Follow-up after curative surgery for pancreatic ductal adenocarcinoma: asymptomatic recurrence is associated with improved survival.

AIM: There is no consensus on the optimal follow-up schedule of patients after surgery for pancreatic cancer. In this retrospective study, recurrence and survival were investigated for patients presenting with either symptomatic or asymptomatic recurrence. Patient, tumor and treatment characteristics that predicted the length of postrecurrence survival were identified. METHODS: Clinical records of 164 patients who underwent a pancreatic resection (R0/R1) for pancreatic ductal adenocarcinoma from January 2000 to December 2010 were retrieved. Patients underwent a systematic follow-up program. Patient, tumor and treatment characteristics were compared between patients with asymptomatic and symptomatic recurrence. RESULTS: Of 164 consecutive patients, 144 patients (88%) had recurrence (29 asymptomatic, 115 symptomatic). The most frequent reported symptoms were abdominal pain, fatigue/weakness, back pain, weight loss, nausea/loss of appetite and jaundice. Median time to recurrence was 12.0 months for asymptomatic and 7.0 months for symptomatic patients (P = 0.036). Median postrecurrence survival was 10.0 months for asymptomatic and 4.0 months for symptomatic patients (P < 0.0001). Median overall survival was 24.5 months for asymptomatic and 11.0 months for symptomatic patients (P < 0.0001). Symptomatic recurrence, disease free survival <12 months, and no adjuvant chemotherapy were the only independent predictors of poor postrecurrence survival. 72% of asymptomatic and 37% of symptomatic patients received oncological treatment. CONCLUSIONS: Patients with asymptomatic pancreatic cancer recurrence have improved recurrence-free, postrecurrence and overall survival. Symptoms when recurrence is diagnosed are a good surrogate marker of biological aggressiveness. Detection of asymptomatic recurrence may facilitate patient eligibility for investigational studies or other forms of treatment.

[Experiences with biological aortic valve at Ullevål hospital]. / Erfaringer med biologiske aortaklaffer ved Ullevål sykehus.

Biological valves have been used at Ullevål Hospital since 1993 in patients over the age of 70, and in younger patients when anticoagulation is contraindicated. We have used two different types of biological valves; Medtronic Freestyle, a non-stented valve made from pigs aortic root; and Carpentier-Edwards, made from calf pericardium. This valve is mounted in a metallic frame (stent), covered by dacron. Both valves are fixed in glutaraldehyde to diminish tissue antigenicity. 91 patients were operated with biological valves during the period 1993 till January 1998; 56 patients received the Carpentier-Edwards and 35 Freestyle. Postoperative complications have been few and time in the intensive care unit and total hospital stay is satisfactory despite the high age of this group of patients. The overall 30 days postoperative mortality was 4.4%. In conclusion, aortic stenosis and insufficiency can be operated with low mortality and short postoperative or intensive care stay. There was no significant difference between the two groups of patients.

The olivonodular projection: a re-examination based on folial cerebellar implants.

In 5 cats implants of crystalline wheat germ agglutinin-horseradish peroxidase complex were placed in one or two folia of the nodulus with no contamination of adjacent cerebellar lobules. In the inferior olive only the dorsal cap with the adjacent ventrolateral outgrowth and the caudalmost part of nucleus beta were found to project to the nodulus. Negative findings were consistently made in all other parts of the inferior olive, some of which have previously been described to contribute to the olivonodular projection.

The origin and termination of the dentatorubral fibres in the cat as studied with retrograde and anterograde transport of peroxidase labelled lectin.

The dentatorubral projection in the cat was studied by means of retrograde and anterograde transport after implantations of crystalline wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the red and dentate nuclei, respectively. Our retrograde transport findings give evidence that rubral afferents originate in the contralateral dentate nucleus, mainly dorsally in its central part. The dentate implantations (with no contamination of the adjacent interposed nuclei) show that in the cat the great majority of the dentatofugal fibres leave the ipsilateral brachium conjunctivum to decussate below the red nucleus. Scattered crossing fibres also penetrate the contralateral red nucleus at all caudorostral levels on their way to the contralateral thalamus. Terminal fibres were found only in the rostral part of the red nucleus, but no retrogradely labelled rubral cells were observed. The findings are discussed in relation to previous studies on the dentatorubral projection.

The cerebellar nucleo-olivary and olivo-cerebellar nuclear projections in the cat as studied with anterograde and retrograde transport in the same animal after implantation of crystalline WGA-HRP. I. The dentate nucleus.

The implantation technique described by Mori et al. has been modified for the implantation of crystalline wheat germ agglutinin-horseradish peroxidase (WGA-HRP) complex. This method permits a detailed analysis of the afferent and efferent connections of the cerebellar nuclei without the complication of uptake and transport of the tracer into passing fibres. We have used this method for studies of the olivo-dentate and dentato-olivary projections in the cat. After implantation of WGA-HRP into the dentate nucleus in all our cases, both anterogradely labelled terminal dentato-olivary fibres and retrogradely labelled olivo-dentate neurons were found in the contralateral inferior olive. It appears from our findings that both projections are topically organized. The dorsal part of dentate nucleus is bidirectionally connected with the rostral part of the principal olive, the ventrolateral part of the dentate is connected with the intermediate portion of the principal olive, while its ventromedial part is connected with the caudal portion of the principal olive. The olivo-dentate and dentato-olivary connections appear to be largely reciprocally organized. The advantages and drawbacks encountered with implantation of crystalline WGA-HRP are discussed, and our observations are considered in relation to previous studies on the olivo-cerebellar and cerebello-olivary connections.

On the projections from the vestibular and perihypoglossal nuclei to the spinal trigeminal and lateral reticular nuclei in the cat.

The projection from the vestibular and perihypoglossal nuclei to the spinal trigeminal and lateral reticular nuclei has been studied in cats where the wheat germ agglutinin-horseradish peroxidase complex has been used as a retrograde tracer. All injections were made at the level of the caudal pole of the inferior olive. The medial and descending vestibular, and the perihypoglossal nuclei were found to project to the spinal trigeminal nucleus. The projection to the lateral reticular nucleus reaches its medial-most part only, and originates in the lateral vestibular nucleus. The lateral part of the reticular formation also appears to be the target for some vestibular efferent fibres, mainly from the descending vestibular nucleus. The retrogradely labelled cells within the medial and descending vestibular nuclei are of all sizes and distributed throughout their entire territory. Certain observations furthermore indicate that the fibres reaching the lateral reticular nucleus are collaterals only from the vestibulospinal tract. The projections are bilateral. The observations confirm and extend previous observations on the afferent projections to the spinal trigeminal and lateral reticular nuclei.

The medullary projection from the mesencephalic trigeminal nucleus. An experimental study with comments on the intrinsic trigeminal connections.

The medullary projection from the mesencephalic trigeminal nucleus has been studied in cats where the wheat germ agglutinin-horseradish peroxidase complex has been used as a retrograde and anterograde tracer. All injections were made at the level of the caudal pole of the inferior olive and show that it is especially the lateral part of nucleus parvicellularis of the reticular formation which is the main area for termination of the fibres. In addition, it can not be excluded that the descending fibres also reach the medialmost part of the spinal trigeminal sensory nucleus (pars magnocellularis and the adjoining pars gelatinosa). All three cell types of the mesencephalic trigeminal nucleus are labelled, the large globular, the small globular and the polygonal cells. Some of these cells are only faintly labelled. The observations confirm previous studies of the intrinsic trigeminal connections, but show that when the wheat germ agglutinin-horseradish peroxidase complex is used as a tracer, the origin as well as the termination for the intrinsic fibres (also the commissural) can be studied in the same section. The use of this sensitive tracer also shows new details within the intrinsic connections. The findings are discussed with special reference to the recent observations by Ruggiero et al. (1982). These authors found that in rabbit and rat there is a more restricted termination for the descending mesencephalic trigeminal fibres. The discrepancies between the observations seem to indicate that there are species differences as regards the connections between the mesencephalic trigeminal nucleus and the nuclei in the lower part of the brain stem.

Is lectin-coupled horseradish peroxidase taken up and transported by undamaged as well as by damaged fibers in the central nervous system?

Uptake and transport of horseradish peroxidase-wheat germ agglutinin conjugate (HRP-WGA) in intact and damaged passing fibers were studied by injections of the medulla and pons in 11 cats. Injections with evidence of damage to olivocerebellar fibers and cranial nerve fibers invariably lead to retrograde labeling of neurons in the inferior olive and cranial motor nuclei. With staining around--but apparently no damage of--cranial nerve root fibers, no labeling was found in their motor nuclei. Injections limited to the medullary pyramid with slight fiber damage and limited staining lead to faint retrograde labeling of a small number of cells in the ipsilateral sensorimotor cortex. More extensive staining and fiber damage of the pyramid gave a higher number of labeled cells in the ipsilateral sensorimotor cortex. From these experiments we conclude that HRP-WGA is taken up and transported retrogradely with subsequent significant cell labeling in damaged but not in intact fibers. Anterograde transport of HRP-WGA in fibers passing through the injected area was found to take place only for a very short distance, as judged from cases with injections of either the pons or the medullary pyramid interrupting many corticospinal fibers.

Olivary afferents from the pretectal nuclei in the cat.

The organization of the projection from the pretectal region to the inferior olive in the cat was studied by means of retrograde protein tracing and experimental degeneration. Small injections of horseradish peroxidase (HRP) were made into various parts of the inferior olive from a ventral approach. The number of nerve cells in the pretectal nuclei retrogradely labelled with HRP was counted and put in relation to the site of injection. Labelled cells were only found in the posterior pretectal nucleus (NPP), the nucleus of the optic tract (NOT) and the anterior pretectal nucleus (NPA). Most labelled cells were found in NPP and NOT in cases in which the rostral or caudal levels of the principal olive were labelled by the injection. NAP labelling occurred in one case with a very rostral injection of the inferior olive. Unilateral electrolytical destruction of the pretectal region produced terminal degeneration in the ipsilateral inferior olive. The heaviest ipsilateral degeneration was found in the upper half of the principal and dorsal accessory olives, and caudally in the ventrolateral outgrowth, the dorsal cap and nucleus beta with the adjacent part of the medial accessory olive. Some functional implications of the findings are discussed.

On retro- and anterograde transport of horseradish peroxidase in the pontocerebellar fibers as studied with the Mesulam TMB technique.

In cats where injections of HRP have been made in the cerebellar cortex, pontocerebellar fibers are visualized throughout their length. Likewise, injections of HRP into the pontine nuclei visualize the pontocerebellar fibers and these anterogradely stained axons can in fortunate sections be followed into the granular layer. A visualization of retrogradely filled pontocerebellar fibers was unexpected and its another example of the sensitivity of the Mesulam8 technique.

A note on the anterograde transport of horseradish peroxidase within the olivocerebellar fibres.

In cats with unilateral injections of horseradish peroxidase in the inferior olive which were processed according to the Mesulam (1978) technique crossed olivocerebellar fibres can be followed on both sides of the brain stem into the cerebellum to the level of the granular layer. The observations indicate that perikaryal uptake of horseradish peroxidase is not a prerequisite for the visualization of the fine preterminal fibres.