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.

Internal Hernia and Volvulus in an Adult Male Caused by Meckel's Diverticulum: A Case Report.

Background: Meckel's diverticulum is a common congenital abnormality of the gastrointestinal tract encountered in about 1-3% of the general population. Although most patients remain asymptomatic, a minority will experience serious complications such as acute abdomen, haemorrhage or obstructive ileus. Of all patients presenting with symptoms of obstruction due to Meckel's diverticulum 7-18% is due to volvulus. Case Report: A 39-year-old male with multiple previous episodes of obstructive ileus presented with an acute abdomen. An exploratory laparotomy was performed in order to reveal the cause of the obstruction. An internal hernia with ileal volvulus and a Meckel's diverticulum was found, which was later confirmed by histopathological examination. Conclusion: Meckel's diverticulum is a rare cause of acute abdomen and obstructive ileus which should be considered when the symptoms date back to childhood. The difficulty of preoperative diagnosis dictates the need for exploratory laparoscopy or laparotomy as diagnostic tools.

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.

Cardiopulmonary Arrest Caused by Large Substernal Goiter-Treatment with Combined Cervical Approach and Median Mini-Sternotomy: Report of a Case.

INTRODUCTION: Substernal goiter is usually defined as a goiter that extends below the thoracic inlet or a goiter with more than 50% of its mass lying below the thoracic inlet. Substernal goiters may compress adjacent anatomical structures causing a variety of symptoms. CASE REPORT: Here we report a rare case of a 75-year-old woman presenting with cardiac arrest caused by acute respiratory failure due to tracheal compression by a substernal goiter. DISCUSSION: Substernal goiters can be classified as primary or secondary depending on their site of origin. Symptoms are diverse and include a palpable neck mass, mild dyspnea to asphyxia, dysphagia, dysphonia, and superior vena cava syndrome. Diagnosis of substernal goiter is largely based on computed tomography imaging, which will show the location of the goiter and its extension in the thoracic cavity. Surgery is the treatment of choice for symptomatic patients with substernal goiter. The majority of substernal goiters are resected through a cervical approach. However, in approximately 5% of patients, a thoracic approach is required. The most important factor determining whether a thoracic approach should be used is the depth of the extension to the tracheal bifurcation on CT imaging. CONCLUSION: Cardiac arrest appearing as the first symptom of a substernal goiter is a very rare condition and should be treated by emergency thyroidectomy via a cervical or thoracic approach depending on the CT imaging findings.

Genes' Interactions: A Major Contributor to the Malignant Transformation of Endometriosis.

The genetic and epigenetic factors that contribute to the malignant transformation of endometriosis are still under investigation. The objective of the present study was to investigate the genetic link between endometriosis and cancer by examining and correlating the latest clinical observations with biological experimental data. We collected updated evidence about the genetic relationship between endometriosis and cancers by conducting a comprehensive search of PubMed and Scopus databases, focusing on the papers published between January 2018 and January 2019. New insights into the mechanism of the malignant transformation of endometriosis have been published recently. The use of state-of-the-art techniques and methods, such as the genome-wide association study analysis and the weighted gene co-expression analysis, have significantly altered our understanding of the association between endometriosis and endometriosis-associated cancer development. Interestingly, the interactions formed between genes seem to play a pivotal role in the phenotypic expression of mutations. Therefore, the effect of single nucleotide polymorphisms and the function of the expression quantitative trait loci on genes' expression have been the subject of many recent works. In addition, it has been discovered that genes, the mutations of which have been related to the development of endometriosis, play a role as hub genes. This may lead to new areas of research for understanding the mechanism of malignant transformation of the disease. Significant steps forward have been made towards the identification of factors that control the malignant transformation of endometriosis. Still, due to rarity of the event, a better-organized scheme for sampling on a global level should be adopted.

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.

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.

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.

HPV-Induced Anal and Peri-Anal Neoplasia, a Surgeon's Experience: 5-Year Case Series.

Purpose: One of the most known sexually transmitted diseases is Condylomata acuminata (CA), a skin lesion occurring due to infection from Human Papilloma Virus (HPV). CA has a typical appearance of raised, skin-colored papules ranging in size from 1 mm to 5 mm. These lesions often form cauliflower-like plaques. Depending on the involved HPV-subtype (either high-risk or low-risk) and its malignant potential, these lesions are likely to lead to malignant transformation when specific HPV subtypes and other risk factors are present. Therefore, high clinical suspicion is required when examining the anal and perianal area. Methods: In this article, the authors aim to present the results of a five-year case series (2016-2021) of anal and perianal cases of CA. Results: A total of 35 patients were included in this study. Patients were categorized based on specific criteria, which included gender, sex preferences, and human immunodeficiency virus infection. All patients underwent proctoscopy and excision biopsies were obtained. Based on dysplasia grade patients were further categorized. The group of patients where high-dysplasia squamous cell carcinoma was present was initially treated with chemoradiotherapy. Abdominoperineal resection was necessary in five cases after local recurrence. Conclusions: CA remains a serious condition where several treatment options are available if detected early. Delay in diagnosis can lead to malignant transformation, often leaving abdominoperineal resection as the only option. Vaccination against HPV poses a key role in eliminating the transmission of the virus, and thus the prevalence of CA.

An Easily Missed But Life-Threatening Diagnosis: A Case Report of Gorlin Syndrome.

BACKGROUND Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), nevoid basal cell carcinoma syndrome (NBCCS), and Jaw cyst-Basal cell nevus-Bifid rib syndrome, is a rare multisystemic syndrome that can affect a remarkable number of tissues and organs in the human body. Patients with this syndrome are in jeopardy of developing basal cell skin cancer during puberty or early adulthood. CASE REPORT Herein, we report a case of a 58-year-old woman who had multiple pigmented skin lesions and a palpable tumor of the left scapula. The patient underwent surgical excision of the above-mentioned lesions. The histopathological examination revealed that 10 of them were basal cell skin carcinomas (BCCs); therefore, the patient was proven to have the syndrome. She had a history of similar skin lesions, which were removed before the age of 20. CONCLUSIONS This case highlights that rare phenomena, such as the presence of multiple BCCs, require additional investigations and a multidisciplinary approach since a rare and potentially life-threating condition might be the underlying cause. Early diagnosis of Gorlin syndrome is of paramount importance to facilitate the appropriate therapeutic approach, as directed by a multidisciplinary team. Patients with multiple skin lesions need to have regular assessments by their general practitioner or dermatologist, with dermoscopy serving as an important preventive measure. Furthermore, because pathogenesis of the syndrome is characterized by development of basal cell carcinomas, consecutive follow-up is of a great significance.

Preoperative Assessment of Perianal Fistulas with Combined Magnetic Resonance and Tridimensional Endoanal Ultrasound: A Prospective Study.

BACKGROUND: we designed a prospective study of diagnostic accuracy that compared pelvic MRI and 3D-EAUS with pelvic MRI alone in the preoperative evaluation and postoperative outcomes of patients with perianal fistulas. METHODS: the sample size was 72 patients and this was divided into two imaging groups. MRI alone was performed on the first group. Both MRI and 3D-EAUS were performed in parallel on the second group. Surgical exploration took place after two weeks and was the standard reference. Park's classification, the presence of a concomitant abscess or a secondary tract, and the location of the internal opening were recorded. All patients were re-evaluated for complete fistula healing and fecal incontinence six months postoperatively. All of the collected data were subjected to statistical analysis. RESULTS: the MRI group included 36 patients with 42 fistulas. The MRI + 3D-EAUS group included 36 patients with 46 fistulas. The adjusted sensitivity and negative predictive value were 1.00 for most fistula types in the group that underwent combined imaging. The adjusted specificity improved for intersphincteric fistulas in the same group. The adjusted balanced accuracy improved for all fistula types except rectovaginal. The combination of imaging methods showed improved diagnostic accuracy only in the detection of a secondary tract. The healing rate at six months was 100%. Fecal incontinence at six months did not present a statistically significant difference between the two groups (Fisher's exact test p-value > 0.9). Patients with complex perianal fistulas had a statistically significant higher probability of undergoing a second surgery (x2 test p-value = 0.019). CONCLUSIONS: the combination of pelvic MRI and 3D-EAUS showed improved metrics of diagnostic accuracy and should be used in the preoperative evaluation of all patients with perianal fistulas, especially those with complex types.

Immunoengineering via Chimeric Antigen Receptor-T Cell Therapy: Reprogramming Nanodrug Delivery.

Following its therapeutic effect in hematological metastasis, chimeric antigen receptor (CAR) T cell therapy has gained a great deal of attention during the last years. However, the effectiveness of this treatment has been hampered by a number of challenges, including significant toxicities, difficult access to tumor locations, inadequate therapeutic persistence, and manufacturing problems. Developing novel techniques to produce effective CARs, administer them, and monitor their anti-tumor activity in CAR-T cell treatment is undoubtedly necessary. Exploiting the advantages of nanotechnology may possibly be a useful strategy to increase the efficacy of CAR-T cell treatment. This study outlines the current drawbacks of CAR-T immunotherapy and identifies promising developments and significant benefits of using nanotechnology in order to introduce CAR transgene motifs into primary T cells, promote T cell expansion, enhance T cell trafficking, promote intrinsic T cell activity and rewire the immunosuppressive cellular and vascular microenvironments. Therefore, the development of powerful CART cells can be made possible with genetic and functional alterations supported by nanotechnology. In this review, we discuss the innovative and possible uses of nanotechnology for clinical translation, including the delivery, engineering, execution, and modulation of immune functions to enhance and optimize the anti-tumor efficacy of CAR-T cell treatment.

Tumor cell metabolic reprogramming and hypoxic immunosuppression: driving carcinogenesis to metastatic colonization.

A significant factor in the antitumor immune response is the increased metabolic reprogramming of immunological and malignant cells. Increasing data points to the fact that cancer metabolism affects not just cancer signaling, which is essential for maintaining carcinogenesis and survival, but also the expression of immune cells and immune-related factors such as lactate, PGE2, arginine, IDO, which regulate the antitumor immune signaling mechanism. In reality, this energetic interaction between the immune system and the tumor results in metabolic competition in the tumor ecosystem, limiting the amount of nutrients available and causing microenvironmental acidosis, which impairs the ability of immune cells to operate. More intriguingly, different types of immune cells use metabolic reprogramming to keep the body and self in a state of homeostasis. The process of immune cell proliferation, differentiation, and performance of effector functions, which is crucial to the immune response, are currently being linked to metabolic reprogramming. Here, we cover the regulation of the antitumor immune response by metabolic reprogramming in cancer cells and immune cells as well as potential strategies for metabolic pathway targeting in the context of anticancer immunotherapy. We also discuss prospective immunotherapy-metabolic intervention combinations that might be utilized to maximize the effectiveness of current immunotherapy regimes.