Phytobezoar-Induced Mechanical Ileus and Incipient Intussusception: A Case Report.

Phytobezoars constitute conglomerates of indigested plant fibers and are a rare cause of acute mechanical ileus. They exhibit an increased prevalence in the elderly population and people with specific predisposing conditions. Radiological imaging can often set a definitive diagnosis and dictate the optimal therapeutic approach, combined with the patient's clinical status. An 81-year-old male presented with deteriorating clinical symptoms of intestinal obstruction, and an exploratory laparotomy was performed following inconclusive radiological findings; multiple phytobezoars and incipient intussusception were revealed intraoperatively. A patient's medical history can often raise clinical suspicion of phytobezoars. However, a careful etiological investigation is imperative in all cases of mechanical ileus in advanced ages; early detection and dissolution of phytobezoars, when applicable, can reduce the need for surgical interventions.

Melanoma: BRAFi Rechallenge.

Melanoma is the most aggressive type of skin cancer. Half of melanoma cases are characterized by the mutation BRAF V600. The case presented concerns a 41-year-old patient with locally advanced melanoma, being positive in mutation BRAF V600. The patient underwent surgery and received additional targeted therapy as part of a clinical study. In subsequent disease progression, immunotherapy was used. When the disease progressed again while the patient was in a good performance status, targeted therapy was administered again, and a good response was noted, making the patient reach a statistically significant overall survival, exceeding four years. Targeted therapy has proven to be an important tool in the treatment of melanoma. The use of BRAFi targeted therapy does not exclude the option of readministration at subsequent disease progression (BRAFi rechallenge). Preclinical models suggest that the resistance mechanism of cancer cells to BRAFi therapy bends, as these cell clones lose their evolutionary advantage after stopping BRAFi. Cell clones sensitive to BRAFi may then outcompete, making the treatment effective again. Therapeutical dilemmas in the management of patients with locally advanced melanoma that progresses to metastatic cancer are discussed.

Giant Echinococcosis of the Liver with Suppuration: A Case Report and Review of the Literature.

Purpose: Cystic echinococcosis (CE) is a common, complex parasitic disease that constitutes a major public health concern. CE demonstrates high endemicity in areas where dogs are used for herding or where animal husbandry practices involve close contact with livestock. It can clinically manifest with a variety of signs and symptoms, such as cholangitis, jaundice, pancreatitis, external biliary fistula, inferior vena cava obstruction, portal hypertension, and superinfection. The latter can notably be related to suppuration, either by rupture or bacteremia. The aim of this study is to report our 76-year-old patient who presented with a primarily infected giant-suppurated hydatid cyst of the liver and its surgical management. Methods: In this case, the diagnosis was based primarily on clinical presentation, computed tomography (CT) scan, and magnetic resonance imaging (MRI) of the patient's abdomen. The surgical procedure of choice was the partial retaining of the pericystic membrane and drainage of the cystic contents (partial pericystectomy). Results: The surgical management and meticulous long-term follow-up of our patient produced a positive outcome without any post-operative complications.

Idiopathic Multicentric Castleman Disease with Cutaneous Manifestation: Case Report.

Castleman disease constitutes a rare class of lymphoproliferative disorders, with an estimated incidence of 21 to 25 per million patient years. The idiopathic subtype exhibits a significantly diverse clinical presentation, which can imitate many autoimmune, malignant, and infectious diseases. Cutaneous manifestations are uncommon and require in-depth investigation, especially when concurrent lymphadenopathy is present. A 79-year-old female, with a chronic, complicated erysipelas-like lesion, presented with bilaterally enlarged inguinal lymph nodes; after surgical excision, their histopathological examination revealed Castleman disease. Even though it is a benign condition, patients are often predisposed to developing certain types of malignancies, which can deteriorate their prognosis. An accurate and early diagnosis, along with effective treatment and prevention of recurrence, is of utmost importance in order to increase the patients' overall survival and quality of life.

Extramammary Paget's Disease of the Vulva: Report of Two Cases.

Extramammary Paget's disease is a rare condition, affecting 6.5% of all patients with Paget's disease. The most common extramammary site is the vulvar area. Although diagnosis in some patients is difficult to set, early diagnosis is of high importance in order to detect the irreversible progression of the lesion early and prevent distant metastasis. An 89-year-old female and a 69-year-old female presented within three months with an eczematous lesion with leukoplakia in the vulva. The incisional biopsy of the skin revealed extramammary Paget's disease. Both patients underwent a surgical wide local excision of the lesion and the specimens were sent for histopathological examination. Extramammary Paget's disease has a high potential for distant malignancies and local recurrence, dictating that surgical excision is the most efficient treatment. The rareness of the condition and the diagnostic difficulties underline the need for early skin biopsy, which is the most efficient diagnostic tool.

Producing the appropriate model and drug for intratumoural ablation.

Local treatment is necessary for several cancer patients. There are situations where cancer tissue induces locally severe symptoms. Therefore, additional local disease control is necessary. There are two major issues for efficient local treatment: the method of application and the penetration of the drug formulation. We need efficient tools to guide the drug formulation to the target point, and an effective drug formulation that is diffused within the tumour microenvironment with a sustained-release effect.

Acute Effects of a Heat-Not-Burn Tobacco Product on Pulmonary Function.

Background and objectives: During the last decade, conventional tobacco smoking is experiencing a decline and new smoking products have been introduced. IQOS ("I-Quit-Ordinary-Smoking") is a type of "heat-not-burn" (HNB) tobacco product. The impact of IQOS on respiratory health is currently not defined. The objectives of this study were to evaluate the acute effects of IQOS on pulmonary function in non-smokers and current smokers. Materials and Methods: Fifty male healthy non-smokers and current smokers with no known co-morbidity underwent an exhaled CO measurement, oximetry (SaO2%), pulmonary function tests (flows, volumes and diffusion capacity), and a measurement of respiratory resistances with an impulse oscillometry system (IOS) before and immediately after IQOS use. Results: In the whole group of 50 participants, SaO2%, forced expiratory flow at 25% and 50% of vital capacity (FEF 25%, FEF 50%, respectively), peak expiratory flow (PEF), and diffusion lung capacity for carbon monoxide/VA (KCO) decreased significantly after IQOS use, whereas exhaled CO and airway resistance (R5 Hz, R10 Hz, r15 Hz, R20 Hz, R25 Hz, R35 Hz) increased. When the groups of smokers and non-smokers were compared, in both groups (all males, 25 smokers and 25 non-smokers), exhaled CO increased and SaO2% decreased after IQOS use (p < 0.001). In the group of non-smokers, PEF (pre 8.22 ± 2.06 vs. post 7.5 ± 2.16, p = 0.001) and FEF 25% (pre 7.6 ± 1.89 vs. 7.14 ± 2.06, p = 0.009) decreased significantly; respiratory resistances R20 Hz (pre 0.34 ± 0.1 vs. post 0.36 ± 0.09, p = 0.09) and R25 Hz (pre 0.36 ± 0.1 vs. post 0.38 ± 0.09, p = 0.08) increased almost significantly. In smokers, PEF (pre 7.69 ± 2.26 vs. post 7.12 ± 2.03, p = 0.007) and expiratory reserve volume (ERV) (pre 1.57 ± 0.76 vs. post1.23 ± 0.48, p = 0.03) decreased and R35 Hz (pre 0.36 ± 0.11 vs. post 0.39 ± 0.11, p = 0.047) increased. The differences in the changes after the use of IQOS did not differ between groups. Conclusions: IQOS had an impact on exhaled CO, SaO2%, and airways function immediately after use. Even though these changes were rather small to be considered of major clinical importance, they should raise concerns regarding the long-term safety of this product. Further research is needed for the short- and long-term effects of IQOS, especially in patients with respiratory disease.

Inhaled Cisplatin for NSCLC: Facts and Results.

Although we have new diagnostic tools for non-small cell lung cancer, diagnosis is still made in advanced stages of the disease. However, novel treatments are being introduced in the market and new ones are being developed. Targeted therapies and immunotherapy have brought about a bloom in the treatment of non-small cell lung cancer. Still we have to find ways to administer drugs in a more efficient and safe method. In the current review, we will focus on the administration of inhaled cisplatin based on published data.

Comparison of Laryngoscopic Views betweenC-MAC™ and Conventional Laryngoscopy in Patients with Multiple Preoperative Prognostic Criteria of Difficult Intubation. An Observational Cross-Sectional Study.

Background and Objectives: Video laryngoscopy has been proven useful under difficult airway scenarios, but it is unclear whether anticipated improvement of visualization is related to specific difficult intubation prognostic factors. The present study evaluated the change in laryngoscopic view between conventional and C-MAC® laryngoscopy and the presence of multiple difficult intubation risk factors. Materials and Methods: Patients scheduled for elective surgery with >2 difficult intubation factors, (Mallampati, thyromental distance (TMD), interinscisor gap, buck teeth, upper lip bite test, cervical motility, body mass index (BMI)) were eligible. Patients underwent direct laryngoscopy (DL) followed by C-MAC™ laryngoscopy (VL) and intubation. Change of view between DL and VL, time for best view, intubation difficulty scale (IDS) and correlation between prognostic factors, laryngoscopic view improvement, and IDS were measured. Results: One-hundred and seventy-six patients completed the study. VL lead to fewer Cormarck-Lehane (C/L) III-IV, compared to DL (13.6% versus 54.6%, p < 0.001). The time to best view was also shorter (VL: 10.82 s, DL: 12.08 s, p = 0.19). Mallampati III-IV and TMD ≤ 6 cm were related to improvement of C/L between DL and VL. Logistic regression showed these two factors to be a significant risk factor of the glottis view change (p = 0.006, AUC-ROC = 0.57, 95% CI: 0.47-0.66). 175/176 patients were intubated with VL. 108/176 were graded as 0 < IDS ≤ 5 and 12/176 as IDS > 5. IDS was only correlated to the VL view (p < 0.0001). Conclusion: VL improved laryngoscopic view in patients with multiple factors of difficult intubation. Mallampati and TMD were related to the improved view. However, intubation difficulty was only related to the VL view and not to prognostic factors.

Pharmacologic and Non-Pharmacologic Interventions for HIV-Neuropathy Pain. A Systematic Review and a Meta-Analysis.

Background and Objectives: Among HIV infection symptoms, sensory neuropathy (HIV-SN) remains a main cause of suffering, with incidence varying from 13-50%. So far, numerous pharmacological and non-pharmacological treatments have been tested, although few evidence-based analgesic options are available. We conducted an up-to-date systematic review and meta-analysis of the literature in order to evaluate the efficacy and safety of pharmacologic and non-pharmacologic treatments for pain control, in patients with HIV neuropathy. Materials and Methods: We searched MEDLINE, EMBASE, Scopus/Elsevier, The Cochrane Central Register of Controlled Trials (CENTRAL), USA Clinical Trials registry, and The International Web of Science up to April 2019. All randomized controlled trials evaluating efficacy and safety of non-pharmacologic and pharmacologic therapies were included. Efficacy was defined as pain reduction during the study period. Safety was estimated from adverse events. A meta-analysis was performed whenever possible. Results: 27 randomized controlled trials (RCTs) were included for analysis (7 evaluating non pharmacologic interventions, 20 pharmacologic therapies). Non-pharmacologic studies (n = 742) involved seven different therapeutic modalities. Only Acupuncture/Moxibustion showed pain reduction over placebo, Gracely Pain Scale Mean (SD): Acu/Moxa 0.85 (0.12), placebo 1.10 (0.09), p = 0.05. Pharmacologic studies, involving 2516 patients revealed efficacy for capsaicin 8% over placebo (mean difference -8.04 [95% CI: -14.92 -1.15], smoked cannabis (where pooling data for meta-analysis was not possible) and recombinant Nerve Growth Factor. Conclusion: Despite various modalities for pain control in HIV-SN, strongest evidence exists for capsaicin 8% and smoked cannabis, although of low methodological quality. Among non-pharmacologic modalities, only Acu/Moxa gave a marginal beneficial effect in one study, possibly limited by inherent methodological flaws.

Comparison between Magnification Techniques and Direct Vision in Thyroid Surgery: A Systematic Review and Meta-Analysis.

Background and Objectives: The most common complications after conventional thyroid surgery in adult patients are recurrent laryngeal nerve (RLN) injury and hypocalcemia. Magnification techniques (surgical loupes or surgical microscope) are used for identification of RLN and parathyroid glands to diminish these complications although more evidence is necessary to assess their safety and efficacy in comparison with direct vision. Methods and Materials: Electronic databases (Pubmed, Cochrane Library, Scopus) as well as gray literature sources were searched for randomized controlled trials (RCTs) comparing the frequency of transient/permanent RLN injury and hypocalcemia after thyroid surgery by using magnification techniques and direct vision for identification of RLN and parathyroid glands until October 17, 2019. The main outcomes were transient/permanent RLN injury and hypocalcemia. For all outcomes, 95% confidence intervals (95% CI) were used. Statistical analysis was performed with RevMan 5.3. Results: Systematic review and meta-analysis included 3 RCTs with 437 patients overall. Magnification techniques did not significantly affect the risk of occurrence of transient RLN injury (OR = 0.38, 95% CI (0.11-1.35), I2 = 0%) and transient hypocalcemia (OR = 0.31, 95% CI (0.09-1.09), I2 = 23%) compared with direct vision. Included RCTs demonstrated only two patients with permanent hypocalcemia and another one with permanent RLN injury, who belonged to the direct vision group. Conclusion: The use of magnification techniques for identification of RLN and parathyroid glands seems to be as safe as direct vision. However, they do not decrease the risk of RLN injury and transient hypocalcemia after thyroid surgery compared with direct vision. Finally, further prospective research should be conducted as the sample among the studies was small.

Hybrid Nanogel Drug Delivery Systems: Transforming the Tumor Microenvironment through Tumor Tissue Editing.

The future of drug delivery offers immense potential for the creation of nanoplatforms based on nanogels. Nanogels present a significant possibility for pharmaceutical advancements because of their excellent stability and effective drug-loading capability for both hydrophobic and hydrophilic agents. As multifunctional systems, composite nanogels demonstrate the capacity to carry genes, drugs, and diagnostic agents while offering a perfect platform for theranostic multimodal applications. Nanogels can achieve diverse responsiveness and enable the stimuli-responsive release of chemo-/immunotherapy drugs and thus reprogramming cells within the TME in order to inhibit tumor proliferation, progression, and metastasis. In order to achieve active targeting and boost drug accumulation at target sites, particular ligands can be added to nanogels to improve the therapeutic outcomes and enhance the precision of cancer therapy. Modern "immune-specific" nanogels also have extra sophisticated tumor tissue-editing properties. Consequently, the introduction of a multifunctional nanogel-based drug delivery system improves the targeted distribution of immunotherapy drugs and combinational therapeutic treatments, thereby increasing the effectiveness of tumor therapy.

Tertiary hyperparathyroidism masking an atypical parathyroid tumor.

Atypical parathyroid tumors represent a group of parathyroid neoplasms of uncertain malignant potential. In view of preoperative diagnostic difficulties, suspicious features for malignancy may guide the surgeon to perform a radical surgical approach.

A Unique Case of Appendiceal Intussusception (Inversion): A Case in Bloom.

A 40-year-old female patient presented to a secondary facility with dull lower abdominal pain and a persistent low-grade fever. Her laboratory results showed elevated inflammation markers. A CT scan revealed two abscesses in the lesser pelvic region in direct contact with the apex of the appendix, the posterior wall of the uterus, and the right-side appendages. The patient responded well to intravenous antibiotics, and an MRI scan revealed the cause to be an appendiceal rupture. The patient was scheduled for an appendectomy. The procedure started laparoscopically but had to be converted to an open one with a midline infra-umbilical incision in order to protect the right appendages. A standard appendectomy was conducted, and the histology report revealed rupture of the appendix with concomitant wall inversion in the context of fibrous adhesions as well as obstruction due to a fecalith. Patient recovery and follow-up were excellent. Acute appendicitis, while frequently encountered in surgical practice, can present a diagnostic conundrum when it manifests in an atypical manner. This unique form of inversion appeared to confer a protective role against peritonitis, primarily through the mechanism of obstruction occurring centrally to the rupture. We suggest that this case should be included in current classifications as a partial inversion of the appendix after rupture and inflammation.

Chronic Obstructive Pulmonary Disease and Non-Small Cell Lung Cancer an association.

Objectives: Lung cancer is known to be associated with chronic obstructive pulmonary disease. Moreover; nutritional status is associated with chronic obstructive disease treatment and lung cancer. Our aim was to evaluate the interaction of the COPD status and treatment of non-small cell lung cancer. Methods: Eighty-two patients were enrolled in our multicenter study. Chronic obstructive disease stage, spirometry and treatment was recorded along with the treatment and Body Mass Index (BMI), Mediterranian Diet Score, Pack Years, Basic Metabolsim (RMR) (kcal/day), VO2 (ml/min), Ve (lt/min) and Physical Activity. The statistical analysis was performed using the JMP 14.3 (SAS Inc 2018) software. Results: The drug pairs showed a steady and unchanged by time health condition for 48 patients. Overall, 31 patients were recorded with worse COPD health conditions. The one-way ANOVA clearly indicated that chemotherapy induced the best FEV1-difference conditions with a positive effect of 8.56 mean FEV volume, the combined treatment simply did not have an effect (-0.9), while immunotherapy and patients receiving radiation decreased their FEV1 volume down to -4.23 and -5.15 mean values. Conclusions: Patients receiving chemotherapy alone had their chronic obstructive disease improved with less drugs and exacerbations, while patients receiving immunotherapy had their chronic obstructive disease stable, while all other treatment combinations worsened the patients chronic obstructive disease. Nutritional status did not affect the chronic obstructive disease of these patients in any way.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Ablation for Single Pulmonary Nodules, Primary or Metastatic. Εndobronchial Ablation Systems or Percutaneous.

Single pulmonary nodules are a difficult to diagnose imagining artifact. Currently novel diagnostic tools such as Radial-EBUS with or not C-ARM flouroscopy, electromagnetic navigation systems, robotic bronchoscopy and cone beam-compuer tomography (CBCT) can assist in the optimal guidance of biopsy equipment. After diagnosis of lung cancer or metastatic disease as pulmonary nodule, then surgery or ablation methods as local treatment can be applied. The percutaneous ablation systems under computed tomography guidance with radiofrequency, microwave, cryo and thermosphere have been used for several years. In the past 10 years extensive research has been made for endobronchial ablation systems and methods. We will present and comment on the two different ablation methods and present up to date data.

Immune Specific and Tumor-Dependent mRNA Vaccines for Cancer Immunotherapy: Reprogramming Clinical Translation into Tumor Editing Therapy.

Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice for future cancer immunotherapy. Ideal personalized tumor-dependent mRNA vaccines could stimulate both humoral and cellular immunity by overcoming cancer-induced immune suppression and tumor relapse. The stability, structure, and distribution strategies of mRNA-based vaccines have been improved by technological innovations, and patients with diverse tumor types are now being enrolled in numerous clinical trials investigating mRNA vaccine therapy. Despite the fact that therapeutic mRNA-based cancer vaccines have not yet received clinical approval, early clinical trials with mRNA vaccines as monotherapy and in conjunction with checkpoint inhibitors have shown promising results. In this review, we analyze the most recent clinical developments in mRNA-based cancer vaccines and discuss the optimal platforms for the creation of mRNA vaccines. We also discuss the development of the cancer vaccines' clinical research, paying particular attention to their clinical use and therapeutic efficacy, which could facilitate the design of mRNA-based vaccines in the near future.

Neuroendocrine Breast Carcinoma: Interesting Images of an Underdiagnosed Entity.

Breast cancer is the most common type of cancer of the female gender. A rare subtype of breast cancer is the invasive breast carcinoma (IBC) with neuroendocrine (NE) differentiation. Its incident is believed to be 0.1% to 5% of all breast cancers. We report a rare case of a 66-year old woman who presented with an isolated nodule of the left breast. The patient underwent modified radical mastectomy. Pathology revealed invasive breast carcinoma with neuroendocrine differentiation. Invasive breast carcinoma is an extremely rare group of neoplasms, the exact frequency of which cannot be determined with current data. Therefore, it is necessary for future studies to focus on the pathophysiology of this subtype of breast cancer and on the potential therapeutic approaches.

Immunotherapy and Chemotherapy Versus Sleep Disturbances for NSCLC Patients.

INTRODUCTION: Cancer patients are known to experience sleep disturbances that differ between disease stages and treatments. Regarding lung cancer patients and immunotherapy, information on their sleep disturbances has been recently acquired, but no comparison has been made between different treatment modalities. PATIENTS AND METHODS: We recruited 98 non-small cell lung cancer patients; 49 had programmed death-ligand 1 expression of ≥50% and received immunotherapy as first-line treatment and 49 had programmed death-ligand 1 expression in the range from 0-49 and received chemotherapy as first-line treatment. All patients were stage IV, but with no bone metastasis. Sleep disturbances were recorded through polysomnography and sleep questionnaires. RESULTS: For immunotherapy patients with PD-L1 expression ≥ 50%, the disease response was rapid and the sleep disturbances decreased rapidly. On the other hand, for chemotherapy patients, the sleep disturbances remained for all those patients that had partial response and stable disease. It was noticed that chemotherapy drugs induce severe adverse effects. DISCUSSION: In our study, it was observed that patients with complete response had reduced sleep disturbances in the case of immunotherapy patients. However, sleep disturbances continued for several patients in the chemotherapy group due to the adverse effects of chemotherapy drugs. IN CONCLUSION: Immunotherapy drugs on their own do not induce sleep disturbances and, through treatment response, alleviate sleep disturbances in lung cancer patients.