Varghese, Chris

ABSTRACT Background Many older adults undergo gastrointestinal (GI) cancer surgery, yet the relative impacts of advanced age, comorbidity, and frailty on postoperative mortality and failure to rescue (FTR) remain unclear. We aimed to compare the impacts of these factors on postoperative outcomes in a large population‐based cohort. Method We conducted a national retrospective linked database study of patients aged ≥ 65 years who underwent resection for GI or hepatobiliary cancer in Aotearoa New Zealand between 2005 and 2020. Age, comorbidity (C3 Comorbidity Score), and frailty (Hospital Frailty Risk Score) were examined as independent predictors of 90‐day mortality, complications, and FTR (death following a complication). Logistic regression models were adjusted for demographic and clinical covariates. Results Among 21,729 patients (mean age 75.8 ± 6.8 years), 49.3% experienced one or more complications and 6.1% died within 90 days (FTR rate of 12.3%). In adjusted models, each additional 5 years of age increased 90‐day mortality odds by 40% (adjusted odds ratio [aOR] 1.40 and 95% CI 1.34–1.46). Although higher comorbidity (C3 > 3) and frailty (Hospital Frailty Risk Score > 15) also independently raised mortality risk (aOR 1.98 and 2.04, respectively), age exerted the largest effect on mortality and FTR. Conclusion Chronological age, comorbidity, and frailty each predict worse outcomes following GI cancer surgery, but advanced age remains the dominant driver of 90‐day mortality and FTR. These findings underscore the need for risk stratification, shared decision‐making, and preoperative optimization as wells as intense surveillance for complications and early definitive care of older adults undergoing major oncologic operations.

INTRODUCTION: Chronic gastroduodenal disorders are highly prevalent and encompass heterogeneous pathophysiology. Autonomic dysfunction may contribute, but its relative contribution to disease pathophysiology and symptoms is unclear. This study aimed to clarify the contributions of autonomic dysfunction in gastroduodenal disorders and symptom associations using multimodal testing, hypothesizing that distinct disorder subgroups would be revealed. METHODS: This prospective observational cohort study included 80 patients with chronic gastroduodenal symptoms. Participants underwent expert clinician-led autonomic evaluation, body surface gastric mapping (BSGM; Gastric Alimetry, New Zealand), and gastric emptying scintigraphy testing. BSGM phenotyping, gastric emptying cutoffs, and autonomic criteria followed standard criteria. RESULTS: Gastroparesis was diagnosed in 27 (33.8%) patients. Autonomic dysfunction was present in 21 (26.3%) patients, and abnormal BSGM in 20 (25%). Autonomic dysfunction and abnormal BSGM were both more prevalent in gastroparesis (51.9% vs 13.2%, P = 0.001; and 44.4% vs 15.1%, P = 0.005, respectively). However, these diagnoses tended not to overlap, with patients having autonomic dysfunction generally exhibiting normal BSGM tests. Autonomic dysfunction independently predicted delayed gastric emptying (OR 13.8, P < 0.001) and was associated with earlier meal responses (higher meal response ratio, P = 0.04) and worse postprandial distress symptoms ( P < 0.05). DISCUSSION: Autonomic dysfunction independently predicted delayed gastric emptying and revealed a gastroparesis mechanism distinct from gastric myoelectrical impairment. Autonomic dysfunction altered the postprandial gastric motor response and was associated with a greater symptom burden. Multimodal physiological testing including autonomic profiling reveals distinct mechanistic subgroups in patients with chronic gastroduodenal symptoms.

Background Patient complaints provide a complementary lens on surgical safety, yet prior analyses have been small and specialty specific. We aimed to characterise themes, perioperative processes, system factors and outcomes in surgical complaints using a scalable, large language model (LLM)-assisted approach. Methods We performed a national, retrospective, cross-sectional, sequential methods study of publicly available investigation reports from the Aotearoa New Zealand Health and Disability Commissioner. All reports published since 1998 were retrieved and screened for relevance across all surgical specialties. A fixed-parameter LLM workflow extracted demographics, clinical context, complications, breached patient rights, system factors and outcomes. An inductive LLM-supported thematic synthesis generated complaint themes, followed by rescoring of theme relevance across reports. Human validation supported the LLM-assisted process (Cohen’s κ >0.85). Results Of 1827 reports screened, 650 involved surgical care. Postoperative complications were frequent (84.2%), commonly accompanied by permanent disability (33.2%) or death (24.2%). Delays in recognition of deterioration (76.1%), escalation (58.3%) and definitive management (49.5%) of complications were common and associated with higher mortality. Prominent themes concerned postoperative clinical management/monitoring, communication/informed consent and professional conduct/competence. Technical/procedural errors and medication errors were comparatively less common. Breaches are most often related to reasonable care and skill, and to informed consent, with marked variation across specialties. Conclusions Complaints about surgical care predominantly reflect postoperative monitoring, escalation and communication rather than intraoperative technical errors. System priorities should include robust deterioration recognition and response, reliable handover and escalation pathways, and strengthened consent and communication processes. An LLM-assisted pipeline can scale complaint analysis to support organisational learning and quality improvement.

ABSTRACT Background Chronic gastroduodenal symptoms arise from heterogeneous gastric motor dysfunctions. This study applied multimodal physiological testing using gastric emptying scintigraphy (GES) with intragastric meal distribution (IMD) and Gastric Alimetry body surface gastric mapping (BSGM) to define motility and symptom associations. Methods Patients with chronic gastroduodenal symptoms underwent simultaneous supine GES and BSGM with a 30 m baseline, 99mTC‐labeled egg meal, and 4 h postprandial recording. IMD (ratio of counts in the proximal half of the stomach to the total gastric counts) was calculated immediately after the meal (IMD0), with < 0.568 defining abnormal IMD. BSGM phenotyping followed a consensus approach, based on normative spectral reference intervals. Results Among 67 patients (84% female, median age 40 years, median BMI 24 kg/m 2 ), median IMD0 was 0.76 (IQR: 0.69–0.86) with 5 (7.5%) meeting abnormal IMD criteria. Delayed gastric emptying ( n = 18) was associated with higher IMD0 (median 0.9 vs. 0.7, p = 0.004). On BSGM, 15 patients had abnormal spectrograms (5 [7.5%] high frequency and 10 [14.9%] low rhythm stability and/or amplitude); and in these patients, higher IMD0 (proximal retention) strongly correlated to delayed BSGM meal responses ( R = −0.71, p = 0.003). Lower IMD, indicating antral distribution, correlated with higher gastric frequencies ( R = −0.27, p = 0.03). BSGM abnormalities paired with abnormal IMD were associated with worse dyspeptic symptoms. Conclusion Proximal retention of food as assessed by IMD correlated with delayed emptying, and in the presence of neuromuscular spectral abnormalities (abnormal frequencies or rhythms), delayed motility responses on BSGM. Patients with multiple motor abnormalities experience worse dyspeptic symptoms.

ABSTRACT Background Chronic neurogastroduodenal disorders are challenging to manage, with therapy often initiated on a trial and error basis. Prokinetics play a significant role in management, but responses are variable and have been associated with adverse events, impacting widespread use. We investigated whether body surface gastric mapping (BSGM) biomarkers (using Gastric Alimetry) could inform patient selection for prokinetic therapy. Methods Patients with chronic gastroduodenal symptoms taking oral prokinetic agents, regardless of gastric emptying status, were prospectively recruited and underwent BSGM (30 m baseline, 482 kcal standardized meal, 4 h postprandial recording) while off‐prokinetic agents. Patients were followed up with daily symptom diaries. A subset was compared to matched patients not taking prokinetic agents. Prokinetic responders were defined based on symptom improvement greater than a minimum clinically important difference methodology. Key Results Forty‐two patients (88% female; median age 36; median BMI 26) taking prokinetics were analyzed. Prokinetic prescribing, compared to matched patients, was independent of BSGM metrics ( p > 0.15). In patients on existing prokinetics (withheld for BSGM), lower amplitudes predicted reduced symptom burden, whereas low rhythm stability predicted a worse symptom burden ( p < 0.05). In prokinetic‐naive patients (i.e., started on a prokinetic during the study), a lower postprandial amplitude predicted responders (mean 37.5 ± 10.6 uV in responders [ n = 5] vs. mean 54.8 ± 6.6 uV among nonresponders [ n = 3], p = 0.047). Conclusions Gastric Alimetry biomarkers may help in the prediction of prokinetic response in patients with chronic gastroduodenal symptoms. Lower postprandial amplitudes, indicating a reduced meal response, appear to predict benefit, while impaired rhythm stability predicted poorer therapeutic response.

INTRODUCTION: Chronic neurogastroduodenal disorders are heterogeneous and thought to lie on a spectrum of disease encompassing both sensory and neuromuscular pathologies. Abnormalities of interstitial cells of Cajal (ICC), a subset of which generate pacemaker signals and subsequently motility, have been implicated in their pathophysiology. We systematically reviewed the literature to pool ICC deficits observed in chronic neurogastroduodenal disorders. METHODS: Studies quantifying gastric ICC from the corpus or antrum, in adult patients with gastroparesis, functional dyspepsia (FD), or chronic nausea and vomiting syndromes (CNVS) were analyzed (PROSPERO: CRD42024613226). MEDLINE, Embase and CENTRAL databases were searched systematically. Random effects meta-analyses were used to compare ICC counts by disorder group with subgroup analysis by quantification methodology. RESULTS: Overall, 2,158 studies were screened and 22 included. Comparative studies (n = 12) showed patients with chronic neurogastroduodenal disorders (n = 167 with gastroparesis, n = 19 with FD ± CNVS) had lower ICC counts than nondiabetic controls (n = 130); standardized mean difference −1.58, 95% confidence interval −2.09 to −1.07, P < 0.0001, with more severe deficits in gastroparesis compared to FD ± CNVS (standardized mean difference [SMD] −0.44, P = 0.048). A spectrum of ICC deficits was evident in a subgroup of studies using gold-standard methods with c-KIT antibody and 4',6-diamidino-2-phenylindole-stained nuclei confirmation (7 studies, 246 patients: mean ICC counts 2.29 in gastroparesis vs 3.49 in FD ± CNVS, and 5.27 in controls; P < 0.001 all comparisons). Most studies were at high risk of bias (n = 21). DISCUSSION: Marked depletion of ICC is a consistent finding in neurogastroduodenal disorders. A spectrum of disease is revealed, with greater depletion associated with delayed emptying. Techniques for clinically defining ICC-driven gastric neuromuscular dysfunction should be prioritized.

Abstract Background Indigenous populations worldwide experience unjust inequities in surgical outcomes. In Aotearoa New Zealand, Indigenous Māori experience poorer health outcomes, including higher rates of postoperative mortality. The aim of this study was to quantify ethnic disparities in ‘failure to rescue’ (FTR), complications, and mortality following gastrointestinal cancer surgery and to analyse trends over time. Methods A retrospective national population-based cohort study of patients undergoing resection for gastrointestinal and hepatopancreatobiliary cancers from 2005 to 2020 was conducted. Self-reported ethnicity data were collected at the time of surgery. The primary outcome was FTR, defined as mortality following a complication within 90 days of surgery. Results In total, 31 185 patients were included; 2479 (7.9%) were Māori, 46.5% were female, and the median age was 71 (interquartile range 62–78) years. Māori patients were younger and had higher levels of socio-economic deprivation and co-morbidity. Māori had higher age-standardized rates of mortality (5.9% versus 3.2%), complications (52.9% versus 42.4%), and FTR (10.8% versus 7.2%), compared with European/Other. Multivariable regression demonstrated higher odds of mortality (adjusted OR (aOR) 1.45 (95% c.i. 1.15–1.82)), complications (aOR 1.30 (95% c.i. 1.17–1.45)), and FTR (aOR 1.29 (95% c.i. 1.01–1.62)) for Māori. Analysis over time showed a significant improvement in risk-adjusted rates of mortality (6.2% in 2005–2008 versus 3.4% in 2017–2020) and FTR (7.3% in 2005–2008 versus 4.0% in 2017–2020) for European/Other, but no change for Māori (rates of mortality were 6.6% in 2005–2008 versus 5.4% in 2017–2020 and rates of FTR were 7.8% in 2005–2008 versus 6.3% in 2017–2020). Conclusion Widening inequities in FTR have worsened disparities in postoperative mortality for Māori patients. ‘Complication rescue’ is a target to reduce inequities and improve perioperative care for Māori patients.

INTRODUCTION: Gastroparesis is a debilitating gastroduodenal disorder for which gastric peroral endoscopic myotomy (GPOEM) has emerged as an efficacious treatment option. However, response to GPOEM varies between 50% and 80%, such that preoperative predictors of treatment success are needed to guide patient selection. METHODS: We performed a systematic review to identify predictors of clinical and functional response to GPOEM among adult patients with gastroparesis (PROSPERO: CRD42023457359). MEDLINE, Embase, and CENTRAL databases were searched systematically for studies reporting outcomes after GPOEM in September 2023. A narrative synthesis of predictive factors on univariable and multivariable analysis was performed with consideration of response rates through meta-analysis and evaluation of discrimination if prognostic models were developed. Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) was used for risk of bias assessment. RESULTS: Of 1899 articles reviewed, 30 were included. The GPOEM response rate was 63.1% (95% confidence interval 56.3%–69.5%) with most studies defining clinical success on the basis of improvement in gastroparesis cardinal symptom index (87%, 26/30). Older age, shorter duration of gastroparesis, nondiabetic etiology, lower body mass index, and response to intrapyloric botulinum toxin were associated with positive response to GPOEM on multivariable analyses. Predictors on physiological tests such as EndoFLIP or gastric emptying scintigraphy were inconsistent. No prognostic models underwent external validation. DISCUSSION: Currently, there are limited reproducible predictors of response to GPOEM among patients with refractory gastroparesis. Robust prospective studies investigating scalable, reproducible, and actionable biomarkers of treatment response are required.

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts, P < 0.001), impaired fed-fasting power ratios (1.1 versus 1.6, P = 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5; P < 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all P > 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%; P = 0.03) and anxiety scores (median, 16.5 versus 13.0; P = 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all r > 0.35, P < 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.