Preoperative Imaging Evaluation after Downstaging of Pancreatic Ductal Adenocarcinoma: A Multi-Center Study

Introduction: Evaluation of pancreatic ductal adenocarcinoma (PDAC) after chemoradiotherapy downstaging is challenging due to computed tomography (CT) overestimation of tumor extension and residual vascular involvement, limiting access to surgery to some patients with potentially resectable tumors. With this study, we wanted to assess which radiological findings are most reliable at pre-operative imaging in the evaluation of PDAC after chemoradiotherapy in order to achieve complete resection. Methods: We retrospectively enrolled 71 patients with locally advanced and borderline resectable PDAC who underwent neoadjuvant chemoradiotherapy. Pre-operative CT or magnetic resonance (MR) have been evaluated by three radiologists to assess major qualitative and quantitative parameters of lesions. Accuracy, sensitivity, and specificity compared to anatomopathological results were evaluated for each parameter. Cohen’s K-coefficient has been calculated to evaluate the inter-observer agreement (IOA). Both single and consensus lecture have been tested. Different dimensional cut-offs were tested to categorize tumors according to their major axis and to compare with anatomopathological diameter, tumor persistence, and margin infiltration. Results: A 25 mm cut-off was 67% sensitive, 90% specific, and 77% accurate in assessing real tumor dimension. 25 mm cut-off reported a 64% sensitivity, 78% specificity, and 69% accuracy in assessing R0 resection. Each 5 mm increment of major axis dimension there is an odds ratio (OR) 1.79 (95% CI 1.13–2.80, p = 0.012) for R+ resection. Imaging presence of the perivascular cuff is not associated with tumor persistence and resection margin infiltration (p = 0.362). Lesion enhancement and pattern homogeneity were not accurate in determining tumor persistence. IOA was generally poor to fair, except for >25 mm cut-off classification where IOA was moderate. Diagnostic accuracy is superior in consensus lecture rather than single lecture. Conclusion: Imaging methods tend to underestimate PDAC resectability after neoadjuvant-CRT. IOA is poor to fair in evaluating most of the qualitative parameters of downstaged pancreatic adenocarcinoma. Surgery should be considered for downstaged borderline resectable PDACs, independently from perivascular cuff presence, especially for tumors smaller than 25 mm.

Application of different techniques to detect Toxoplasma gondii in slaughtered sheep for human consumption

The aim of this study was to investigate occurrence of Toxoplasma gondii in sheep slaughtered in the state of Alagoas, Brazil, by means of different diagnosis techniques. Serum samples and tissues from 100 slaughtered sheep were used. To detect antibodies, the indirect immunofluorescence antibody test (IFAT) was used, and tissues from seropositive animals (cut-off ≥1:64) were submitted to Polymerase Chain Reaction (PCR) and immunohistochemistry (IHC). To assess the concordance between the direct techniques, the kappa test was used. In the IFAT, it was observed that 14% (14/100) of the ovine samples were serum-positive. In the PCR, 21.43% (3/14) of the animals were positive and in IHC, it was observed that 7.14% (1/14) were positively stained for T. gondii in cerebral tissue. Histopathologically, the predominant finding was the presence of mononuclear cell infiltrate in the heart and a perivascular cuff in the cerebrum and cerebellum. The concordance between the direct diagnosis techniques was moderate (k=0.44). Thus, it is important to use different direct techniques in diagnosing toxoplasmosis in naturally infected sheep.

Assessment of gain of tachycardia and bradycardia responses of cardiac baroreflex

The cardiac baroreflex was studied in humans by means of vasoactive drugs and in conscious rabbits by the drug and perivascular cuff methods, which provide somewhat different afferent drive. Mean arterial pressure (MAP)-heart rate (HR) curves were derived using 1) a single symmetric logistic function and 2) a compound function, where the two halves of separate logistic functions were centered on the resting value, one for the tachycardia response and the other for the bradycardia response. There were some differences in overall reflex parameters (plateaus, HR range, gain) between the two methods because of minor degrees of asymmetry. But the differences were small, and the single symmetric logistic adequately describes the overall properties. With the compound function, we assessed average gain, Gt and Gb, for the tachycardia and bradycardia responses and the corresponding normalized (range-independent) gains, Ct and Cb. The resting HR has a large effect on Gt/Gb, since it determines the HR range of each logistic. Moreover, Gt/Gb depends on both resting autonomic tone and reflex changes. However, Ct and Cb provide information about "intrinsic" differences in sensitivity; they are independent of resting HR but entirely dependent on reflex autonomic changes. In rabbits Ct and Cb tended to be larger with the cuff than with the drug method; in addition, with the former Ct less than Cb, whereas with the drug method Ct greater than or equal to Cb, which was consistent with differences in afferent drive. There were also differences between humans and rabbits in Ct/Cb of the vagal component of the reflex. The assessment of the normalized gains of the compound logistic function has substantial advantages over previous methods for assessing gain of the tachycardia and bradycardia responses.

Distribution of extravascular lung water after acute smoke inhalation

Anesthetized dogs with thoracotomy were injected with Evans blue dye and were exposed acutely (5 min) to wood smoke inhalation. Thin slices from freeze-dried samples were photographed and assessed for periarterial and perivenous cuff area and for blue coloration with a score of 0 to 5. Bloodless extravascular lung water (EVLW) was also measured. The smoke-exposed animals were compared with controls and with animals exposed to alloxan or to high-pressure-induced pulmonary edema. EVLW at 2 h after smoke (6.46 +/- 0.80) was above control value (4.30 +/- 0.63) but not different from the alloxan (6.13 +/- 0.70) or high-pressure (6.88 +/- 1.30) groups. Despite the similarity in EVLW in the edematous lungs, there were marked differences in the intensity of blue color and size of cuffing around arteries and veins: the smoke, alloxan, and high-pressure groups had blue color scores of 1.0 +/- 0.1, 2.9 +/- 0.3, and 0.3 +/- 0.1, respectively. These scores indicated a large increase in microvascular permeability to proteins in the alloxan group, a moderate increase in the smoke group, and minimal change in the high-pressure group. The perivascular cuff area was largest in the alloxan group and moderate in the smoke and high-pressure groups. The cuff area was higher for arteries than for veins in all groups except the 0.5-h smoke group. We conclude that smoke inhalation causes a moderate increase in permeability and EVLW compared with alloxan. The extravascular lung water accumulates preferentially around the arteries, but the size of the perivascular cuff is not similar for all causes of pulmonary edema.

Sequence of interstitial liquid accumulation in liquid-inflated sheep lung lobes

In the initial stages of pulmonary edema, liquid accumulates in the lung interstitium and appears as cuffs around pulmonary vessels. To determine the pattern, rate, and magnitude of cuff formation, we inflated sheep lungs to capacity with liquid (inflation pressure 19 cmH2O) for 3–300 min. After freezing the lobes in liquid N2, we measured perivascular cuff size and total perivascular volume in frozen blocks of each lobe and compared the results with previous measurements in dog lungs. Total cuff volume in sheep lungs reached a maximum value of 5% of air space volume, compared with 9% in dog lungs. In sheep lungs 94% of vessels greater than or equal to 0.5 mm diam and 16% of smaller vessels were surrounded by cuffs. In dog lungs these values were 99 and 47%, respectively. The ratio of cuff area to vessel area reached a maximum of 2.3 in sheep lungs and 3.4 in dog lungs. In an electrical analogue model designed to simulate cuff growth, estimated interstitial resistance to liquid flow was 6–15 times higher than similar estimates in dog lungs. These species differences might be the result of differences in the composition of the interstitial gel or to differences in the mechanical linkage between the lung parenchyma and vessel wall.

How does positive end-expiratory pressure reduce intrapulmonary shunt in canine pulmonary edema?

We ventilated separately the right and left lungs of seven dogs having thoracotomies and catheters in both lower lobe veins. Two hours after right atrial injection of oleic acid, shunt (Qs/QT) in each lower lobe increased from 0.10 to 0.47. Ten minutes after positive end-expiratory pressure (PEEP) was increased from 3 to 13 cmH2O in one lung, mean lobar Qs/QT decreased to 0.06 with no change in its fraction of pulmonary blood flow measured by microsphere techniques. At the same time mean Qs/QT in the other lower lobe was 0.48. At end expiration each lower lobe hilum was then clamped, and the excised lobe was quickly frozen over liquid N2. There was no difference in the extravascular lung liquid per gram blood-free dry lobe between the lower lobes (7.5 +/- 2.6 ml/g), but perivascular cuff liquid was greater in the lower lobe with PEEP (3.8 +/- 2.8 ml/g) than in the lower lobes without PEEP (2.4 +/- 1.7 ml/g). Light microscopy revealed that 77.8 +/- 9.0% of the alveoli were flooded in the lobe without PEEP, but only 22.2 +/- 11.8% were flooded in the lobe with PEEP. The mean linear intercepts of the flooded alveoli were not different between lower lobes, and both were reduced to about 50% of the size of adjacent unflooded units in the same lobe. Alveolar septum thickness was greater without PEEP. We conclude that PEEP reduces Qs/QT by inflating previously flooded and collapsed air spaces and by redistributing the excess alveolar water into the compliant perivascular space, thus eliminating the obstacle to pulmonary O2 transfer.