Endoscopic Therapies for Early Stage Esophageal and Gastric Cancers.

Early detection of esophageal and gastric cancers offers the possibility of curative treatments with less-invasive interventions than traditional surgical approaches. This review highlights the main endoscopic therapeutic modalities used for early esophageal and gastric malignancies. Endoscopic resection techniques include endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). EMR is beneficial for smaller, well-defined lesions and involves resecting the superficial layer of the mucosa. In contrast, ESD permits en bloc resection of larger lesions, including those involving the superficial submucosa, offering precise histopathological assessments and reduced recurrence rates. As such, multidisciplinary collaboration is essential to achieve optimal outcomes.

Endoscopic stenting for malignant biliary obstruction is technically successful in patients with preexisting duodenal stents.

Background and study aims There are limited data on the success of endoscopic retrograde cholangiopancreatography (ERCP) in patients with malignant biliary and duodenal obstruction with a preexisting duodenal stent. The aim of this study was to evaluate patient and procedural outcomes of a cohort of patients with preexisting duodenal stents who underwent an attempt at ERCP for malignant biliary obstruction (MBO). Patients and methods This was a single-center retrospective study on consecutive patients with a preexisting duodenal stent who underwent attempted ERCP for MBO. Technical success was defined as successful cannulation of the common bile duct, with successful dilation and/or deployment of a biliary stent under fluoroscopy. Clinical success was defined as number of patients in the entire group who underwent ERCP successfully with resolution of symptoms. Results We identified 64 patients (73 % men, 74 % white, median age 62 years) with a preexisting duodenal stent who underwent 85 attempts at ERCP. ERCP was technically successful in 50 of 85 procedures (59 %). Overall ERCP was successful in 41 of 85 patients (48 %). ERCP was more likely to be successful in patients with Type 1 and 3 duodenal strictures than with Type 2 strictures (83 % and 92 % vs. 42 %, P  < 0.01), in patients with a preexisting sphincterotomy (79% vs. 20 %, P  = 0.01) or preexisting biliary stent (66 % vs. 34 %, P  = 0.04). Adverse events included bleeding (n = 3), post-procedure fever (n = 3) and abdominal pain (n = 1). Conclusions Although biliary stenting via ERCP is often technically challenging in patients with a prior duodenal stent, it is a safe and effective method of biliary drainage. ERCP should be attempted in patients with Type 1 and 3 duodenal strictures, a prior sphincterotomy or an indwelling biliary stent.

The Role of the TP53 Pathway in Predicting Response to Neoadjuvant Therapy in Esophageal Adenocarcinoma.

PURPOSE: In patients with locally advanced esophageal adenocarcinoma, response to neoadjuvant therapy strongly predicts survival, but robust molecular predictors of response have been lacking. We therefore sought to discover meaningful predictors of response in these patients. EXPERIMENTAL DESIGN: We retrospectively identified all patients with adenocarcinoma of the lower esophagus or gastroesophageal junction who (i) were treated with multimodality therapy with curative intent at our institution from 2014 through 2020 and (ii) underwent prospective sequencing by Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. Clinicopathologic and genomic data were analyzed to identify potential genomic features, somatic alterations, and oncogenic pathways associated with treatment response. RESULTS: In total, 237 patients were included. MDM2 amplification was independently associated with poor response to neoadjuvant therapy [OR, 0.10 (95% confidence interval, 0.01-0.55); P = 0.032], when accounting for significant clinicopathologic variables, including clinical stage, tumor grade, and chemotherapy regimen. Moreover, TP53 pathway alterations, grouped according to inferred severity of TP53 dysfunction, were significantly associated with response to neoadjuvant therapy (P = 0.004, q = 0.07). Patients with MDM2 amplifications or truncating biallelic TP53 mutations had similar outcomes in terms of poor responses to neoadjuvant therapy and, consequently, shorter progression-free survival, compared with patients with TP53 pathway wild-type tumors. Thus, worsening TP53 dysfunction was directly correlated with worse outcomes. CONCLUSIONS: MDM2 amplification and TP53 status are associated with response to therapy in patients with esophageal adenocarcinoma. Given the dearth of actionable targets in esophageal adenocarcinoma, MDM2 inhibition, in combination with cytotoxic chemotherapy, may represent an important therapeutic strategy to overcome treatment resistance and improve outcomes in these patients.

Next-Generation Sequencing of 487 Esophageal Adenocarcinomas Reveals Independently Prognostic Genomic Driver Alterations and Pathways.

PURPOSE: To delineate recurrent oncogenic driver alterations and dysregulated pathways in esophageal adenocarcinoma and to assess their prognostic value. EXPERIMENTAL DESIGN: We analyzed a large cohort of patients with lower esophageal and junctional adenocarcinoma, prospectively sequenced by MSK-IMPACT with high-quality clinical annotation. Patients were subdivided according to treatment intent, curative versus palliative, which closely mirrored clinical staging. Genomic features, alterations, and pathways were examined for association with overall survival using Cox proportional hazard models, adjusted for relevant clinicopathologic factors knowable at the time of diagnosis. RESULTS: Analysis of 487 patients revealed 16 oncogenic driver alterations, mostly amplifications, present in ≥5% of patients. Patients in the palliative-intent cohort, compared with those in the curative-intent cohort, were more likely to have metastatic disease, ERBB2 amplifications, Cell-cycle and RTK-RAS pathway alterations, as well as a higher fraction of genome altered and rate of whole-genome doubling. In multivariable analyses, CDKN2A alterations, SMAD4 alterations, KRAS amplifications, Cell-cycle and TGFß pathways, and overall number of oncogenic drivers were independently associated with worse overall survival. ERBB2 amplification was associated with improved survival, presumably due to trastuzumab therapy. CONCLUSIONS: Our study suggests that higher levels of genomic instability are associated with more advanced disease in esophageal adenocarcinoma. Furthermore, CDKN2A, KRAS, and SMAD4 represent prognostic biomarkers, given their strong association with poor survival.

Direct Percutaneous Endoscopic Jejunostomy: Procedural and Nutrition Outcomes in a Large Patient Cohort.

BACKGROUND: Direct percutaneous endoscopic jejunostomy (DPEJ) is used for enteral nutrition (EN) in patients with postoperative anastomotic leaks after esophagectomy/gastrectomy and at high risk for aspiration. We characterized the indications, technical success, procedural/nutrition outcomes, and adverse events in a large cohort of patients undergoing DPEJ insertion. METHODS: Patients undergoing DPEJ insertion between January 2009 and March 2015 were identified from an institutional endoscopy database. Demographic, procedural, and nutrition outcome data were collected from electronic medical records. Regression analyses were used to identify predictors of adverse events and procedural success. RESULTS: A total of 452 patients underwent 480 attempts at DPEJ insertion. Indications included preoperative or postoperative weight loss (64%), postoperative upper gastrointestinal (UGI) anastomotic leak (13%), aspiration prevention (10%), and other (13%). Of attempted procedures, 398 (83%) were successful. Feeding was initiated in 389 (98%) of patients; a median of 1775 calories was delivered daily. Median body mass index (BMI) at baseline was 22.9 (11.4-44.7) and did not change over follow-up. Median change in BMI after DPEJ was similar in groups that received EN with palliative and curative intent. Adverse events following 480 attempted DPEJ insertions included 13 (3%) immediate and 74 (15%) delayed, 13 (3%) of which were serious. Patients with head and neck cancer had more adverse events than those with esophageal cancer (P = .020). CONCLUSION: DPEJ is a successful and safe procedure that effectively provides access for EN support in malnourished patients and patients with postoperative UGI cancer.

Predictors of clinical outcome of colonic stents in patients with malignant large-bowel obstruction because of extracolonic malignancy.

BACKGROUND AND AIMS: Colonic stent placement in patients with large-bowel obstruction (LBO) secondary to extracolonic malignancy (ECM) has been evaluated in small series with heterogeneous results. Our aim is to better characterize the technical and clinical success of colonic stent placement and to identify factors that affect this success in ECM patients. METHODS: All patients at a single high-volume center who presented for colonic stent placement for LBO because of ECM between 2001 and 2012 were retrospectively identified. The outcomes of interest were technical success, clinical success, stent occlusion rate, and overall survival. RESULTS: A total of 187 patients were identified. Mean age was 61.9 years (range, 23-89), and 150 (80.2%) were women. The most common malignancy type was urogynecologic (n = 104) and most common location sigmoid colon (n = 128). Overall, 142 patients (75.9%) achieved technical success and 102 patients (54.5%) clinical success. Radiographic presence of peritoneal carcinomatosis (P < .001) and multifocal disease (P < .001) were associated with both decreased technical and clinical success. Procedure-related adverse events were seen in 12 patients (6.4%). In patients with clinical success, the incidence of stent occlusion at 3 months was 14.7% (95% confidence interval, 7.8%-21.6%) and was higher in patients with prior radiation therapy (P = .011). The median overall survival for all patients from time of attempted stent placement was 3.3 months (95% confidence interval, 3.0-4.1). CONCLUSIONS: This study represents the largest retrospective series of colonic stent placement for LBO in ECM patients in the literature. Our technical success rate of 75.9%, clinical success rate of 54.5%, and 3-month stent occlusion rate of 14.7% suggest that stent placement is a viable palliative option for patients with advanced disease because of ECM. Patients with peritoneal carcinomatosis and multifocal disease have reduced technical and clinical success. However, these factors should not dissuade an attempt at stent placement, if risk-to-benefit analysis is favorable.

Screening and prevention strategies and endoscopic management of early esophageal cancer.

Esophageal cancer is the 8th most common cancer worldwide and the 6th most common cause of cancer-related death. Its two main subtypes, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), have varying incidences globally, but recent decades have seen a demonstrated rise of EAC in Western countries whereas ESCC remains highly prevalent in Eastern Africa, Central Asia, and China. Screening interventions have focused on using endoscopy to identify Barrett's esophagus (BE) as a precursor to EAC, and squamous cell dysplasia prior to onset of ESCC. However, additional cost-effective screening interventions that can be applied to larger populations at risk for esophageal cancer are needed. Advances in endoscopic ablative techniques and endoscopic resection via endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) have proven to be effective in eradicating dysplasia and early stage cancer. Preventive strategies involving reduction in tobacco and alcohol consumption as well as regular use of proton pump inhibitors and nonsteroidal anti-inflammatory drugs are aimed at reducing the incidence of dysplasia and esophageal cancer, but require further study before being recommended for widespread use.

Imaging for pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers worldwide due to its aggressiveness and the challenge to early diagnosis. Complete surgical resection is the only curative option, but fewer than 20% of patients have potentially resectable disease at the time of the diagnosis. Radiologists can assess whether PDAC is resectable, borderline resectable, locally advanced or metastatic based on current imaging tests. This review will outline the role of imaging in both the diagnosis and staging of PDAC, with the goal of assisting the multidisciplinary team in tailoring the best treatment for patients.

Endoscopic options for early stage esophageal cancer.

Surgery has traditionally been the preferred treatment for early stage esophageal cancer. Recent advances in endoscopic treatments have been shown to be effective and safe. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) allow endoscopists to remove small, superficial lesions, providing tumor specimen that can be examined for accurate pathologic tumor staging and assessment of adequacy of resection. Endoscopic ablation procedures, including photodynamic therapy (PDT) and radio frequency ablation (RFA), have also been shown to safely and effectively treat esophageal dysplasia and early stage neoplasia, with excellent long-term disease control. Both approaches are becoming more widely available around the world, and provide an alternative, safe, low risk strategy for treating early stage disease, making combined endoscopic therapy the recommended treatment of choice for early stage esophageal cancers.

Reproductive characteristics in relation to ovarian cancer risk by histologic pathways.

STUDY QUESTION: Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification? SUMMARY ANSWER: Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer. WHAT IS KNOWN ALREADY: Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways. DESIGN: This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center. MAIN RESULTS AND THE ROLE OF CHANCE: We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥ 3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥ 3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility. LIMITATIONS, REASONS FOR CAUTION: A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study. WIDER IMPLICATIONS OF THE FINDINGS: This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types. STUDY FUNDING/COMPETING INTEREST(S): This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Safety of endoscopic removal of self-expandable stents after treatment of benign esophageal diseases.

BACKGROUND: Temporary placement of self-expandable stents has been increasingly used for the management of benign esophageal diseases. OBJECTIVE: To evaluate the safety of endoscopic removal of esophageal self-expandable stents placed for the treatment of benign esophageal diseases. DESIGN: Multicenter retrospective study. SETTING: Six tertiary care centers in the United States and Europe. PATIENTS: A total of 214 patients with benign esophageal diseases undergoing endoscopic stent removal. INTERVENTION: Endoscopic stent removal. MAIN OUTCOME MEASUREMENTS: Endoscopic techniques for stent removal, time to stent removal, and adverse events related to stent removal. RESULTS: A total of 214 patients underwent a total of 329 stent extractions. Stents were mainly placed for refractory strictures (49.2%) and fistulae (49.8%). Of the removed stents, 52% were fully covered self-expandable metal stents (FCSEMSs), 28.6% were partially covered self-expandable metal stents (PCSEMSs), and 19.5% were self-expandable plastic stents. A total of 35 (10.6%) procedure-related adverse events were reported, including 7 (2.1%) major adverse events. Multivariate analysis revealed that use of PCSEMSs (P < .001) was a risk factor for adverse events during stent removal. Favorable factors for successful stent removal were FCSEMSs (P ≤ .012) and stent migration (P = .010). No significant associations were found for stent indwelling time (P = .145) and stent embedding (P = .194). LIMITATIONS: Retrospective analysis, only tertiary care centers. CONCLUSIONS: With an acceptable major adverse event rate of 2.1%, esophageal stent removal in the setting of benign disease was found to be a safe and feasible procedure. FCSEMSs were more successfully removed than self-expandable plastic stents and PCSEMSs. Adverse events caused by stent removal were not time dependent.

A pilot study on vaginally assisted laparoscopic sacrocolpopexy for patients with uterovaginal prolapse.

OBJECTIVES: : The primary objective of this pilot study was to compare the short-term anatomic outcomes and complication rates of vaginally assisted laparoscopic sacrocolpopexy (VALS) with those of conventional laparoscopic sacrocolpopexy (LS) in patients undergoing concurrent hysterectomy. The secondary objective was to compare operative times of the 2 different techniques. METHODS: : This is a retrospective pilot study comparing VALS-a method using transvaginal mesh attachment to the vaginal apex-to conventional LS in patients undergoing concurrent hysterectomy. RESULTS: : Forty-four women underwent VALS, and 26 women underwent LS. There was no significant difference in intraoperative complication rates (2.3% vs 3.8%, not statistically significant), postoperative complication rates (4.5% vs 0.0%, P = 0.526), mesh extrusion rates (2.3% vs 0%, not statistically significant), or postoperative pelvic organ prolapse quantification scores. The mean total operative time was 55 minutes shorter for the VALS group (215.2 [SD, 41.0] minutes) than the LS group (269.7 [SD, 55.6] minutes; P < 0.001). CONCLUSIONS: : There was no significant difference in short-term anatomic outcomes or complication rates between groups. Vaginally assisted LS was associated with significantly shorter operative times than conventional LS.

Synthesis of novel acyclic nucleoside analogues with anti-retroviral activity.

A series of novel acyclic thymine nucleoside analogues were prepared by the Mitsunobu reaction from appropriately protected chiral triols. The enantiomeric triols were obtained from substituted gamma-lactone acids, prepared by asymmetric oxidation of 3-substituted-1,2-cyclopentanediones. The cytotoxic activity of new analogues was evaluated on MCF-7 human breast cancer and HeLa cells, and antiviral activities on human immunodeficiency virus type 1 and hepatitis C virus models. The synthesized compounds revealed specific anti-retroviral activity and no cytotoxic side effects.

A shifty diagnosis: Cogan's syndrome. A case report and review of the literature.

Cogan's syndrome is defined as a chronic inflammatory disease of unknown origin, an autoimmune disease, characterized by bilateral sensorineural hearing loss, vestibular symptoms, inflammatory ocular manifestations with variable risk of developing into a systemic disease. The onset of disease is variable but is often characterized by isolated ocular symptoms or acute ear and/or vestibular manifestations, variably associated. The diagnosis of Cogan's syndrome can be a challenge as is evident in the case described here since it is based only on the association between bilateral ocular and vestibuloauditory symptoms with no specific diagnostic tests available.

[Non-Hodgkin's lymphomas of the salivary gland: analysis of prognostic factors in 28 cases]. / I linfomi non Hodgkin delle ghiandole salivari: analisi dei fattori prognostici su 28 casi.

Primary malignant lymphomas of the major salivary glands are rare and usually arise in the parotid gland (2% of all neoplastic disorders). In this report clinical records of 28 cases of NHL of salivary glands (27 in the parotid gland and one in the submandibular gland) are reviewed and problems related to diagnosis and management strategies are discussed. The 5-year overall survival rate was 72% and did non differ from the survival of other NHL of the head and neck. Statistical evaluation of prognostic factors (age, histology, clinical stage, grading, bulky and surgical approach--biopsy versus parotidectomy), are presented. Analysis of these factors showed that prognosis was not influenced by age, histology, clinical stage and grading of disease. Poor survival was significantly correlated to bulky lesions (tumor size greater than 6 cm). In our experience surgical treatment did not significantly affect survival rate. It is concluded that diagnostic surgical procedures in case of suspected NHL of the parotid gland are fine needle aspiration biopsy. (FNAB) or incisional biopsy. The treatment of choice is radiotherapy associated with chemiotherapy in cases of localized-bulky or disseminated disease.