[Operability and Pathological Response of Non-Small Cell Lung Cancer (NSCLC) after Neoadjuvant Therapy with Immune Checkpoint Inhibition]. / Operabilität und pathologisches Ansprechen des Lungenkarzinoms nach neoadjuvanter Therapie mit Immun-Checkpoint-Inhibitoren.

BACKGROUND: The blockade of immune escape mechanisms (e. g. PD1 /PD-L1) using immune checkpoint inhibition (ICI) can significantly prolong survival and induce remission in patients with advanced non-small cell lung cancer (NSCLC). Less is known about neoadjuvant ICI in patients with resectable (UICC stage III) or oligometastatic (UICC stage IVa) NSCLC. METHODS: Tissue biopsies from patients with advanced or oligometastatic NSCLC were screened for PD-L1 expression. In case of PD-L1-expression > 50 %, ECOG status of 0 or 1 and expected operability, patients received ICI. After about four weeks, patients underwent thoracic surgical resection. In all patients, a complete staging, including PET-CT, cMRI, and endobronchial ultrasound, was performed. The tolerability, the radiological and the histopathological tumor response as well as the surgical and oncological outcomes were analyzed. FINDINGS: Four patients (2 male, 2 female, age 56 - 78 years, n = 3 adenocarcinoma, n = 1 squamous cell carcinoma) with local advanced tumors received ICI before surgical resection. In three cases the mediastinal lymph nodes were positive. One patient had a single cerebral metastasis which was treated with radiotherapy. All four patients underwent therapy with two to six cycles of ICI (3â€Š× pembrolizumab, 1â€Š× atezolizumab) without any complication, and ICI did not delay the time of surgical resection. According to iRECIST, three patients showed partial response (PR), one patient had stable disease (SD). All tumors were completely resected. The thoracic surgical procedures proved to be technically unproblematic despite inflammatory changes. There were neither treatment-related deaths nor perioperative complications. In the resectates, complete pathological response (CPR, regression grade III ) and regression grade IIb were detected twice. The average time of follow-up was 12 (1 - 24) months. Patients with PPR developed distant metastasis after six months or a local recurrence after four months. The CPR patient is relapse free to date. CONCLUSION: In selected patients, neoadjuvant therapy with ICI is well tolerated and can induce a complete remission of the tumor. Treatment with ICI has no negative impact on the surgical procedure. Prognosis seems to be promising in CPR and limited in PPR.

Intravascular (post-hysterectomy) leiomyoma (IVL) as late tumor thrombus within the inferior vena cava (IVC)-A rare case primarily imposing as IVC thrombus originating from left renal vein after former left nephrectomy status.

INTRODUCTION: Intravascular leiomyoma is a rare type of myoma. It was firstly described by Birch-Hirschfeld in 1896, however, its intracardiac subtype was firstly reported by Durck in 1907. Most patients are asymptomatic. The tumor invades mostly the tributaries of the inferior vena cava (IVC) with upward extension that may approach the intracardiac space. AIM: By means of a scientific case report, a patient with the very rare diagnosis of an endocaval leiomyoma thrombus post-hysterectomy is described based on the clinical experiences obtained in the specific case management and selective references from the literature. CASE PRESENTATION: A 48-years old female was diagnosed with intravascular tumor growth within the IVC with intracardiac extension using chest and abdominal CT scan, ECG and echocardiography which was approached by an interdisciplinary (vascular and cardiothoracic) surgical intervention (278 min) including heart-lung machine (99 min) with favorable postoperative result (R0 resection status with mid-term outcome, no recurrent tumor growth). Histopathological investigation diagnosed leiomyoma origin already from ovarian vein most likely in context to the former hysterectomy (3 years ago). DISCUSSION AND CONCLUSION: Intravascular leiomyoma is a benign tumor with invasive tendency, which can be considered a diagnostic and therapeutic challenge. It should be thoroughly investigated to be planned for a radical surgical removal. By possible adherence to the intraabdominal or -thoracic organs, an interdisciplinary and eventually step-wise surgical approach (combining vascular, abdominal, thoracic and heart surgery as well as gynecology and urology), which can be demanding, is recommended to be seriously considered to i) reliably achieve R0 resection status and, thus, ii) provide best outcome, quality of life and prognosis.

[Hybrid prosthesis for vascular reconstruction of the internal carotid artery near the skull base after radical excision of a very rare malignant glomus caroticum paraganglioma]. / Hybridprothese als schädelbasisnahes Interponat für die A. carotis interna bei radikaler Entfernung eines äußerst seltenen malignen Glomus-caroticum-Paraganglioms.

BACKGROUND: Neck tumors are challenging regarding the diagnostic and therapeutic management particularly in cases of malignant growth near relevant vessels to achieve R0 resection status and the best prognosis. AIM: The aim of this case report on a patient with a rare malignant tumor of the glomus caroticum (paraganglioma) is to present the successful outcome of a demanding interdisciplinary surgical approach (otorhinolaryngology and vascular surgery). Surgical re-intervention was necessary due to malignant tumor growth (detected in the histopathological investigation of the first specimen) including vascular resection using a hybrid graft for vascular reconstruction of the internal carotid artery near the skull base. CASE REPORT: A 38-year-old male patient underwent magnetic resonance angiography and digital subtraction angiography to clarify the diagnosis of a tumor in the right neck. This was preoperatively embolized and subsequently resected including vascular reconstruction using a prosthetic interposition graft (7 cm; W.L. Gore, Putzbrunn, Germany) between the common and internal carotid arteries. HISTOLOGY: malignant paraganglioma 40 mm in diameter with haemangiosis et lymphangiosis carcinomatosa demonstrating lymph node metastasis and prompting re-operation (neck dissection levels II, III, IV, V). This was followed by a novel vascular reconstruction using a GORE® hybrid vascular graft prosthetic stent (W.L. Gore) as interposition graft because of the short extracranial stump of the distal internal carotid artery near the skull base and to limit clamping time. Early postoperative outcome revealed no complications and after 24 months there were no signs or symptoms of recurrent tumor growth. CONCLUSION: Extended resections, if necessary including vascular (arterial) segments, aim at achieving R0 classification as shown in this extremely rare and usually challenging malignant tumor. Hybrid vascular prostheses are suitable for time-saving vascular reconstruction (>50%) to provide sufficient blood supply.

Clinical symptom tool that raises the index of suspicion for eosinophilic oesophagitis in adults and drives earlier biopsy for definitive diagnosis.

BACKGROUND: Eosinophilic oesophagitis (EoE) and gastro-oesophageal reflux disease (GERD) present with overlapping symptomatology and it is challenging to distinguish EoE from GERD clinically before endoscopy. AIM: To investigate the prognostic value of a set of clinical symptoms and laboratory values in patients with EoE and GERD. METHODS: In this prospective, single-centre, observational study, we compared clinical and laboratory data from 202 patients with EoE or GERD (10 relevant characteristics). Those characteristics showing potential significance in a univariate analysis were then included in a multivariate analysis. RESULTS: The set of 10 characteristics (10-marker set) was able to distinguish between EoE and GERD with good reliability (correct assignment, i.e. agreement with subsequent EGD, of 94.4%). Reduction of the set to the six statistically and clinically most relevant markers continued to give good reliability (88.9%), and further stepwise reduction led to four-marker sets comprising history of atopy, history of food impaction, proton pump inhibitor refractory symptoms and either immunoglobulin E or peripheral eosinophilia, with correct assignment rates of 91.3% and 85.1% respectively. CONCLUSIONS: We have developed a simple and easily applicable clinical/laboratory marker set that helps to distinguish EoE from GERD earlier in the treatment course, thus guiding the endoscopist to perform biopsies from the oesophagus to ensure the diagnosis. The application of the scoring system is expected to diagnose EoE earlier and avoiding delay of adequate treatment.

Leukotriene receptor expression in esophageal squamous cell cancer and non-transformed esophageal epithelium: a matched case control study.

BACKGROUND: Leukotriene B4 (LTB4R and LTB4R2) and cysteinyl leukotriene receptors (CYSLTR1 and CYSLTR2) contribute to malignant cell transformation. We aimed to investigate the expression of LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 in esophageal squamous cell carcinoma and adjacent non-transformed squamous epithelium of the esophagus, as well as in control biopsy samples from esophageal squamous epithelium of patients with functional dyspepsia. METHODS: Expression of LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 was analyzed by immunohistochemistry (IHC) and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) in biopsy samples of 19 patients with esophageal squamous cell cancer and 9 sex- and age-matched patients with functional dyspepsia. RESULTS: LTB4R, LTB4R2, CYSLTR1 and CYSLTR2 were expressed in all biopsy samples. Major findings were: 1) protein levels of all leukotriene receptors were significantly increased in esophageal squamous cell cancer compared to control mucosa (p < 0.05); 2) CYSLTR1 and CYSLTR2 gene expression was decreased in cancer tissue compared to control at 0.26-fold and 0.23-fold respectively; 3) an up-regulation of LTB4R (mRNA and protein expression) and a down-regulation of CYSLTR2 (mRNA expression) in non-transformed epithelium of cancer patients compared to control (p < 0.05) was observed. CONCLUSIONS: The expression of leukotriene receptors was deregulated in esophageal squamous cell cancer. Up-regulation of LTB4R and down-regulation of CYSLTR2 gene expression may occur already in normal squamous esophageal epithelium of patients with esophageal cancer suggesting a potential role of these receptors in early steps of esophageal carcinogenesis. Larger studies are warranted to confirm these observations.

[Contralateral hepatic hypertrophy following unilateral yttrium-90 radioembolization : Implications for liver surgery]. / Kontralaterale Leberhypertrophie nach einseitiger Yttrium-90-Radioembolisation : Implikationen für die Leberchirurgie.

BACKGROUND: Preservation of an adequate future liver remnant (FLR) is the principal limitation to liver surgery in patients with primary or secondary liver malignancies. Hence, methods to increase the volume of the FLR in preparation for liver resection are gaining in importance. OBJECTIVE: In addition to the traditional methods for induction of FLR hypertrophy, such as portal vein embolization (PVE) or portal vein ligation (PVL) with or without parenchymal dissection (ALPPS, in situ split), radioembolization (RE) using yttrium-90 microspheres also leads to a volume increase of non-embolized liver parenchyma. This review outlines its potential role as an alternative procedure for induction of liver hypertrophy. MATERIAL AND METHODS: Synopsis and critical discussion of the available literature on the mechanisms of induction of liver hypertrophy, the advantages and drawbacks of the traditional methods, and current research on volume changes associated with RE as well as their implications for possible clinical use in preparation for liver surgery. RESULTS: Both PVE and PVL can achieve a substantial contralateral volume gain of up to 70 %. The development of contralateral hypertrophy can be accelerated by dissecting the liver parenchyma along the intended plane of resection in addition to PVL (in situ split). Compared to these methods, RE achieves less contralateral liver hypertrophy; however, this effect should not be disregarded as RE provides effective treatment of ipsilateral liver tumors along with induction of hypertrophy and may be associated with a reduced risk of tumor progression compared to PVE and PVL. CONCLUSION: The available data suggest that RE can complement the armamentarium of methods for induction of FLR hypertrophy in specific situations. Further studies are needed to establish its definitive role for this indication and are in preparation.

Impact of the angulus biopsy for the detection of gastric preneoplastic conditions and gastric cancer risk assessment.

BACKGROUND: Gastric atrophy and intestinal metaplasia (IM) are preneoplastic conditions in the development of gastric cancer. Histopathological assessment is based on the updated Sydney system and superordinate staging systems, operative link on gastritis assessment (OLGA) and operative link on gastritis assessment using IM (OLGIM), all requiring a biopsy from the incisura angularis (angulus). AIM: To determine the value of the angulus biopsy for the detection of preneoplastic conditions and cancer risk evaluation using OLGA and OLGIM prospectively. METHODS: Biopsies from antrum (2), angulus (1) and corpus (2) were obtained from 213 patients (age 19-94 years, median 54 years, female to male ratio 138:75) undergoing upper endoscopy. Histological assessment according to the updated Sydney system, OLGA and OLGIM staging was performed by gastrointestinal pathologists. Statistical analysis used exact confidence limits for dichotomous variables and repeated measurement analysis of variance. RESULTS: 8% of the cases with atrophic gastritis and 3% with IM (17 vs 6/213) would have been missed without the angulus biopsy. More patients were diagnosed with a preneoplastic condition when the angulus biopsy was considered (13.1%, CI 8.9% to 18.4%), but the grade of atrophy, if present at both sides, did not vary significantly in angulus and antrum. OLGA and OLGIM scores dropped significantly when recalculated without the angulus (difference in means±SD 0.131±0.402 and 0.075±0.313, respectively). The impact on the identification of high-risk stages is limited. CONCLUSIONS: The angulus biopsy adds to the detection of mild gastric atrophy in particular. It allows identifying a small additional number of patients with high-risk gastritis.

Autoimmune gastritis in autoimmune thyroid disease.

BACKGROUND: Autoimmune gastritis leads to oxyntic gastric atrophy, a condition at increased risk for gastric cancer. Autoimmune gastritis in conjunction with autoimmune thyroid disease has been reported previously. AIM: In a case-control study in patients with autoimmune thyroid disease to evaluate the usefulness of serum pepsinogens for the identification of oxyntic gastric atrophy, and to determine the relationship of Helicobacter pylori with oxyntic gastric atrophy. METHODS: Patients with autoimmune thyroid disease (cases) and goitre (controls) were prospectively enrolled in the study. Pepsinogen (PG) I levels ≤25 µg/mL and PG I/II ratio ≤3 were indicative for oxyntic gastric atrophy. Antibodies against H. pylori, CagA and parietal cells were also determined. Esophagogastroduodenoscopy with biopsies was offered to patients with serological oxyntic gastric atrophy. RESULTS: In total, 34 autoimmune thyroid disease patients and 30 controls were enrolled. Serological oxyntic gastric atrophy was present only in autoimmune thyroid disease patients (8/34, 23.5%, OR 8.3, 95% CI = 1.9-36.2). In all eight patients oxyntic gastric atrophy was confirmed by histology. OLGA stage I, II, III and IV was described in 0%, 33%, 50% and 17% of the cases, respectively. About, 89% and 11% of oxyntic gastric atrophy patients were seropositive for antibodies against parietal cells or H. pylori infection, respectively. Gastric atrophy involved the angulus/antrum in 50% of patients with autoimmune gastritis. CONCLUSIONS: The seroprevalence of oxyntic gastric atrophy is high in patients with autoimmune thyroid disease, and testing of serum pepsinogens should be included in the clinical assessment of these patients. H. pylori infection is unlikely to be a principal factor in the pathogenesis of oxyntic gastric atrophy in patients with autoimmune thyroid disease. In autoimmune gastritis, gastric atrophy can spread from the oxyntic towards the antral mucosa.

Histomorphological differentiation of non-erosive reflux disease and functional heartburn in patients with PPI-refractory heartburn.

BACKGROUND: Proton pump inhibitor (PPI)-refractory heartburn may be due to persistent gastro-oesophageal reflux, oesophageal hypersensitivity or functional heartburn (FH). The differentiation between non-erosive reflux disease (NERD) and FH may be very difficult. However, this differentiation is important for appropriate therapeutic management. Dilated intercellular spaces (DIS), papillary elongation (PE) and basal cell hyperplasia (BCH) can be all assessed by light microscopy. Whether these mucosal abnormalities allow the differentiation of NERD from FH in PPI-refractory patients is uncertain. AIM: To assess histopathological findings by light microscopy in patients with refractory heartburn to differentiate NERD from FH. METHODS: Sixty-two patients with PPI-refractory symptoms underwent EGD and MII-pH after pausing PPI medication for 2 weeks before investigation. Twenty-five subjects without upper gastrointestinal symptoms were included as controls. Symptom assessment was based on the reflux disease questionnaire (RDQ). Biopsies were taken 3-5 cm above the gastro-oesophageal junction. DIS, PE, BCH and infiltration of immune cells were evaluated and a sum score was calculated. RESULTS: Based on endoscopy and MII-pH, GERD was diagnosed in 43 patients (NERD: 20; ERD: 23) and FH in 19 patients. There was no difference in symptoms between the groups. Each individual histopathological item was different between the groups (P < 0.0001). Between NERD and FH, the most significant difference was found for DIS and the histopathological sum score (P < 0.001). CONCLUSIONS: These findings suggest that oesophageal biopsies are useful to differentiate NERD from FH. Increased DIS and a histological sum score are the most significant histopathological abnormalities in NERD as compared with FH.