Lymphatic mapping and sentinel node biopsy: is the method applicable to patients with colorectal and gastric cancer?

The current status of lymphatic mapping and sentinel node biopsy in the treatment of patients with malignant melanoma and breast cancer is described. The possible use of a similar method in patients with colorectal and gastric cancer is outlined. Peroperative lymphatic mapping and identification of sentinel node(s) in patients with gastrointestinal cancer may lead to modified (tailored) resections and extended lymph node dissections only in those patients in whom the sentinel node(s) contains tumour cells. The method offers the possibility of improving staging by identification of patients with early disseminated disease who should be considered for adjuvant treatment or be included in trials of adjuvant treatment to speed up the breakthrough of more effective adjuvant regimens. Large studies are needed to find out if the sentinel node concept is as valid in gastrointestinal cancer as studies so far have shown that it is for malignant melanoma and breast cancer.     

Oncogenes, granules and breast cancer: what has c-myc to do with apocrine changes?

This issue of The Breast includes an elegant study by Selim et al. on c-myc gene amplification and protein overexpression in apocrine metaplasia (APM) and apocrine adenosis (AA) of the breast using paraffin-embedded tissue. In their report, the authors observe that all cases of APM and AA harbored c-myc protein overexpression, but no definitive gene amplification was found. Most importantly, they observed that the percentage of cells expressing c-myc in APM and AA was significantly correlated with cell proliferation, as assessed by Ki-67 immunolabeling index. On the basis of their findings and of previously reported studies, the authors suggest that c-myc overexpression occurs in early stages of breast carcinogenesis, that c-myc gene amplification may be a late event, and that in APM and AA c-myc overexpression is related to cell proliferation. Selim et al. findings have brought to our attention two thorny but rather important issues regarding current concepts of apocrine changes and their association with breast carcinomas, and also the role of c-myc in breast carcinogenesis.     

The hemodynamic interactions of combination therapy with α-blockers and phosphodiesterase-5 inhibitors compared to monotherapy with α-blockers: a systematic review and meta-analysis

International Urology and Nephrology - The present study systematically reviewed the safety of combined treatment with an alpha blocker and phosphodiesterase-5 inhibitor. The study was performed...     

Compulsive Eating and Gastric Bypass Surgery: What does Hunger have to do with It?

Background: Binge eating and other patterns of disordered eating in obese patients need further investigation. In a previous study by this author, one-third of patients presenting for bariatric surgery met strict criteria for Binge Eating Disorder. It is important to clarify the role of such eating behaviors on outcome of surgery to determine whether treatments targeted specifically at these behaviors and associated psychological issues can improve surgical outcome. The aim of this paper is to raise awareness of the range of disordered eating patterns in bariatric patients, describe an approach used, and discuss issues reported by patients after surgery. Methods: Patients completed questionnaires before surgery (QWEP, BES, BDI) and were seen for a pre-surgery mental health evaluation. High risk patients were identified and invited to attend a postsurgery group (CBT approach) as a preventive measure to help them deal with eating patterns as well as emotional adjustment. Results: Disordered eating patterns can persist after surgery. While surgery may decrease actual physical hunger and reduce physical capacity for food, it is still possible to eat compulsively,although the patterns may change somewhat due to the surgical procedure. Conclusion: Since long-term weight maintenance depends on post-operative changes in eating behaviors, it is important to identify patients at risk for a range of disordered eating patterns so that a comprehensive treatment plan that targets the eating disturbances and associated psychological components can be implemented.     

“Priming” with neostigmine: failure to accelerate reversal of single twitch and train-of-four responses

Train-of-four stimulation can shorten the apparent onset time of neuromuscular blocking drugs. This study was designed to verify whether the same occurred with neostigmine-assisted recovery, and whether this apparent acceleration could explain the previously reported effectiveness of the priming technique for reversal agents. Fourteen adults received atracurium, 0.5 mg.kg-1, during a thiopentone-nitrous oxide-enflurane anaesthetic. The ulnar nerves of both arms were stimulated with train-of-four stimulation every 12 seconds until 1 per cent recovery of first twitch, at which time stimulation in one arm was switched to single twitch. When mean first twitch height reached 10 per cent of control, neostigmine, 0.04 mg.kg-1, was administered either as a single bolus, or as a "priming" dose of 0.01 mg.kg-1, followed 3 min later by 0.03 mg.kg-1. No statistically significant differences were observed between single twitch in one arm and first twitch height of the train-of-four in the other arm for the next 10 min. With priming, first twitch height was 45 +/- (SEM) 5 per cent at 5 min and 85 +/- 6 per cent at 10 min, compared with 72 +/- 5 per cent (p less than 0.05) and 91 +/- 2 per cent (NS) respectively without priming. Train-of-four ratio was 28 +/- 3 per cent at 5 min and 65 +/- 5 per cent at 10 min with priming, versus 53 +/- 4 per cent (P less than 0.05) and 73 +/- 3 per cent (NS) respectively without priming.(ABSTRACT TRUNCATED AT 250 WORDS)     

Back pain in patients with degenerative spine disease and intradural spinal tumor: what to treat? when to treat?

Background

Back pain is common in industrialized countries and one of the most frequent causes of work incapacity. Successful treatment is, therefore, not only important for improving the symptoms and the quality of life of these patients but also for socioeconomic reasons. Back pain is frequently caused by degenerative spine disease. Intradural spinal tumors are rare with an annual incidence of 2–4/1,00,000 and are mostly associated with neurological deficits and radicular and nocturnal pain. Back pain is not commonly described as a concomitant symptom, such that in patients with both a tumor and degenerative spine disease, any back pain is typically attributed to the degeneration rather than the tumor.

Objective

The aim of the present retrospective investigation was to study and analyze the impact of microsurgery on back/neck pain in patients with intradural spinal tumor in the presence of degenerative spinal disease in adjacent spinal segments.

Methods

Fifty-eight consecutive patients underwent microsurgical, intradural tumor surgery using a standardized protocol assisted by multimodal intraoperative neuromonitoring. Clinical symptoms, complications and surgery characteristics were documented. Standardized questionnaires were used to measure outcome from the surgeon’s and the patient’s perspectives (Spine Tango Registry and Core Outcome Measures Index). Follow-up included clinical and neuroradiological examinations 6 weeks, 3 months and 1 year postoperatively.

Results

Back/neck pain as a leading symptom and coexisting degenerative spine disease was present in 27/58 (47 %) of the tumor patients, and these comprised to group under study. Patients underwent tumor surgery only, without addressing the degenerative spinal disease. Remission rate after tumor removal was 85 %. There were no major surgical complications. Back/neck pain as the leading symptom was eradicated in 67 % of patients. There were 7 % of patients who required further invasive therapy for their degenerative spinal disease.

Conclusions

Intradural spinal tumor surgery improves back/neck pain in patients with coexisting severe degenerative spinal disease. Intradural spinal tumors seem to be the only cause of back/neck pain more often than appreciated. In these patients suffering from both pathologies, there is a higher risk of surgical overtreatment than undertreatment. Therefore, elaborate clinical and radiological examinations should be performed preoperatively and the indication for stabilization/fusion should be discussed carefully in patients foreseen for first time intradural tumor surgery.     

Levels of antibodies to endotoxin and cytokine release in patients with severe trauma: does posttraumatic dysergy contribute to organ failure?

BACKGROUND: We conducted a prospective study in patients with multiple injuries investigating the time course of trauma-related changes of systemic immunologic defense mechanisms. METHODS: Patients with multiple injuries with Injury Severity Scores of more than 20 were included if they survived for more than 4 days after injury. Further inclusion criteria were no local or systemic infection (pneumonia, sepsis, soft-tissue infection, acquired immunodeficiency syndrome, tuberculosis, etc.) at the time of injury and no history of liver disease, bowel disease, or abdominal surgery. Serum endotoxin levels were measured from peripheral venous blood, as were the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against lipid A and against the core polysaccharide of endotoxin (lipopolysaccharide [LPS]), during the course of intensive care management. Serial central venous levels of interleukin-6 were determined as a marker of the inflammatory response. RESULTS: The patients were grouped according to their survival, with the survivors belonging to group S (48 patients) and the nonsurvivors belonging to group N (16 patients). The time of death for the nonsurvivors was between days 10 and 32 after the initial trauma. Thirteen of these patients (81%) died of multiple organ failure between days 12 and 17, two died of head trauma, and one died of sepsis. In patients who died of multiple organ failure, a significantly lower production of the IgM and IgG antibodies (AB) against lipid A and LPS was found before death (lipid A IgM-AB, day 11: group N, 29 +/- 11 U/mL; group S, 106 +/- 16 U/mL; p = 0.008; lipid A IgG-AB, day 11: group N, 18 +/- 9 U/mL; group S, 57 +/- 18 U/mL; p = 0.007; LPS IgM-AB, day 11: group N, 36 +/- 14 U/mL; group S, 122 +/- 23 U/mL; p = 0.009; LPS IgG-AB, day 11: group N, 17 +/- 12 U/mL; group S, 56 +/- 19 U/mL; p = 0.03). Interleukin-6 levels were significantly increased in the nonsurvivors (day 1: group N, 1,095 +/- 112 pg/mL; group S, 393 +/- 67 U/L; p = 0.008). CONCLUSION: In patients who died of severe trauma and in whom the cause of death was multiple organ failure, a significantly lower production of antiendotoxin antibodies was measured shortly before death. An insufficient immune defense (dysergy) may be involved in the pathomechanisms leading to the development of organ dysfunction.     

Experimental liver preservation with Celsior: a novel alternative to University of Wisconsin and histidine-tryptophan-alpha-ketoglutarate solutions?

Celsior, a low viscosity and low potassium preservation solution, has recently been tested successfully in the cold preservation of heart, lung, kidney and small intestine. The purpose of the present study was to evaluate the potential of Celsior in the cold preservation of the liver. Livers were harvested from male Wistar rats and then flushed with either Celsior (CE), University of Wisconsin solution (UW) or histidine-tryptophan-alpha-ketoglutarate solution (HTK) and stored for 24 h at 4 degrees C in the respective solution. The reperfusion was performed in vitro using a recirculating model with oxygenated (95% O(2), 5% CO(2)) Krebs-Henseleit buffer at 37 degrees C. To simulate the slow rewarming during the surgical implantation in vivo, all livers were stored for 30 min at room temperature prior to reperfusion. After ischemic storage and also after reperfusion some samples were freeze-clamped for analysis of tissue metabolites while others were tested for structural and functional integrity by the isolated perfusion. CE vs. UW vs. HTK: Metabolic preservation of tissue ATP (micromol/g dry weight) during cold storage was best with Celsior (0. 46 +/- 0.17 vs. 0.26 +/- 0.03 vs. 0.35 +/- 0.07; p < 0.05 CE vs. UW), but upon reperfusion energetic recovery was comparable in the three groups (3.45 +/- 0.66 vs. 4.27 +/- 0.41 vs. 3.63 +/- 0.64 micromol/g/dry weight). There appeared to be structural integrity during reoxygenation irrespective of the used preservation solution with comparable values of parenchymal enzyme release (ALT: 575 +/- 82 vs. 547 +/- 106 vs. 593 +/- 38 mU/g/l), bile production (18.0 +/- 1.0 vs. 18.5 +/- 2.5 vs. 18.7 +/- 1.4 microl/g/ min), and the release of acid phosphatase, an indicator for activated Kupffer cells (89 +/- 13 vs. 90 +/- 5 vs. 123 +/- 21 mU/g/l) in this in vitro model. Vascular flow characteristics were approximated by the portal perfusion pressure, which tended to be elevated upon initial reperfusion in the UW group (8.4 +/- 0.6 mm Hg) compared to 6.6 +/- 1.0 and 7.3 +/- 0.4 mm Hg in Celsior and HTK, respectively. However, the pressure values decreased to the normal range even in the UW group with ongoing perfusion. The sensitivity of our model in detecting protective effects of the tested solution was confirmed by a negative control group of livers stored in Ringer's solution at 4 degrees C, yielding an impaired recovery which differed by one magnitude from the three other groups. Within the limits of an in vitro study it is concluded from these results that Celsior may become a suitable alternative for liver preservation and further studies including a transplantation in vivo are strongly encouraged.     

HIZ’s relation to axial load and low back pain: investigated with axial loaded MRI and pressure controlled discography

Purpose

The aims were to investigate if the detection of high-intensity zones (HIZ) is affected by axial load, and to study the correlation between HIZ and discogenic pain provoked with pressure controlled discography (PCD).

Methods

41 consecutive patients with chronic low back pain, referred for discography, were included. Each patient underwent PCD, CT, MRI, and axial loaded MRI (alMRI) within 24 h. 35 patients completed all MRI sequences (140 discs). The detection of HIZ was compared between conventional MRI and alMRI. PCD was performed in 119 of the discs examined at MRI. Provoked pain at PCD was classified into four categories (none/unfamiliar/similar/exact), with the patients’ daily pain as reference, and correlated with presence of HIZ.

Results

AlMRI did not affect the detection of HIZ compared with conventional MRI. No significant correlation between HIZ and the 4-graded pain response at discography was found (p = 0.34), neither when combining similarly/exactly reproduced pain (p = 0.08). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HIZ in detecting discs with exactly reproduced pain were 49, 69, 39 and 76 %. When combining similarly/exactly reproduced pain, PPV was higher but still only 70 %.

Conclusions

The detection of HIZ was not influenced by axial load. With strict PCD, discogenic pain can neither be confirmed when having HIZ (PPV 39 %) nor ruled out in discs without HIZ (NPV 76 %). Larger PCD studies including quantification of HIZ at conventional and alMRI are needed, before any dynamic component affected by axial load can be ruled out completely.     

Centralization in patients with sciatica: are pain responses to repeated movement and positioning associated with outcome or types of disc lesions?

Aim

To determine the frequency of different patterns of centralization and their association with outcomes and MRI findings in patients experiencing sciatica.

Methods

A prospective longitudinal cohort study of 176 patients with radicular pain below the knee, who all had an MDT clinical assessment. Based on their pain response, patients were divided into five groups: abolition centralization, reduction centralization, unstable centralization, peripheralization, and “no effect”. Patients had an MRI.

Results

Overall, 84.8% of patients reported experiencing centralization, 7.3% peripheralized and 7.9% reported “no effect”. The median reduction in RMQ scores across all the three centralization groups was 9.5 points at 3 months, and 12.0 points at 12 months. The peripheralization group improved similarly. The ‘no effect’ group improved significantly lower (p < 0.001), by 3.0 at both time points. Patients who centralized, and peripheralized had a significantly reduction in leg pain, the “no effect” group demonstrated a less favorable outcome (p < 0.02). There was no association between pain responses and the type of disc lesion.

Conclusion

In patients with sciatica, centralization was common and associated with improvement in activity limitation and leg pain. Centralization was very common in ruptured disc therefore the study does not support the theory, that centralization only occurs if the intra-discal hydrostatic mechanism is functional.

     

Erratum to: Is endoscopic closure with clips effective for both diagnostic and therapeutic colonoscopy-associated bowel perforation?

Background  

Colonic perforation is an uncommon but serious colonoscopy-associated complication. This study assessed the effectiveness of conservative management with endoscopic clipping for colonoscopy-associated perforations.     

Running with the Hares and Hunting with the Hounds: An Impossibility?

Vascular surgery has emerged as an independent speciality in India. The growth and development of vascular surgery in India has been slow, yet steady. It is a matter of concern that almost a quarter century down the line this speciality is faced with several problems. This article examines the issue of whether it is feasible for vascular surgery to exist as an independent subspeciality. Does one follow a conciliatory or a confrontational approach with the ‘competing specialities’?     

Damage- and pathogen-associated molecular patterns and alarmins: keys to sepsis?

The concept that sepsis is the result of an uncontrolled inflammatory response of the host's innate immune system towards invading pathogens has recently been challenged. Evidence is accumulating that, in addition, host-derived alarm molecules are released during sepsis- and trauma-associated cell death, thus triggering the host's immune response. The identification and characterization of exogenous as well as endogenous danger molecules allowed significant advances in our understanding of the pathophysiology of sepsis and may provide potential targets for therapeutic interventions.     

Locally advanced pancreatic cancer treated with radiation and 5-fluorouracil: a first step to neoadjuvant treatment?

AIM OF THE STUDY: In two institutions, a retrospective analysis was performed on patients with histologically proven locally advanced pancreatic cancer without distant metastases. The aim of this analysis is to assess whether chemoradiotherapy provides survival benefit for patients with locally advanced pancreatic cancer. METHODS: Forty-five patients from the Erasmus Medical Centre (Erasmus MC), Rotterdam, received 5-fluorouracil (5-FU) and radiotherapy and, 38 patients from the Academic Medical Centre Amsterdam (AMC) were offered the best supportive care. Radiotherapy consisted of 50 Gy external upper abdomen radiation in two courses, concomitant with intravenous 5-FU 25 mg/kg/ 24 h continuously on the first 4 days of each treatment course. RESULTS: The treatment protocol was completed in 38 of 45 patients (84%) without complications. Radiological response was evaluated in 38 patients. Ten patients (26%) showed a partial response, stable disease was seen in 6 (16%) patients and progressive disease in 22 (58%) patients. A second-look operation was performed in 8 of 10 patients (72%) showing a radiological response, in 3 patients the tumour could be resected. Median overall survival time for the Erasmus MC group (n = 45) was 9.8 months compared to 7.6 months when the best supportive care was given (AMC group, p = 0.04). CONCLUSION: Although overall survival remains poor, treatment with 5-FU and radiotherapy might benefit some patients with locally advanced pancreatic cancer.