Gastrointestinal cancers, including malignancies of the esophagus, stomach, intestines, liver, biliary tract, and pancreas, account for a substantial share of global cancer morbidity and mortality, and surgery remains central to curative-intent treatment for many patients. Yet postoperative outcomes differ widely among patients undergoing apparently similar operations. Beyond tumor site and technical complexity, nutritional reserve, systemic inflammation, anemia, hepatic function, renal function, and coagulation status all shape a patient’s ability to tolerate major gastrointestinal surgery. Clinical nutrition research has increasingly emphasized malnutrition as a potentially modifiable perioperative risk state. In an international cancer-surgery cohort, malnutrition was associated with adverse early surgical outcomes, and perioperative nutrition management and enhanced-recovery pathways are now considered part of gastrointestinal cancer surgery quality improvement. Recent gastrointestinal oncology studies have linked albumin, prognostic nutritional indices, frailty, C-reactive protein-albumin composites, and other nutritional markers to complications or survival, motivating the question of how much a combined laboratory panel adds to clinical variables alone.

The research team turned to two large perioperative electronic health record datasets to answer that question at scale. The primary cohort was derived from INSPIRE version 1.4.2, a publicly available perioperative dataset containing operation records, diagnosis codes, laboratory values, intraoperative vital signs, medication summaries, and outcome timestamps. External validation used MIMIC-IV version 3.1, an independent hospital electronic health record dataset. The original INSPIRE cohort comprised 11,471 operations among 10,728 patients with a recorded gastrointestinal malignancy diagnosis before or at operation start and a qualifying digestive procedure code. The largest cancer groups were colorectal or anal malignancies with 4,413 operations, gastric cancer with 3,906, liver cancer with 1,445, pancreatic cancer with 712, and gallbladder or biliary cancer with 694. Multiple operations were retained, with 658 patients contributing more than one operation, and patients rather than operations were allocated in a 75:25 split, yielding 8,587 development and 2,884 test operations with no patient overlap.

The laboratory panel itself reads like the standard preoperative workup that virtually every surgical patient already receives. The researchers included albumin, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, prothrombin time international normalized ratio, platelet count, C-reactive protein, white blood cell count, hemoglobin, creatinine, lactate, glucose, HbA1c, blood urea nitrogen, sodium, and potassium. They also derived composite indices such as the albumin-bilirubin score, the AST-to-platelet ratio index, and the fibrosis-4 index. Clinical variables comprised age, sex, body mass index, American Society of Anesthesiologists class, emergency status, anesthesia type, cancer group, department, operation duration, and operating-room duration. The full model added intraoperative physiologic and treatment summaries. The primary outcome was all-cause death within 365 days after operation end, and 893 deaths were recorded in the full cohort, a mortality rate of 7.8 percent.

The modeling approach used nested L2-penalized logistic regression, a technique that applies a regularization penalty to keep coefficients stable when many correlated predictors are present. The primary full design contained 63 non-intercept columns and 660 development events, roughly 10.5 events per column, a ratio that respects the classical rule of thumb for avoiding overfitting in regression models. Training-set medians and standardization were applied to numeric predictors, with categorical missingness coded as a distinct category and all categories one-hot encoded. Confidence intervals were recomputed by 500 patient-level bootstrap samples, retaining all records of each sampled patient, and for internal optimism assessment the entire development pipeline, including preprocessing, was refitted in 500 patient-level bootstrap samples. This full-pipeline bootstrap analysis yielded an optimism-corrected AUROC of 0.837, a figure that accounts for the slight inflation that arises when a model is evaluated on the same data used to build it.

The results show a clear and graded improvement as laboratory data entered the picture. In the unchanged 2,884-operation test set with 233 deaths, the clinical model achieved an area under the receiver operating characteristic curve of 0.783, with a 95 percent confidence interval of 0.752 to 0.811. Adding the full laboratory panel raised the AUROC to 0.843, with a confidence interval of 0.820 to 0.868, and the full perioperative model reached 0.856, with a confidence interval of 0.834 to 0.879. The average precision rose from 0.289 to 0.379, and the Brier score fell from 0.188 to 0.156. Notably, adding albumin and hemoglobin alone yielded an AUROC of 0.828, an increment of 0.045 over the clinical model, while the remaining laboratory panel added a further 0.015 beyond those two measurements. Internal sensitivity analyses using narrower 7-day and 14-day laboratory windows, missingness indicators, and first operations only produced test AUROCs of 0.852, 0.853, 0.854, and 0.860 respectively, supporting the stability of the finding within the original cohort.

When the researchers transported a portable model, built from age, sex, cancer group, the 17 laboratory measurements, and four derived indices, to the external MIMIC-IV dataset, performance dropped substantially. That dataset included 8,456 admissions among 5,546 patients, with 3,800 recorded deaths within 365 days. After harmonizing C-reactive protein units from the milligram-per-liter to the milligram-per-deciliter scale, the portable-model AUROC was 0.676 for one-year mortality and 0.724 for recorded hospital death. Calibration drift was substantial: for one-year mortality the observed-to-expected ratio was 1.792, meaning far more deaths occurred than the model predicted. Cross-fitted recalibration reduced the one-year Brier score from 0.277 to 0.227 without materially improving discrimination, indicating that adjusting absolute risks alone did not resolve limited risk separation. Hospital-death discrimination deteriorated when procedure-day laboratory measurements were excluded, with the AUROC falling from 0.724 to 0.611, showing that the result was sensitive to laboratory timing and limiting interpretation of the model as a strictly preoperative tool.

Descriptive risk profiles across predicted-risk strata revealed a striking graded pattern. After correcting an admission-level many-to-many merge, INSPIRE risk tertiles totaled exactly 2,884 operations and 233 deaths: low-risk operations saw 15 of 962 deaths, a mortality rate of 1.56 percent; intermediate-risk operations saw 36 of 961 deaths, or 3.75 percent; and high-risk operations saw 182 of 961 deaths, or 18.94 percent. The corrected high-to-low mortality ratio was 12.15. In MIMIC-IV, mortality ranged from 29.02 to 63.39 percent across tertiles. Higher-risk groups showed lower albumin and hemoglobin levels, consistent with the idea that nutritional and hematologic vulnerability tracks with predicted risk. However, the researchers emphasized that these profiles are descriptive because the same laboratory variables contribute to the risk score, and they do not independently establish biological phenotypes or treatment thresholds. Cancer-specific discrimination also varied, with AUROCs of 0.867 in colorectal cancer, 0.903 in gastric cancer, 0.779 in liver cancer, and 0.698 in pancreatic cancer, showing that performance is not uniform across gastrointestinal malignancies.

The contribution of albumin and hemoglobin fits a growing body of research on nutrition-related vulnerability in gastrointestinal cancer. Studies of nutritional indices, oral frailty, and albumin combined with functional measures provide clinical context for interpreting these laboratory associations. The additional information from the wider panel suggests that risk prediction may benefit from considering nutrition-related measurements alongside inflammatory and organ-function indicators, though the researchers caution that this interpretation concerns prognostic information rather than a specific nutritional mechanism. The datasets lacked the direct nutritional and functional assessments needed to distinguish nutritional depletion from other sources of laboratory abnormalities, and the 2025 ESPEN surgical nutrition guideline considers frailty, sarcopenia, and prehabilitation within perioperative care, highlighting dimensions that were not captured here. Nutritional intervention and prehabilitation studies address whether treatment improves outcomes; the present prediction analysis does not answer that question.

Several limitations affect interpretation and potential use. Broad procedure codes do not establish curative intent or tumor resection, and the colorectal grouping includes anal malignancies. Tumor stage, histology, neoadjuvant treatment, frailty, sarcopenia, dietary intake, formal nutritional assessment, nutritional intervention, and postoperative complications were not consistently available, so laboratory signals may reflect disease burden or organ dysfunction as well as nutritional vulnerability. Median imputation and missingness indicators cannot eliminate bias from informative missingness, and source outcome timestamps and non-equivalent intensive care unit definitions limit interpretation of secondary endpoints. No prospective intervention, actionable threshold, reclassification rule, or impact evaluation was defined, so clinical benefit from score-guided care remains untested. In conclusion, nutrition-related laboratory measurements improved discrimination for recorded one-year mortality beyond clinical variables in the original cohort, and their incremental prognostic information supports further study of perioperative risk stratification in patients with gastrointestinal cancer. Limited external discrimination, calibration drift, and timing-sensitive secondary outcomes warrant further validation before any clinical use.

Subject of Research: Perioperative nutrition-related laboratory profiles predict outcomes after digestive procedures in patients with gastrointestinal cancer

Article Title: Perioperative nutrition-related laboratory profiles predict outcomes after digestive procedures in patients with gastrointestinal cancer

Article References: Perioperative nutrition-related laboratory profiles predict outcomes after digestive procedures in patients with gastrointestinal cancer. (n.d.). https://doi.org/10.3389/fnut.2026.1927720

Image Credits: AI Generated

DOI: 10.3389/fnut.2026.1927720

Keywords: Perioperative, nutrition-related, laboratory, profiles, predict, outcomes, digestive, procedures, patients, gastrointestinal, cancer, scientific research

A comprehensive review published in the journal Crop Health synthesizes decades of research on how parasitoids, a group of more than 100,000 described insect species that kill their hosts during development, use semiochemicals to locate mates and hosts. The review traces the field from its earliest documented records, including a description of tachinid fly parasitism on silkworm caterpillars in China dating to 1096 AD, through the landmark intercontinental introductions of the late nineteenth century, to the sophisticated laboratory and field applications being developed today. The authors argue that semiochemicals serve three critical purposes in biological control: monitoring parasitoid population dynamics, optimizing mating conditions in mass-rearing facilities, and improving host orientation and localization by parasitic wasps in the field.

Parasitoids are deployed through three primary biological control approaches: classical biological control, which involves importing and establishing exotic species; augmentative biological control, which relies on mass rearing and periodic release of established species; and conservation biological control, which focuses on preserving natural enemies through environmental manipulation. Among these, augmentative biological control has attracted significant attention, with commercially developed rearing systems for the egg parasitoid Trichogramma operating worldwide. The successful release of parasitoids depends on synchronizing deployment with the vulnerable life stages of pests, achieved through either inoculative release, which re-establishes declining natural enemy populations, or inundative release, which seeks immediate pest suppression through large-scale deployment.

Once released, parasitoids face a fundamental challenge: finding mates and hosts in complex, unfamiliar environments. They navigate this challenge using a sequence of chemical cues that vary in detectability and reliability. Plant volatiles, emitted from host habitats, are abundant and highly detectable but less reliable indicators of host presence. Sex pheromones, herbivore-induced plant volatiles, and host-derived compounds, by contrast, are highly reliable but harder to detect from a distance. This trade-off, known as the reliability-detectability dilemma, shapes every stage of parasitoid foraging behavior and has driven the evolution of specialized chemosensory systems in these insects.

Sex pheromone communication in parasitoids, while less studied than in Lepidoptera, has yielded remarkable discoveries. Since the identification of bombykol in the silkworm moth, research on insect sex pheromones has been a cornerstone of chemical ecology. In parasitoids, volatile sex pheromones include aldehydes, ketones, esters, and olefins with diverse structures. Recently, tetradecanal and 2-heptadecanone, applied in a 1:4.6 ratio, were identified as sex pheromones released by female Campoletis chlorideae, restoring male attraction and eliciting characteristic courtship wing-fanning behavior when applied to washed female wasps. In addition to female-produced pheromones, some parasitoids use male-released pheromones to attract females, with the jewel wasp Nasonia vitripennis producing two hydroxy-decanolide isomers that mark the first identified male sex pheromones in parasitoids. Cuticular hydrocarbons serve as contact pheromones at close range, with compounds such as 3-methylnonacosane in Dibrachys cavus and 7-methyltetracosane in Urolepis rufipes providing critical mate suitability information.

Host localization by parasitoids involves two primary stages: long-distance host habitat searching and close-range host localization. During habitat searching, parasitoids rely on abundant but less reliable environmental cues, including plant volatiles and, increasingly recognized, microbial emissions. Recent research has shown that odors from nectar fermented by bacteria isolated from buckwheat are attractive to the egg parasitoid Trissolcus basalis, while styrene and benzaldehyde emitted by bacterial strains from the habitat of the generalist aphid parasitoid Aphidius colemani attract this parasitoid. Upon arriving at the host habitat, female parasitoids search within 1 to 2 centimeters of host-associated plants, using antennae and other chemosensory organs to probe plant tissues damaged by hosts. The chemical cues for this close-range localization fall into two categories: distress signals released by plants in response to host damage, and kairomones emitted by the host itself, including sex pheromones, aggregation pheromones, fecal odors, and body scales.

Herbivore-induced plant volatiles, or HIPVs, serve as synomones that guide parasitoids to concealed hosts. Since the 1980s, researchers have recognized that plants damaged by herbivores emit volatile compounds to recruit parasitoids for indirect defense. HIPV profiles have been characterized for crops including cotton, maize, tobacco, kidney bean, and tomato, with common components including green leaf volatiles such as (Z)-3-hexen-1-ol and (Z)-3-hexenyl acetate, monoterpenes such as (E)-beta-ocimene and linalool, sesquiterpenes such as (E)-beta-caryophyllene, and homoterpenes such as DMNT and TMTT. Recent advances in sequencing technologies have enabled what the authors call reverse chemical ecology to identify active HIPV components. In Campoletis chlorideae, transcriptome sequencing revealed that an odorant receptor called CchlOR62 is exclusively expressed in female antennae and responds to (Z)-jasmone, an HIPV component from cotton and tobacco that strongly attracts female parasitoids and significantly enhances their parasitism efficiency in early-instar bollworm larvae.

Beyond feeding-induced volatiles, oviposition by herbivorous insects induces the emission of oviposition-induced plant volatiles, or OIPVs, that function as synomones, particularly for attracting egg parasitoids. Oviposition by the pine sawfly Diprion pini on pine needles triggers volatile emissions that attract the egg parasitoid Chrysonotomyia ruforum, while volatiles emitted by bean plants following oviposition by the southern green stink bug Nezara viridula strongly attract the egg parasitoid Trissolcus basalis. Remarkably, recent research indicates that OIPVs convey precise information about egg age, with the egg parasitoid Trichogramma japonicum strongly preferring the odor of rice plants bearing 2-day-old eggs of the rice leaf folder over plants with younger or older eggs, mediated by detection of the OIPV components D-limonene and alpha-pinene. Plant pathogen infections also induce the release of volatile bouquets that parasitoids exploit, with Cotesia glomerata showing stronger preference for volatiles emitted by aphid-infested plants infected with a compatible pathogen compared with healthy plants.

Host-derived kairomones provide some of the most reliable cues for parasitoid host localization. Insect sex pheromones, owing to their high species specificity, serve as critical kairomones for natural enemies. The egg parasitoids Trichogramma chilonis and Cotesia plutellae showed significant attraction to the sex pheromone blend of the diamondback moth in olfactometer assays, while Telenomus busseolae was attracted to the sex pheromone blend of its host Sesamia nonagrioides during the calling period. Intriguingly, larval parasitoids also respond to host sex pheromones, which can persist in the environment for days and be adsorbed onto plant tissues, providing a temporal window for parasitoids to detect residual cues and locate host larvae. In wind tunnel experiments, the larval parasitoid Leptopilina heterotoma exhibited a strong preference for the sex pheromone of its host Drosophila melanogaster, specifically (Z)-11-vaccenyl acetate. Other host pheromones, including alarm, aggregation, and trail pheromones, also serve as host-finding kairomones, with the aphid alarm pheromone (E)-beta-farnesene acting as a kairomone for several aphid parasitoids and the specialist parasitoid Pseudacteon tricuspis using alarm pheromones released by worker ants to locate its host.

Decades of laboratory research on semiochemicals have opened new avenues for manipulating parasitoid behaviors through synthetic biology. By engineering plant or yeast metabolic pathways, researchers can produce specific semiochemicals, including HIPVs, host alarm pheromones, and host sex pheromones, that function as synomones and kairomones to attract parasitoids. Transgenic Arabidopsis thaliana expressing the peppermint (E)-beta-farnesene synthase gene produces this sesquiterpene, eliciting strong alarm and repellent responses in the green peach aphid while attracting and retaining the parasitoid Diaeretiella rapae. Similarly, Arabidopsis overexpressing the maize terpene synthase gene TPS10 emits a sesquiterpene blend including (E)-beta-farnesene and (E)-alpha-bergamotene, attracting the parasitoid Cotesia marginiventris. Cotton plants engineered to express DMNT-synthesis genes emit 10- to 15-fold higher DMNT levels than wild-type controls, significantly increasing recruitment of the parasitoid Peristenus spretus. Yeast cell factories have also been utilized to produce moth sex pheromones through metabolic engineering of oleaginous yeasts, with notable examples including (Z)-11-hexadecenal, the primary sex pheromone component of the cotton bollworm, and (Z)-9-tetradecenyl acetate, the primary sex pheromone component of the fall armyworm.

Companion planting, or intercropping, represents another widely adopted habitat manipulation strategy that increases the abundance of natural enemies. Intercropping maize with the molasses grass Melinis minutiflora significantly reduces stem-borer infestation and increases larval parasitism by Cotesia sesamiae, an effect attributed to volatiles such as DMNT emitted by the companion plant that repel female stem borers while attracting foraging female parasitoids. Similarly, the cornflower Centaurea cyanus is highly attractive to the parasitoid Microplitis mediator, enhancing its survival and parasitism rates. Companion plants including Desmodium intortum, Desmodium uncinatum, and Brachiaria Mulato deter oviposition by the fall armyworm on maize while attracting its larval endoparasitoids Cotesia icipe and Coccygidium luteum, effects likely driven by behavior-modifying compounds such as (Z)-3-hexenyl acetate, (E)-beta-ocimene, DMNT, (E)-beta-caryophyllene, camphor, methyl salicylate, and TMTT.

Despite these advances, field applications of semiochemicals to increase parasitoid efficacy face significant challenges stemming from the complexity of natural environments. Deploying the attractant borneol in apple orchards elevated the densities of the egg parasitoid Cyzenis albicans, which targets the winter moth, yet parasitism rates remained unaffected, likely due to the absence of oviposition-determining cues. Wheat genetically engineered to constitutively emit the aphid alarm pheromone (E)-beta-farnesene repelled aphids and attracted the parasitoid Aphidius ervi in olfactometer assays, but field trials revealed no decline in aphid populations or increase in parasitism, potentially resulting from olfactory habituation caused by prolonged odorant exposure. Parasitoids are also highly sensitive to abiotic stressors, with parasitism by Trichogramma brassicae decreasing by nearly 40 percent at temperatures exceeding 35 degrees Celsius. Plants subjected to heat, drought, or elevated ozone levels release volatile blends that closely resemble HIPVs, acting as deceptive cues that diminish parasitoid foraging efficiency, while atmospheric pollutants degrade HIPVs, further hindering host location.

The authors identify several research gaps that warrant further investigation to enhance the practical application of semiochemicals in biological control. Plants typically emit complex blends of volatile compounds, yet most studies have focused on single compounds, overlooking potential synergistic and antagonistic interactions. For example, (Z)-jasmone and (Z)-3-hexenyl acetate individually increased the parasitism efficiency of Campoletis chlorideae on bollworm larvae in indoor cage experiments, but their combination had no effect, while combining (Z)-jasmone with sex pheromones attracted both female and male parasitoids, significantly improving host location and mating success. The interactions among plants, pests, and parasitoids are highly intricate, with the maize HIPV indole attracting the parasitoid Microplitis rufiventris but also modifying the volatile profile on the body surface of Spodoptera littoralis larvae, reducing their attractiveness to the parasitoid and lowering parasitism rates. Hyperparasitoids can exploit plant-emitted synomones and host-derived kairomones to locate and parasitize primary parasitoids, undermining their efficacy in pest control. The semiochemical redundancy hypothesis posits that high local chemical diversity and concentrations may disrupt herbivore foraging through chemical disorientation and masking, which may similarly impair the ability of specialized natural enemies to locate their prey.

Current research on the regulatory effects of semiochemicals on parasitoid behavior remains largely confined to laboratory or semi-field studies, and no commercially available parasitoid attractants have been developed to date. Future efforts should prioritize large-scale field experiments to validate laboratory findings under real-world conditions, incorporating real plants and large-scale greenhouse setups to simulate field conditions. The development of effective methods for releasing semiochemicals in the field is critical, with transgenic plants engineered to emit key semiochemicals representing a promising solution, particularly with advancements in gene-editing technologies. In commercially important genera such as Trichogramma and Telenomus, no odorant receptor functions have been reported, likely due to the minute body size of these parasitoids, which poses significant challenges for behavioral monitoring and physiological manipulation. Recent advances in machine learning, such as quantitative structure-activity relationship modeling, have achieved up to 95 percent success in predicting ligands for lepidopteran odorant receptors, and the application of this approach to predict ligands for parasitoid receptors, followed by functional validation, provides a rapid method for identifying novel semiochemicals for pest control. Taken together, the metabolic engineering of plant volatiles has shown significant potential for enhancing indirect plant defense by attracting parasitoids, with transgenic plants producing and emitting (E)-beta-farnesene, (E)-beta-caryophyllene, and (E)-beta-ocimene demonstrating dual functionality, repelling pests while attracting parasitoids, making them promising candidates for novel push-pull pest management systems.

Subject of Research: Harnessing semiochemicals for parasitoid-based biological control: from laboratory identification to field applications

Article Title: Harnessing semiochemicals for parasitoid-based biological control: from laboratory identification to field applications

Article References: Guo, H., & Wang, C.-Z. (2025). Harnessing semiochemicals for parasitoid-based biological control: from laboratory identification to field applications. Crop Health, 3(1), Article 21. https://doi.org/10.1007/s44297-025-00061-4

Image Credits: AI Generated

DOI: 10.1007/s44297-025-00061-4

Keywords: Harnessing, semiochemicals, parasitoid-based, biological, control, laboratory, identification, field, applications, scientific research