The influence of training level and surgical experience on survival in colorectal cancer

Background and aims The effect of surgical training level, experience, and operation volume on complications and survival in colorectal cancer during a 10-year period in a medium-volume university hospital was retrospectively studied.Patients and methods Four hundred and fifty-six patients were resected for primary colorectal adenocarcinoma during the 10-year period of 1981–1990, and of these, 387 patients underwent resection with curative intent. The surgeons were divided into three groups according to training level and volume: group 1, surgeons in training and other surgeons operating annually on only 1–4 patients; group 2, surgeons specializing in gastrointestinal surgery (average annual volume 4–13 operations); group 3, specialists in gastrointestinal surgery (average annual volume 3–8 operations). Postoperative morbidity and mortality rates, as well as long-term survival rates, were analysed, and comparisons were made between the patients in the three groups.Results There were no statistically significant differences between the three groups in postoperative morbidity or mortality. Cancer-specific 5-year survival rate of all patients was 57%, and that of those resected in the aforementioned three groups was 51%, 63%, and 55%, respectively, P=0.087. The 5-year survival rates for colon cancer were 59% (total), 52%, 69%, and 58%, respectively, P=0.067, and for rectal cancer were 51% (total), 42%, 53%, and 52%, respectively, P=0.585.Conclusion There were no significant differences in the rates of postoperative mortality, morbidity, and long-term overall survival between the volume groups. However, in patients with colon cancer, there was a trend for better survival for those operated on by the surgeons specializing in gastrointestinal surgery, and in rectal cancer patients, a tendency of fewer local recurrences in those operated on by the specialist surgeons.     

<Superscript>123</Superscript>I-β-CIT binding and recovery from depression

Abstract. Eighteen depressive outpatients were investigated using single-photon emission computerized tomography (SPECT) with a high-affinity dopamine (DA) and serotonin transporter (SERT) specific radioligand, ¹²³I-labeled -CIT (2-carbomethoxy-3-(4-iodophenyl)-tropane). The patients were tested at the beginning of the study and on follow-up after six months. The severity of depression was evaluated using the 17-item Hamilton Rating Scale of Depression (HRSD). Eight of the eighteen patients had an HRSD score below the median (12 points) on follow-up, and they had a significantly greater increase in ¹²³I--CIT binding in the midbrain region compared with those patients who did not recover (ANCOVA: F = 8.12; df = 1, 14; p = 0.013). These results indicate that recovery from depression is associated with an increase in ¹²³I--CIT binding in the midbrain.     

Integrin chains beta1 and alphav as prognostic factors in human metastatic melanoma

The expression pattern of integrin-type cell adhesion receptors is often changed during malignant transformation. In the present work, we studied the prognostic significance of beta1 and alphav integrin chains for survival of patients with metastatic melanoma. The expression levels of beta1 integrin were also compared with those of Bcl-2, an anti-apoptotic protein, the presence of which is associated with treatment response and survival in melanoma. The expression of beta1 and alphav integrins in 68 melanoma metastases obtained from 55 patients treated with combined chemoimmunotherapy was studied by immunohistochemistry using anti-beta1 and anti-alphav antibodies. The patients were divided into two groups (using a cut-off point of >/= 81%) for beta1 integrin expression levels and into three categories (negative/low, median, high) for alphav integrin expression levels. All tumours were positive for beta1 integrin, and the tumours (n = 6) which had the highest alphav score were also strongly positive for beta1 (94%; P = 0.0055). Patients (n = 43) with 80% or less beta1 integrin-positive tumour cells in their samples had a median disease-free survival (DFS) of 17.0 months, and patients (n = 12) with 81% or more beta1 integrin-positive tumour cells had a DFS of only 5.7 months (P = 0.0001). Patients (n = 32) with low alphav integrin expression levels had shorter DFS (median 12.3 months; P = 0.0146) than patients (n = 20) with median expression levels (median 16.7 months; P = 0.0146). However, three patients who had a very strong alphav expression in their tumours had a median DFS of only 1.8 months (P = 0.0146). Median level expression of beta1 integrin was associated with the presence of Bcl-2 in tumour cells (P = 0.0033). Our results suggest that beta1 and alphav integrin chains are independently expressed in metastatic melanoma and may have an effect on the metastatic potential of melanoma cells.     

Tryptophan depletion effects on EEG and MEG responses suggest serotonergic modulation of auditory involuntary attention in humans

Involuntary attention shifting, i.e., detecting and orienting to unexpected stimulus changes, may be altered at low brain serotonin (5-hydroxytryptamine; 5-HT) levels. This was studied in 13 healthy subjects (21–30 years old; 6 females) by using a dietary challenge, acute tryptophan depletion (ATD), which decreases 5-HT synthesis in the brain. Five hours after ingestion of either ATD or control mixture (randomized, double-blinded, crossover design), brain responses indexing involuntary attention were measured with simultaneous 64-channel electroencephalography (EEG) and 122-channel magnetoencephalography (MEG). During the measurement, the subjects were instructed to discriminate equiprobable 200- and 400-ms tones by pressing one of two buttons rapidly. Occasionally, the frequency of the tones changed (10% increase/decrease), causing involuntary attention shifting. ATD significantly lowered plasma tryptophan concentrations (total tryptophan decreased by 75%, free tryptophan decreased by 35%). As compared to the control condition, ATD reduced the amplitude of the deviant-tone N2 wave, including the overlapping mismatch negativity (MMN) and N2b subcomponents, which are suggested to reflect change detection in the brain. The EEG results were accompanied by a significant increase in the peak latency of the magnetic counterpart of MMN. However, no ATD effects were observed in P3 to task-irrelevant frequency change. Reaction time (RT) to deviants per se was not significantly affected, but RT in trials succeeding the deviant-frequency tones was increased by ATD, which suggested impaired reorienting to the task-relevant activity. In conclusion, the results suggest that decreased level of central 5-HT function after ATD may decrease involuntary attention shifting to task-irrelevant sound changes and thus modulate resource allocation to the task-relevant activity.     

Local lactate and histamine changes in small bowel circulation measured by microdialysis in pig hemorrhagic shock

Hemorrhagic shock results in inadequate tissue oxygenation. Plasma lactate (L) can characterize the degree of systemic oxygen debt (OD), but gives no information on local changes. The aim of this study was to characterize different degrees of hemorrhagic shock by microdialysis measurement of L and histamine (H) in small bowel circulation. Thirty-eight pigs were randomized to five groups of increasing OD (< 50 --> 120 ml/kg). The OD was accrued by hemorrhage over 60 min and was followed by retransfusion and observation for 3 days. In parallel to plasma probes, subserosa(ss)-, submucosa(sm)-, and intraluminal(il)-L- and H-probes were obtained by small bowel microdialysis every 30 min for 210 min. Ss- and sm-L increased during hemorrhage from 1.2 +/- 0.06 and 1.18 +/- 0.06 to 2.57 +/- 0.15 and 2.96 +/- 0.27 mmol/L. Highest mean L > 3.5mmol/L resulted 90 and 120 min after induction of hemorrhage. Although ss- and sm- levels hardly differed, il-L was significantly decreased with 0.27 +/- 0.02 mmol/L at 0 min and highest mean il-L at 120 min: 2.45 +/- 0.51 mmol/L. Sm-L was significantly increased after 60, 90, 120, and 150 min of highest hemorrhage severity (OD > 100 mL/kg). In parallel, systemic L increased significantly during hemorrhage and correlated well with the severity of shock. Although systemic H increased significantly during hemorrhage (from 1.3 +/- 0.31 to 15.2 +/- 0.67 ng/mL), H-dialysates showed no effect either over time nor with the degree of hemorrhage. In conclusion, microdialysis allows evaluation of local L changes in small bowel circulation in pig hemorrhagic shock. Sm-L levels appear to correlate with the degree of shock. Local H changes were not observed during hemorrhagic shock in this study.     

The effects of vasopressin on systemic and splanchnic hemodynamics and metabolism in endotoxin shock

We compared the effects of vasopressin and norepinephrine on systemic and splanchnic circulation and metabolism in endotoxin shock in pigs. Twenty-one pigs were randomized to endotoxin shock (Escherichia coli endotoxin infusion) (n = 6), endotoxin and vasopressin (VASO; n = 6), endotoxin and norepinephrine (NE; n = 6), and controls (n = 3). Endotoxin infusion was increased to induce hypotension, after which vasopressin or norepinephrine was started to keep systemic mean arterial blood pressure >70 mm Hg. Regional blood flows and arterial and regional lactate concentrations were measured. Tonometers with microdialysis capillaries were inserted into the stomach, jejunum, and colon. Systemic mean arterial blood pressure >70 mm Hg was achieved in the VASO and NE groups. Vasopressin decreased cardiac output, superior mesenteric artery, and portal vein blood flow, whereas hepatic arterial blood flow increased. Arterial lactate concentration increased from 2.0 mM (1.6-2.1 mM) to 4.7 mM (4.7-4.9 mM) (P = 0.007). Systemic and mesenteric oxygen delivery and consumption decreased and oxygen extraction increased in the VASO group. Vasopressin increased mucosal-arterial PCO(2) gradients in all three locations, whereas luminal lactate release occurred only in the jejunum. Animals in the NE group remained stable. Vasopressin reversed hypotension but decreased systemic and gut blood flow. This was associated with hyperlactatemia, signs of visceral dysoxia, and jejunal luminal lactate release. IMPLICATIONS: Although vasopressin induces vasoconstriction in visceral region, its effects on splanchnic circulation and metabolism during septic-endotoxin shock are still poorly characterized. We evaluated the metabolic and hemodynamic effects of vasopressin and norepinephrine within the splanchnic area in porcine endotoxin shock.     

Pinhole single-photon emission tomography reconstruction based on median root prior

The maximum likelihood expectation maximisation (ML-EM) algorithm can be used to reduce reconstruction artefacts produced by filtered backprojection (FBP) methods in pinhole single-photon emission tomography (SPET). However, ML-EM suffers from noise propagation along iterations, which leads to quantitatively unpleasant reconstruction results. To avoid this increase in noise, the median root prior (MRP) algorithm for pinhole SPET was implemented. Projection data of a line source and Picker's thyroid phantom were collected using a single-head gamma camera with a pinhole collimator. MRP was added to existing pinhole ML-EM reconstruction algorithm and the phantom studies were reconstructed using MRP, ML-EM and FBP for comparison. Coefficients of variation, contrasts and full-widths at half-maximum were calculated and showed a clear reduction in noise without significant loss of resolution or decrease in contrast when MRP was applied. MRP also produced visually pleasing images even with high iteration numbers, free of the checkerboard-type noise patterns which are typical of ML-EM images.     

Boron Neutron Capture Therapy of Brain Tumors: Clinical Trials at the Finnish Facility Using Boronophenylalanine

Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400mg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61Gy (W), and the average normal brain dose from 3 to 6Gy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50–60Gy, were treated with BPA-based BNCT using the BPA dosage of 290mg/kg. The average planning target dose in these patients was 25–29Gy (W), and the average whole brain dose 2–3Gy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.     

Treatment improves serotonin transporter binding and reduces binge eating

Rationale Serotonin (5-HT) is involved in the control of eating behaviour by inhibiting food intake. Obese women with binge-eating disorder (OB-BED) were recently found to have reduced 5-HT transporter binding. Objectives The aim of this study was to investigate the effect of a successful treatment on 5-HT transporters in OB-BED. Methods The 5-HT transporter binding of seven OB-BED was measured by single-photon emission computed tomography (SPECT), by using iodine-123-labelled nor-β-CIT as a tracer, before treatment and after successful treatment, when the OB-BED were asymptomatic. Treatment consisted of group psychotherapy and fluoxetine medication. The control subjects, six obese women without eating disorders, were also studied twice by using SPECT. Results The 5-HT transporter binding of the symptomatically recovered OB-BED increased significantly (24±22%) after treatment, whereas in the control group, binding remained unchanged. Conclusions The results tentatively suggest that 5-HT transporter binding in OB-BED is an adaptive mechanism, which can be affected by treatment. Furthermore, there seems to be a link between improved 5-HT transporter binding and reduced binge eating.     

Dose-dependent suppression by ethanol of transient auditory 40-Hz response

Rationale: Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. Objectives: The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. Methods: Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0.25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0.425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. Results: The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. Conclusions: Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits. Received: 20 January 1999 / Final version: 9 August 1999