mechanism of VES anti-tumor and anti-metastatic activity in vivo appears to involve promotion of tumor apoptosis and inhibition of cell proliferation. These findings support further investigation of VES as a micronutrient to promote colon cancer tumor dormancy and prevent metastases.     

Prehospital Index: a scoring system for field triage of trauma victims

The Prehospital Index (PHI) is a triage-oriented trauma severity scoring system comprising four components: systolic blood pressure, pulse, respiratory status, and level of consciousness, each scored 0 to 5. The PHI was developed after analysis of 313 cases to provide an objective prehospital scoring system for distinguishing less seriously injured patients (minor trauma) from those patients who are likely to die within 72 hours after injury or who require general or neurosurgical operative intervention within 24 hours (major trauma). A PHI of 0 to 3 indicated minor trauma, and a PHI of 4 to 20 signified major trauma. Retrospective analysis of an additional 465 consecutive trauma cases revealed that patients with a PHI of 0 to 3 (minor trauma) had a 0% mortality and a 2% rate of general or neurosurgical operative intervention. Those with a PHI of 4 to 20 (major trauma) carried a 16.4% mortality and an emergency operative rate of 49.1%. The PHI was applied prospectively to 388 consecutive trauma cases presenting to the Butterworth Hospital Emergency Department from October through December 1984. Of the 351 patients scored as minor trauma in the field, there was a 0% mortality and only a 0.3% operative rate. Those scored as major trauma in the field had a mortality of 27% (PHI 4 to 7, 0%; PHI 8 to 20, 53%) and an operative rate of 40.5% (PHI 4 to 7, 22%; PHI 8 to 20, 57.9%). These data demonstrate the ability of the PHI to predict mortality (P less than .001) and the need for emergency general or neurosurgical operative intervention (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)     

A pilot study evaluating the effect of mindfulness-based stress reduction on psychological status, physical status, salivary cortisol, and interleukin-6 among advanced-stage cancer patients and their caregivers

Purpose: To investigate whether a mindfulness-based stress reduction program for cancer (MBSR-C) improved psychological and physical symptoms, quality of life (QOL), and stress markers among advanced-stage cancer patients and caregivers. Design: A pilot within-subject design was used. Method: Patients previously diagnosed with advanced-stage breast, colon, lung, or prostate cancer and on treatment were recruited from the Moffitt Cancer Center and Research Institute. Twenty-six patient-caregiver dyads completed a modified 6-week, self-study MBSR-C program based on the Kabat-Zinn model. Psychological and physical symptoms and QOL were compared pre- and post-MBSR-C sessions. Salivary cortisol and interleukin-6 were assessed pre- and post-MBSR-C session at 1, 3, and 6 weeks. Findings: Following the 6-week MBSR program, patients showed improvements in stress and anxiety (p < .05); caregivers' psychological and QOL also improved but were not statistically significant. Both patients and caregivers had decreases in cortisol at Weeks 1 and 3 (p < .05) but not at Week 6. Similar to cortisol levels at Week 6, salivary interleukin-6 levels were lower overall (before/after an MBSR-C session), compared with Week 1 for patients and caregivers. Conclusions: MBSR-C may be a beneficial intervention for reducing stress, anxiety, cortisol levels, and symptoms in advanced-stage cancer patients and may also benefit caregivers.     

Outcomes of resected pancreatic cancer in patients age ≥70

Objective

To determine outcomes of patients ≥70 years with resected pancreatic cancer.

Methods

A study was conducted to identify pancreatic cancer patients ≥70 years who underwent surgery for pancreatic carcinoma from 2000 to 2012. Patients were excluded if they had neoadjuvant therapy. The primary endpoint was overall survival (OS).

Results

We identified 112 patients with a median follow-up of surviving patients of 36 months. The median patient age was 77 years. The median and 5 year OS was 20.5 months and 19%, respectively. Univariate analysis (UVA) showed a significant correlation for increased mortality with N1 (P=0.03) as well as post-op CA19-9 >90 (P<0.001), with a trend towards decreased mortality with adjuvant chemoradiation (P=0.08). Multivariate analysis (MVA) showed a statistically significant increased mortality associated with N1 (P=0.008), post-op CA19-9 >90 (P=0.002), while adjuvant chemoradiation (P=0.04) was associated with decreased mortality.

Conclusions

These data show that in patients ≥70, nodal status, post-op CA19-9, and adjuvant chemoradiation, were associated with OS. The data suggests that outcomes of patients ≥70 years who undergo upfront surgical resection are not inferior to younger patients.     

Combining muscle-sparing serratus flap with acellular dermal matrix in immediate breast reconstruction

Background

Submuscular placement of tissue expanders is a common method of reconstruction in the postmastectomy patient. Though the pectoralis muscle provides ample coverage of the expander superomedially, it is insufficient for complete coverage. Inferior coverage has been described using both local muscle and fascial flaps as well as the more recently introduced acellular dermal matrix (ADM). Each method possesses advantages and disadvantages, while the use of both in conjunction may serve to provide a superior, cost-effective result.

Methods

A retrospective review was undertaken of all patients undergoing immediate breast reconstruction from January 2008 to December 2011. Patients who underwent reconstruction with the use of combined ADM and muscle-sparing serratus flap were selected for further review. A total of 16 patients (27 reconstructed breasts) were identified. Data were collected regarding patient demographics, operative details, and complications.

Results

Of the 16 patients, 6 received postoperative radiation and 9 received perioperative chemotherapy. Mean follow-up was 20.8 months. A single 8?×?16-cm sheet of ADM was sufficient for bilateral reconstruction. Complications included infection (three patients), mastectomy flap necrosis (two patients), expander exposure (one patient), wound dehiscence (one patient), hematoma (one patient), and seroma (one patient). There were no cases of capsular contracture. All patients were noted to have sufficient lateral fullness and optimal contour.

Conclusions

Combined use of a muscle-sparing serratus anterior flap with ADM is a safe and viable method of complete inferior expander coverage in immediate breast reconstruction, which has not yet been described in the literature. Potential advantages include decreased donor site morbidity, improved lateral fullness, and greater efficiency in ADM use. Level of Evidence: Level IV, therapeutic study.     

Complications of hepatic artery infusion

Purpose: The resurgence of hepatic artery infusion (HAI) for the treatment of colorectal liver metastases has been dampened by concern over its complications. We have reviewed the incidence and frequency of complications associated with HAI and discussed the factors associated with these complications. Methods: A PUBMED search was conducted from 1950–2001 using various combinations of these keywords: hepatic arterial infusion, colorectal carcinoma, complications, and trials. The main inclusion criterion was the reporting of HAI complications. The main exclusion criterion was duplicated patients. Extracted data included chemotherapeutic agents, catheter technique, drug toxicities, and catheter related complications. Relative risks and 95% confidence intervals were calculated. Results: We reviewed 437 articles/abstracts and included 101 studies. 4580 patients with 4582 toxicities and complications were reported. The mortality rate was 1%. The most common toxicities were: GI symptoms 22%, chemical hepatitis 19%, and bone marrow toxicity 8%. 5-fluorouracil (5-FU) HAI had statistically significant risk for GI symptoms and bone marrow toxicity. Floxuridine (FUDR) HAI had statistically significant risk for chemical hepatitis, sclerosing cholangitis, and biliary toxicity. The most common catheter complications were: hepatic artery occlusion 6%, catheter thrombosis 5%, and catheter displacement 7%. Conclusions: This literature review of the complications of HAI confirms a low mortality associated with HAI. Sclerosing cholangitis and chemical hepatitis are associated with the use of FUDR, while the use of 5-FU is associated with bone marrow toxicity. Our observations support the development of hepatic cytoprotective agents and other effective anti-tumor agents to improve the results and morbidity of HAI for colorectal liver metastases.     

Histopathologic tumor response after induction chemotherapy and stereotactic body radiation therapy for borderline resectable pancreatic cancer

Background

While clinical outcomes following induction chemotherapy and stereotactic body radiation therapy (SBRT) have been reported for borderline resectable pancreatic cancer (BRPC) patients, pathologic response has not previously been described.

Methods

This single-institution retrospective review evaluated BRPC patients who completed induction gemcitabine-based chemotherapy followed by SBRT and surgical resection. Each surgical specimen was assigned two tumor regression grades (TRG), one using the College of American Pathologists (CAP) criteria and one using the MD Anderson Cancer Center (MDACC) criteria. Overall survival (OS) and progression free survival (PFS) were correlated to TRG score.

Results

We evaluated 36 patients with a median follow-up of 13.8 months (range, 6.1-24.8 months). The most common induction chemotherapy regimen (82%) was GTX (gemcitabine, docetaxel, capecitabine). A median SBRT dose of 35 Gy (range, 30-40 Gy) in 5 fractions was delivered to the region of vascular involvement. The margin-negative resection rate was 97.2%. Improved response according to MDACC grade trended towards superior PFS (P=061), but not OS. Any neoadjuvant treatment effect according to MDACC scoring (IIa-IV vs. I) was associated with improved OS and PFS (both P=0.019). We found no relationship between CAP score and OS or PFS.

Conclusions

These data suggest that the increased pathologic response after induction chemotherapy and SBRT is correlated with improved survival for BRPC patients.     

Vitamin E inhibits melanoma growth in mice.

BACKGROUND: Previous work has demonstrated that vitamin E succinate (VES), an ester analogue of vitamin E, inhibits the growth of melanoma in vitro. However, there is no information about the effect of VES on melanoma in vivo. We investigated the effect of VES on melanoma in vitro and in vivo. METHODS: The effect of VES on the proliferation and apoptosis of the B16F10 murine melanoma cell line was determined by a modified Cell Titer 96 AQ assay and a cell death detection enzyme-linked immunosorbent assay, respectively. The in vivo effect of VES on B16F10 melanoma cells allografted in athymic nude mice was investigated. The mechanism of the in vivo antitumor effect of VES was determined by immunohistochemical detection of proliferation and apoptosis. RESULTS: VES decreased cell proliferation (P =.0001) and increased cell apoptosis (P =.0001) in a dose-dependent manner in vitro. Also, VES significantly inhibited melanoma growth in mice (P =.0013). The VES antitumor effect in vivo was associated with a significant increase in the melanoma apoptosis rate (P =.0256). CONCLUSIONS: This is the first report of the antimelanoma effect of VES in vivo. The mechanism of the antimelanoma effect of VES in vivo involves the promotion of tumor cell apoptosis. These findings support future investigations of VES as a therapeutic micronutrient against melanoma.