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 After restaging, nine (31%) patients were excluded (interval metastasis, clinical deterioration, or withdrawn consent).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.

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.

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.

The prognostic value of abnormal findings on radiographic swallowing studies after total laryngectomy.

Pharyngocutaneous fistulae are a common complication after total laryngectomy. Our study evaluates the correlation of postoperative radiographic swallowing studies and clinical symptoms. We also propose a grading system to classify leaks radiographically. The records of 45 patients who underwent total laryngectomy were retrospectively reviewed. All patients had a radiographic swallowing study (RSS) on or around the tenth postoperative day. A grading system was developed to classify radiographic findings (grade 0-5). Twenty-two patients had an abnormal RSS (grade 2-5). Three patients (13.6%) had clinical signs of impending fistula whereas radiography showed moderate leakage (grade 3) in one patient and a pharyngocutaneous fistula (grade 5) in two. The other 19 patients with radiographically demonstrated leakage had no clinical signs of anastomotic complications. After total laryngectomy, radiography may reveal anastomotic complications of varying severity. The grading system used in this study enabled us to objectively classify the radiological abnormalities on swallowing studies. Because most radiographic leakages were clinically silent and not all clinically apparent fistula were radiographically visible in our study, the role of routine postoperative radiographic swallowing studies in the absence of clinical signs or fistula remains unclear.

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.

[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.

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.

[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 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.

[Pasteurella anatipestifer: a controllable farm problem]. / Pasteurella anatipestifer: een beheersbaar bedrijfsprobleem.

The performance of 13 flocks of ducks on a duck farm decreased markedly. Post-mortem and bacteriological examinations indicated that Pasteurella anatipestifer was a major cause, although Salmonella spp., Escherichia coli and Treponema spp. were also detected. Use of an autovaccine against Pasteurella anatipestifer markedly reduced the signs and symptoms in the second part of fattening period.

[A severe Aspergillus flavus infection in slaughtering chicks and the effect of disinfection with enilconazole: a case study]. / Een ernstige Aspergillus flavus-infectie bij slachtkuikens en het effect van desinfectie met enilconazole: een case study.

In a flock of chicks, the number of birds dying per day from infection with especially Aspergillus flavus increased up to 1% during the second half of the fattening period. Levels of Aspergillus flavus were measured before and after cleaning of the chicken house with the anti-mycotic agent eniconazole (Clinafarm, Janssen Pharmaceutical Company, BV). The cleaning and disinfection schedule followed reduced levels if Aspergillus flavus to zero.

Comparison of the enzyme linked immunosorbent assay, the haemagglutination inhibition test and the agar gel precipitation test for the detection of antibodies against infectious bronchitis and Newcastle disease in commercial broilers.

Serological results as obtained by the agar gel precipitation (AGP) test, haemagglutination inhibition (HI) test (M41, D274, D1466) and an enzyme linked immunosorbent assay (ELISA) from commercial broiler flocks, which had suffered from a clinical infectious bronchitis (IB) infection in the fattening period, were compared with serological findings of control broiler flocks. In addition the Hi-test and ELISA for Newcastle disease (ND) were compared. The AGP results differ significantly between groups. The test had a low sensitivity. The results of the HI-IBV tests were similar for both groups and no difference was seen between flocks with or without clinical IB problems. The IBV ELISA showed a highly significant difference between the two groups. In contrast to the low and not significant correlation coefficients (r) between the IBV HI tests and the ELISA, the value of r between the NDV HI and ELISA was high. The results indicate an ELISA as the preferred test for the diagnosis of IB in broilers.

[Candida albicans infection in Japanese nightingales: diagnosis therapy and supplementary measures]. / Infectie met Candida albicans bij Japanse nachtegalen: diagnose, therapie en aanvullende maatregelen.

Yeast and fungal infections may constitute a major problem in aviary birds. A case of yeast infection is reported, which was possibly due to antibiotherapy and malnutrition. Ketoconazole is effective in controlling this type of infection. Methods by which these infections may be prevented are recommended, as well as examinations which are useful in aviary birds.

[A case of cryptosporidiosis in breeding laying hens with Marek's disease]. / Een geval van cryptosporidiose bij opfokleghennen met de ziekte van Marek.

The simultaneous occurrence of Marek's disease and cryptosporidiosis in two flocks of rearing pullets on a multi-age farm with rearing-pullets and layers, is reported. This is the first report of cryptosporidiosis in rearing pullets in the Netherlands and also the first time that the combination of this infection with Marek's disease is mentioned.

[Gumboro's disease continues to claim attention: a case report]. / De ziekte van Gumboro blijft de aandacht vragen: een 'case study'.

An outbreak of Gumboro disease occurred at the end of 1988 on a broiler farm having four houses and birds of two different age groups. The infection 'lingered' in the subsequent flocks, a striking feature consisting in the fact that the pattern of disease was identical in almost every case. Symptoms of Gumboro disease were not observed in the compartment housing the oldest broilers. The birds in this house continued to show low titres at the close of the fattening period. Gumboro disease was observed on the 19th and 20th days of life or on the 29th-33rd days of life in the other houses. Mortality was highest in the latter case. The final conclusion is that the difference in age between the houses probably makes the high pressure of infection possible. Consistent vaccination reduced the problem of Gumboro disease on the farm.