Safety and Feasibility of Robot-Assisted Minimally Invasive Esophagectomy (RAMIE) with Three-Field Lymphadenectomy and Neoadjuvant Chemoradiotherapy in Patients with Resectable Esophageal Cancer and Cervical Lymph Node Metastasis.

BACKGROUND: In the West, patients with cervical lymph node metastasis of resectable esophageal cancer at diagnosis are generally precluded from curative treatment. This study prospectively explored the safety and feasibility of neoadjuvant chemoradiotherapy followed by robot-assisted minimally invasive esophagectomy (RAMIE) with three-field lymphadenectomy for these patients. METHODS: Between 2015 and 2021, patients with resectable thoracic esophageal cancer and cervical lymph node metastasis were recruited nationwide in the Netherlands. Patients without interval metastasis following neoadjuvant chemoradiotherapy and good physical condition underwent RAMIE with bilateral three-field lymphadenectomy. Safety was predefined as ≤50% Clavien-Dindo grade ≥3b postoperative complications. RESULTS: Neoadjuvant chemoradiotherapy was administered to 29 patients (19 (66%) adenocarcinoma and 10 (34%) squamous cell carcinoma). After restaging, nine (31%) patients were excluded (interval metastasis, clinical deterioration, or withdrawn consent). RAMIE was performed in 20 patients (R0-rate 95%). A median of 42 [range 21-71] lymph nodes were resected of which 13 [range 2-35] were cervical. Only 1 (5%) patient had an unexpected contralateral cervical lymph node metastasis. Complications grade ≥3b occurred in 50%. Most frequent complications of any grade were recurrent laryngeal nerve palsy (45%) and pneumonia (40%). Overall survival at 1 year was 85% and quality of life at 6 months was comparable to esophageal cancer patients treated with curative intent. CONCLUSIONS: RAMIE with three-field lymphadenectomy following neoadjuvant chemoradiotherapy for patients with resectable esophageal cancer presenting with cervical lymph node metastasis is feasible in a Western population. Because contralateral cervical metastasis is rare, a unilateral neck dissection would suffice in the majority of cases. CLINICAL TRIAL: gov Identifier: NCT02426879. Dutch trial register Identifier: NTR 4552.

The value of postoperative anticoagulants to improve flap survival in the free radial forearm flap: a systematic review and retrospective multicentre analysis.

BACKGROUND: Free radial forearm flap (FRFF) reconstruction is a valuable technique in head and neck surgery, which allows closure of large defects while striving to maintain functionality. Anticoagulative drugs are often administered to improve flap survival, although evidence regarding effectiveness is lacking. OBJECTIVE OF REVIEW: To investigate the effectiveness of postoperative anticoagulants to improve survival of the FRFF in head and neck reconstruction. TYPE OF REVIEW: Systematic review and multicentre, individual patient data meta-analysis. SEARCH STRATEGY: MEDLINE, EMBASE, Web of Science and CINAHL were searched for synonyms of 'anticoagulants' and 'free flap reconstruction'. EVALUATION METHOD: Studies were critically appraised for directness of evidence and risk of bias. Authors of the highest quality publications were invited to submit their original data for meta-analysis. RESULTS: Five studies were of adequate quality, and data from four studies (80%) were available for meta-analysis, describing 759 FRFF procedures. Anticoagulants used were as follows: aspirin (12%), low molecular weight dextran (18.3%), unfractioned heparin (28.1%), low molecular weight heparin (49%) and prostaglandin-E1 (2.1%). Thirty-one per cent did not receive anticoagulants. Flap failure occurred in 40 of 759 patients (5.3%) On univariate analysis, use of unfractioned heparin was associated with a higher rate of flap failure. However, these regimens were often administered to patients who had revision surgery of the anastomosis. In multivariate logistic regression analysis, anticoagulant use was not associated with improved flap survival or flap-related complications. CONCLUSIONS: The studied anticoagulative drugs did not improve FRFF survival or lower the rate of flap-related complications. In addition, some anticoagulants may cause systemic complications.

Observing stage-shifts in head and neck squamous cell carcinoma from initial clinical outpatient staging to definite clinical tumour board staging using radiological and endoscopical investigations: will less do?

OBJECTIVES: Staging head and neck squamous cell carcinoma usually is initiated in the outpatient department (OPD) using patient history and physical examination. To reach consensus on stage and therapy, imaging and panendoscopy are more or less routinely applied as additional staging tests. Staging results from the outpatient department were evaluated for tumour and neck stage. We investigated in which situations additional staging tests are needed. DESIGN: Prospective cohort study. SETTING: Head and Neck Oncology Group, University Medical Centre. PARTICIPANTS: Of 341 patients, initial staging results from the outpatient department were compared with the ultimate staging results from the tumour board review, which provides the basis for decisions on therapy. MAIN OUTCOME MEASURES: Tumour stage and neck stage migrations during this staging tract. RESULTS: In staging head and neck tumours are squamous cell carcinomas, additional staging tests like imaging and/or panendoscopy remain necessary to evaluate the primary tumour stage. Average accuracies of T-staging in oral cavity, pharynx and larynx only amount to 71%, 47% and 61%, respectively. For T1N0 and T2N0 oral cavity tumours, neck assessment in the outpatient department was accurate in 100% (95% CI: 91-100%) and 93% (95% CI: 80-98%), respectively. In the larynx group, this was 100% (95% CI: 91-100%) and 97% (95% CI: 86-100%), respectively. CONCLUSIONS: For oral cavity and laryngeal tumours staged as T1-2N0 in the outpatient department, we concluded that the outpatient department staging is highly predictive of the final pre-treatment staging. In these cases, computer tomography and/or MRI remain a necessity but additional ultrasound with or without fine needle aspiration cytology can be omitted. In our institution, this would have resulted in a 46% reduction in ultrasound procedures. If T-stage is upgraded during imaging or panendoscopy, additional staging tests for N-stage should still be considered.

A nation-wide epidemiological study on the risk of developing second malignancies in patients with different histological subtypes of nasopharyngeal carcinoma.

OBJECTIVE: Risk assessment of second head/neck and Epstein Barr Virus (EBV)-related malignancies in patients with different nasopharyngeal carcinoma (NPC) subtypes. METHODS: This is a cross-sectional study. Pathology records were retrieved from PALGA (a Dutch pathology registry database) between 1995 and 2013. Second primary malignancy (SPM) data was extracted from PALGA. Odds ratios (OR) for SPM in the head/neck, and the upper/lower airways were calculated using logistic regression. Pearson X(2)-test and Fisher's exact test were used to assess the relationship between NPC (and EBV-status) with SPM. Standardized incidence rates (SIR) were calculated. RESULTS: Histologically diagnosed NPC (keratinizing and undifferentiated and differentiated non-keratinizing subtypes) (n=1175) were identified. NPC patients have an increased risk of second head/neck malignancies (SIR 4.7 95% CI 3.3-6.5). Keratinizing NPCs have an OR of 1.947 (95% CI 1.362-2.782) for SPM, an OR of 4.026 (95% CI 2.308-7.023) for carcinomas of the upper/lower airways, an OR of 4.306 (95% CI 2.299-8.066) for head/neck malignancies, an OR of 5.289 (95% CI 2.740-10.211) for HNSCC with a SIR of 4.7 (95CI 3.3-6.5). Non-keratinizing NPCs also have an increased risk of head/neck malignancies with a SIR of 3.2 (95% CI 1.8-5.1), but less than keratinizing NPCs (p=<0.001). Positive EBV-status is not associated with (EBV-related) SPM. CONCLUSION: NPCs have a higher risk of SPM regardless of EBV status. SPM (especially HNSCC and malignancies of the upper aerodigestive tract) are more prevalent in keratinizing NPC compared to non-keratinizing NPC. Close clinical follow-up of NPC patients, with specific attention on SPM, is justified.

Eimeria acervulina: influence of corticosterone-induced immunosuppression on oocyst shedding and production characteristics in broilers, and correlation with a computer simulation model.

An experiment was conducted to investigate the effects of immune responsiveness on excretion of oocysts after E. acervulina infection and subsequent effects on production characteristics of broilers (Gallus domesticus). These effects were determined in broilers repeatedly infected with 2.85 x 10(3) oocysts of E. acervulina and treated with various dosages of corticosterone in the diet (0, 10, 20 and 30 p.p.m.). Corticosterone treatment did not have an effect on the peak oocyst excretion, although it was administered from 4 days before initial infection. The number of oocysts excreted shortly after the peak and the length of the excretion period were increased in corticosterone-treated groups. The absence of a difference in peak oocyst excretion was ascribed to the existence of a time-lag between first contact with the parasite and rate of development of protective immunity. In a recently developed computer simulation model this period was assumed to be 5 days. Assuming that immunosuppression, through corticosterone, is only effective when protective immunity is in operation, the results indicate a time-lag of at least a few days, which supports the inclusion of such a time-lag in the computer simulation model. General immunosuppressive effects of the corticosterone treatment, monitored by antibodies and mitogen-induced lymphocyte stimulation confirmed that immunosuppression occurred shortly after medication started. Infection did not have a significant influence on production characteristics in animals without dietary corticosterone. However, with increasing corticosterone levels the negative effects of infection on production also increased.

Revision surgery for chronic otitis media: a learning experience. Report on 389 cases with a long-term follow-up.

The objective of this study was to evaluate, during a long-term follow-up period, the results of revision surgery for chronic otitis media with or without cholesteatoma. Intact canal wall and canal wall down procedures were performed. The surgical history of every patient was assessed before the operation. A dry, relatively safe, and disease-free ear was created in 90% of the reoperated ears (N = 389). The recurrence rate of cholesteatoma was 5% for the total group. Reperforations of the tympanic membrane occurred in 10%, and persistent or recurrent otorrhea was present in 10% of cases. The functional hearing results were quite satisfactory. A residual air-bone gap of < or =30 dB was reached in 70.3% of the cases after revision tympanoplasty only (N = 41). Revision mastoidectomy with revision tympanoplasty as a one-stage procedure led subsequently, in 76% of intact canal wall procedures (N = 113) and 55% of canal wall down procedures (N = 98), to a residual air-bone gap of < or =30 dB.

Influence of coccidiosis on growth rate and feed conversion in broilers after experimental infections with Eimeria acervulina and Eimeria maxima.

Under experimental conditions, the effects of subclinical Eimeria (E.) acervulina and E. maxima infections on growth and feed conversion in broilers of different ages were analysed. It was concluded that infection with E. acervulina and E. maxima led to a process which was independent of the age at which the birds were infected. The infection adversely affected growth and feed conversion for 2 to 3 weeks, followed by a recovery period of 2 to 3 weeks when compensatory growth took place. From this study it may be concluded that subclinical coccidiosis in the first weeks of life and in the last week of life of broilers does not lead to appreciable damage on growth and feed conversion. Since coccidiosis cannot be avoided in practice, systems in which broilers contact subclinical coccidiosis either in the first weeks of life or in the last week of life should be aimed for. It is suggested that in a coccidiostat programme an efficient anticoccidiosis agent is particularly desirable in the 3rd and 2nd week before slaughter. Examinations performed one week or less before slaughter can hardly be justified, on the grounds that there is a risk of a negative effect on growth an feed conversion due to subclinical coccidiosis.

[Treatment of Frey's syndrome with botulinum A toxin]. / Behandeling van het syndroom van Frey met botuline A toxine.

A 74-year-old woman suffered from severe gustatory sweating and flushing of the preauricular skin following parotidectomy (Frey's syndrome). She was treated with intracutaneous botulinum A toxin injections in the affected skin area. Minor's test was used to determine the extent of the affected area. Within one week, the symptoms disappeared. After three weeks, Minor's test was repeated and showed minimal residual hyperhidrosis. These small areas were treated again. No side effects were noted. At follow-up one year later, the patient was free of symptoms.

[More than 10 years of revision-cleaning and revision-reconstructive ear surgery in chronic otitis media; good long-term results]. / Meer dan 10 jaar revisie-sanerende en revisie-reconstructieve oorchirurgie bij chronische otitis media; goede langetermijnresultaten.

OBJECTIVE: To describe the long-term results of revision surgery in patients with chronic otitis media. SETTING: University Hospital, Utrecht, the Netherlands. METHODS: A personal series of 323 revision mastoidectomies and (or) revision tympanoplasties was evaluated. Surgery was performed between 1981-1995 with a follow-up of one (minimal) to 14 years (maximal). Anatomical and functional results of various subgroups were compared. RESULTS: A preoperative incidence of cholesteatoma of 34% (n = 99) dropped after revision surgery to 11% residual/recurrent cholesteatomas (n = 9). A dry, safe and disease-free ear with a closed tympanic membrane was obtained in nearly 90% of the cases. However, in 5% (n = 10) without pre-existent cholesteatoma (n = 199), a cholesteatoma developed de novo after revision surgery. A residual air-bone hearing gap < or = 30 dB resulted in 79% of the patients after revision tympanoplasty only (n = 27). Revision mastoidectomy with revision tympanoplasty in open (n = 91) and closed (n = 92) procedures lead to a residual air-bone gap < or = 30 dB in 56% of the open cases (n = 91) and in 73% of the closed cases (before the operation the figures were 37% and 55% respectively). CONCLUSION: Revision mastoid surgery and (or) revision tympanoplasty can be quite rewarding and successful.

[Coccidiosis control: current status concerning preventive and therapeutic possibilities]. / Coccidiose-bestrijding: de huidige stand van zaken betreffende preventieve en therapeutische mogelijkheden.

A summary is presented of the present situation in coccidiosis control in poultry, regarding the use of anticoccidial drugs and of therapeutics. Also attention is payed to the development of vaccines, which usage is limited up till now. Monitoring the incidence of coccidiosis will be necessary in future to enable efficient use of anticoccidial drugs and therapeutics.

[Effect of Baytril (Bay Vp 2674) on young turkeys with respiratory tract infections]. / Effect van Baytril (Bay Vp 2674) op jonge kalkoenen lijdende aan luchtweginfecties.

Severe intestinal and respiratory infections were detected in young birds on a turkey farm. Treatment with various antibiotics produced varying results. Administration of Baytril (Bay Vp 2674), a new chemotherapeutic agent against Mycoplasma, was found to have a satisfactory effect.

[Epidemiology of Eimeria in broiler chicks as influenced by anticoccidial agents]. / Epidemiologie van Eimeria bij slachtkuikens onder invloed van anticoccidia.

1,729 Flocks from seventy-three broiler farms, belonging to three integrated groups, were studied for the presence of coccidiosis during a five-year period. An overall average of 50.3 per cent of the flocks was found to be infected. There were marked difference between the integrated groups. Differences were also observed in the severity of infections, expressed in a relative coccidiosis score. A relatively high incidence of coccidiosis was particularly observed in autumn and winter flocks. Other conditions such as respiratory tract infections and leg defects were found to present a different seasonal pattern. Variations in the incidence of Eimeria species were observed during treatment with anticoccidial drugs. Repeated administration of the same agents resulted in changes in the spectrum; among other things, the number of mixed infections increased. Particularly so-called shuttle programmes using nicarbazin were found to be effective in suppressing coccidiosis.

[Coccidiosis in broiler chicks: the prevalence of oocysts in feces in relation to necropsy findings in (sub)clinical coccidiosis and the effect of nicarbazin on these findings]. / Coccidiose bij slachtkuikens: het vóórkomen van oöcysten in faeces in relatie tot sektiebevindingen bij (sub)klinische coccidiose en het effekt hierop van nicarbazin.

Faecal samples were also collected from broiler farms presenting birds for autopsy. 126 Samples were examined, using two methods. Oocysts were detectable 3.5 days previously on an average before the presence of coccidiosis was determined at autopsy. Of the faecal samples 65.9 per cent were positive, and 46.0 per cent of the findings at autopsy were positive for coccidiosis. Examination of the faeces showed that more cases of mixed infection were present than could be concluded from autopsy. The largest number of oocysts was observed in E. acervulina infection, though large numbers of oocysts were also detected in cases of mixed infection. Treatment with nicarbazin during te first three weeks of life was found to delay the appearance of coccidiosis. The frequent use of withdrawal periods in the administration of anticoccidial drugs in view of 'thinning' showed high excretion rates.

[Monensin/sulfachlorpyrazine poisoning in turkeys]. / Monensin/sulfachloorpyrazine intoxicatie bij kalkoenen.

Symptoms of paralysis were observed in seven-week-old turkeys on a farm following administration of sulphachlorpyrazine for coccidiosis. Paralysis was particularly common in the females which were separated from the male birds. Of monensin 122 ppm were found to be present in the feed, whereas the amount stated on the label was 100 ppm. When a new batch was substituted for this feed, the symptoms abated. As the result of a possible interaction of monensin and sulphachlorpyrazine, mortality was 1.7 per cent in the male and 11.2 per cent in the female birds.

[Blue wing disease and chicken anemia agent in broilers]. / Blauwe Vleugeltjes Ziekte en Chicken Anaemia Agent bij slachtkuikens.

Cases of typical dermatitis were observed on nineteen broiler farms in the province of Gelderland, the Netherlands, ever since 1984. These bloody inflammations occasionally caused a large number of rejects, particularly during the second and third weeks of life. A relationship with Gumboro disease was identified in a number of cases. The causative agent probably is a virus originating from birds of the broiler-breeding poultry flocks. This may possibly be the Chicken Anaemia Agent virus.

[The mystery of the staggering turkeys: a differential diagnostic puzzle]. / Het mysterie van de wankelende kalkoenen: een differentieel diagnostisch zoekplaatje.

Over a short period of time, turkeys of various ages from three flocks were sent in with a history of paralysis. In the first necropsies there were no clear signs of the cause of the paralysis. On clinical examination of the flocks it was noted that the birds staggered as if drunk and that standing caused them pain. It was only with the last case that it became clear that the cause was rickets. Analysis of the feed demonstrated that level of vitamin D3 was too low, possibly even in the premix.

Coccidiosis in Broilers. / Coccidiose bij slachtkuikens.

The Eimeria species in chickens are discussed in a review of the literature. Besides the development of the parasite, attention is paid to the relationship between host and parasite. Recently, immunological features of coccidiosis in broilers are also arousing increasing interest. Not only because of the fact that immunity has been found to play a role in Eimeria infections in broilers despite the use of anticoccidial agents, but also in view of the possibility of vaccination.

[Poisoning due to ionophore anticoccidial drugs in poultry]. / Intoxicatie door ionofore anticoccidia bij pluimvee.

Ionophore polyether antibiotics are used as anticoccidial drugs in poultry. However, these pharmaceutical agents are also being increasingly used as growth-promoting substances in stock and pig farming. Overdosage of ionophore anticoccidial drugs may cause typical symptoms of poisoning, viz. paralysis and an increased proportion of rejects. In addition to providing a method for detecting a high dosage in the feed, histological examination and determination of the creatine phosphokinase level of the serum are found to be of importance. The ionophore anticoccidial drugs used and their incompatibility with therapeutical agents are reviewed in tabular form. Seven cases of poisoning in broilers, laying hens, breeding birds and turkeys in the province of Gelderland are also reported.