Long-term disease control of a non-operable neuroendocrine tumor of the lung with lanreotide: a case study.

Bronchopulmonary neuroendocrine tumors (NETs) are malignant tumors that represent approximately 20% of all lung cancers. The therapeutic option for advanced or metastatic bronchopulmonary NETs is mainly palliation of symptoms; options need to be individualized and, therefore, rely on the knowledge of multidisciplinary teams. Somatostatin analogs have been widely used in NETs for control of hormonal syndromes and are currently under evaluation for their antiproliferative activity. Here, we present a case of NET of the lung, for which we achieved long-term disease control with a treatment comprising the somatostatin analog lanreotide Autogel(®) in a patient with limited therapeutic options due to considerable comorbidity, while preserving his quality of life.

Lessons to learn from EORTC study 08981: a feasibility study of induction chemoradiotherapy followed by surgical resection for stage IIIB non-small cell lung cancer.

The present EORTC phase II feasibility study in stage IIIB (T4-N3) NSCLC was conducted to investigate whether an induction regimen with concurrent chemoradiotherapy followed by surgery after restaging by re-mediastinoscopy and/or fluorodeoxyglucose-positron emission tomography (FDG-PET) was feasible in a multicenter setting. Unfortunately, the study closed prematurely because of poor accrual. The combination of more stringent selection criteria, the incorrect prevailing view of Ethical Boards that a tri-modality approach is too toxic, competing studies in the participating centers and the fact that patients with N3 disease could only be enrolled if a re-mediastinoscopy could be performed, underlie the low accrual. Although this study illustrates that the conduct of a tri-modality study across Europe appeared to be difficult at that time, the number of centers with highly qualified and experienced specialists involved in this kind of multi-modality approaches is rapidly increasing. Future initiatives should, therefore, certainly be encouraged. Minimally invasive procedures such as EUS and EBUS should preferably be used for up-front mediastinal staging, mediastinoscopy with or without EUS should preferably be reserved for restaging, and especially right-sided pneumonectomies should be avoided. Though evident, the feasibility to complete this kind of studies within a reasonable time period is still a condition sine qua non.

Alpha-adrenergic contribution to the cardiovascular response to acute hypoxemia in the chick embryo.

Fetal responses to acute hypoxemia include bradycardia, increase in blood pressure, and peripheral vasoconstriction. Peripheral vasoconstriction contributes to the redistribution of the cardiac output away from ancillary vascular beds toward myocardial, cerebral, and adrenal circulations. We investigated the effect of alpha-adrenergic receptor blockade on this fetal response. Fluorescent microspheres were used to measure cardiac output distribution during basal and hypoxemic conditions with and without phentolamine treatment. Phentolamine altered basal cardiac output distribution, indicating a basal alpha-adrenergic tone, but this was mainly noted at the earlier stages of incubation. During hypoxemia, phentolamine prevented vasoconstriction in the carcass. At day 19 of incubation, the percent cardiac output distributed to the carcass increased by 20% compared with a decrease in the control group by 17%. Phentolamine markedly attenuated the subsequent redistribution of the cardiac output toward the brain (from +102% in the control group to -25% in the phentolamine-treated group) and the heart (from +196% in the control group to +69% in the phentolamine-treated group). In the chick embryo, alpha-adrenergic mechanisms contribute to the maintenance of basal vascular tone and to the redistribution of the cardiac output away from the peripheral circulations toward the brain and heart during hypoxemic conditions.

Unilateral fixed dilated pupil in a ventilated child with asthma.

An 11-year-old boy known to have asthma was referred to our intensive care unit (ICU) with progressive respiratory distress. He was sedated, paralysed, and intubated approximately 3 hours after arrival and nebulization with salbutamol and ipratropium was continued on the ventilator. About 16 hours later, he presented with transient unilateral fixed dilated pupils which resolved spontaneously without any neurological deficit. Computerized tomography scan revealed no signs of generalized cerebral oedema. Local contamination with ipratropium was most likely to be the cause of pupil dilatation, which could have occurred during connecting and disconnecting the nebulization system or through contaminated hands.

Bone marrow content measured in radioimmune bone marrow scintigraphy: intra- and inter-observer variability.

The aim of this study was to assess the possible quantification of vertebral residual bone marrow content relative to the bone marrow content of a non-irradiated vertebra. This method is based on the vertebral count activity, measured using radioimmune bone marrow scintigraphy. First, however, we had to evaluate intra- and inter-observer variability. In three patients who underwent radioimmune bone marrow scintigraphy, two independent observers measured the count density in 51 (15 lumbar and 36 thoracic) vertebrae using a manually drawn region of interest. To evaluate intra- and inter-observer variability, we calculated the means and standard deviations of the differences between measurements. Bland-Altman plots were drawn for all vertebrae as well as for three subgroups of vertebrae (the upper thoracic spine, D1-D6; the lower thoracic spine, D7-D12; and the lumber spine, L1-L5). For all vertebrae, the mean (+/- S.D.) difference, expressed as a percentage of the overall mean, was -0.44 +/- 3.3% for observer 1 and -0.3 +/- 2.1% for observer 2 for intra-observer variability; inter-observer variability varied from 0.55 +/- 3.9% to 1.28 +/- 3.7%. On the Bland-Altman plots, the data points were evenly distributed above and below the 0-line and the linear regression equations matched the line of equality almost perfectly. This pattern was observed for all the vertebrae as well as for the subgroups of vertebrae. In conclusion, our results show that the intra- and inter-observer variabilities are not great, confirming that this technique is simple and robust and can be used for further quantification of bone marrow content in the axial skeleton.

Palliative effectiveness of radiation therapy in the treatment of superior vena cava syndrome.

A study was made of 34 patients concerning the palliation effect of radiation therapy in the treatment of superior vena cava syndrome (SVCS). They were seen between 1986-1993, at the Department of Radiotherapy in Middelheim General Hospital, Belgium, Antwerp. All patients had a syndrome of superior vena cava obstruction secondary to malignancy. The histologic diagnosis delivered an equal distribution of small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). All patients with a SCLC received chemotherapy as initial treatment, but showed no response, relapse or evolution during treatment. Each treatment began with rapid-high dose irradiation, to continue after re-evaluation with rapid high-dose in cases of poor response or with the conventional fractionation of 2 Gy daily in patients showing good relief of symptoms. The initial rapid-high dose schedules depended on the performance status of the patients. Seventy-six percent of the patients with NSCLC showed good relief of their symptoms. It was very unexpected but the majority of NSCLC patients responded more quickly than SCLC patients, within three days after initiating treatment. In SCLC, 94% of the patients responded up until death. The palliation index defined as the ratio of the symptom-free period on the total survival which is 1 in ideal circumstances, was 0.55 in NSCLC and 0.90 in SCLC. In this last group, death was mainly due to disease progression in distant sites.

Radiotherapy for T2 and T3 carcinoma of the bladder: the influence of overall treatment time.

The influence of overall treatment time on local control rate was studied on a group of 147 patients with muscle invasive T2 or T3 transitional cell carcinoma of the urinary bladder. All patients received external radiotherapy at the Catharina Hospital, Eindhoven, The Netherlands between January 1974 and December 1984. Patients treated with overall treatment times shorter than 75 days (n = 92) were irradiated during a continuous course; all but one patient, with overall treatment times of 75 days or more (n = 55), received split-course radiotherapy. Actuarial local relapse-free probability at 3 years (LRFP3) was computed from the onset of radiotherapy. LRFP3 proved to be dependent on overall treatment time. For T2 stage, LRFP3 was 80 +/- 18% (n = 5) and 54 +/- 13% (n = 13) for overall times between 15-44 and 45-74 days, respectively, 36 +/- 14% (n = 11) for overall times between 75 and 104 days and 64 +/- 15% (n = 11) for overall times longer than 105 days. For T3 stage, LRFP3 was 33 +/- 19% (n = 6) and 48 +/- 10% (n = 25) for overall times between 15-44 and 45-74 days, respectively, 25 +/- 14% (n = 12) for overall times between 75 and 104 days and 22 +/- 14% (n = 9) for overall times longer than 105 days. The figures between brackets are numbers of patients relapsing within 3 years or at risk of relapse during at least 3 years. Patients who died without local relapse before 3 years were censored. We have reasons to believe that patient selection bias leads to overestimation of LRFP3 for the split-course radiotherapy in retrospective studies where the 'intention to treat' cannot be recalled. This retrospective study suggests that prolonging overall time of radiotherapy has an effect on local control in T2 and T3 transitional cell carcinoma of the urinary bladder. Local control was the worst for patients treated by split-course radiotherapy with a gap of approximately one month. Local control was not further decreased (and seemed even improved) by longer gaps, but this observation is possibly biased as explained in the discussion section. For patients treated by continuous course radiotherapy we could not find a difference in local control rates between patients treated with overall times of 44 days or less and those treated with overall times of 45-74 days.

Patterns of axillary lymph node metastasis in breast cancer.

The pattern of axillary lymph node involvement was analyzed in a review of 377 cases of T1-4 breast cancers. Clinical judgment of the axillary status proved to be wrong in approximately one-third of the cases. In univariate analysis, a strong correlation (P < .01) between the number of involved nodes, tumor size, and blood vessel invasion was found. Other features of the primary tumor (lymphatic invasion, degree of differentiation, presence of necrotic areas) were related to a lesser degree (P < .05). While others (age, site) were not at all significant. However, the number of nodes resected proved to be the most important determinant of all (P = .003). Also, the simple distinction between node-negative and node-positive cases is strongly dependent on the extent of axillary dissection (P = .009). In multivariate analysis, only the number of resected nodes and T stage showed a good relationship with the number of positive nodes. Skip metastases above levels 1 and 2 were seen in only 2% of the cases. A clear influence of the number of invaded nodes on survival could be demonstrated. These findings are discussed, especially as concerns the technique, prognostic significance, and therapeutic usefulness of axillary dissection.

Carcinoma of the urinary bladder: long-term results of interstitial radiotherapy.

Between January 1974 and December 1988, 46 patients with cancer of the urinary bladder, stages T1 or T2, and one patient with stage T3, were treated with an interstitial implant at the radiotherapy department of the Catharina Ziekenhuis at Eindhoven, The Netherlands. Prior to implantation, one patient received no external radiotherapy, all other 46 patients were treated by either a low dose (40 patients: 12 Gy median) or an intermediate dose (six patients: 38-40 Gy) of external radiotherapy. Loco-regional relapse was observed in 14/47 (30%) of the patients (1/14 also had distant metastases). The site of loco-regional relapse was the bladder in 11 patients and the immediate vicinity of the bladder in three patients. Only four patients died due to uncontrolled locoregional disease. A salvage cystectomy was performed in five patients. Distant metastases alone were observed in 3/47 (6.4%) of patients. The intercurrent death corrected actuarial 5 and 10-year survival was 79.5% (72.2% for T1; 85.7% for T2). The difference between T1 and T2 tumors was not significant (P = 0.55). During follow-up, 17/47 (36%) patients died. Cause of death was intercurrent disease in eight patients, bladder cancer in eight patients and unknown cause in one patient. For the whole group, seven patients developed second or third malignancies. Multivariate analyses using survival as the endpoint showed no significant prognostic variables, while using relapse-free survival (RFS) as the endpoint (calculated from the date of interstitial implant and with censoring for death from intercurrent disease) the number of TUR before implant (P = 0.01) and the dose of external radiation before interstitial implant (P = 0.045) were of prognostic significance, both being negatively correlated with RFS. As six patients had received an intermediate dose of interstitial radiotherapy, separate multivariate analyses were performed on the subgroup of 41 patients who had received a high dose of interstitial radiation. Using survival as the endpoint, again no prognostic significant factors were found, but in the analyses using local relapse-free period (LRFP) as the endpoint, dose rate (P = 0.026) and duration of implant (P = 0.021) were inversely correlated with LRFP. The higher the dose rate, the better the LRFP, while a long duration of implantation had a negative impact on the LRFP. Information concerning radiotherapy-related complications was not available in one patient, ulceration of the bladder mucosa was observed in 9/46 (19.6%) and bladder stone formation in 3/46 (6.5%) patients.(ABSTRACT TRUNCATED AT 400 WORDS)

T1 and T2 carcinoma of the urinary bladder: long term results with external, preoperative, or interstitial radiotherapy.

Between January 1974 and December 1984, 273 consecutive patients with cancer of the urinary bladder, Stages T1 or T2, any N, M0, were referred to the radiotherapy department of the Catharina Hospital at Eindhoven, The Netherlands and 265 were treated in a non-randomized fashion according to one of the three following schedules: 137 patients (67 T1, 70 T2) received radiotherapy only; 96 (44 T1, 52 T2) had preoperative radiotherapy followed by cystectomy and diversion according to the Bricker technique in 94/96; 32 patients (13 T1, 19 T2) had low total dose (12 Gy median) external radiotherapy followed by an interstitial cesium implant. The external radiotherapy fields included the pelvic structures. Total dose was 64 Gy median in the radiotherapy-only group and 40 Gy median in the preoperative irradiated group. The median follow-up in survivors was 81 months (range: 15-203). Locoregional relapse was observed in 50% in the group treated by external radiotherapy alone versus 17% in the group treated by preoperative radiation plus surgery and 28% of the patients who received cesium implant. During follow-up, 106/137 (77%), 67/96 (70%) and 13/32 (41%) patients died. In the radiotherapy-alone group, 38 died from intercurrent diseases, 36 from bladder cancer, two from therapy-related complications and cause of death was unknown in 30 patients. In the preoperative radiation group, the figures were 17 for intercurrent deaths, 26 related to progressive bladder cancer, 14 died due to perioperative complications and cause of death was unknown in 10. Cause of death was intercurrent in six and due to bladder cancer in seven patients treated by cesium implant. Probability of survival (calculated from the date of histological diagnosis) for the whole group, with censoring death to intercurrent disease was 53% at 5 years (56% for T1; 51% for T2) and 41% (40% for T1; 43% for T2) at 10 years. No significant difference was observed between T1 and T2 (p = 0.76). Survival in the treatment subgroups was, for patients treated by external radiotherapy only: 50% at 5 years and 33% at 10 years; for patients treated by external radiotherapy and surgery: 49% at 5 years and 42% at 10 years; for patients treated by cesium implant: 76% at 5 years and 76% at 10 years. Survival of patients in the cesium implant group was significantly better than in the other groups (p = 0.0001). Following variables were analyzed using the Cox proportional hazards model: age, gender, T1 or T2 stage, grade, cesium implant or not, and surgery or not.(ABSTRACT TRUNCATED AT 400 WORDS)

Incompletely resected rectum, recto-sigmoid, or sigmoid carcinoma: results of postoperative radiotherapy and prognostic factors.

Postoperative radiotherapy was given in 40 patients with gross or microscopic pathologically proven residual disease after surgical resection of rectum, recto-sigmoid, or sigmoid carcinoma. The radiotherapy target volume included the pelvis with (9 patients) or without (31 patients) the perineum. Median total dose of radiation was 50 Gy (range 30-60). One patient received 30 Gy, 10 received greater than 30 to 40 Gy, 13 received greater than 40 to 50 Gy, and 16 patients received greater than 50 to 60 Gy. The median follow-up in the survivors (16 patients) was 53 months (range: 16-85). Probability of survival with censoring for death due to intercurrent disease was 36% at 5 years. Survival for patients with microscopic residual disease (21 patients) was 40% at 5 years compared to 12% for those with gross residual disease (19 patients) (p = 0.09). Twenty-five patients relapsed. All but one relapse occurred earlier than 50 months after radiotherapy. Approximately half (12/25) of the relapses were observed within 6 months after radiotherapy. Local relapse inside the radiotherapy portals was observed in 9/40 (22%) patients. Therapy-related urogenital complications occurred in no patient and gastro-intestinal complications in three patients (7%). In one patient they were scored WHO grade 4 and in two patients WHO grade 3. Prognostic factors were analyzed using the Cox proportional hazards model. For survival differentiation, grade (p less than 0.001), stage (p = 0.04), and perineal irradiation (p = 0.03) were independent prognostic factors. With relapse-free survival as the endpoint, only stage (p = 0.003) was a statistically significant prognostic factor. There was a trend toward a better relapse-free survival when the perineum was included in the radiation portals (p = 0.09).

Bilateral horizontal gaze paralysis due to pontine hemorrhage. A case report.

In a case of bilateral horizontal gaze paralysis, vertical gaze was clinically intact but eye movement recordings demonstrated a transient reduction of vertical saccadic velocities. Horizontal caloric vestibulo-ocular responses were absent. CT scanning and NMR imaging showed a hematoma in the median pontine tegmentum. This case provides additional evidence that vertical and horizontal saccade genesis may be independent of caudal paramedian pontine reticular formation lesions.

The influence of physostigmine on visual-vestibular interaction in hereditary ataxias.

Visual suppression of caloric nystagmus was studied in five patients with hereditary ataxia before and after administration of physostigmine. All patients had an initial abnormal ocular fixation index that improved after physostigmine was given. The data indicate that there is a partly reversible disturbance of visual-vestibular interaction in patients with hereditary ataxia, caused by an impairment of a central cholinergic mechanism.

Cerebrospinal fluid glutamine levels and EEG findings in patients with hepatic encephalopathy.

The cerebrospinal fluid glutamine level was determined and an electro-encephalogram was made at roughly the same time in 41 patients on 55 occasions. A modified electro-encephalographic grading for practical use was introduced, because the classical electroencephalographic grading described by PARSONS-SMITH et al. (1957) does not apply to patients in deep coma. A significant correlation was found between the natural logarithms of cerebrospinal fluid glutamine levels and the electro-encephalic grade. In combination, these parameters provide valuable diagnostic and prognostic information in hepatic encephalopathy, and each can serve separately for follow-up purposes.

Cutaneous silent period in masseter muscles: a clinical and electrodiagnostic evaluation.

In 35 normal subjects electromyographic silent periods were constantly evoked bilaterally in the masseter muscles during maximal contraction after unilateral electrical stimulation over the infraorbital or mental nerve. Findings in this study and data obtained in 30 patients suffering from trigeminal (26) and facial (four) nerve lesions suggest that the silent period evoked according to our methods is cutaneous in origin. The trigeminal sensory root forms the afferent limb of the silent period reflex. Its central pathway is thought to pass both crossed and uncrossed through the pons. Determination of the cutaneous silent period might be of value for the demonstration of trigeminal nerve lesions and to supplement results concerning other brain-stem reflexes.

[Volitional postural dyskinesia with hypertrophic neuropathy]. / Dyskinésie volitionnelle d'attitude avec neuropathie hypertrophique

Two cases of voluntary postural dyskinesia with hypertrophic neuropathy are reported. Electron-microscope studies revealed in one case a hypertrophic neuropathy with onion bulb formation, in the other axonal degeneration. The findings are compared with those of Pierre Marie-Boveri disease, of Roussy-Lévy disease and with the case of Salisachs and Lapresle (1973).

Jaw and blind reflexes in trigeminal nerve lesions. An electrodiagnostic study.

Eighteen patients with intracranial trigeminal nerve lesions were investigated electrodiagnostically. The trigeminal motor root function was studied on the basis of the jaw reflex and masseter myograms and was disturbed in all cases. The jaw reflexes were abnormal in 16 and the masseter myograms in eight cases. An impressive trigeminal sensory root function was obtained from blink reflex, which was abnormal in 12 cases. The results show the diagnostic value of bilateral recording of the jaw reflex in such patients.