Integrated multi-omics and functional analysis uncovers the structural and regulatory significance of Nucleophosmin 1 in the metabolic progression of esophageal carcinoma.

Aerodigestive fistulas (ADFs) cause significant morbidity and mortality, especially in advanced malignancies. This review summarizes current knowledge on etiology, diagnostic, and management strategies. Esophageal carcinoma is the predominant cause of malignant ADFs with their development influenced by tumor location, most often involving the upper and middle thirds of the esophagus, and by prior interventions such as radiotherapy or esophageal stenting.Benign acquired ADFs typically result from iatrogenic injuries including pressure necrosis from cuffed tubes, stent erosion, endoscopy, and surgery. Diagnosis often is delayed by nonspecific symptoms, requiring combined imaging and endoscopic evaluation. Benign ADFs are typically amenable to surgical repair, whereas malignant fistulas usually require individualized palliation, notably airway and esophageal stenting. Dual airway-esophageal stenting has advantages over single stenting for malignant ADFs due to superior quality of life and survival outcomes. Emerging minimally invasive techniques include endoscopic clips, occluder devices, and tissue adhesives. Optimal management of ADFs requires high clinical vigilance, timely diagnostic evaluation, and individualized multidisciplinary approaches. Further research into emerging therapies and standardized management algorithms is essential for improving patient outcomes and guiding evidence-based clinical practice.

Background/Objectives: Since 1988, the IARC has classified alcohol as a type 1 carcinogen, causally linked to seven types of cancer (oral cavity, pharynx, larynx, esophagus, colorectum, liver and breast carcinomas). Several agencies, such as the WHO and the IARC, hold that there is a direct monotonic association between any gram of alcohol consumed and the risk of cancer, regardless of the drinking pattern. On the other hand, an expanding body of evidence indicates that drinking pattern may substantially modify the effect of alcohol consumption. The Mediterranean alcohol-drinking pattern (MADP) includes different aspects of alcohol consumption, such as preference for red wine, moderate alcohol consumption with meals, spreading consumption over the week and avoiding binge drinking. Conformity to this pattern has shown inverse associations with all-cause mortality, cardiovascular disease and diabetes. However, its relationship with cancer incidence has not been studied yet. Our objective was to assess how alcohol consumption patterns, with particular emphasis on the MADP, relate to the incidence of the seven alcohol-related cancers. This information is needed to support cancer prevention recommendations that may go beyond the amount of alcohol consumed to also include the drinking pattern. Methods: We prospectively followed 19,541 participants in the SUN (“Seguimiento Universidad de Navarra”) cohort for a median of 13.8 years. We classified participants into four groups, namely, abstainers and three further groups according to their adherence to the MADP score (low, moderate and high). Results: A substantial reduction in the risk of alcohol-related cancer incidence was observed only in men for high versus low adherence to the MADP, with an adjusted hazard ratio (HR) of 0.44 (95% confidence intervals (CIs) (0.21–0.92)). The category of moderate adherence to the MADP showed a lower risk of cancer incidence with a tendency towards statistical significance (HR = 0.56, 95% CI, 0.30–1.06). For women, no result reached statistical significance. Conclusions : Based on the available evidence, separate messages by sex should be delivered. In men, the association between alcohol and cancer goes beyond the amount of alcohol consumed, and a Mediterranean drinking pattern may be beneficial even for alcohol-related cancers. Men should, therefore, receive an additional message: among alcohol consumers, greater adherence to the MADP may help lower their risk of developing alcohol-related cancers. No benefit is supported for the MADP against alcohol-related cancers in women.

Achromobacter denitrificans is a rare, opportunistic, non-fermenting Gram-negative bacillus increasingly implicated in nosocomial infections, particularly among immunocompromised and critically ill patients. Its intrinsic resistance to multiple antimicrobials poses a diagnostic and therapeutic challenge. We present a series of five patients diagnosed with A. denitrificans bloodstream infections, each from a different clinical background: advanced esophageal carcinoma post-chemotherapy, ovarian carcinoma with duodenal obstruction, drug-resistant (DR) pulmonary tuberculosis, acute myelomonocytic leukemia with febrile neutropenia, and extrahepatic portal vein obstruction with esophageal varices. All patients exhibited signs of systemic infection, and blood cultures flagged positive for A. denitrificans , confirmed through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Antimicrobial susceptibility profiles revealed consistent sensitivity to piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and meropenem, though some isolates showed carbapenem resistance. Treatment regimens were tailored accordingly, three patients responding favorably and two succumbing to septic shock and multi-organ dysfunction. This case series highlights the emerging significance of A. denitrificans as a pathogen in diverse hospital settings. Early identification using advanced diagnostic modalities such as MALDI-TOF MS, along with targeted antimicrobial therapy, is crucial for improved outcomes. Our findings underscore the need for heightened clinical awareness and robust infection control strategies to manage such multi-DR organisms effectively.

Abstract Aim Small cell oesophageal carcinoma (SCOC) is a rare, aggressive neuroendocrine carcinoma with no established treatment guidelines. Its low incidence and rapid progression limit the feasibility of randomised trials. This retrospective study evaluated treatment patterns and associated survival outcomes. Method All patients with histologically confirmed SCOC treated at a single centre between 2007 and 2024 were included. Patients with mixed histopathology or disease involving the oesophagogastric junction were also eligible. Results Sixty-three patients were identified, with a median age of 67 years; 37 (58.7%) were male. Metastatic disease at diagnosis was present in 37 patients (58.7%). Among those with non-metastatic disease, radical chemoradiotherapy achieved the longest median overall survival of 23 months, followed by palliative chemotherapy given sequentially rather than concurrently with radiotherapy (18 months), surgery (with or without chemotherapy – 13 months), and palliative chemotherapy alone (5 months). Patients with metastatic disease had a median overall survival of 7 months. Notably, four patients treated with definitive chemoradiotherapy in this cohort remain alive at 183, 82, 32, and 13 months after initial diagnosis. Conclusions These findings support radical chemoradiotherapy as the optimal treatment for selected patients with non-metastatic SCOC.

Abstract Background Pembrolizumab was approved by NICE in 2021 for use with platinum- and fluoropyrimidine-based chemotherapy in patients with locally advanced unresectable, or metastatic PD-L1 expressing carcinoma of the oesophagus. We describe a case of locally advanced oesophageal adenocarcinoma in which treatment with pembrolizumab resulted in a complete pathological response. Case Presentation A 70-year-old gentleman presented with T3N2M0 moderately differentiated lower oesophageal adenocarcinoma. He underwent neoadjuvant chemotherapy with fluorouracil, oxaliplatin, and docetaxel (FLOT), resulting in a partial radiological response. Upon completion of neoadjuvant therapy, the tumour was deemed operable, however the patient initially declined surgery. Surveillance imaging at three months demonstrated disease progression. Eight cycles of carboplatin and capecitabine were then completed. Although initially radiologically stable, subsequent disease progression resulted in dysphagia. Pembrolizumab was started and continued for six months. Three months into treatment, worsening dysphagia prompted oesophageal stenting, with only temporary symptomatic relief and nasojejunal feeding was commenced. Restaging PET-CT demonstrated operable disease, with focal uptake adjacent to the primary tumour and ongoing left gastric node avidity. The patient underwent an uncomplicated robotic-assisted oesophagogastrectomy. Final histopathology revealed a complete pathological response, with no residual tumour, dysplasia, or lymph node involvement. Conclusions This case demonstrates the use of pembrolizumab in the management of patients with PD-L1 expressing oesophageal carcinoma and highlights the evolving role of immunotherapy in oesophagogastric cancer treatment.

Bisphenol A (BPA) is a pervasive endocrine-disrupting chemical with estrogenic activity and has been implicated in the development of multiple malignancies. However, its molecular mechanisms in esophageal carcinoma (ESCA) remain unclear. This study aimed to elucidate the potential oncogenic pathways through which BPA contributes to ESCA progression. Network toxicology was applied to collect BPA-related targets and ESCA-associated genes from multiple public databases. Overlapping targets were identified for further protein–protein interaction (PPI) and enrichment analyses to investigate functional pathways. Molecular docking was performed to assess binding affinities between BPA and core targets. The Cancer Genome Atlas (TCGA) was used for expression and survival validation, while mutation profiles were examined via cBioPortal. A total of 100 BPA-related targets and nearly 50,000 ESCA-associated genes were retrieved, yielding 95 overlapping targets. PPI network analysis and enrichment results highlighted HSP90AA1 and HSP90AB1 as central hub genes associated with protein kinase regulation, telomerase activity, and immune–inflammatory signaling pathways. Molecular docking confirmed strong binding affinities between BPA and HSP90AA1/HSP90AB1 (−7.5 and −7.0 kcal/mol, respectively). TCGA analyses showed that both genes were significantly upregulated in ESCA tissues, and high expression correlated with poorer overall survival. Mutation profiling indicated that HSP90AB1 exhibited a higher alteration frequency (13%), predominantly driven by gene amplification. This integrative multi-omics analysis provides compelling evidence that BPA may facilitate ESCA progression through HSP90AA1/HSP90AB1-mediated oncogenic and immune–inflammatory pathways. These findings deepen understanding of environmental carcinogenesis and suggest potential molecular targets for ESCA prevention and treatment.

Outcomes for upper gastrointestinal (UGI) cancers are poor except for those patients whose cancers are diagnosed at a very early stage. Unique socioeconomic factors may result in worse outcomes in the safety-net setting given that these patients often seek care later in the disease course. This study aims to understand the survival outcomes of patients with UGI cancers in a safety-net health care (SNH) setting. Patients diagnosed with esophageal squamous (ES), esophageal adenocarcinoma (EA), and gastric carcinomas (G) at JPS Health Network in Fort Worth, Texas from January 1, 2018, to December 31, 2022, were identified in the tumor registry database. The electronic health record was queried for clinical characteristics, pathology variables, and management outcomes. Kaplan-Meier curve was used to illustrate the difference in survival time across cancer stages from an index date of diagnosis with censoring at date of last contact. A total of 171 patients were included: the median age was 57 years, but 15 patients were under 40 years. By ethnicity, 40% were Hispanic. The majority were male (71%) and uninsured (65%). G was the most common primary site (n = 92, 54%), followed by EA (n = 58, 34%) and ES (n = 21, 12%). Of the 125 stage 4B patients, 69 (55%) did not receive any treatment, 6 received only palliative radiation, and the remainder received systemic therapy. In patients with stage 4B, the median overall survival for patients with systemic treatment was 7.9 months (95% CI: 6.7-11), compared with 2.1 months (95% CI: 1.5-3.0) without treatment. In an urban safety-net population with a high percentage of Hispanic population, most patients with advanced UGI cancers did not receive systemic therapy. Interventions to improve outcomes must consider the unique socioeconomic needs of this vulnerable population to translate clinical trial results into improved outcomes.

The mode of organ resection and reconstruction that has been used to treat digestive tract tumors (DTTs) can cure the disease. However, it involves the surgical resection of critical structures (such as the cardia, pylorus, and anus) and gastrointestinal reconstruction, which alter the physiological anatomy of the digestive system. These changes often lead to numerous postoperative complications and severely affect the patient’s quality of life (e.g., refractory gastroesophageal reflux following proximal gastrectomy, dumping syndrome after subtotal gastrectomy, loss of anal function after low rectal surgery). For the defect of this mode, professor Linghu Enqiang proposed the new mode that was “curing the disease and restoring normal function” in 2016, which was named as this new mode: Super Minimally Invasive Surgery (SMIS). To accomplish various types of SMIS, four operative channels were developed: the natural cavity channel, the tunnel channel, the puncture channel, and the multi-cavity channel. SMIS, with its advantages of minimal trauma and organ function preservation, has been recognized by authoritative domestic and international organizations and has developed rapidly. Based on its clinical value and the need for wider application, there is an urgent need to establish standardized guidelines to guide practice. This guideline was developed by leading organizations such as the SMIS committee of World Endoscopy Organization (WEO) and Chinese Society of Digestive Endoscopy (CSDE), in collaboration with multidisciplinary experts from gastroenterology, general surgery, and pathology. Systematic searches were conducted in nine major databases, including PubMed, Embase, and China National Knowledge Infrastructure (CNKI), for both Chinese and English literature published before 2025. Evidence from randomized controlled trials (RCTs), observational studies, and case series was included, with the quality of evidence and recommendation strength evaluated using the GRADE system (high-level evidence:RCTs; low-level evidence: observational studies). The recommendations were refined through several rounds of expert discussions and voting, and were reported following the AGREE II and RIGHT reporting standards. This guideline has been registered on the PREPARE (Practice Guideline REgistration for transPAREncy; registration number: PREPARE-2024CN1183). This guideline addresses 15 issues related to SMIS treatment for esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), their corresponding precancerous lesions, and precancerous lesions of the duodenal papilla. It provides corresponding recommendations in three main areas: (1) Definitions and principles: SMIS should meet ten core criteria, including organ preservation, complete resection (R0), and sterile procedures. It also standardizes naming conventions (e.g., “Super minimally invasive non-full-thickness resection of lower esophageal squamous carcinoma via the oral cavity”). (2) Surgical recommendations: EC: For early and precancerous lesions, SMIS of non-full-thickness resection (non-FTR) is preferred. For circumferential involvement ≥ 1/2, SMIS via tunnel channel for non-FTR is recommended. If the wound circumference is ≥ 75%, the use of corticosteroids or stents to prevent stenosis is advised. GC: For T1a-T1b stage and precancerous lesions, SMIS non-FTR or full-thickness resection (FTR) is preferred, with individualized plans based on the risk of lymph node metastasis (LNM). CRC: SMIS of non-FTR or FTR is recommended as the first-line treatment for T1a-T1b stage and precancerous lesions. For locally advanced rectal cancer (LARC) that achieves clinical remission after neoadjuvant therapy, SMIS of FTR can be considered to assess pathological remission. Duodenal papilla precancerous lesions: SMIS resection via the oral cavity is preferred. Postoperatively, whether to add pancreaticoduodenectomy and follow-up strategies should be determined based on pathology. (3) Postoperative management: A SMIS treatment cure evaluation system for early gastric cancer (EGC) was established, divided into SMIS-Cure A(cured), SMIS-Cure B (clinically cured), and SMIS-Cure C (surgical reassessment), which guides follow-up. For CRC or precancerous lesions, R0 resection is the standard for cure, and follow-up plans are developed according to risk stratification. This guideline systematically integrates the evidence from SMIS in the treatment of DTTs with expert consensus, establishing a standardized pathway centered on organ function preservation. It shifts the treatment model from “cure first” to “cure-function balance”. Its application is expected to reduce overtreatment, improve the patient’s quality of life, and provide a framework for future technological iterations and the expansion of indications. It should be continuously optimized with multicenter clinical data and long-term follow-up results to achieve more precise, individualized treatment.

Esophageal cancer is one of the malignant tumors with high incidence and mortality rates worldwide. Its occurrence and development involve abnormal regulation of multiple signaling pathways. In recent years, the role of Hippo signaling and PEST-containing nuclear protein (PCNP) in esophageal cancer has gradually received attention. As a key regulator of organ size and tissue homeostasis, the Hippo pathway exerts its biological effects primarily through its core effector Yes-associated protein (YAP)/TAZ; accumulating evidence confirms that aberrant activation of YAP is closely linked to esophageal cancer occurrence, progression, lymph node metastasis, and chemoresistance, making it a critical oncogenic driver. PCNP, a highly conserved nuclear protein, together with its E3 enzyme NIRF, is involved in modulating cell cycle progression, DNA damage repair, and apoptotic signaling under physiological conditions. However, its overexpression in esophageal cancer tissues has been associated with accelerated tumor growth and unfavorable patient outcomes, potentially through interactions with downstream oncogenic mediators such as NRF2. This review summarizes the research progress on the Hippo pathway and PCNP, and proposes a possible mechanistic interplay between them in esophageal cancer based on their functions, focusing on exploring their mechanisms of action, regulatory relationships, and potential therapeutic targets in the occurrence and development of esophageal cancer, in order to provide ideas for diagnosis, prognosis, and targeted therapy of esophageal cancer.

Esophageal adenosquamous carcinoma (EASC)-a rare, aggressive esophageal cancer with poor prognosis-has no guideline-specified prognostic tools. Current models developed for pure adenocarcinoma or squamous-cell carcinoma may misclassify EASC risk. We identified 551 eligible EASC cases in the SEER database (2000-2021) for the training cohort (n=486) and consecutively enrolled 65 patients from two independent centres as an external validation cohort. Risk factors for overall survival were identified using LASSO cox regression analysis. A nomogram for both overall survival (OS) and cancer-specific survival (CSS) was then developed. Performance was evaluated using bootstrap-internal validation (1,000 resamples), time-dependent ROC curve, calibration curve and DCA, and was further externally validated. On multivariable cox analysis, older age (≥80 vs <60years: HR 1.93, 95% CI 1.35-2.75, p < 0.001), advanced T stage (T4 vs T1: HR 2.13, 95% CI 1.41-3.22, p < 0.001)) and distant metastasis (M1 vs M0: HR 1.36, 95% CI 1.03-1.80, p=0.030) were associated with increased mortality. Surgical resection (HR 0.33, 95% CI 0.23-0.46, p < 0.001) and chemotherapy (HR 0.41, 95% CI 0.31-0.53, p < 0.001) conferred significant survival benefits. The nomogram showed AUCs 0.80-0.87 at 1-, 3- and 5-year, good calibration and positive net benefit in both cohorts. The dual OS/CSS nomograms enable individualized EASC risk counselling. Prospective, multi-ethnic validation and assessment of decision impact are needed before clinical deployment.

BackgroundEsophageal carcinoma (ESCA) is a highly lethal malignancy with poor prognosis and limited treatment options. The identification of effective prognostic biomarkers and therapeutic targets remains an important goal in improving outcomes for patients with ESCA. While the involvement of programmed cell death (PCD) mechanisms in cancer remains underexplored, they are thought to influence some aspects of tumor biology. The purpose of this study was to construct a prognostic signature derived from PCD-related long non-coding RNAs (lncRNAs) in ESCA.MethodsTranscriptome and clinical data from ESCA patients were sourced from The Cancer Genome Atlas (TCGA) database. Candidate lncRNAs associated with PCD and patient prognosis were identified and subjected to univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression to build a prognostic signature. The signature’s predictive performance was validated internally. To explore possible mechanisms underlying risk stratification, we employed multiple approaches, including weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and assessment of immune cell infiltration patterns.ResultsEight PCD-related lncRNAs (AC109347.1, BLACE, AP001527.2, AP001001.1, LINC00402, AC087289.5, FAM83C-AS1, and AL132655.2) were screened and incorporated into the prognostic signature. The signature appeared capable of distinguishing between high- and low-risk groups with distinct survival outcomes. Downregulation of immune-related pathways was observed in high-risk patients based on WGCNA and GSEA analyses. Immune cell infiltration and immune scoring metrics were comparatively lower in high-risk individuals. Based on drug response predictions, we identified potential agents that could be preferentially effective in high-risk ESCA patients.ConclusionsIn conclusion, the PCD-related lncRNAs signature constructed in this study may contribute to prognosis assessment in ESCA and offers preliminary indications of immune involvement worthy of further investigation.

Objectives: Oncological patients often require supplemental feeding due to an inability to consume adequate nutrition. Most surgeons prefer to place a feeding jejunostomy at the time of primary surgery during major oncological cases, but these are not free of complications. In the current era of enhanced recovery protocols, minimal tubes are propagated, and when required, supplementation is provided with parenteral nutrition (PN). We aimed to evaluate the role, benefits, and hazards of feeding jejunostomy in oncologic practice. Material and Methods: This was a retrospective study conducted at a specialized oncology unit over a span of 5 years, from January 2020 to December 2024, including all adult patients undergoing feeding jejunostomy as a part of an oncological procedure or as a standalone procedure. Data were extracted from medical records and the operation theatre (OT)logs. Demographic, clinical, procedure and follow-up data were collected. Standard surgical technique of modified Witzel’s method was used for tube insertion and postoperative feeding with personalised diet charts. Complications were managed as per the treating surgeon's discretion. Results: Out of 613 patients, 534 were included in the final analysis. The mean age of the patients was 52.8 ± 12.3 years. There were 282 males (52.8%) and 252 females (47.2%) in the population. The most common indication for feeding jejunostomy (FJ) was carcinoma oesophagus, followed by periampullary carcinoma (20.2%) and gastric carcinoma. 29% tubes were placed as part of another surgery, and the remaining 21% were for palliative feeding. The most frequently performed procedure was video-assisted thoracoscopic (VATS) esophagectomy (32.5%), followed by Whipple’s procedure (25.8%). Fifty patients received a standalone tube procedure for various indications. FJ-related complications were seen in 97 (18.1%) patients. The most common complication was feed intolerance, seen in 45 (8.4%) patients. Other minor complications, such as tube dislodgement,were seen in 2.8% cases, and 2.2% had peritubal leak. Major complications were seen in 8 cases over the study period. 4 had a leak resulting in enterocutaneous (EC) fistula, 2 cases of obstruction, 1 small bowel volvulus and 1 case of peritonitis. Four patients required re-exploration for obstruction, volvulus and peritonitis. There was no FJ-related mortality. The highest overall complication rate was observed in patients undergoing Whipple’s procedure (29.7%), followed by total gastrectomy (27.8%) and D2 gastrectomy (16.7%). Mean pre - op albumin was 3.2(±0.34), and mean post-operative albumin at day 15 was 2.9 (±0.28). FJ was retained for a mean duration of 17 (±0.7.3) days among the patients where the tube was placed with curative intent surgeries. In 104 patients where there were postoperative complications such as anastomotic leaks, sepsis, or other surgical complications, the mean tube duration was 35 (±0.8.5) days. Conclusion: Feeding jejunostomy is still a viable option for patients undergoing major oncological procedures to supplement nutrition postoperatively, aiding speedy recovery. It has minimal complications, which can be managed conservatively and can be safely removed within a month post-procedure. It is also a well-tolerated option for prolonged sustenance in cases of advanced malignancy.

BackgroundEsophagectomy is a highly complex surgical procedure, and it is associated with significant morbidity and mortality. The postoperative complication rate is high, with pneumonia being the most common. These are thought to arise from (micro-)aspiration of bacteria residing in the oropharyngeal and gastrointestinal (GI) tract. Selective decontamination of the digestive tract (SDD) is a prophylactic antibiotic strategy aimed at preventing these infections. SDD decolonizes the oropharyngeal and GI tract from pathogenic aerobic gram-negative rods, fungi and yeasts, while anaerobic, protective microbiota are preserved. The PERSuaDER trial aims to evaluate whether perioperative SDD can reduce postoperative pneumonia after esophagectomy.MethodsThe PERSuaDER-trial is a randomized, controlled, open-label, superiority, multicenter, pragmatic, group-sequential trial aiming to include 854 patients with primary resectable esophageal carcinoma ((y)cT1-4a N0-3 M0) scheduled for transthoracic esophagectomy. The intervention group will receive SDD prophylaxis in addition to the standard care regimen. The SDD treatment comprises two oral liquids: an oral suspension containing amphotericin B and an oral solution containing both colistin sulfate and tobramycin. Participants are required to swallow the SDD suspension four times a day for 1 week, starting 3 days prior to the surgical procedure, with two doses on the day of surgery. All other aspects of care are identical to those provided to the control group (standard care without SDD). Participants will be asked to keep a diary and fill out quality of life, medical consumption, and productivity cost questionnaires. Interim analyses will take place after 30% and 60% of the participants have completed follow-up of 30 days after surgery, and after completion or termination of the trial.DiscussionIt is hypothesized that the addition of SDD to the standard peri-operative care in esophageal cancer surgery will result in a reduction in the incidence of postoperative pneumonia. Furthermore, the trial will evaluate the impact of SDD on postoperative (infectious) complications and quality of life, and its cost-effectiveness.Trial registrationThe PERSuaDER trial is registered in ClinicalTrials.gov (NCT05865743) and the European Clinical Trials Information System (CTIS) (EU Trial number: 2023-504144-33), Trial authorization date: 25.03.2024, protocol version 1.1, date: 03.03.2024.

Esophageal cancer is a significant health concern globally. In Punjab, where pesticides use and heavy metal exposure are widespread esophageal squamous cell carcinoma is among the leading cancers. This study aims to investigate the association between these environmental factors and esophageal carcinoma, for instituting preventive strategies. We conducted a case-control study in Punjab, with 380 carcinoma cases and 760 age, gender, and district-matched controls from hospital and community settings. The participants completed a case report form with validated questions on risk factors. The urine, water, oral cytology, blood, and esophageal biopsies samples were collected from a subset of the population to evaluate pesticide metabolites, heavy metal exposure, cytological changes and infections like H. pylori and HPV. The mean age of cases was 57.17 ± 9.54 (SD) years, similar to that of controls, 56.96 ± 8.93 (SD)years (p>0.05).The key risk factors for esophageal carcinoma were, Dimethylphosphate presence in urine (5.41 (95% CI: 1.42-20.67, p<0.05), tobacco use (OR 1.60, 95% CI 1.24-2.06, p < 0.001), alcohol use (OR 1.65, 95% CI 1.31-2.08, p < 0.001) and hot beverages (OR 1.81, 95% CI 1.44-2.28, p < 0.001), with population attributable fraction of 86.7%, 10.8%, 16.5%, and 16.7%, respectively.. The daily intake of fruits (OR 0.74, 95% CI 0.59-0.92, p = 0.008) and vegetables (OR 0.81, 95% CI 0.65-0.99, p = 0.045) had protective association, with inadequate intake contributing to 27% and 26.8% of risk, respectively. The exposure to heavy metals from drinking water was higher in both groups but not statistically significant. This study confirms established risk factors like tobacco, alcohol, and diet contribute to esophageal squamous cell carcinoma in Punjab, while identifying pesticide exposure as a new risk factor. It calls for stricter regulations, public health interventions, and further research into environmental risks.

Long-term outcomes of S-1-based chemoradiotherapy in inoperable elderly patients with esophageal carcinoma: A multicenter, randomized, phase III clinical trial.

Thoracoscopic versus open oesophagectomy for patients with oesophageal cancer (JCOG1409 MONET): a multicentre, open-label, randomised, controlled, phase 3, non-inferiority trial.

Human Papillomavirus Infection Is a Favorable Prognostic Factor for Patients With Stages I to IVA Esophageal Squamous Cell Carcinoma but not Adenocarcinoma.

BackgroundIn recent years, the significance of sirtuins in cancer biology has become increasingly evident, but their molecular mechanisms and prognostic impacts remain elusive.ObjectiveThe present study aimed to investigate the differential expression of the sirtuin gene family across cancers and to evaluate their prognostic value.MethodsWe used various bioinformatics databases and methodologies, including Oncomine, GEPIA, OncoDB, cBioPortal, R2 Kaplan-Meier Scanner, STRING, etc., to determine the expression pattern of the sirtuin family genes, along with their mutations and prognostic values in human cancers.ResultsIn the current study, SIRT1, SIRT2, SIRT4, and SIRT5 were downregulated in lymphoma, whereas SIRT6 and SIRT7 were overexpressed. In breast cancer, SIRT3, SIRT5, and SIRT7 were overexpressed, and in terms of kidney cancer, higher expression of SIRT2, SIRT3, and SIRT5 was observed. In contrast, for leukemia, bladder, and brain cancers, most sirtuin family members showed reduced expression. We found that most mutations occurred in uterine cancer, chRCC (chromophobe renal cell carcinoma), DLBCL (diffuse large B-cell lymphoma), melanoma, pRCC (papillary renal cell carcinoma), and esophageal cancer. Moreover, we identified the relevant functional proteins through protein-protein interaction analysis to evaluate copy number alterations (CNAs) in sirtuins. The most frequent alterations were amplifications and deep deletions. Survival analysis demonstrated that SIRT1 and SIRT2 overexpression correlated with improved overall survival in low-grade glioma but predicted poorer outcomes in ovarian cancer. Downregulation of SIRT1, SIRT3, and SIRT5 was associated with better prognosis in DLBCL, while SIRT3 and SIRT4 upregulation predicted favorable survival in testicular germ cell tumors. SIRT6 overexpression was linked to favorable prognosis in esophageal carcinoma and sarcoma, while unfavorable outcomes were observed in hepatocellular carcinoma and cholangiocarcinoma. SIRT7 upregulation was significantly associated with reduced survival in esophageal, liver, and uterine cancers, but surprisingly correlated with improved outcomes in urothelial carcinoma and cervical squamous cell carcinoma.ConclusionsTogether, this multi-omics analysis reveals the correlation and prognostic values of sirtuins across multiple types of human cancers and suggests that sirtuins may serve as promising biomarkers for different cancers.

Nivolumab is a first-line treatment for unresectable esophageal cancer; however, immune-related adverse events (irAEs) can be severe. We report a rare case of long-term survival without chemotherapy after the resolution of lung metastases potentially triggered by a nivolumab-induced irAE. A 70-year-old man with cStage III cervical esophageal squamous cell carcinoma received definitive chemoradiotherapy. One month later, lung and bone metastases were detected. Chemotherapy with fluorouracil and cisplatin was continued, followed by palliative radiotherapy. Although the primary tumor disappeared, the lung metastases progressed, and nivolumab was administered. After a single dose, the patient developed multiple irAEs, including interstitial pneumonia, hypophysitis, and polymyalgia rheumatica. These were managed with corticosteroids. Subsequently, the pulmonary metastases regressed and eventually disappeared. Radiotherapy was also performed for later local recurrences. No further systemic therapy was given, and the patient has remained alive in the 45months. This case suggests that not only nivolumab-induced immune activation but also multidisciplinary treatment, including chemotherapy and radiotherapy, may contribute to durable tumor control in advanced esophageal cancer.