Perioperative or only adjuvant gemcitabine plus nab-paclitaxel for resectable pancreatic cancer (NEONAX)-a randomized phase II trial of the AIO pancreatic cancer group.

BACKGROUND: Data on perioperative chemotherapy in resectable pancreatic ductal adenocarcinoma (rPDAC) are limited. NEONAX examined perioperative or adjuvant chemotherapy with gemcitabine plus nab-paclitaxel in rPDAC (National Comprehensive Cancer Network criteria). PATIENTS AND METHODS: NEONAX is a prospective, randomized phase II trial with two independent experimental arms. One hundred twenty-seven rPDAC patients in 22 German centers were randomized 1 : 1 to perioperative (two pre-operative and four post-operative cycles, arm A) or adjuvant (six cycles, arm B) gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) on days 1, 8 and 15 of a 28-day cycle. RESULTS: The primary endpoint was disease-free survival (DFS) at 18 months in the modified intention-to-treat (ITT) population [R0/R1-resected patients who started neoadjuvant chemotherapy (CTX) (A) or adjuvant CTX (B)]. The pre-defined DFS rate of 55% at 18 months was not reached in both arms [A: 33.3% (95% confidence interval [CI] 18.5% to 48.1%), B: 41.4% (95% CI 20.7% to 62.0%)]. Ninety percent of patients in arm A completed neoadjuvant treatment, and 42% of patients in arm B started adjuvant chemotherapy. R0 resection rate was 88% (arm A) and 67% (arm B), respectively. Median overall survival (mOS) (ITT population) as a secondary endpoint was 25.5 months (95% CI 19.7-29.7 months) in arm A and 16.7 months (95% CI 11.6-22.2 months) in the upfront surgery arm. This difference corresponds to a median DFS (mDFS) (ITT) of 11.5 months (95% CI 8.8-14.5 months) in arm A and 5.9 months (95% CI 3.6-11.5 months) in arm B. Treatment was safe and well tolerable in both arms. CONCLUSIONS: The primary endpoint, DFS rate of 55% at 18 months (mITT population), was not reached in either arm of the trial and numerically favored the upfront surgery arm B. mOS (ITT population), a secondary endpoint, numerically favored the neoadjuvant arm A [25.5 months (95% CI 19.7-29.7months); arm B 16.7 months (95% CI 11.6-22.2 months)]. There was a difference in chemotherapy exposure with 90% of patients in arm A completing pre-operative chemotherapy and 58% of patients starting adjuvant chemotherapy in arm B. Neoadjuvant/perioperative treatment is a novel option for patients with resectable PDAC. However, the optimal treatment regimen has yet to be defined. The trial is registered with ClinicalTrials.gov (NCT02047513) and the European Clinical Trials Database (EudraCT 2013-005559-34).

Changes in diagnosis and operative treatment of insulinoma over two decades.

PURPOSE: Most insulinomas are small solitary, benign neoplasms. Imaging and surgical techniques improved over the last 20 years. Thus, the aim of the present study was to analyze changes in diagnosis and surgery of insulinoma patients in a referral center over two decades. METHODS: Operated patients with a histologically proven insulinoma were retrieved from a prospective database. Clinico-pathological characteristics and outcomes were retrospectively analyzed with regard to the time periods 2000-2010 (group 1) and 2011-2020 (group 2). RESULTS: Sixty-one of 202 operated patients with pNEN had an insulinoma, 37 (61%) in group 1 and 24 (39%) in group 2. Of those 61 insulinomas, 49 (80%) were sporadic benign, 8 (13%) benign MEN1-associated insulinomas, and 4 (7%) sporadic malignant insulinomas. In 35 of 37 (95%) patients of group 1 and all patients of group 2, the insulinoma was preoperatively identified by imaging. The most sensitive imaging modality was endoscopic ultrasound (EUS) with correctly diagnosed and localized insulinomas in 89% of patients in group 1 and 100% in group 2. In group 1, significantly less patients were operated via minimally invasive approach compared to group 2 (19% (7/37) vs. 50% (12/24), p = 0.022). Enucleation was the most frequently performed operation (31 of 61, 51%), followed by distal resection (15 of 61, 25%) without significant differences between groups 1 and 2. The rate of relevant postoperative complications was not different between groups 1 and 2 (24% vs. 21%, p = 0.99). Two patients with benign insulinoma (1 out of each group) experienced disease recurrence and underwent a second resection. After a median follow-up of 134 (1-249) months, however, all 57 (100%) patients with benign insulinoma and 3 out of 4 patients with malignant insulinoma had no evidence of disease. CONCLUSION: Insulinoma can be preoperatively localized in almost all patients, allowing for a minimally invasive, parenchyma-sparing resection in selected patients. The long-term cure rate is excellent.

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.

Radical Resection in Entero-Pancreatic Neuroendocrine Tumors: Recurrence-Free Survival Rate and Definition of a Risk Score for Recurrence.

BACKGROUND: Surgery with radical intent is the only potentially curative option for entero-pancreatic neuroendocrine tumors (EP-NETs) but many patients develop recurrence even after many years. The subset of patients at high risk of disease recurrence has not been clearly defined to date. OBJECTIVE: The aim of this retrospective study was to define, in a series of completely resected EP-NETs, the recurrence-free survival (RFS) rate and a risk score for disease recurrence. PATIENTS AND METHODS: This was a multicenter retrospective analysis of sporadic pancreatic NETs (PanNETs) or small intestine NETs (SiNETs) [G1/G2] that underwent R0/R1 surgery (years 2000-2016) with at least a 24-month follow-up. Survival analysis was performed using the Kaplan-Meier method and risk factor analysis was performed using the Cox regression model. RESULTS: Overall, 441 patients (224 PanNETs and 217 SiNETs) were included, with a median Ki67 of 2% in tumor tissue and 8.2% stage IV disease. Median RFS was 101 months (5-year rate 67.9%). The derived prognostic score defined by multivariable analysis included prognostic parameters, such as TNM stage, lymph node ratio, margin status, and grading. The score distinguished three risk categories with a significantly different RFS (p < 0.01). CONCLUSIONS: Approximately 30% of patients with EP-NETs recurred within 5 years after radical surgery. Risk factors for recurrence were disease stage, lymph node ratio, margin status, and grading. The definition of risk categories may help in selecting patients who might benefit from adjuvant treatments and more intensive follow-up programs.

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.

Management of primary and renal hyperparathyroidism: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: The purpose of this review is to provide updated recommendations for the surgical management of primary (pHPT) and renal (rHPT) hyperparathyroidism, formulating a new guideline of the German Association of Endocrine Surgeons (CAEK). METHODS: Evidence-based recommendations for the diagnosis and therapy of pHPT and rHPT were assessed by a multidisciplinary panel using PubMed for a comprehensive literature search together with a structured consensus dialogue (S2k guideline of the Association of the German Scientific Medical Societies, AWMF). RESULTS: During the last 20 years, a variety of new preoperative localization procedures, such as sestamibi-SPECT, 4D-CT, and various PET/CT procedures, were established for pHPT. High-resolution imaging, together with intraoperative parathyroid hormone (IOPTH) measurement, enabled focused or minimally invasive surgery to become the most favored surgical technique. Patients with pHPT and nonlocalizing imaging have a higher risk of multiglandular disease. Surgical therapy provides very high cure rates, with a clear relation to the surgeon's experience in parathyroid procedures. Reoperative parathyroidectomy, children with pHPT or familial forms, and parathyroid carcinoma are addressed and require special surgical expertise. A multidisciplinary team of experienced nephrologists, transplant, and endocrine surgeons should assess the diagnosis and treatment of renal HPT. CONCLUSION: Surgery is the only curative treatment for pHPT and should be considered for all patients with pHPT. For rHPT, a more selective approach is required, and parathyroidectomy is indicated only when conservative treatment options fail. In parathyroid carcinoma, the adequacy of local resection influences local disease control.

A retrospective comparison of robotic versus laparoscopic distal resection and enucleation for potentially benign pancreatic neoplasms.

PURPOSE: The present study aimed to compare robotic-assisted versus laparoscopic distal pancreatic resection and enucleation for potentially benign pancreatic neoplasms. METHODS: Patients were retrieved from a prospectively maintained database. Demographic data, tumor types, and the perioperative outcomes were retrospectively analyzed. RESULTS: In a 10-year period, 75 patients (female, n = 44; male, n = 31; median age, 53 years [range, 9-84 years]) were identified. The majority of patients had pancreatic neuroendocrine neoplasms (n = 39, 52%) and cystic neoplasms (n = 23, 31%) with a median tumor size of 17 (3-60) mm. Nineteen (25.3%) patients underwent enucleation (robotic, n = 11; laparoscopic, n = 8) and 56 (74.7%) patients underwent distal pancreatic resection (robotic, n = 24; laparoscopic, n = 32), of those 48 (85%) underwent spleen-preserving procedures. Eight (10.7%) procedures had to be converted to open surgery. The rate of vessel preservation in distal pancreatectomy was significantly higher in robotic-assisted procedures (62.5% vs. 12.5%, p = 0.01). Twenty-six (34.6%) patients experienced postoperative complications (Clavien-Dindo grade > 3). Twenty (26.7%) patients developed a pancreatic fistula type B. There was no mortality. After a median follow-up period of 58 months (range 2-120 months), one patient (1.3%) developed local recurrence (glucagonoma) after enucleation, which was treated with a Whipple procedure. CONCLUSION: The robotic approach is comparably safe, but increases the rate of splenic vessel preservation and reduces the risk of conversion to open surgery.

Anaplastic thyroid carcinoma: changing trends of treatment strategies and associated overall survival.

PURPOSE: The prognosis of anaplastic thyroid cancer (ATC) is poor. Despite various attempts to modify common treatment modalities, including surgery, external beam radiation (EBRT) and chemotherapy (CTX), no standardized treatment is yet established. This study aimed to analyze the changing trends of treatment concepts and associated overall survival (OS) over the last two decades. METHODS: A retrospective analysis was conducted on 42 patients with histologically confirmed ATC. The outcome measures included the evaluation of clinical characteristics and treatments performed with regard to OS. RESULTS: Median OS for all tumor stages was 6 (range 1 week-79) months, 6.5 months for stage IVA/B and 4 months for stage IVC carcinoma patients. Twenty-one patients with stage IVA/B carcinomas underwent curative treatment, including thyroidectomy with lymphadenectomy (TTX plus LAD, n = 11) or multimodal treatment with TTX plus LAD and EBRT plus/minus CTX (n = 10). The median OS of patients with stage IVA/B carcinomas was significantly prolonged after multimodal treatment than after surgery alone (25 vs. 3 months, p = 0.04). Fifteen of 18 patients with stage IVC carcinomas received palliative, 3 patients multimodal treatment. The median OS of stage IVC patients after trimodal therapy was not significantly longer than after debulking procedures (6 vs. 7 months, p = 0.25). In the time period 1999-2009, only 4 (21%) patients received multimodal treatment compared to 9 (39%) in the period from 2009 to 2019, but this did not result in a significantly prolonged survival in the latter period (8.5 vs. 15 months, p = 0.61). CONCLUSION: Concurrent radio- and/or chemotherapy in combination with surgery seems to result in improved survival in stage IVA/B ATC, whereas this is not the case in patients with stage IVC tumors. Novel treatment regimens are urgently needed to improve the dismal prognosis of ATC.

Surgical therapy of adrenal tumors: guidelines from the German Association of Endocrine Surgeons (CAEK).

BACKGROUND AND AIMS: Previous guidelines addressing surgery of adrenal tumors required actualization in adaption of developments in the area. The present guideline aims to provide practical and qualified recommendations on an evidence-based level reviewing the prevalent literature for the surgical therapy of adrenal tumors referring to patients of all age groups in operative medicine who require adrenal surgery. It primarily addresses general and visceral surgeons but offers information for all medical doctors related to conservative, ambulatory or inpatient care, rehabilitation, and general practice as well as pediatrics. It extends to interested patients to improve the knowledge and participation in the decision-making process regarding indications and methods of management of adrenal tumors. Furthermore, it provides effective medical options for the surgical treatment of adrenal lesions and balances positive and negative effects. Specific clinical questions addressed refer to indication, diagnostic procedures, effective therapeutic alternatives to surgery, type and extent of surgery, and postoperative management and follow-up regime. METHODS: A PubMed research using specific key words identified literature to be considered and was evaluated for evidence previous to a formal Delphi decision process that finalized consented recommendations in a multidisciplinary setting. RESULTS: Overall, 12 general and 52 specific recommendations regarding surgery for adrenal tumors were generated and complementary comments provided. CONCLUSION: Effective and balanced medical options for the surgical treatment of adrenal tumors are provided on evidence-base. Specific clinical questions regarding indication, diagnostic procedures, alternatives to and type as well as extent of surgery for adrenal tumors including postoperative management are addressed.

Preoperative Imaging Overestimates the Tumor Size in Pancreatic Neuroendocrine Neoplasms Associated with Multiple Endocrine Neoplasia Type 1.

BACKGROUND: Radiological tumor size of non-functioning pancreatic neuroendocrine neoplasms (Nf-pNENs) associated with multiple endocrine neoplasia type 1 (MEN1) is a crucial parameter to indicate surgery. The aim of this study was to compare radiological size (RS) and pathologic size (PS) of MEN1 associated with pNENs. METHODS: Prospectively collected data of MEN1 patients who underwent pancreatic resections for pNENs were retrospectively analyzed. RS was defined as the largest tumor diameter measured on endoscopic ultrasound (EUS), magnetic resonance imaging (MRI) or computed tomography (CT). PS was defined as the largest tumor diameter on pathological analysis. Student's t test and linear regression analysis were used to compare the median RS and PS. p < 0.05 was considered significant. RESULTS: Forty-four patients with a median age of 37 (range 10-68) years underwent primary pancreatic resections for pNENs. Overall, the median RS (20 mm, range 3-100 mm) was significantly larger than the PS (13 mm, range 4-110 mm) (p = 0.001). In patients with pNENs < 20 mm (n = 27), the size difference (median RS 15 mm vs PS 12 mm) was also significant (p = 0.003). However, the only modality that significantly overestimated the PS was EUS (median RS 14 mm vs 11 mm; p = 0.0002). RS overestimated the PS in 21 patients (21 of 27 patients, 78%). Five of 11 patients (12%) with a Nf-pNEN and a RS > 20 mm had in reality a PS < 20 mm. MRI was the imaging technique that best correlated with PS in the total cohort (r = 0.8; p < 0.0001), whereas EUS was the best correlating imaging tool in pNENs < 20 mm (r = 0.5; p = 0.0001). CONCLUSION: Preoperative imaging, especially EUS, frequently overestimates the size of MEN1-pNENs, especially those with a PS < 20 mm. This should be considered when indicating surgery in MEN1 patients with small Nf-pNENs.

Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms.

BACKGROUND: The incidence of asymptomatic, sporadic, small non-functioning pancreatic neuroendocrine neoplasms (NF-PNENs) has increased in recent decades. Conservative treatment has been advocated for these tumours. The aim of this study was systematically to evaluate the literature on active surveillance and to compare this with surgical management for asymptomatic sporadic small NF-PNENs. METHODS: PubMed, Embase and the Cochrane Library were searched systematically for studies that compared the active surveillance of asymptomatic, sporadic, small NF-PNENs with surgical management. PRISMA guidelines for systematic reviews were followed. RESULTS: After screening 3915 records, five retrospective studies with a total of 540 patients were included. Of these, 327 patients (60·6 per cent) underwent active surveillance and 213 (39·4 per cent) had surgery. There was wide variation in the tumour diameter threshold considered as inclusion criterion (2 cm to any size). The median length of follow-up ranged from 28 to 45 months. Measurable tumour growth was observed in 0-51·0 per cent of patients. Overall, 46 patients (14·1 per cent) underwent pancreatic resection after initial conservative treatment. In most patients the reason was an increase in tumour size (19 of 46). There were no disease-related deaths in the active surveillance group in any of the studies. CONCLUSION: This systematic review suggests that active surveillance of patients affected by sporadic, small, asymptomatic NF-PNENs may be a good alternative to surgical treatment.

Effect of high laser output on the central bronchi and pulmonary artery.

A diode-pump Nd:YAG high-power laser (wavelength 1320 nm, power 100 W) is routinely used to surgically remove lung metastases. Even pulmonary lesions in central locations are resectable via this method, yet it also carries a potential risk of damaging the larger bronchi and vessels in the vicinity. Studies investigating the safety of using high-power lasers are lacking. We therefore aimed to examine the direct effects of a 100-watt laser on the bronchi and pulmonary artery at a standard working velocity. From freshly slaughtered pigs, we isolated cylindrical specimens of the trachea, the main and lobar bronchi, and the central pulmonary artery from the both lungs. These specimens were fixed consecutively in rows behind each other on a Styrofoam surface in the laboratory. The laser's handle was clamped into a hydraulic feed unit so that the laser was focused at constant distance perpendicular to the tissue and would move at 10 mm/s over the specimens. The Nd:YAG Laser LIMAX® 120 functioned at a consistent power of 100 W during all the experiments. The lasered specimens were examined macroscopically and histologically for tissue damage. None of the trachea or bronchial walls were perforated. Compared to the pulmonary parenchyma, we observed no vaporization effects-only minor superficial coagulation (with a mean depth of 2.1 ± 0.8 mm). This finding was histologically confirmed in each specimen, which revealed mild superficial coagulation and no damage to the cartilage. In the presence of a residual peribronchial fatty tissue, the laser effect was even attenuated. The pulmonary arteries presented no lumen openings whatsoever, merely a discrete trace of coagulation. The vessel wall revealed increased vacuolization without alteration of the remaining vessel wall. In conclusion, laser resection at 100 W of the central lung areas is safe with respect to airways and blood vessels and the laser output does not need to be reduced when treating these areas.

Refinement of screening for familial pancreatic cancer.

OBJECTIVE: Surveillance programmes are recommended for individuals at risk (IAR) of familial pancreatic cancer (FPC) to detect early pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC). However, the age to begin screening and the optimal screening protocol remain to be determined. METHODS: IAR from non-CDKN2A FPC families underwent annual screening by MRI with endoscopic ultrasonography (EUS) in board-approved prospective screening programmes at three tertiary referral centres. The diagnostic yield according to age and different screening protocols was analysed. RESULTS: 253 IAR with a median age of 48 (25-81) years underwent screening with a median of 3 (1-11) screening visits during a median follow-up of 28 (1-152) months. 134 (53%) IAR revealed pancreatic lesions on imaging, mostly cystic (94%), on baseline or follow-up screening. Lesions were significantly more often identified in IAR above the age of 45 years (p<0.0001). In 21 IAR who underwent surgery, no significant lesions (PDAC, pancreatic intraepithelial neoplasia (PanIN) 3 lesions, high-grade intraductal papillary mucinous neoplasia (IPMN)) were detected before the age of 50 years. Potentially relevant lesions (multifocal PanIN2 lesions, low/moderate-grade branch-duct IPMNs) occurred also significantly more often after the age of 50 years (13 vs 2, p<0.0004). The diagnostic yield of potentially relevant lesions was not different between screening protocols using annual MRI with EUS (n=98) or annual MRI with EUS every 3rd year (n=198) and between IAR screened at intervals of 12 months (n=180) or IAR that decided to be screened at ≥24 months intervals (n=30). CONCLUSIONS: It appears safe to start screening for PDAC in IAR of non-CDKN2a FPC families at the age of 50 years. MRI-based screening supplemented by EUS at baseline and every 3rd year or when changes in MRI occur appears to be efficient.

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 Veins with 5 mm and 10 mm Instruments - Bursting Pressures Measured in an Ex-Vivo Model]. / Bipolare Versiegelung von Lungenvenen mit einem 5- und -10-mm-Instrument - Bestimmung der Berstdrücke an einem Ex-vivo-Modell.

BACKGROUND: In every anatomic lung resection, lung veins need to be sealed and divided. If open surgery is performed, veins are usually treated with ligatures. In minimally-invasive procedures a vascular stapler is used. Blood vessels can be securely closed with modern bipolar sealing technology. Since this method has rarely been used in lung veins, we carried out the present study on an ex-vivo model to test whether satisfactory bursting pressures can be achieved using 5 mm and 10 mm MARSEAL® sealing instruments. MATERIAL AND METHODS: The experimental investigations were carried out on heart-lung preparations (including both lungs) from freshly-slaughtered pigs (weight: 199 lbs). After the lung veins were dissected, three groups were formed according to size: group 1: 1-7 mm, group 2: 8-10 mm and group 3: > 10 mm. Bipolar sealing was performed with a 5 mm or 10 mm MARSEAL® sealing device and the special SealSafe® G5 electric current. Vessels closed by simple ligation served as a control group. A pressure sensor was implanted into the unsealed end of the blood vessel. Air was pumped into the blood vessel and the bursting pressure - the pressure (in mbar) at which the vessel began to leak - was determined digitally. The mean bursting pressures were compared using the non-parametric Mann Whitney U test (the level of significance was p < 0.05). RESULTS: In group 1 the mean bursting pressures for the 5 mm and 10 mm instruments were found to be 167.1 ± 38.7 mbar and 113.8 ± 23.3 mbar, respectively. Both were significantly inferior to the pressure of 178.8 ± 44.5 mbar achieved by the control group. In group 2 the bursting pressures were 122.7 ± 27.8 mbar with the 5 mm instrument and 93.5 ± 39.6 mbar with the 10 mm instrument. The mean bursting pressure for the control group was 180.7 ± 35.8.mbar. In group 3 the mean bursting pressures were 98.2 ± 28.8 mbar with the 5 mm instrument and 65.5 ± 19.7 mbar with the 10 mm instrument. All attempts to seal the entire left atrium failed. CONCLUSION: In our ex-vivo model of lung veins, acceptable bursting pressures were achieved in blood vessels with a maximum diameter of 10 mm. Bipolar impedance-controlled sealing may create an adequate seal on pulmonary veins up to a diameter of 10 mm. The use of a 10 mm instrument has no advantage compared to a 5 mm instrument. Secure sealing of the left atrium is not possible.

[Multifocal Pulmonary Neuroendocrine Tumours: Genesis, Diagnostics and Treatment]. / Multifokale neuroendokrine Lungentumoren: Entstehung, Diagnostik und Behandlung.

Multifocal neuroendocrine lung tumour is a rare diagnosis. Multiple lung foci of different sizes are usually apparent on chest CT scans. It is assumed that multifocal neuroendocrine lung tumours originally develop from diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH). This results in cell aggregations formed by proliferation of neuroendocrine cells that are already physiologically present in the bronchial system. If these cell proliferations break through the bronchial basement membrane, they are considered to constitute tumourlets if they measure ≤ 5 mm and carcinoid tumours if they are larger than 5 mm. The speed of proliferation of the cell hyperplasias appears to vary. Many of the patients are completely asymptomatic, the multifocal neuroendocrine lung tumours being diagnosed by chance. However, other patients complain of breathlessness, reduced physical capacity and cough. There may also be reduction of lung function. In these cases, chest HRCT often reveals peribronchial fibrosis or bronchiectasis in addition to the lung foci. Bronchoscopy is usually not helpful. Surgical lung biopsy is considered to be the diagnostic gold standard. Histological examination typically shows a mixture of cell hyperplasias, tumourlets and carcinoid tumours. There is no consensus on the treatment of multifocal neuroendocrine tumours. Taking the clinical situation and the chest HRCT findings as our starting point, we developed a stepwise approach that is guided by the success of the individual therapeutic procedures. The most favourable prognosis is found in affected people without clinical symptoms whose lung foci all measure less than 5 mm. In these cases the 5-year survival rate is over 90%.

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.

Well-differentiated neuroendocrine neoplasia: relapse-free survival and predictors of recurrence after curative intended resections.

BACKGROUND: Resection with curative intention is the cornerstone of treatment in patients with neuroendocrine tumors. A proportion of patients will relapse after R0 resection, but the factors predictive of recurrence are not well understood. METHODS: A database established 1998 at the University Hospital Marburg was queried for all patients with documented R0 resection. Recurrence-free survival and overall survival were estimated using the Kaplan-Meier method. Uni- and multivariate analyses were performed. RESULTS: 180 patients with a median age of 52 years entered the analysis. We observed 77 recurrences after a median time of 2.9 years. 24% of the recurrences occurred later than 5 years after operation. Median recurrence-free survival of the whole cohort was 101 months. In univariate analysis grade by Ki-67, stage, high lymph node ratio and microangioinvasion were significant predictors of recurrence. On multivariate analysis these parameters were confirmed as independent prognostic parameters with stage and microangioinvasion being the most important predictors. CONCLUSIONS: After R0 resection of neuroendocrine tumors, postoperative surveillance should be extended to at least 10 years. Patients with distant metastases and microangioinvasion are at high risk of recurrence. Clinical trials of adjuvant treatment protocols are indicated in these patients.

Heat dissipation after nonanatomical lung resection using a laser is mainly due to emission to the environment: an experimental ex vivo study.

Laser-directed resection of lung metastases is performed more frequently in recent years. The energy-loaded laser rays heat up the lung tissue, considerably. It is still unclear which mechanism is more important for tissue heat dissipation: the lung perfusion or the tissue emission. Therefore, we created a special experimental model to investigate the spontaneous heat dissipation after nonanatomical lung resection using a diode-pumped laser with a high output power. Experiments were conducted on paracardiac pig lung lobes (n = 12) freshly dissected at the slaughterhouse. Nonanatomical resection of lung parenchyma was performed without lobe perfusion in group 1 (n = 6), while group 2 (n = 6) was perfused at a physiological pressure of 25 cm H2O at 37 °C with saline via the pulmonary artery. For this, we used a diode-pumped neodymium-doped yttrium aluminum garnet (Nd:YAG) LIMAX® 120 laser (Gebrüder Martin GmbH & Co. KG, Tuttlingen, Germany) with a wavelength of 1,318 nm and a power output of 100 W. Immediately after completing laser resection, the lungs were monitored with an infrared camera (Type IC 120LV; Trotec, Heinsberg, Germany) while allowed to cool down. The resection surface temperature was taken at 10-s intervals and documented in a freeze-frame until a temperature of 37 °C had been reached. The temperature drop per time unit was analyzed in both groups. Immediately after laser resection, the temperature at the lung surface was 84.33 ± 8.08 °C in group 1 and 76.75 ± 5.33 °C in group 2 (p = 0.29). Group 1 attained the final temperature of 37 °C after 182.95 ± 53.76 s, and group 2 after 121.70 ± 16.02 s (p = 0.01). The temperature drop occurred exponentially in both groups. We calculated both groups' decays using nonlinear regression, which revealed nearly identical courses. The mean time of tissue temperature of >42 °C, as a surrogate marker for tissue damage, was 97.14 ± 26.90 s in group 1 and 65.00 ± 13.78 s in group 2 (p = 0.02). Heat emission to the environment surpasses heat reduction via perfusion in nonanatomically laser-resected lung lobes. In developing a cooling strategy, a topical cooling method would be promising.