Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer

Esophageal cancer (EC) is an aggressive form of cancer, including squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) as two predominant histological subtypes. Accumulating evidence supports the existence of cancer stem cells (CSCs) able to initiate and maintain EAC or ESCC. In this review, we aim to collect the current evidence on CSCs in esophageal cancer, including the biomarkers/characterization strategies of CSCs, heterogeneity of CSCs, and the key signaling pathways (Wnt/β-catenin, Notch, Hedgehog, YAP, JAK/STAT3) in modulating CSCs during esophageal cancer progression. Exploring the molecular mechanisms of therapy resistance in EC highlights DNA damage response (DDR), metabolic reprogramming, epithelial mesenchymal transition (EMT), and the role of the crosstalk of CSCs and their niche in the tumor progression. According to these molecular findings, potential therapeutic implications of targeting esophageal CSCs may provide novel strategies for the clinical management of esophageal cancer

Factors Influencing the Severity of Menopause Symptoms in Korean Post-menopausal Women

We have relatively limited knowledge of symptomatic aspects of the postmenopause, rather than perimenopause. We tried to determine the factors associated with experiencing menopausal symptoms by Korean postmenopausal women. A total of 657 Korean women who underwent a natural menopause completed multiple questionnaires, which included questions regarding their attitudes to menopause, depressive symptoms, state anxiety, self-esteem, dyadic relationships, sociodemographic variables, and 11-item Menopause Rating Scale (MRS). Multiple regression analyses were performed to collectively examine the relative impact of each independent variable on the quality of life, as determined by the MRS. Decreased severity of menopausal symptoms was associated with more time spent in education, an employed status, a history of pregnancy, longer postmenopausal duration, positive attitudes to menopause, higher state anxiety, heightened self-esteem, and higher dyadic consensus. Increased severity of menopausal symptoms was also associated with absence of a partner, alcohol consumption, a history of hormone replacement therapy, a history of probable premenstrual dysphoric disorder, and increased severity of depressive symptoms. Sociodemographic characteristics, lifestyle factors, premenstrual dysphoric disorder, attitudes to menopause, a dyadic relationship with a partner, and the inner psychological status can be associated with the severity of menopause symptoms specifically in Korean postmenopausal women

Endoscopic treatment options for adenocarcinoma of the esophagogastric junction

Background The incidence of adenocarcinoma of the esophagogastric junction has increased in recent years. While a multimodal treatment concept is established for advanced carcinomas, the treatment of early stage carcinoma is still not clearly defined. Objective Presentation and overview of the endoscopic treatment options according to current data and knowledge. Material and methods A selective literature search was conducted in PubMed regarding endoscopic treatment of adenocarcinoma of the esophagogastric junction. Results and discussion Patients with a low risk of nodal metastasis are suitable for interventional endoscopic treatment. The indications apply particularly to carcinomas (T1a) limited to the mucosa and can in exceptional cases also apply to carcinomas with submucosal infiltration (T1b). Endoscopic treatment of these tumors should be performed in a two-step approach consisting of resection and an ablative procedure. The former is performed by endoscopic mucosal resection or endoscopic submucosal dissection. Subsequently, if residual Barrett epithelium is still present, radiofrequency ablation or argon plasma coagulation is recommended to minimize the likelihood of neoplastic recurrence. When endoscopic treatment is conducted at a large center with experienced endoscopists an oncological outcome equivalent to operative care can be achieved with a relevant complication rate <3%. The complications include bleeding, iatrogenic perforations or strictures. After successful endoscopic resection a close follow-up care must be performed. If a recurrence occurs endoscopic treatment can be repeated

A rare case of tined lead migration of InterStim device into the rectum with subsequent novel combined surgical-endoscopic removal technique

After the introduction of self-anchoring tined leads in 2002, lead migration after sacral neuromodulation (SNM) in the form of InterStim (TM) (Medtronic, Minneapolis, MN) has been reduced; however, it remains a considerable complication of this otherwise low-risk procedure. As intestinal perforation through lead migration or primary incorrect positioning portrays a rarity and has been scarcely reported in the literature, no algorithm for explantation in such cases has been determined. We present a case of a young man with an SNM device implant (InterStim II (R)) because of neurogenic urinary retention, who was admitted with inflammation, localized at the sacral lead insertion site. Our diagnostic algorithm revealed a tined lead electrode protruding into the rectum without concomitant abscess. We performed an interdisciplinary surgical approach combining regular incisions over the sacrum and buttocks for dissection of the lead and the implanted pulse generator, respectively, with an endoscopic transanal lead extraction. This method prevented further bacterial seeding in the surrounding tissues of the colon and, therefore, presacral abscess formation or sacral osteomyelitis. Combined surgical-endoscopic removal of the InterStim device is an effective and safe procedure that should be included in the armamentarium of urologists performing neuromodulation surgery in cases of intestinal perforation

Subculture and Cryopreservation of Esophageal Adenocarcinoma Organoids: Pros and Cons for Single Cell Digestion

The lack of suitable translational research models reflecting primary disease to explore tumorigenesis and therapeutic strategies is a major obstacle in esophageal adenocarcinoma (EAC). Patient-derived organoids (PDOs) have recently emerged as a remarkable preclinical model in a variety of cancers. However, there are still limited protocols available for developing EAC PDOs. Once the PDOs are established, the propagation and cryopreservation are essential for further downstream analyses. Here, two different methods have been standardized for EAC PDOs subculture and cryopreservation, i.e., with and without single cell digestion. Both methods can reliably obtain appropriate cell viability and are applicable for a diverse experimental setup. The current study demonstrated that subculturing EAC PDOs with single cell digestion is suitable for most experiments requiring cell number control, uniform density, and a hollow structure that facilitates size tracking. However, the single cell -based method shows slower growth in culture as well as after re-cultivation from frozen stocks. Besides, subculturing with single cell digestion is characterized by forming hollow structures with a hollow core. In contrast, processing EAC PDOs without single cell digestion is favorable for cryopreservation, expansion, and histological characterization. In this protocol, the advantages and disadvantages of subculturing and cryopreservation of EAC PDOs with and without single cell digestion are described to enable researchers to choose an appropriate method to process and investigate their organoids

Laparoscopic Surgery for Gastric Cancer: The European Point of View

Objective. Multiple Asian studies have proved the feasibility of laparoscopic approach for surgical treatment of gastric cancer. The difference between Asian and European patients could limit their application in Europe. We reviewed the literature for European studies comparing open gastrectomy with laparoscopic approach in the treatment of gastric cancer. Method. We searched the keywords gastric cancer and laparoscopy in MEDLINE and EMBASE. We included all studies published between 1990 and 2016 and conducted in Europe. Result. We found 1 randomized and 13 cohort studies which compared laparoscopic with open gastrectomy. We found no mean difference in the number of lymph nodes harvested between laparoscopic and open group (mean difference: -0.49; 95% CI: -2.42; 1.44, p=0.62) and no difference of short-term or long-term mortality (short-term odds ratio: 0.74, p=0.47; long-term odds ratio: 0.65, p=0.11). We found a longer operative time in the laparoscopic group (mean difference: 35.75 minutes, p<0.01) but lesser reoperation rate than the open group (odds ratio: 1.55 p=0.01). Conclusion. European based population studies found results comparable with their Asian counterpart. In the current state of evidence, minimally invasive surgery for gastric cancer is safe and can achieve the same oncological results

GERD and Barett: Natural Course of One Disease - Update Diagnostics and Therapy

Berlth F, Lorenz F, Kleinert R, Langhammer N, Hadzijusufovic E, Chon S-H. GERD und Barrett. Natürlicher Verlauf einer Erkrankung – Update Diagnostik und Therapie. Therapeutische Umschau. Revue therapeutique. 2022;79(3-4):151-158.GERD and Barett: Natural Course of One Disease - Update Diagnostics and Therapy Abstract. The gastroesophageal reflux disease (GERD) represents a relatively frequent condition, which clinically includes orocervical, thoracic and abdominal complaints. GERD is defined as pathological gastroesophageal acidic reflux, which consecutively leads to mucosal damage of the esophagus such as reflux esophagitis. The most common symptom of GERD is heartburn but GERD symptoms include various complaints, which need to be considered in diagnosis and therapy. Besides endoscopy, barium swallow, pH metry and manometry are counted among the routine diagnostics for GERD patients. For therapy, dietary and lifestyle measures come along with medication such as proton pump inhibitors (PPI) as daily medication and antacids on demand. It has been demonstrated that anti-reflux surgery, minimally invasive fundoplication or magnet augmentation of the lower esophageal sphincter, produces an equal and lasting effect on GERD compared to PPI. Surgery is preferred in case of large hiatal hernia of voluminous reflux. Success of therapy is given if esophageal exposure to acid is reduced, which shows in remission of esophagitis or which can be demonstrated through pH-metry control. Additionally, improvement of quality of life stands in the focus of GERD treatment, which is to be considered for every therapeutic step. Barrett esophagus represents a subtype of GERD with rising incidence in Western countries. As potential precancerous lesion, the Barrett's esophagus is to be diagnosed early and needs to undergo a risk stratified surveillance in order to prevent dysplasia or carcinoma. Patients with low grade dysplasia, high grade dysplasia or early Barrett's carcinoma should be treated endoscopically. Soon artificial intelligence might contribute to improvement of Barrett's esophagus surveillance and treatment

Preoperative staging of nodal status in gastric cancer

An accurate preoperative staging of nodal status is crucial in gastric cancer, because it has a great impact on prognosis and therapeutic decision-making. Different staging methods have been evaluated for gastric cancer in order to predict nodal involvement. So far, no technique could meet the necessary requirements, which include a high detection rate of infiltrated lymph nodes and a low frequency of false-positive results. This article summarizes different staging methods used to assess lymph node status in patients with gastric cancer, evaluates the evidence, and proposes to establish new methods