Vasculogenic stem cell mobilization and wound recruitment in diabetic patients: Increased cell number and intracellular regulatory protein content associated with hyperbaric oxygen therapy

Diabetic patients undergoing hyperbaric oxygen therapies (HBO₂T) for refractory lower extremity neuropathic ulcers exhibit more than a twofold elevation (p=0.004) in circulating stem cells after treatments and the post‐HBO₂T CD34⁺ cell population contains two‐ to threefold higher levels of hypoxia inducible factors‐1, ‐2, and ‐3, as well as thioredoxin‐1 (p<0.003), than cells present in blood before HBO₂T. Skin margins obtained from 2‐day‐old abdominal wounds exhibit higher expression of CD133, CD34, hypoxia inducible factor‐1, and Trx‐1 vs. margins from refractory lower extremity wounds and expression of these proteins in all wounds is increased due to HBO₂T (p<0.003). HBO₂T is known to mobilize bone marrow stem cells by stimulating nitric oxide synthase. We found that nitric oxide synthase activity is acutely increased in patients' platelets following HBO₂T and remains elevated for at least 20 hours. We conclude that HBO₂T stimulates vasculogenic stem cell mobilization from bone marrow of diabetics and more cells are recruited to skin wounds.     

Update on DCIS Outcomes from the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial

Background

Since the initial reports on use of MammoSite accelerated partial breast irradiation (APBI) for treatment of ductal carcinoma in situ (DCIS), additional follow-up data were collected. We hypothesized that APBI delivered via MammoSite would continue to be well tolerated, associated with a good cosmetic outcome, and carry a low risk for recurrence in patients with DCIS.

Materials and Methods

From 2002–2004, 194 patients with DCIS were enrolled in a registry trial to assess the MammoSite. Follow-up data were available for all 194 patients. Median follow-up was 54.4 months; 63 patients had at least 5 years of follow-up. Data obtained included patient-, tumor-, and treatment-related factors, and recurrence incidence.

Results

Of the 194 patients, 87 (45%) had the MammoSite placed at lumpectomy; 107 patients (55%) had the device placed postlumpectomy. In the first year of follow-up, 16 patients developed a breast infection, though the method of device placement was not associated with infection risk. Also, 46 patients developed a seroma that was associated with applicator placement at the time of lumpectomy (P = 0.001). For patients with at least 5 years of follow-up, 92% had favorable cosmetic results. There were 6 patients (3.1%) who had an ipsilateral breast recurrence, with 1 (0.5%) experiencing recurrence in the breast and axilla, for a 5-year actuarial local recurrence rate of 3.39%.

Conclusions

During an extended follow-up period, APBI delivered via MammoSite continued to be well tolerated for patients with DCIS. Use of this device may make lumpectomy possible for patients who would otherwise choose mastectomy because of barriers associated with standard radiation therapy.     

Guideline Recommended Gastric Cancer Care in the Elderly: Insights into the Applicability of Cancer Trials to Real World

Background

Given the underrepresentation of older persons in cancer trials, the association between increasing age and receipt of recommended gastric cancer care in the United States was examined.

Materials and Methods

Using the 1998–2006 SEER database, 8637 Medicare-eligible patients, aged ≥65 years who underwent gastrectomy for nonmetastatic gastric adenocarcinoma were identified. Multivariate analyses was used to assess the effect of increasing age on receipt of recommended gastric cancer care (adequate lymph node evaluation [≥15 lymph nodes] and adjuvant radiation therapy for AJCC Ib–IVM0) and cancer-specific mortality controlling for covariates.

Results

While 61% of gastric cancer operations were performed in patients ≥65 years, less than 30% received adequate lymphadenectomy or adjuvant radiation therapy. Older patients were less likely to receive adequate nodal evaluation and adjuvant radiotherapy (P < 0.0001). These findings persisted on multivariate analyses. Older age was also associated with worse cancer-specific mortality. Because an age-tumor location interaction for cancer mortality (P = 0.047) was observed, stratified analyses were performed which showed that the adverse effect of older age on cancer-specific mortality was augmented in proximal gastric cancers.

Conclusions

This population-based study showed significant age-based variations in gastric cancer care. These results should encourage assessment of generalizability of gastric cancer trials to this expanding population of elderly in the era of comparative effectiveness research.     

Hepatic Intra-Arterial Injection of Drug-Eluting Bead, Irinotecan (DEBIRI) in Unresectable Colorectal Liver Metastases Refractory to Systemic Chemotherapy: Results of Multi-Institutional Study

Introduction

Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy.

Methods

This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival.

Results

Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1–5), median treatment dose was 100 mg (range 100–200 mg), with total hepatic treatment of 200 mg (range 200–650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1–3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months.

Conclusions

Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.     

Toward Optimization of Imaging System and Lymphatic Tracer for Near-Infrared Fluorescent Sentinel Lymph Node Mapping in Breast Cancer

Background

Near-infrared (NIR) fluorescent sentinel lymph node (SLN) mapping in breast cancer requires optimized imaging systems and lymphatic tracers.

Materials and Methods

A small, portable version of the FLARE imaging system, termed Mini-FLARE, was developed for capturing color video and two semi-independent channels of NIR fluorescence (700 and 800 nm) in real time. Initial optimization of lymphatic tracer dose was performed using 35-kg Yorkshire pigs and a 6-patient pilot clinical trial. More refined optimization was performed in 24 consecutive breast cancer patients. All patients received the standard of care using ^99mTechnetium-nanocolloid and patent blue. In addition, 1.6 ml of indocyanine green adsorbed to human serum albumin (ICG:HSA) was injected directly after patent blue at the same location. Patients were allocated to 1 of 8 escalating ICG:HSA concentration groups from 50 to 1000 μM.

Results

The Mini-FLARE system was positioned easily in the operating room and could be used up to 13 in. from the patient. Mini-FLARE enabled visualization of lymphatic channels and SLNs in all patients. A total of 35 SLNs (mean = 1.45, range 1–3) were detected: 35 radioactive (100%), 30 blue (86%), and 35 NIR fluorescent (100%). Contrast agent quenching at the injection site and dilution within lymphatic channels were major contributors to signal strength of the SLN. Optimal injection dose of ICG:HSA ranged between 400 and 800 μM. No adverse reactions were observed.

Conclusions

We describe the clinical translation of a new NIR fluorescence imaging system and define the optimal ICG:HSA dose range for SLN mapping in breast cancer.     

Multimodal analgesic approach incorporating paravertebral blocks for open radical retropubic prostatectomy: a randomized double-blind placebo-controlled study

Introduction

Perioperative pain management influences both the quality as well as the speed of recovery following surgery.

Methods

This was a randomized double-blind placebo-controlled study designed to assess the effectiveness of a multimodal analgesic approach (MMA) vs patient-controlled analgesia (PCA) alone in patients undergoing open prostatectomy. Prior to surgery, paravertebral blocks (PVBs) were performed with either 0.5% ropivacaine in the MMA group or saline in the PCA group. Patients in the MMA group also received celecoxib (400 mg po prior to surgery and 200 mg po bid for seven days following surgery) and ketamine 10 mg iv. Following surgery, every patient had free access to morphine PCA. A pain numerical rating scale (NRS) at 24 hr was chosen as the primary endpoint. Secondary endpoints included morphine consumption at 24 hr and SF-36 (36-Item Short-Form Health Survey) scores from two weeks to 24 weeks following surgery.

Results

The primary endpoint, average pain NRS at 24 hr, was 2.6 in the MMA group compared with 3.9 in the PCA group (difference = ?1.6, 95% confidence interval [CI]: ?2.3 to ?0.4; P = 0.01). The average morphine consumption at 24 hr was 4.8 mg in the MMA group compared with 10.5 mg in the PCA group (difference = ?5.7, 95% CI: ?13.0 to 0.5; P = 0.01). Higher SF-36 scores at two, four, eight, and 12 weeks were observed in the MMA group compared with the PCA group, but no statistically significant (P < 0.05) between-group difference was found after Bonferroni correction of comparisons conducted repeatedly over time. Postoperative adverse effects included low episodes of postoperative nausea and vomiting, bladder spasms, constipation, and pruritus.

Conclusion

This study demonstrates that PVBs combined with celecoxib and ketamine provide better immediate postoperative pain control and facilitate earlier functional recovery in patients undergoing an open radical prostatectomy when compared with PCA alone.     

Antinociceptive effect of intrathecal administration of taurine in rat models of neuropathic pain

Purpose

Taurine is the most abundant amino acid in many tissues. Although taurine has been shown to be antinociceptive, in this report, our focus is to elucidate the mechanism and action site on neuropathic pain. This study used behavioural assessments to determine whether taurine attenuates neuropathic pain in the spinal cord.

Methods

Chronic constriction injury (CCI) to the sciatic nerve and streptozotocin-induced diabetic neuropathy were introduced to male Sprague-Dawley rats. We then assessed the antinociceptive effect of spinal injections of taurine (100, 200, 400, or 800 μg) using electronic von Frey, paw pressure, and plantar tests. To explore the effect of taurine on motor function, a rotarod test was performed, and in order to determine which neurotransmitter pathway is involved in taurine’s action, we examined how several antagonists of spinal pain processing receptors altered the effect of taurine 400 μg in a paw pressure test.

Results

Taurine alleviated mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia in CCI rats and suppressed mechanical allodynia and hyperalgesia in diabetic rats. Significant effects were observed at 200 μg in both models. On the other hand, taurine dose-dependently affected motor performance, and a significant effect was seen at 400 μg. The antinociceptive effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist.

Conclusion

The present study demonstrated that intrathecal administration of taurine attenuates different models of neuropathic pain, and these effects seem to be mediated by the activation of glycinergic neurotransmission. These findings suggest that taurine may be a candidate remedy for neuropathic pain.     

Aggressive Surgical Approach for Patients with T4 Gastric Carcinoma: Promise or Myth?

Background

Surgical outcomes of multiorgan resection (MOR) for T4 gastric carcinoma reported in the literature are widely variable. We herein report a large surgical series of T4 gastric carcinoma.

Methods

One hundred seventy-nine patients with cT4 gastric carcinoma were recruited onto the study. Patient characteristics, surgical strategy and related complications, long-term survival, and prognostic factors of T4 gastric carcinoma were analyzed.

Results

Of 179 cT4 gastric carcinoma, there were 57 cT4 (pT3) with MOR, 91 pT4 with MOR, and 31 cT4 without MOR. pT4 with MOR were more likely to be associated with nodal metastasis, cellular dedifferentiation, and lymphoperineural infiltration compared to those of pT0–3 (P < 0.01 for all). For 91 pT4 with MOR, their surgical mortality and morbidity rates were 4.4 and 28.6%, respectively; their 1-, 3-, and 5-year overall survival rates were 55.2, 22.4, and 12.2%, respectively. The long-term survival of cT4 (pT3) with MOR was superior to pT4 with MOR (P = 0.006) and cT4 without MOR (P = 0.004). There was a striking difference between pT4 with MOR, R0 and pT4 with MOR, and R1 or R2 (P = 0.007). By means of multivariate analysis, lymph node status, liver invasion, and positive surgical margin were independent prognostic factors.

Conclusions

Aggressive surgical management of pT4 gastric carcinoma should be limited to patients without adverse prognostic factors such as advanced nodal involvement and pancreatic invasion.     

Diffuse idiopathic skeletal hyperostosis of the cervical spine: an underestimated cause of dysphagia and airway obstruction

Background context

Diffuse idiopathic skeletal hyperostosis (DISH) is a common but underdiagnosed condition relating to ossification of spinal ligaments that can cause compression of the esophagus and trachea. According to case reports, dysphagia or airway obstruction resulting from DISH is a rare occurrence.

Purpose

This study was intended to identify all published cases of dysphagia and/or airway obstruction resulting from DISH to increase the epidemiologic/clinical knowledge of these related conditions.

Study design

A systematic review of the literature was performed.

Methods

The articles resulting from the systematic PubMed/EMBASE search of the literature were closely read, and predefined parameters were scored.

Results

The search yielded a total of 118 articles (95 case reports and 23 case series) describing 204 patients with dysphagia and/or airway obstruction resulting from DISH. The number of cases demonstrated a steady increase from 1980 to 2009. This might be a real effect not ascribable to publication bias or expansion of the medical literature alone.

Conclusions

Diffuse idiopathic skeletal hyperostosis as a cause of dysphagia and/or airway obstruction may be an increasing and underappreciated phenomenon. Diffuse idiopathic skeletal hyperostosis should be included in the differential diagnosis of dysphagia and airway obstruction.