Mode mixing and losses in misaligned microcavities.

We present a study on the optical losses of Fabry-Pérot cavities subject to realistic transverse mirror misalignment. We consider mirrors of the two most prevalent surface forms: idealised spherical depressions, and Gaussian profiles generated by laser ablation. We first describe the mode mixing phenomena seen in the spherical mirror case and compare to the frequently-used clipping model, observing close agreement in the predicted diffraction loss, but with the addition of protective mode mixing at transverse degeneracies. We then discuss the Gaussian mirror case, detailing how the varying surface curvature across the mirror leads to complex variations in round trip loss and mode profile. In light of the severe mode distortion and strongly elevated loss predicted for many cavity lengths and transverse alignments when using Gaussian mirrors, we suggest that the consequences of mirror surface profile are carefully considered when designing cavity experiments.

Pneumoperitoneum, pneumomediastinum and subcutaneous emphysema following argon plasma coagulation treatment of colonic angioectasia.

INTRODUCTION: The paper presents unusual symptoms as a complication of therapeutic colonoscopy. CASE REPORT: A 70-year-old polymorbid female patient in chronic dialysis program underwent argon plasma coagulation treatment of leaking angioectasias in the cecum and ascending colon. Shortly after the procedure she presented with shortness of breath and subcutaneous emphysema of the neck which was initially misdiagnosed as swelling. Further tests revealed pneumoperitoneum, subcutaneous emphysema and pneumomediastinum. Considering the high risks for our patient (comorbidities, obesity), a laparoscopic approach was indicated. During laparoscopy neither peritonitis nor intestinal perforation were found. The patient recovered without complications after further complex treatment. CONCLUSION: Shortness of breath and subcutaneous emphysema are not typically among the first symptoms of colonoscopic perforation. Our case confirms that we should bear this complication in mind and when suspected, the diagnostic process should be started without delay.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

Rationale and design of the CRAFT (Continuous ReAssessment with Flexible ExTension in Rare Malignancies) multicenter phase II trial.

BACKGROUND: Approvals of cancer therapeutics are primarily disease entity specific. Current molecular diagnostic approaches frequently identify actionable alterations in rare cancers or rare subtypes of common cancers for which the corresponding treatments are not approved and unavailable within clinical trials due to entity-related eligibility criteria. Access may be negotiated with health insurances. However, approval rates vary, and critical information required for a scientific evaluation of treatment-associated risks and benefits is not systematically collected. Thus clinical trials with optimized patient selection and comprehensive molecular characterization are essential for translating experimental treatments into standard care. PATIENTS AND METHODS: Continuous ReAssessment with Flexible ExTension in Rare Malignancies (CRAFT) is an open-label phase II trial for adults with pretreated, locally advanced, or metastatic solid tumors. Based on the evaluation by a molecular tumor board, patients are assigned to combinations of six molecularly targeted agents and a programmed death-ligand 1 (PD-L1) antagonist within seven study arms focusing on (i) BRAF V600 mutations; (ii) ERBB2 amplification and/or overexpression, activating ERBB2 mutations; (iii) ALK rearrangements, activating ALK mutations; (iv and v) activating PIK3CA and AKT mutations, other aberrations predicting increased PI3K-AKT pathway activity; (vi) aberrations predicting increased RAF-MEK-ERK pathway activity; (vii) high tumor mutational burden and other alterations predicting sensitivity to PD-L1 inhibition. The primary endpoint is the disease control rate (DCR) at week 16; secondary and exploratory endpoints include the progression-free survival ratio, overall survival, and patient-reported outcomes. Using Simon's optimal two-stage design, 14 patients are accrued for each study arm. If three or fewer patients achieve disease control, the study arm is stopped. Otherwise, 11 additional patients are accrued. If the DCR exceeds 7 of 25 patients, the null hypothesis is rejected for the respective study arm. CONCLUSIONS: CRAFT was activated in October 2021 and will recruit at 10 centers in Germany. TRIAL REGISTRATION NUMBERS: EudraCT: 2019-003192-18; ClinicalTrials.gov: NCT04551521.

High tumour mutational burden and EGFR/MAPK pathway activation are therapeutic targets in metastatic porocarcinoma.

BACKGROUND: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Due to the lack of effective therapies, metastasis is associated with a high mortality rate. OBJECTIVES: To investigate the drivers of EPC progression. METHODS: We carried out genomic and transcriptomic profiling of metastatic EPC (mEPC), validation of the observed alterations in an EPC patient-derived cell line, confirmation of relevant observations in a large patient cohort of 30 tumour tissues, and successful treatment of a patient with mEPC under the identified treatment regimens. RESULTS: mEPC was characterized by a high tumour mutational burden (TMB) with an ultraviolet signature, widespread copy number alterations and gene expression changes that affected cancer-relevant cellular processes such as cell cycle regulation and proliferation, including a pathogenic TP53 (tumour protein 53) mutation, a copy number deletion in the CDKN2A (cyclin dependent kinase inhibitor 2A) region and a CTNND1/PAK1 [catenin delta 1/p21 (RAC1) activated kinase 1] gene fusion. The overexpression of EGFR (epidermal growth factor receptor), PAK1 and MAP2K1 (mitogen-activated protein kinase kinase 1; also known as MEK1) genes translated into strong protein expression and respective pathway activation in the tumour tissue. Furthermore, a patient-derived cell line was sensitive to EGFR and MEK inhibition, confirming the functional relevance of the pathway activation. Immunohistochemistry analyses in a large patient cohort showed the relevance of the observed changes to the pathogenesis of EPC. Our results indicate that mEPC should respond to immune or kinase inhibitor therapy. Indeed, the advanced disease of our index patient was controlled by EGFR-directed therapy and immune checkpoint inhibition for more than 2 years. CONCLUSIONS: Molecular profiling demonstrated high TMB and EGFR/MAPK pathway activation to be novel therapeutic targets in mEPC.

Avian schistosome species in Danish freshwater lakes: relation to biotic and abiotic factors.

Due to the increased prevalence of human infections with bird schistosome larvae (cercarial dermatitis) associated with bathing in Danish lakes, a nationwide survey of infected intermediate host snails was conducted in 2018-2020. Pulmonate snails (10,225 specimens) were collected from 39 freshwater lakes (in the four major geographic regions in Denmark) and subjected to shedding. Released schistosome cercariae were isolated and identified by polymerase chain reaction and sequencing whereby Trichobilharzia regenti, Trichobilharzia franki, Trichobilharzia szidati and Trichobilharzia anseri were recorded. Infections were primarily determined by biotic factors such as the presence of final host birds and intermediate host snails and water temperature was noted as an important abiotic parameter associated with the infection. No clear connection with other abiotic factors (conductivity, alkalinity, pH, nitrogen, phosphorous) was seen. The widespread occurrence of infected snails, when compared to previous investigations, suggests that climate changes at northern latitudes could be responsible for the increased risk of contracting cercarial dermatitis.

Is high age a contraindication to pulmonary resection?

INTRODUCTION: As the population ages, there are increasing numbers of elderly patients diagnosed with operable primary pulmonary malignancy or other lesions requiring pulmonary resection. The objective of the study was to evaluate post-operative outcomes in the elderly group and compare them with younger patients undergoing the same surgery. METHODS: Retrospectively, we evaluated our own set of 424 patients undergoing anatomical pulmonary resection for primary lung cancers and other resectable lesions in 20112020. 328 patients underwent open procedures, and VATS lobectomy was performed 96 times. We evaluated the set of patients in terms of 30-day morbidity and mortality using Clavien-Dindo classification modified for pulmonary resections. We compared the patient subgroups by age (under 55, 5564 years old, 6574 years and over 75 years). RESULTS: A non-biometric Kruskal-Wallis test was used to compare the groups. We have not shown a statistically significant difference in the number of complications (p=0.220). CONCLUSION: Standard surgical treatment for non-small cell lung carcinoma, lobectomy with systematic mediastinal lymphadenectomy, is safe also for a well-indicated group of seniors. With careful preoperative assessments and consideration of the extent of resection, we can expect a comparable rate of complications in the elderly compared to younger patients. Sublobar resection or radiotherapy should be considered in case of patients at risk. For seniors over 70 years of age, comparable outcomes of oncological treatment can be reached, taking into account their shorter life expectancy.

Delirious conditions in surgical ICU - case report.

Delirious conditions are encountered in daily practice in the surgical ward, especially in intensive care units (ICUs). An ordinary surgeon must deal with these conditions very often. The case report of a patient with alcoholic delirium is presented. For a comprehensive view of the issue, we present a simple communication on delirious situations in the ICU. Deliria are classified according to their manifestations, and their etiology is briefly described. For practice, an outline of examinations and treatments is provided which is fundamentally different for alcoholic and nonalcoholic delirium.

Postpneumonectomy MRSA empyema treated with vacuum therapy - case report and literature review.

INTRODUCTION: Postpneumonectomy empyema is one of serious complications with high mortality and lethality. In this paper, the authors describe the treatment of methicillin-resistant Staphylococcus aureus-induced postpneumonectomy empyema by vacuum therapy in a patient operated on for malignant pleural mesothelioma. CASE REPORT: A 64-year-old patient was operated on at our clinic for epithelioid mesothelioma of the right pleural cavity. We performed extrapleural pneumonectomy with intraoperative hyperthermic intrathoracic chemotherapy. Seven weeks after surgery the patient was readmitted for right pleural cavity empyema caused by methicillin-resistant Staphylococcus aureus (MRSA). Following pleural cavity debridement and mesh explantation we applied vacuum therapy. In total, we performed 4 dressing changes with final application of an antibiotic solution into the pleural cavity and wound closure. The patient showed no evidence of recurrent empyema during subsequent 12-month follow-up and underwent chemotherapy. CONCLUSION: Vacuum therapy is an effective treatment of postpneumonectomy empyema in patients without a bronchopleural fistula; nevertheless, specific postpneumonectomy patient care is required.

Bronchogenic cyst of gastric cardia - case report and literature review.

INTRODUCTION: Intramural bronchogenic cysts of the esophagus are very rare. They are mostly found in the upper mediastinum. Symptoms are caused by compression of surrounding structures by the cyst or complications of the cyst. However, the majority are asymptomatic. CASE REPORT: We describe the case of a 30-year-old female patient who underwent surgery at our institution for a tumor of the gastric cardia protruding intraluminally. The tumor was found incidentally during upper endoscopy before a planned bariatric surgery. A solid lesion originating from the muscle layer of the cardia wall was described based on endoscopic ultrasound. A CT scan did not show any infiltration of surrounding structures or disease dissemination. We performed laparoscopic enucleation of the tumor combined with partial fundoplication to close the defect in the muscular layer of the esophagus. Histopathology report surprisingly confirmed a bronchogenic cyst in the gastric cardia wall. The patient healed primarily and was soon discharged without complications. Two months later she underwent sleeve gastrectomy for obesity. Seven months following the bronchogenic cyst enucleation an endoscopic balloon dilation was performed on the patient with good effect upon diagnosing a relative gastric cardia stenosis. CONCLUSION: The diagnosis of esophageal bronchogenic cysts is usually difficult. Histopathology results are crucial to determine the definitive diagnosis. Endoscopy and imaging techniques, including endoscopic ultrasound, play an important role in the diagnostic process. Most authors prefer complete removal of the cyst, endoscopic or surgical, due to possible cyst complications, diagnostic uncertainty, and certainly in symptomatic patients. The complication rate is minimal.

Pulmonary metastases in pseudomyxoma peritonei - case report and review of the literature.

Pseudomyxoma peritonei is a rare disease caused by dissemination of cancer forming mucous and gelatinous masses in the peritoneal cavity. Local recurrence is frequent; however, dissemination outside the peritoneal cavity is rare.  Case report: We present the case report of a female patient treated for bilateral pulmonary metastases from pseudomyxoma peritonei. We removed 1 metastasis from her left lung and 12 metastases form her right lung. The patient remained in a good clinical state; however, additional lung metastases developed, as well as a metastasis in L2 vertebra for which the patient underwent a surgical procedure. Conclusion: Cytoreductive surgeries for intrathoracic involvement in pseudomyxoma peritonei with additional hyperthermic cytostatic intrapleural lavage in case of pleural involvement can lead to a longer lifespan in indicated patients.

The most recent recommendations for the surgical treatment of inguinal hernia.

INTRODUCTION: The publication of new guidelines in recent years shows that surgical treatment of inguinal hernia remains topical. The main goal is to improve patient outcomes, specifically to decrease recurrence rates and reduce chronic pain. The main purpose of this article is to summarize the latest recommendations in surgical treatment of the groin hernias, especially in the case of strangulation. METHODS: The authors made literature review of all the guidelines published by the hernia societies, including related articles, in the last ten years. RESULTS: The use of the EHS classification system is suggested. In elective operations, mesh repair is recommended. The Lichtenstein technique is the standard in open inguinal hernia repair. Transabdominal preperitoneal and totally extraperitoneal approach have comparable outcomes. Their clear advantages include minimal invasiveness. Mesh repair is recommended also in the case of strangulation, but only in clean and clean-contami-nated operations. A laparoscopic approach should be considered as well. Inter alia, it allows an assessment of bowel viability during the whole procedure. The need of bowel resection is hence lower compared to open surgery. If it is not possible to use the mesh, the Shouldice method is regarded as the best non-mesh repair technique. If there is concern about bowel viability, visualization, either by formal laparoscopy, hernia sac laparoscopy or laparotomy, is recommended. Hernioscopy is a simple and safe procedure that uses the hernia sac for insertion of a port following insufflation and diagnostic examination. It requires less advanced laparoscopic skills than does emergency laparoscopic hernia repair. It can be performed even by surgeons who lack sufficient experience with laparoscopy. CONCLUSION: In elective procedures, the mesh repair is recommended. It is recommended also in the case of strangulation, but not in a contaminated-dirty surgical field. If there is concern about bowel viability, visualization, either by formal laparoscopy, hernia sac laparoscopy or laparotomy, is needed.

Splenic abscess as a rare symptom of the extrapulmonary tuberculosis - case report.

INTRODUCTION: Extrapulmonary tuberculosis can involve any organ or tissue. It is a rare disease in the Czech Republic with an incidence rate of 0.62 cases per 100.000 persons. It affects mostly immunocompromised patients. The most common sites include lymph nodes, the urogenital system, skin, joints, bones and serous epithelium - the peritoneum, pleura, and pericardium. Splenic involvement is rare. Mycobacterium is a slow growing intracellular parasite. The diagnostic process is very difficult; microbiological diagnosis is critical. CASE REPORT: An 84 years old female patient with subcapsular splenic rupture with no trauma history as a cause of anemia. Splenic abscess was diagnosed during surgical revision and splenectomy. Tuberculosis was suspected based on subsequent histological analysis, which was confirmed after nine weeks of peritoneal fluid culture. The surgical procedure and postoperative hospitalization were not associated with any complications. The patient was referred to the respiratory clinic for further treatment. CONCLUSION: The diagnosis of extrapulmonary tuberculosis including splenic localization should always be considered. A sample from the affected tissue or effusion must be collected in the case of unclear perioperative findings and sent for complete bacteriological testing, including mycobacterial culture. If a tuberculous splenic abscess is found, the therapeutic process should involve its complete drainage in combination with long-term anti-TB medication.

[Personalized oncology]. / Personalisierte Onkologie.

CLINICAL ISSUE: Innovative next generation sequencing (NGS) technologies and comprehensive sequencing investigations in large patient cohorts have paved the way for very promising personalized treatment strategies based on the molecular characteristics of individual tumors. STANDARD TREATMENT: Targeted therapies, such as tyrosine kinase inhibitors, antibodies and modern immunotherapeutic approaches are well established as monotherapy and combination therapy for many hematological and oncological malignancies. TREATMENT INNOVATIONS: A plethora of innovative therapies targeting various components of intracellular signaling cascades and effective mechanisms against oncogenes as well as the availability of NGS technologies enable personalized cancer treatment based on the molecular profiles of individual tumors and genetic stratification, within clinical trials. DIAGNOSTIC WORK-UP: Comprehensive genetic approaches including cancer gene panel sequencing, whole exome, whole genome and transcriptome sequencing are carried out to a varying extent and particularly in the academic setting. PERFORMANCE: Principally, a comprehensive characterization of tumors in addition to DNA and RNA sequencing that also incorporates epigenetic, metabolomic, and proteomic alterations would be desirable. A comprehensive clinical implementation of integrative, multidimensional genetic typing is, however, currently not possible. ACHIEVEMENTS: It remains to be demonstrated whether these approaches will translate into significantly better outcomes for patients and whether they can be increasingly implemented in the routine diagnostic work-up. PRACTICAL RECOMMENDATIONS: The selection of diagnostic tools in individual cases and the extent of genomic analyses in the clinical context, need to take the availability of methods as well as the present clinical situation into account.

[Double incision laparoscopic surgery]. / Laparoskopická chirurgie ze dvou incizí.

INTRODUCTION: Single incision laparoscopic surgery (SILS) is a common alternative to classical laparoscopic surgery. However, material costs of SILS significantly limit the spreading of this method to most of surgical departments in the Czech Republic. Therefore we introduced DILS, which is technically more difficult than 3- to 4-incision laparoscopy but comparable cost-wise and its result approaches the cosmetic effect of SILS. METHODS: We describe the technical approach for DILS. We evaluate our own group of patients who were operated on in 2012-2014. RESULTS: Nine minor complications evaluated as Clavien-Dindo grade I-IIIb were seen in the group of 64 patients undergoing laparoscopic cholecystectomy, appendectomy or TAPP operation of groin hernias using DILS method. DILS-cholecystectomy was converted to multiple-ports laparoscopy 4 times. CONCLUSION: In our group, DILS did not present a higher complication rate than laparoscopic surgery using multiple incisions. This method is well-regarded by the patients in terms of its aesthetic results, and economically it is more advantageous than SILS. KEY WORDS: minimally invasive surgery - SILS - double incision laparoscopic surgery.

Including sheath effects in the interpretation of planar retarding potential analyzer's low-energy ion data.

The interpretation of planar retarding potential analyzers (RPA) during ionospheric sounding rocket missions requires modeling the thick 3D plasma sheath. This paper overviews the theory of RPAs with an emphasis placed on the impact of the sheath on current-voltage (I-V) curves. It then describes the Petite Ion Probe (PIP) which has been designed to function in this difficult regime. The data analysis procedure for this instrument is discussed in detail. Data analysis begins by modeling the sheath with the Spacecraft Plasma Interaction System (SPIS), a particle-in-cell code. Test particles are traced through the sheath and detector to determine the detector's response. A training set is constructed from these simulated curves for a support vector regression analysis which relates the properties of the I-V curve to the properties of the plasma. The first in situ use of the PIPs occurred during the MICA sounding rocket mission which launched from Poker Flat, Alaska in February of 2012. These data are presented as a case study, providing valuable cross-instrument comparisons. A heritage top-hat thermal ion electrostatic analyzer, called the HT, and a multi-needle Langmuir probe have been used to validate both the PIPs and the data analysis method. Compared to the HT, the PIP ion temperature measurements agree with a root-mean-square error of 0.023 eV. These two instruments agree on the parallel-to-B plasma flow velocity with a root-mean-square error of 130 m/s. The PIP with its field of view aligned perpendicular-to-B provided a density measurement with an 11% error compared to the multi-needle Langmuir Probe. Higher error in the other PIP's density measurement is likely due to simplifications in the SPIS model geometry.

Inter-modal four-wave mixing study in a two-mode fiber.

We demonstrate efficient four-wave mixing among different spatial modes in a 1-km long two-mode fiber at telecommunication wavelengths. Two pumps excite the LP01 and LP11 modes, respectively, while the probe signal excites the LP01 mode, and the phase conjugation (PC) and Bragg scattering (BS) idlers are generated in the LP11 mode. For these processes we experimentally characterize their phase matching efficiency and bandwidth and find that they depend critically on the wavelength separation of the two pumps, in good agreement with the numerical study we carried out. We also confirm experimentally that BS has a larger bandwidth than PC for the optimum choice of the pump wavelength separation.

Mid-infrared supercontinuum generation in suspended core tellurite microstructured optical fibers.

We report the fabrication of a tellurite optical fiber with a suspended core design, formed on a 220-nm-wide filament of glass. The fiber was pumped at two different wavelengths (1500 and 2400 nm) using femtosecond pulses generated from an optical parametric oscillator (OPO) in order to produce mid-infrared supercontinuum (SC). We observed that SC spectra extending to 3 µm were readily generated. To further optimize the design, detailed numerical study was performed, which revealed how the fiber structural characteristics dramatically influence the spectral broadening because of the changes in the dispersion profile and in turn, the interplay of nonlinear effects that give rise to SC generation. We found that an accurate control of the core shape can be employed to contain the generated SC spectra within well-defined spectral regions or to provide a broad extension of the continuum to beyond 4 µm.