Mutation-based, short-term "neoadjuvant" treatment allows resectability in stage IVB and C anaplastic thyroid cancer.

INTRODUCTION: Few available data indicate that a mutation-based "neoadjuvant" therapy in advanced anaplastic thyroid carcinoma (ATC) might convert an initially unresectable primary tumor to resectable and optimize local tumor control. We evaluated a preoperative short-term "neoadjuvant" therapy with a BRAF-directed therapy or, in case of BRAF non-mutated tumors, an mKI/checkpoint inhibitor combination in three patients with ATC stage IVB and C. METHODS: In the context of preoperative diagnostics, immunohistochemistry (IHC) assessment and genetic analysis was started as soon as possible. The antiangiogenetic therapy with lenvatinib was immediately after diagnosis of ATC started as bridging therapy. In case of a BRAF-mutated ATC, a combination therapy of dabrafenib and trametinib, in case of BRAF-wildtype ATC a combination of pembrolizumab and lenvatinib was given for 4 weeks. If re-staging has shown a significant therapy response due to a decrease in size of > 50%, surgical resection was reconsidered. A primary tumor resection was performed first. As a second step, limited distant metastasis have been resected approximately 4 weeks after thyroid surgery. After postoperative recovery, the targeted systemic therapy was continued. PATIENTS: Two patients presented with BRAF-wildtype ATC stage IVC, one with BRAF-mutated ATC stage IVB. All patients were evaluated by surgery, nuclear medicine and oncology upon diagnosis of ATC. RESULTS: In all three cases, the "neoadjuvant" therapy induced a dramatic response and led to local resectability in primarily non-resectable ATC stage IVB or C. We have chosen for the first time a short-term "neoadjuvant" treatment period to reduce the risk of bleeding and/or fistula due to potential rapid tumor shrinkage. The results of surgery after only short-term "neoadjuvant" therapy showed two R0 und one R1 resections. Postoperative histopathological findings confirmed an extent of tumor necrosis or regressive fibrotic tissue between 60 and > 95% in our patients. CONCLUSIONS: A short-term mutation-based "neoadjuvant" therapy can achieve local resectability in initially unresectable ATC stage IVB or C. A neoadjuvant treatment period of about 4 weeks seems to show similar response as a treatment duration of at least 3 months.

Local lung coagulation post resection: an ex-vivo porcine model.

Following non-anatomical resection of lung parenchyma with a Nd:YAG laser, a coagulated surface remains. As ventilation starts, air leakage may occur in this area. The aim of the present study was to investigate, whether additional coagulation either before or after ventilation has an additional sealing effect. Freshly slaughtered porcine heart-lung blocks were prepared. The trachea was connected to a ventilator. Using a Nd:YAG laser (wavelength: 1320 nm, power: 60 W), round lesions (1.5 cm in diameter) with a depth of 1.5 cm were applied to the lung using an 800-µm laser fiber (5 s per lesion). Group 1 (n = 12) was control. Additional coagulation was performed in group 2 (n = 12) without and in group 3 (n = 12) with ventilation restarted. Air leakage (ml) from the lesions was measured. The thickness of each coagulation layer was determined on histological slices. Differences between individual groups were analyzed by one-way ANOVA (significance p < 0.05). After resection, 26.2 ± 2.7 ml of air emerged from the lesions per single respiration in group 1. Air loss in group 2 was 24.6 ± 2.5 ml (p = 0.07) and in group 3 23.7 ± 1.8 ml (p = 0.0098). In comparison to groups 1 and 2 thickness of the coagulation layers in group 3 was significantly increased. After non-anatomical porcine lung resection with a Nd:YAG laser, additional coagulation of the ventilated resection area can reduce air leakage.

Cell-free cartilage repair in large defects of the knee: increased failure rate 5 years after implantation of a collagen type I scaffold.

INTRODUCTION: Cartilage defects of the knee remain a challenging problem in orthopedic surgery despite the ongoing improvements in regenerative procedures such as the autologous chondrocyte transplantation. Due to the lack of donor-site morbidity and the single-stage procedure cell-free scaffolds are an interesting alternative to cell-based procedures. But as currently mid- and long-term data are lacking, the aim of the present study was to present mid-term clinical, radiological and histological results of a cell-free collagen type I scaffolds for cartilage repair. MATERIALS AND METHODS: Twenty-eight patients were followed prospectively. Clinical evaluation using patient-reported outcome measures (KOOS, IKDC; VAS for pain, Tegner score for activity) as well as radiologic evaluation of the repair tissue (MOCART) was performed at 1 year, 2 years and 5 years. Histologic evaluation of the repair tissue was done in case of revision surgery using the ICRS II score for human cartilage repair. RESULTS: In these large cartilage defects with a mean defect size of 3.7 ± 1.9 cm2, clinical failure necessitating revision surgery was seen in 5 of 28 patients (18%). While the remaining patients showed good-to-excellent clinical results (KOOS, IKDC, VAS, Tegner), the radiologic appearance of the repair tissue showed a reduction of the MOCART score between the 2- and 5-year follow-up. Histologic evaluation of the repair tissue showed a cartilage-like appearance with no signs of inflammation or cell death but an overall medium tissue quality according to the ICRS II Score. CONCLUSION: The use of this cell-free collagen type I scaffold for large defects showed increased wear of the repair tissue and clinical failure in 18% of cases at 5-year follow-up.

Investigations of initial airtightness after non-anatomic resection of lung parenchyma using a thulium-doped laser with different optical fibres.

Lung metastases in healthy patients should be removed non-anatomically whenever possible. This can be done with a laser. Lung parenchyma can be cut very well, because of its high energy absorption at a wavelength of 1940 nm. A coagulation layer is created on the resected surface. It is not clear, whether this surface also needs to be sutured to ensure that it remains airtight even at higher ventilation pressures. It would be helpful, if suturing could be avoided, because the lung can become too puckered, especially with multiple resections, resulting in considerable restriction. We carried out our experiments on isolated and ventilated paracardiac lung lobes of pigs. Non-anatomic resection was carried out reproducibly using three different thulium laser fibres (230, 365 and 600 µm) at two different laser power levels (10 W, 30 W) and three different resection depths (0.5, 1.0 and 2.0 cm). Initial airtightness was investigated while ventilating at normal frequency. We also investigated the bursting pressures of the resected areas by increasing the inspiratory pressure. When 230- and 365-µm fibres were used with a power of 10 W, 70 % of samples were initially airtight up to a resection depth of 1 cm. This rate fell at depths of up to 2 cm. All resected surfaces remained airtight during ventilation when 600-µm fibres were used at both laser power levels (10 and 30 W). The bursting pressures achieved with 600-µm fibres were higher than with the other fibres used: 0.5 cm, 41.6 ± 3.2 mbar; 1 cm, 38.2 ± 2.5 mbar; 2 cm, 33.7 ± 4.8 mbar. As laser power and thickness of laser fibre increased, so the coagulation zone became thicker. With a 600-µm fibre, it measured 145.0 ± 8.2 µm with 10 W power and 315.5 ± 6.4 µm with 30 W power. Closure with sutures after non-anatomic resection of lung parenchyma is not necessary when a thulium laser is used provided a 600-µm fibre and adequate laser power (30 W) are employed. At deeper resection levels, the risk of cutting small segmental bronchi is considerably increased. They must always be closed with sutures.

Bipolar sealing of lung parenchyma: tests in an ex vivo model.

BACKGROUND: Almost every pulmonary lobe resection requires cutting the lung parenchyma in the area of a lung fissure. A monopolar cutter or stapler is often used for this purpose. The seal should be absolutely airtight to prevent post-operative pulmonary fistulas. In the present study, the bipolar sealing technique was evaluated regarding air tightness of the seals during normal ventilation and its burst pressure in an ex vivo animal model. MATERIALS AND METHODS: The investigations were carried out on paracardial lung lobes obtained from heart-lung preparations taken from freshly killed pigs at a slaughter house. In the laboratory, each individual lobe was perfused with Ringer's solution at body temperature and protectively ventilated through a tube (frequency: 20 1/min, p insp = 20 mbar, PEEP +5 mbar). Non-anatomic resection was carried out in the periphery of the lung lobe. The two control groups (12 lobes per group; Group 1-stapler, Group 2-parenchyma suture) were compared to three groups in which different bipolar sealing instruments were used. They were Group 3-MARSEAL(®) 10 mm (KLS Martin, Tuttlingen); Group 4-MARSEAL(®) 5 mm; and Group 5-MARCLAMP(®) (KLS Martin, Tuttlingen). The SealSafe(®) G3 electric current was used in all cases. Ventilation was continued for 20 min following parenchymal resection. Parenchymal sealing was then judged visually in a water bath and given a score (0-3). Burst pressure (mbar) was measured by increasing the inspiration pressure stepwise. Group mean values were compared (nonparametric Mann-Whitney U test, p < 0.005). RESULTS: Parenchymal seals were airtight under ventilation throughout the observation period in all groups. Mean burst pressures were as follows: Group 1: 47.1 ± 6.2 mbar; Group 2: 32.9 ± 3.9 mbar; Group 3: 38.8 ± 2.2 mbar; Group 4: 25.0 ± 6.4 mbar; and Group 5: 32.9 ± 5.8 mbar. Group 1, the stapler group, thus exhibited the highest burst pressures. Burst pressures for Group 3 were significantly greater than those for Group 2 (p < 0.006). Burst pressures for groups 2 and 5 were similar (p = 0.97). However, the burst pressures for Group 4 were significantly lower than those for Group 2 (p < 0.001). CONCLUSION: MARSEAL(®) 10 mm and MARCLAMP(®) achieved adequate burst pressures compared to the two control groups and thus might be suitable for clinical use.