Pathologic Complete Response, Total Neoadjuvant Therapy and the Survival Paradox in Locally Advanced Rectal Cancer.

BACKGROUND: Pathologic complete response (pCR) after preoperative chemoradiation (nCRT) correlates with improved overall survival for patients with locally advanced rectal cancers (LARCs). Escalation protocols including total neoadjuvant therapy (TNT), which delivers multi-agent chemotherapy and chemoradiation before surgery, are associated with increased complete response rates. However, TNT is not associated with improved overall survival. The authors hypothesized that the route to pCR may be an important predictor of oncologic outcome. METHODS: Adults with LARC between 2006 and 2017 were identified in the National Cancer Database. The cohort was limited to those who received neoadjuvant radiation (45-70 Gy) and underwent proctectomy. RESULTS: Of 25,880 patients, 16 % received TNT and 84 % had nCRT followed by either multi-agent (27 %), single-agent (14 %), or no adjuvant chemotherapy (44 %). Overall, 18 % achieved pCR, with higher rates in the TNT cohort than in the nCRT (18 %) or multi-agent (14 %) chemotherapy cohorts. With control for covariates, the OS in the pCR cohort was similar for the patients that received single-agent therapy and those that received multi-agent adjuvant therapy, and superior to the TNT and no adjuvant therapy cohorts. Conversely, among the patients who did not achieve pCR, those who received single-agent chemotherapy had OS comparable with those who had multi-agent adjuvant therapy and TNT, which was better than no adjuvant therapy. CONCLUSION: Patients achieving pCR after TNT had worse OS than those who had CRT alone, suggesting that the neoadjuvant route by which pCR is achieved is prognostically relevant. Therefore, in the era of neoadjuvant therapy escalation, pCR does not necessarily portend a uniformly favorable prognosis.

SAGES guidelines for the use of laparoscopy during pregnancy.

BACKGROUND: When pregnant patients present with nonobstetric pathology, the physicians caring for them may be uncertain about the optimal management strategy. The aim of this guideline is to develop evidence-based recommendations for pregnant patients presenting with common surgical pathologies including appendicitis, biliary disease, and inflammatory bowel disease (IBD). METHODS: The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Guidelines Committee convened a working group to address these issues. The group generated five key questions and completed a systematic review and meta-analysis of the literature. An expert panel then met to form evidence-based recommendations according to the Grading of Recommendations Assessment, Development, and Evaluation approach. Expert opinion was utilized when the available evidence was deemed insufficient. RESULTS: The expert panel agreed on ten recommendations addressing the management of appendicitis, biliary disease, and IBD during pregnancy. CONCLUSIONS: Conditional recommendations were made in favor of appendectomy over nonoperative treatment of appendicitis, laparoscopic appendectomy over open appendectomy, and laparoscopic cholecystectomy over nonoperative treatment of biliary disease and acute cholecystitis specifically. Based on expert opinion, the panel also suggested either operative or nonoperative treatment of biliary diseases other than acute cholecystitis in the third trimester, endoscopic retrograde cholangiopancreatography rather than common bile duct exploration for symptomatic choledocholithiasis, applying the same criteria for emergent surgical intervention in pregnant and non-pregnant IBD patients, utilizing an open rather than minimally invasive approach for pregnant patients requiring emergent surgical treatment of IBD, and managing pregnant patients with active IBD flares in a multidisciplinary fashion at centers with IBD expertise.

Management and staging of anal adenocarcinoma in the United States: a population-based analysis.

BACKGROUND: Anal adenocarcinoma is rare with no standardized treatment regimen or staging system. Therefore, different combinations of chemotherapy, radiation, and surgery are used in management. Within the staging system, tumor stage can be based on the depth of invasion, as for rectal adenocarcinoma, or size, as in anal squamous cell carcinoma. This study aimed to analyze patterns of care and clinically available staging systems for anal adenocarcinoma using a national database. METHODS: Adults diagnosed with anal adenocarcinoma were identified in the Surveillance, Epidemiology, and End Results database (2004-2019). In addition, 6 different treatment regimens were identified. Stages were categorized according to the American Joint Committee on Cancer classifications of rectal adenocarcinoma and anal squamous cell carcinoma. RESULTS: Of 1040 patients, 48% were female, the median age was 67 years, and 18% had distant metastases. Chemoradiotherapy + abdominoperineal resection was the most common treatment regimen (22%). Moreover, 5-year overall survival (OS) and disease-specific survival (DSS) were the highest for local excision only (67% and 85%) and the lowest in the alternative group (34% and 48%). After adjustment, the treatment groups that did not include surgery were associated with worse 5-year OS. In multivariable analysis, the T stage based on depth of invasion showed incrementally lower OS for T2 and T3 anal adenocarcinomas. CONCLUSION: Omission of surgical resection in combination with chemoradiotherapy was associated with worse OS and DSS, suggesting the relevance of surgery in anal adenocarcinoma management. Prognostically, rectal staging based on depth of invasion better discriminated between T stages, indicating that providers should consider using this system in practice.

Analysis of dataset on reduction of high temperature stress by green net shade alleviate oxidative stress and augments the growth and vase life of gladiolus cut flower.

The study was conducted to investigate the effect of green net shade during staggered planting times on growth, biochemical, antioxidant enzymes and vase life of gladiolus cut flowers. The green net shade effectively reduces the internal temperature, particularly during extremely hot planting times. Under the green net shade conditions, high quality morphological and biochemical observations were observed during the months of March and April planting times. These included longer plant height, spike length, a higher number of leaves plant-1, larger leaf area, maximum spike diameter, greater number of florets spike-1, heavier flower diameter, higher fresh and dry weight, elevated photosynthetic rate, and reduced time taken for flowering. Additionally, chlorophyll contents and transpiration rate showed significant increases, while antioxidant enzyme activity (POD and CAT) was recorded at higher levels. This resulted in reduced electrolyte leakage and an extended vase life of the gladiolus cut flowers. Moreover, the application of green net shade conditions during the planting in May and June significantly enhanced the quality characteristics of gladiolus cut flowers. Effectiveness of green net shade is evident in reducing temperature of growing environment, leading to improved growth, alleviate oxidative stress, enhanced quality features and vase life of the gladiolus flowers.

NSQIP 5-factor modified frailty index and complications after ileal anal pouch anastomosis for ulcerative colitis.

Background: Frailty has been associated with worse postoperative outcomes. The 5-factor modified frailty index (mFI-5) is an objective measure although its validity in measuring frailty in patients undergoing ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis (CUC) has not been reported. Methods: This study used the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) targeted proctectomy database. The mFI-5 was calculated by five preoperative diagnoses: insulin-dependent or noninsulin-dependent diabetes, congestive heart failure, hypertension, chronic obstructive pulmonary disease, and dependent or partially dependent functional status. The impact of mFI-5 on minor and major postoperative morbidity in CUC patients undergoing IPAA was analyzed. Results: The cohort included 1454 patients (median age 38 years, median body mass index [BMI] 26 kg/m2) of which 87 % had a mFI-5 = 0, 11 % had a mFI-5 = 1, and 2.5 % a mFI-5 ≥ 2. In multivariable logistic regression, mFI-5 ≥ 2 was significantly associated with minor complications (OR = 2.29, 95 % CI [1.00-5.22], p = 0.049), but not with major complications (p = 0.860). Conclusion: IPAA for CUC is associated with high postoperative morbidity, however, the mFI-5 alone has limited utility in determining which patients are at a higher risk of complications due to frailty. These observations suggest there is a need for more relevant instruments to measure frailty in this patient cohort.

Evaluation of association between center colorectal neuroendocrine neoplasm volume and survival among patients with colorectal neuroendocrine carcinoma.

BACKGROUND: Although correlation between center volume and survival has been reported for several complex cancers, it remains unknown if this is true for colorectal neuroendocrine carcinomas (CRNECs). We hypothesized that higher center annual volume of colorectal neuroendocrine neoplasm resections would be associated with overall survival (OS) for patients with CRNECs. METHODS: Patients in the National Cancer Database diagnosed with stages I-III CRNEC between 2006 and 2018 and who underwent surgical resection were identified. The mean annual colorectal neuroendocrine neoplasm resection volume threshold associated with significantly worse mortality hazard was determined using restricted cubic splines. Kaplan-Meier (KM) method was used to compare OS, while Cox proportional hazards model was used for multivariable analysis. RESULTS: There were 694 patients with CRNEC who met inclusion criteria across 1229 centers. Based on the cubic spline, centers treating fewer than one colorectal neuroendocrine neoplasm patient every 3 years on average had worse outcomes. Centers below this threshold were classified as low-volume (LV) centers corresponding with 42% of centers and about 15% of the patient cohort. In unadjusted survival analysis, LV patients had a median OS of 14 months (95% confidence interval [CI]: 10-19) while those treated at HV centers had a median OS of 33 months (95% CI: 25-49). In multivariable analysis, resection at a LV center was associated with increased risk of mortality (1.42 [95% CI: 1.01-2.00], p = 0.04). CONCLUSION: CRNEC patients have a dire prognosis; however, treatment at an HV center may be associated with decreased risk of mortality.

The performance of artificial intelligence large language model-linked chatbots in surgical decision-making for gastroesophageal reflux disease.

BACKGROUND: Large language model (LLM)-linked chatbots may be an efficient source of clinical recommendations for healthcare providers and patients. This study evaluated the performance of LLM-linked chatbots in providing recommendations for the surgical management of gastroesophageal reflux disease (GERD). METHODS: Nine patient cases were created based on key questions addressed by the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines for the surgical treatment of GERD. ChatGPT-3.5, ChatGPT-4, Copilot, Google Bard, and Perplexity AI were queried on November 16th, 2023, for recommendations regarding the surgical management of GERD. Accurate chatbot performance was defined as the number of responses aligning with SAGES guideline recommendations. Outcomes were reported with counts and percentages. RESULTS: Surgeons were given accurate recommendations for the surgical management of GERD in an adult patient for 5/7 (71.4%) KQs by ChatGPT-4, 3/7 (42.9%) KQs by Copilot, 6/7 (85.7%) KQs by Google Bard, and 3/7 (42.9%) KQs by Perplexity according to the SAGES guidelines. Patients were given accurate recommendations for 3/5 (60.0%) KQs by ChatGPT-4, 2/5 (40.0%) KQs by Copilot, 4/5 (80.0%) KQs by Google Bard, and 1/5 (20.0%) KQs by Perplexity, respectively. In a pediatric patient, surgeons were given accurate recommendations for 2/3 (66.7%) KQs by ChatGPT-4, 3/3 (100.0%) KQs by Copilot, 3/3 (100.0%) KQs by Google Bard, and 2/3 (66.7%) KQs by Perplexity. Patients were given appropriate guidance for 2/2 (100.0%) KQs by ChatGPT-4, 2/2 (100.0%) KQs by Copilot, 1/2 (50.0%) KQs by Google Bard, and 1/2 (50.0%) KQs by Perplexity. CONCLUSIONS: Gastrointestinal surgeons, gastroenterologists, and patients should recognize both the promise and pitfalls of LLM's when utilized for advice on surgical management of GERD. Additional training of LLM's using evidence-based health information is needed.

Evaluate the aluminum concentrations in whey milk samples of cows from different areas using deep eutectic solvent-based ultrasound-assisted dispersive liquid-liquid microextraction method.

This study investigates the contamination of cow milk with aluminum (Al) and its potential health implications, particularly for children. Cow milk samples were collected from both nonexposed and exposed areas in Sindh, based on the source of livestock drinking water (fresh canals and groundwater). An environmental friendly deep eutectic solvent (DES) was used with ultrasonic-assisted dispersive liquid-liquid microextraction (UDLLµE) to enrich trace amounts of Al in whey milk and water samples. The enriched samples were then analyzed using inductively coupled plasma optical emission spectrometry. Certified reference materials were employed to validate the methodology, and the experimental results exhibited acceptable conformity. The DES-based dispersive liquid-liquid microextraction method was environmental friendly, devoid of acids and oxidizing agents, and used safe and inexpensive components for routine trace metal analysis in diverse samples. The resulting data revealed that Al in whey milk samples was observed in the range of 31-45 %, corresponding to (160-270) µg L-1 and (700-1035) µg L-1 in nonexposed and exposed whole cow milk samples, respectively. Additionally, it was observed that milk boiling in Al utensil for 10-20 min enhanced the Al levels from 3 to 8% of its total contents in milk samples.

A population-based analysis on the incidence of metachronous colon cancer after endoscopic resection of advanced adenomas with high-grade dysplasia: does location matter?

BACKGROUND: Advanced adenomas (AAs) with high-grade dysplasia (HGD) represent a risk factor for metachronous neoplasia, with guidelines recommending short-interval surveillance. Although the worse prognosis of proximal (vs distal) colon cancers (CCs) is established, there is paucity of evidence on the impact of laterality on the risk of subsequent neoplasia for these AAs. METHODS: Adults with HGD adenomas undergoing polypectomy were identified in the Surveillance, Epidemiology, and End Results database (2000-2019). Cumulative incidence of malignancy was estimated using the Kaplan-Meier method. Fine-Gray models assessed the effect of patient and disease characteristics on CC incidence. RESULTS: Of 3199 patients, 26% had proximal AAs. A total of 65 cases of metachronous adenocarcinoma were identified after polypectomy of 35 proximal and 30 distal adenomas with HGD. The 10-year cumulative incidence of CC was 2.3%; when stratified by location, it was 4.8% for proximal vs 1.4% for distal adenomas. Proximal location was significantly associated with increased incidence of metachronous cancer (adjusted hazard ratio, 3.32; 95% CI, 2.05-5.38). CONCLUSION: Proximal location of AAs with HGD was associated with >3-fold increased incidence of metachronous CC and shorter time to diagnosis. These data suggest laterality should be considered in the treatment and follow-up of these patients.

Determination of Toxic Elements in Cannabinoid and Opioid Drugs and Their Impact on Addicts' Health: A Comparative Study.

Drug addiction is associated with significant health risks, including cardiovascular complications, cancer, and mental disorders. Illicit drugs, such as cannabinoids and opioids, including prescription medications, are widely consumed and have profound health consequences. Understanding the health effects of the toxic elements in these substances is critical for overdose prevention and effective recovery strategies. This study aimed to determine toxic elements, including arsenic (As), cadmium (Cd), mercury (Hg), and nickel (Ni), in cannabinoid and opioid drugs and in biological samples (whole blood, scalp hair, and serum) from 311 male drug abuse patients aged 15-60 years with a history of drug abuse. The participants were categorized into three age groups. The comparative analysis involved 113 reference subjects of the same age groups. The sample preparation employed microwave-assisted acid digestion, and the toxic elements were quantified using atomic absorption spectrophotometry. Accuracy was ensured using certified reference materials for hair, whole blood, and serum samples. Drug-addicted subjects had significantly higher concentrations of toxic elements (arsenic, cadmium, mercury, and nickel) in biological samples than referent subjects (p > 0.001). Elevated levels of these toxic elements may increase susceptibility to infections, possibly due to malnutrition, drug-related effects, and additional contaminants. These findings necessitate further studies to explore the long-term health outcomes, potential treatment options, and broader socioeconomic impacts of substance abuse. This study serves as a baseline for future research in this critical public health field.

Epidemiology and survival outcomes of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinoma.

BACKGROUND: Mixed neuroendocrine-non-neuroendocrine neoplasms are a rare subtype of neuroendocrine neoplasm consisting of ≥30% each of neuroendocrine and non-neuroendocrine differentiation. Neuroendocrine carcinomas are poorly differentiated neuroendocrine tumors. The epidemiology and prognosis of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas are not clearly defined in the literature. We sought to examine the presentation, patterns of care, and outcomes of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. METHODS: We identified patients diagnosed with stage I-III colorectal (excluding appendix) mixed neuroendocrine-non-neuroendocrine neoplasms or neuroendocrine carcinomas with only one-lifetime cancer diagnosis who underwent surgical resection between 2010 and 2018 from the National Cancer Database. We performed bidirectional selection to identify variables to include in a multivariable Cox proportional hazards model. RESULTS: We identified 189 patients with a diagnosis of stage I to III colorectal mixed neuroendocrine-non-neuroendocrine neoplasms, 66% of whom had poorly differentiated tumors and 482 with neuroendocrine carcinomas. Among patients with stage III disease, 68% of patients with mixed neuroendocrine-non-neuroendocrine neoplasms and 54% of patients with neuroendocrine carcinomas received adjuvant chemotherapy. The median survival for the overall patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas cohorts were 38 and 42 months, respectively (P = .22), and the median survival for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas with stage III disease were 30 and 25 months, respectively (P = .27). In multivariable analysis, fewer number of positive nodes and receipt of adjuvant chemotherapy were independently associated with decreased risk of mortality for patients with mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. CONCLUSION: Adjuvant chemotherapy is associated with improved survival in stage III mixed neuroendocrine-non-neuroendocrine neoplasms and neuroendocrine carcinomas. Future studies are warranted to identify subsets of patients benefiting most from adjuvant therapy.

Conditional Overall Survival After Diagnosis of Non-Metastatic Colon Cancer: Impact of Laterality, MSI, and KRAS Status.

BACKGROUND: The prognostic relevance of laterality, microsatellite instability (MSI), and KRAS status in colon cancer has been established. However, their effect on conditional overall survival (COS) remains unknown. METHODS: COS is the probability of surviving additional years after a time from diagnosis. The National Cancer Database (2010-2017) was queried for adults with non-metastatic colon cancer and known mutation status undergoing curative resection. COS was investigated at 2 years. RESULTS: Of 4838 patients, 3716 survived at least 2 years: 15% had stage I, 38% stage II, and 46% stage III disease. Fifty-nine percent had a right-sided tumor, 16% were MSI-high, and 37% were mutated KRAS (mKRAS). The proportion of patients alive at 2 years was higher for stage I compared with stage II and III (65 vs. 61 vs. 54%). The 5-year overall survival for stage I-III was 80, 76, and 67% for the initial cohort, and 90, 88, and 86% for those alive at 2 years. After adjustment, higher pathologic T and N stage, tumor deposits, and no chemotherapy were associated with worse COS (p < 0.01). While laterality and MSI status were not associated with COS, mKRAS was independently associated with decreased COS (HR 1.35, 95% CI 1.12-1.62). CONCLUSION: Patients with mKRAS had worse COS, suggesting that these mutations confer an aggressive biologic behavior, with patients remaining at higher risk of death 2 years after diagnosis. Routine evaluation of KRAS status should be considered in patients with non-metastatic disease for prognostication and to identify those who might benefit from modified surveillance protocols.

Perspectives on Referring for Rectal Cancer Surgery: a Survey Study of Gastroenterologist and General Surgeons in Iowa.

PURPOSE: To understand referral practices for rectal cancer surgical care and to secondarily determine differences in referral practices by two main hypothesized drivers of referral: the rurality of the community endoscopists' practice and their affiliation with a colorectal surgeon. METHODS: Community gastroenterologists and general surgeons in Iowa completed a mailed questionnaire on practice demographics, volume, and referral practices for rectal cancer patients. Rurality was operationalized with RUCA codes. RESULTS: Twenty-two of 53 gastroenterologists (42%) and 120 of 188 general surgeons (64%) (total 144/241, 60%) in Iowa responded. Most performed colonoscopies, including 22 gastroenterologists (100%) and 96 general surgeons (80%). Regular referral of rectal cancer patients to colorectal surgeons was reported for 57% of urban physicians affiliated with a colorectal surgeon, 33% of urban physicians not affiliated with a colorectal surgeon, and 57% and 72% of physicians in large and small rural areas, respectively, who were not affiliated with a colorectal surgeon. High surgeon volume, high hospital volume, and colorectal surgeon specialty were important factors in the referral decisions for over half the physicians. 69% of diagnosing urban general surgeons reported performing rectal cancer surgery about half the time or more, while 85% of small rural and 60% of large rural diagnosing general surgeons reported never or rarely performing rectal cancer surgery. CONCLUSIONS: Diagnosing physicians have variable rectal cancer referral practices, including consistency in referred to surgeon and prioritization of volume and specialization. Prioritizing specialized or high-volume rectal cancer surgical care would require changing existing referring patterns.

Retraction: Ménétrier's Disease and Its Atypical Presentation in Four Siblings.

[This retracts the article DOI: 10.7759/cureus.30759.].