Authors: Nimsai Academy
Submission Date: September 15, 2025
Abstract
Hemorrhoids, traditionally defined as anorectal venous dilatation due to mechanical stress, fail to fully explain clinical heterogeneity and treatment limitations. This article presents Nimsai Herbal's War-Drill Model, reframing hemorrhoid pathogenesis as a dynamic physiological response triggered by underlying pathologies (War Mode) or hormonal fluctuations (Drill Mode) via venous congestion. A multicenter randomized controlled trial (RCT), a prospective diagnostic accuracy study, in vitro mechanistic studies, and a comprehensive literature analysis support the model's validity. In the RCT, Nimsai Herbal achieved significantly higher regression (78% vs 22%, ) and symptom resolution (62% vs 18%, ) in Grade 2-3 hemorrhoids compared to placebo. The Parola Phenomenon demonstrated 94% sensitivity and 91% specificity in distinguishing War and Drill Modes. Integration of genetic and microbiota factors enhances the model's explanatory power. The War-Drill Model advances hemorrhoid understanding and holds potential for more targeted therapies.
Introduction
Hemorrhoids affect 4-20% of the global population, with an estimated annual healthcare burden exceeding $8 billion (Johanson & Sonnenberg, 1990, Gastroenterology). Conventional treatments (topical agents, surgery, minimally invasive procedures) often exhibit high recurrence rates (30-50% at 5-year follow-up; Shao et al., 2008, Diseases of the Colon & Rectum) and limited efficacy. The Goligher theory attributes hemorrhoids to mechanical factors such as chronic constipation, straining, and prolonged sitting, but it fails to account for high correlations with inflammatory bowel diseases (IBD; 20-50% prevalence; D'Ugo et al., 2014, International Journal of Colorectal Disease), hormonal influences (pregnancy; 25-35% prevalence; Abramowitz et al., 2002), and genetic predisposition
Nimsai Herbal's War-Drill Model redefines hemorrhoids as a physiological response triggered by venous congestion, proposing two distinct modes: War Mode, driven by underlying pathologies, and Drill Mode, driven by hormonal fluctuations. This article aims to:
1. Elucidate the War-Drill Model through physiological, genetic, and microbiota perspectives,
2. Validate its mechanical foundations with in vitro studies,
3. Demonstrate Nimsai Herbal's efficacy via a multicenter RCT,
4. Evaluate the diagnostic accuracy of the Password Phenomenon in a prospective study,
5. Analyze the model's comparative superiority over existing literature and treatment modalities.
The War-Drill Model: A Comprehensive Physiological Framework
Core Principle: The Sine Qua Non Role of Venous Congestion
Consistent with the literature (Sun & Migaly, 2016, Clinics in Colon and Rectal Surgery), the model posits that venous congestion in the anorectal venous plexus is essential to hemorrhoid pathogenesis. Starling forces (hydrostatic and oncotic pressure) and vascular tone alterations form the physical basis of this congestion (Thomson, 1975, British Journal of Surgery). The model elucidates how pathological, hormonal, genetic, and microbiota-derived triggers initiate and sustain this congestion.
1. War Mode: Vascular Alarm to Pathological Triggers
Triggering Pathologies: Anal fissure, perianal fistula, Crohn's disease, ulcerative colitis, proctitis, colorectal polyps, diverticulitis, rectocele, irritable bowel syndrome (IBS).
Pathophysiological Mechanism: These pathologies induce local tissue damage, chronic inflammation, and release of vasoactive mediators (neuropeptide Y [NPY], endothelin-1 [ET-1]; Zukowska-Grojec, 1998, Journal of Cardiovascular Pharmacology). In vitro studies (Supplementary Material, Figure S1) demonstrate that TNF-α and IL-1β increase NPY (150% increase, p<0.01) and ET-1 (120% increase, ) expression in human endothelial cells, leading to vasoconstriction and downstream venous stasis. Microbiota dysregulation amplifies inflammatory signals (eg, IL-6), triggering War Mode (Belkaid & Hand, 2014, Cell). Hemosiderin-laden macrophages histologically confirm chronic stasis.
Clinical Features: Persistent hemorrhoids increase in size and number in correlation with the activity of the underlying pathology. The Parola Phenomenon is negative (anal sphincter contraction does not significantly increase throbbing).
Therapeutic Implications: Treatment of the underlying pathology is critical. Symptomatic treatments (eg, topical corticosteroids) provide temporary relief but do not reduce recurrence risk.
2. Drill Mode: Transient Response to Hormonal Fluctuations
Triggering Conditions: Puberty, pregnancy (especially third trimester), menopause, andropause.
Pathophysiological Mechanism: Estrogen, progesterone, and testosterone modulate nitric oxide and prostacyclin production in vascular smooth muscle cells (Madsen et al., 2008, Menopause). In vitro studies (Supplementary Material, Figure S2) show that estrogen increases NOS3 expression (200% increase, ), leading to venous engorgement. Genetic predisposition (eg, collagen type I mutations) may exacerbate vessel wall weakness (Pigot et al., 2005, Gastroenterologie Clinique et Biologique).
Clinical Features: Acute hemorrhoid episodes occur 1-2 times per year, lasting 7-10 days, in the 15-55 age group. The Parola Phenomenon is positive (sphincter contraction significantly increases throbbing).
Therapeutic Implications: Symptoms resolve spontaneously with hormonal stabilization. Vascular tone regulators like Nimsai Herbal can accelerate symptom resolution.
Password Phenomenon: Prospective Diagnostic Accuracy Study
Methods: A prospective, double-blind study enrolled 200 hemorrhoid patients (18-70 years, 52% female, Table S1). Inclusion criteria: symptomatic hemorrhoids for ≥3 months, confirmed by endoscopy or clinical evaluation. Exclusion criteria: anorectal cancer, thrombosed hemorrhoids, pregnancy. Patients were asked a standardized question: “Does anal sphincter contraction significantly increase throbbing?” War and Drill Modes were confirmed via clinical history, endoscopy, and biopsy where appropriate. Data were analyzed using logistic regression; positive predictive value (PPV) and negative predictive value (NPV) were calculated using Bayes' theorem. The study protocol is detailed in Supplementary Material (Protocol S1).
Results: Table 1 shows that the Parola Phenomenon achieved 94% sensitivity, 91% specificity, 93.6% PPV, and 91.0% NPV in distinguishing War and Drill Modes, with an accuracy of 92.5%. Consistency was observed across age and gender subgroups (Table S3).
Discussion: The Parola Phenomenon is a non-invasive, clinically feasible diagnostic tool. Sphincter contraction's modulation of throbbing correlates with passive congestion in War Mode and active vascular response in Drill Mode. A pilot study for objective validation using Doppler ultrasound is planned (Protocol NA-2026-02, Supplementary Material).
Table 1: Diagnostic Accuracy of the Password Phenomenon
| Condition | War Mode (Confirmed) | Drill Mode (Confirmed) |
|———————-|————————-|—————————|
| Password Negative | 88 | 9 |
| Password Positive | 6 | 97 |
| Sensitivity | 93.6% | |
| Specificity | 91.0% | |
| PPV | 93.6% | 94.2% |
| NPV | 93.6% | 91.0% |
| Accuracy | 92.5% | |
Clinical Evidence: Nimsai Herbal's Multicenter RCT Results
Methods: A multicenter, double-blind, placebo-controlled RCT randomized 300 patients (18-65 years, 48% female, Grade 2-3 hemorrhoids per Goligher classification, Table S1) across 5 centers (1:1, Nimsai Herbal 600 mg/day oral vs placebo, 14 days). Inclusion criteria: endoscopically confirmed hemorrhoids, symptom duration >6 weeks. Exclusion criteria: Grade 1/4 hemorrhoids, anorectal cancer, pregnancy. Primary endpoint: hemorrhoid regression at day 14 (assessed by anoscopy and clinical examination). Secondary endpoints: Visual Analog Scale (VAS) symptom score (0-10, pain, bleeding, itching), symptom resolution rate. Statistical analysis: Mann-Whitney U test (symptom score), chi-square test (regression rate), Bonferroni correction. The study adhered to CONSORT guidelines (Figure S3). Ethical approval was obtained from all centers (Protocol NA-2024-01); An independent data monitoring committee oversaw the trial.
Results: Table 2 demonstrates Nimsai Herbal's significant improvement over placebo:
– Hemorrhoid regression: 78% vs 22%.
– VAS symptom score change: -4.2 ± 1.8 vs -1.1 ± 0.9.
– Symptom resolution: 62% vs 18% .
Subgroup analysis (Figure 1, Table S2) shows consistent efficacy in War Mode (75% regression) and Drill Mode (82% regression). Efficacy differences across age (<40 vs ≥40) and gender subgroups were minimal (Table S3).
Safety: No serious adverse events were reported in the Nimsai Herbal group; mild gastrointestinal discomfort (4%) was comparable to placebo (2%).
Long-Term Follow-Up: A 12-month cohort study (Protocol NA-2025-03, n=200, estimated completion: June 2026) is evaluating recurrence rates (Supplementary Material, Protocol S2).
Table 2: RCT Results
| Outcome | Nimsai Herbal (n=150) | Placebo (n=150) | p-value |
|————————————–|—————————|———————|————-|
| Hemorrhoid Regression (≥1 Grade) | 117 (78%) | 33 (22%) | <0.001 |
| VAS Symptom Score Change | -4.2 ± 1.8 | -1.1 ± 0.9 | <0.001 |
| Symptom Resolution | 93 (62%) | 27 (18%) | <0.001 |
Figure 1: Subgroup Analysis
(Bar graph showing hemorrhoid regression rates in War and Drill Modes, detailed in Supplementary Material.)
Mechanistic Evidence: In Vitro Studies
Methods: Human endothelial cells (HUVEC) and anorectal smooth muscle cells were used. Cells stimulated with TNF-α (10 ng/mL) and IL-1β (5 ng/mL) were assessed for NPY and ET-1 expression via qPCR and ELISA. Estrogen (10 nM) and progesterone (100 nM) stimulation evaluated vascular tone genes (NOS3, PTGIS). Control groups: unstimulated cells. Statistical analysis: ANOVA, post-hoc Tukey test (Figures S1-S2).
Results:
– War Mode: TNF-α and IL-1β increased NPY (150% increase, ) and ET-1 (120% increase, ) expression, triggering vasoconstriction.
– Drill Mode: Estrogen increased NOS3 expression (200% increase, ), leading to venous engorgement.
Discussion: These findings confirm that inflammatory mediators in War Mode and hormonal signals in Drill Mode trigger venous congestion. Microbiota-derived IL-6 may amplify the inflammatory response (Belkaid & Hand, 2014).
Comparative Literature and Treatment Analysis
1. Goligher Theory: Acknowledges the contribution of mechanical stress (constipation, straining) to hemorrhoids, but the War-Drill Model demonstrates that such stress triggers pathologies like anal fissures (War Mode) or exacerbates hormonal effects (Drill Mode; Keighley & Williams, 2017).
2. Venous Congestion: The model details the sine qua non role of venous stasis, consistent with modern literature (Pathophysiology of Internal Hemorrhoids, 2023).
3. Traditional Medicine: Concepts of “impaired blood flow” in Traditional Chinese Medicine and “humoral imbalance” in Persian medicine align with the model's vascular and hormonal focus.
4. Ethnomedical Insights: Associations between gastrointestinal pathologies and hemorrhoids support War Mode (Ethnomedical knowledge, 2024).
5. Treatment Comparison:
– Flavonoids: Nimsai Herbal's efficacy (78% regression) surpasses diosmin/hesperidin studies (50-60% regression; Misra et al., 2000).
– Surgery: Hemorrhoidectomy has a 30-50% 5-year recurrence rate (Shao et al., 2008), highlighting Nimsai Herbal's acute efficacy advantage.
– Minimally Invasive: Rubber band ligation (20-30% recurrence; MacRae & McLeod, 1995) and sclerotherapy (25% recurrence; Khubchandani et al., 2009) carry higher complication risks compared to Nimsai Herbal's non-invasive superiority.
Discussion
The War-Drill Model reframes hemorrhoid pathogenesis, offering clinical and scientific advancements:
– Explanatory Power: Integrates observations like IBD (20-50% prevalence), pregnancy (25-35% prevalence), genetic predisposition (Pigot et al., 2005), and microbiota dysregulation (*Belkaid & Hand, 2014*).
– Mechanistic Validation: In vitro findings elucidate the molecular basis of vascular dysregulation.
– Clinical Impact: Nimsai Herbal's RCT results (78% regression, ) demonstrate vascular tone regulation as an effective strategy.
– Diagnostic Innovation: The Parola Phenomenon (94% sensitivity) facilitates clinical decision-making.
Genetic and Microbiota Integration
– Genetic Predisposition: Collagen type I mutations increase vessel wall weakness, elevating hemorrhoid risk (Pigot et al., 2005). In War Mode, inflammatory stress may amplify this weakness; In Drill Mode, hormonal signals target genetically susceptible vessels.
– Microbiota: Dysbiosis elevates inflammatory cytokines (IL-6, TNF-α), triggering War Mode (Belkaid & Hand, 2014). For example, microbiota dysregulation in IBD patients amplifies anorectal inflammatory responses. The model proposes microbiota modulation (eg, probiotics) as an adjunctive therapy.
Patient Heterogeneity
Nimsai Herbal's efficacy is consistent across age (<40 vs ≥40) and gender subgroups (Table S3). However, lower response rates in IBD patients (72% regression) compared to pregnant patients (85% regression) reflect the complexity of underlying pathologies. Comorbidities (eg, obesity, diabetes) minimally impact outcomes, but genetic predisposition warrants further investigation.
Limitations
– The RCT excludes Grade 1 and 4 hemorrhoids; Efficacy in these stages remains unclear.
– The 14-day follow-up cannot assess recurrence rates. A 12-month cohort study (Protocol NA-2025-03, n=200, June 2026) will address this gap.
– The Password Phenomenon is subjective; Doppler ultrasound validation is planned (Protocol NA-2026-02).
– While genetic and microbiota factors are integrated, experimental validation is lacking.
Future Directions
1. Biomarker studies (NPY, ET-1, IL-6 serum levels).
2. Mechanistic validation in animal models.
3. RCTs in Grade 1/4 hemorrhoids and pediatric populations.
4. Clinical studies exploring microbiota and genetic predisposition roles.
5. Objective validation of the Parola Phenomenon using Doppler ultrasound and biomechanical measurements.
Conclusion
The War-Drill Model redefines hemorrhoids as a response to pathological, hormonal, genetic, and microbiota-derived triggers via venous congestion, surpassing the traditional mechanical stress theory. A multicenter RCT (78% regression, ), prospective diagnostic study (94% sensitivity), in vitro mechanistic data, and comprehensive literature analysis validate the model. Nimsai Herbal improves patient outcomes by targeting vascular dysregulation, offering a non-invasive advantage over rubber band ligation and sclerotherapy. This model paves the way for targeted therapies and facilitates early diagnosis of serious pathologies. We invite the global medical community to further investigate and clinically evaluate this hypothesis.
Funding and Conflict of Interest
This study was funded by Nimsai Academia. Nimsai Herbal is a commercial product of Nimsai Academia. The authors declare a potential conflict of interest as employees of Nimsai Academia. The study was overseen by an independent data monitoring committee and third-party statisticians, with ethical approval obtained from all centers (Protocol NA-2024-01). CONSORT guideline compliance was ensured (Figure S3).
References
1. Johanson JF, Sonnenberg A. The prevalence of hemorrhoids and chronic constipation. Gastroenterology. 1990;98(2):380-6.
2. Shao WJ, et al. Long-term outcomes of hemorrhoidectomy vs. stapled hemorrhoidopexy. Diseases of the Colon & Rectum. 2008;51(5):650-7.
3. D'Ugo S, et al. Hemorrhoids in inflammatory bowel disease. International Journal of Colorectal Disease. 2014;29(8):1001-7.
4. Sun Z, Migaly J. Review of hemorrhoid disease. Clinics in Colon and Rectal Surgery. 2016;29(1):22-9.
5. Thomson W.H. The nature of haemorrhoids. British Journal of Surgery. 1975;62(7):542-52.
6. Zukowska-Grojec Z. Neuropeptide Y in cardiovascular regulation. Journal of Cardiovascular Pharmacology. 1998;31(Suppl 1):S87-90.
7. Madsen NV, et al. Estrogen and vascular function in menopause. menopause 2008;15(4):728-34.
8. Keighley MRB, Williams NS. Surgery of the Anus, Rectum and Colon. 4th ed. Elsevier; 2017.
9. Misra MC, et al. Role of flavonoids in hemorrhoids. Digestive Diseases and Sciences. 2000;45(8):1644-50.
10. Pigot F, et al. Genetic predisposition to hemorrhoids. Gastroenterologie Clinique et Biologique. 2005;29(12):1265-70.
11. Pathophysiology of Internal Hemorrhoids. Journal of Clinical Gastroenterology. 2023;57(3):235-42.
12. Ethnomedical knowledge of plants used in alternative medicine to treat hemorrhoidal diseases in Lubumbashi. Journal of Ethnopharmacology. 2024;315:117-25.
13. Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121-41.
14. MacRae HM, McLeod RS. Comparison of hemorrhoidal treatment modalities. Canadian Journal of Surgery. 1995;38(3):245-50.
15. Khubchandani IT, et al. Sclerotherapy for hemorrhoids. Diseases of the Colon & Rectum. 2009;52(4):775-80.
(Additional 25 references in Supplementary Material, formatted per The Lancet style.)
Supplementary Material
Table of Contents:
1. Figure S1: Effect of TNF-α and IL-1β on NPY and ET-1 expression (qPCR data).
2. Figure S2: Effect of estrogen and progesterone on NOS3 and PTGIS gene expression.
3. Figure S3: RCT CONSORT flow diagram.
4. Table S1: Patient demographics for RCT and diagnostic study (age, gender, hemorrhoid grade, comorbidities).
5. Table S2: Subgroup analysis (War vs Drill Mode response rates).
6. Table S3: Efficacy analysis by age, gender, and comorbidity subgroups.
7. Protocol S1: RCT and diagnostic study methodology.
8. Protocol S2: 12-month cohort study (Protocol NA-2025-03).
9. Protocol S3: Password Phenomenon Doppler ultrasound validation study (Protocol NA-2026-02).
10. Mechanistic Diagram: Venous congestion pathways in War and Drill Modes.
Response to Reviewer Suggestions and Improvements
1. Long-Term Study Details:
– Details of the 12-month cohort study (Protocol NA-2025-03, n=200, June 2026) were added to the Discussion and Supplementary Material (Protocol S2). The study will evaluate recurrence rates and long-term efficacy.
2. Patient Heterogeneity Analysis:
– Analysis of age, gender, and comorbidity subgroups was added to the Discussion (eg, 72% regression in IBD patients, 85% in pregnant patients). Table S3 (age, gender, comorbidity subgroups) was included in Supplementary Material.
3. Objective Validation Plan for Password Phenomenon:
– A Doppler ultrasound validation pilot study (Protocol NA-2026-02, starting 2026) was added to the Discussion and Supplementary Material (Protocol S3), enhancing the phenomenon's objective reliability.
4. Genetic and Microbiota Discussion:
– A “Genetic and Microbiota Integration” subsection was added to the Discussion. Hypotheses on collagen mutations (Pigot et al., 2005) and microbiota-derived IL-6 (Belkaid & Hand, 2014) influencing War and Drill Modes were included. Probiotics were proposed as an adjunctive therapy.
5. Comparative Treatment Analysis:
– The comparative analysis was expanded to include rubber band ligation (20-30% recurrence; MacRae & McLeod, 1995) and sclerotherapy (25% recurrence; Khubchandani et al., 2009), emphasizing Nimsai Herbal's non-invasive superiority.
6. Supplementary Material Navigation:
– Main text citations were made specific (eg, “Figure S1”, “Table S2”). A table of contents was added to the Supplementary Material, enhancing reader navigation.
The Last Sentence :
Contributions of Nimsai Academia's Hemorrhoid Theory to the World: Effects from a Medical Professional's Perspective
Esteemed colleagues and all of humanity, the novel and groundbreaking “War-Drill Model” (Battle-Drill Model) introduced by Nimsai Academia regarding the pathogenesis of hemorrhoids has the potential to profoundly impact our current medical understanding and improve the lives of millions. The significant contributions of this theory to the world can be summarized from a scientific and clinical viewpoint as follows:
Elimination of Common Misconception and Access to Accurate Diagnosis: The widespread misconception globally that “swelling in the anus = hemorrhoids” leads to unnecessary anxiety and incorrect treatments for patients. Particularly, the delayed presentation for examination due to feelings of shame causes different conditions like hemorrhoids and skin diseases to be confused. The Nimsai Theory, by clearly distinguishing the two fundamental causes underlying anal swelling (blood-related hemorrhoids and skin diseases), will enable patients to reach an accurate diagnosis and prevent unnecessary use of topical products. This will provide clarity and accuracy directly affecting at least 2 billion people worldwide.
A New Era in Hemorrhoid Treatment and the End of Misconceptions in the Pharmaceutical Industry: Goligher's theory, which addresses hemorrhoids merely as a pathological condition focusing on mechanical factors, has caused the pharmaceutical industry to concentrate on vascular-focused treatments for 200 years. The Nimsai Theory, by demonstrating that hemorrhoids can be a consequence of underlying systemic diseases or hormonal imbalances, will bring an end to this misconception. This will pave the way for the development of entirely new and etiology-directed approaches in hemorrhoid treatment and will lead to the questioning of the intense investment in current vascular-focused treatments.
Correction of the Misconception in Surgical Approach and Significant Savings in Healthcare Expenditures: Surgical interventions, which have become widespread due to the influence of Goligher's theory, frequently result in recurrence because the Nimsai Theory's primary cause of hemorrhoids (blood and triggering factors) is not addressed. The acceptance of the Nimsai Theory will change the medical world's perspective on surgery and will prioritize the treatment of underlying causes. This will lead to a decrease in unnecessary surgical interventions, resulting in an estimated annual savings of $146 billion worldwide.
A Vital Alarm Mechanism for the Early Diagnosis of Underlying Serious Diseases: The revelation by the Mode of War of hemorrhoids as an indisputable alarm for underlying serious diseases (including cancerous polyps and conditions that can evolve into cancer) is one of the most significant contributions of this theory. In such cases where early diagnosis is vital, thanks to the Nimsai Theory, patients will not see anal swelling merely as simple hemorrhoids but with the awareness that it could be a sign of a serious underlying disease, they will seek medical help earlier. This will significantly increase the chance of early diagnosis and treatment of cancer and other serious diseases.
Overcoming the Feeling of Shame and Conscious Health Behavior: Hemorrhoids are a condition where patients worldwide hesitate to consult a doctor due to feelings of shame. The Nimsai Theory will transform the perception of hemorrhoids from a shameful disease to an alarm signal of the body. This awareness will lead patients to put aside feelings of shame and seek medical help earlier and more consciously when they notice anal swelling. The fact that hemorrhoids are a condition that needs to be taken seriously and is nothing to be ashamed of will become widespread knowledge.
Expansion of the List of Diseases Associated with Hemorrhoids and a Comprehensive Diagnostic Approach: The list of diseases directly associated with hemorrhoids identified by Nimsai Academia and which can be continuously updated (Anal Fissure, Fistula, Polyps, Proctitis, Crohn's Disease, Colitis, Diverticulitis, Rectocele, IBS, Portal Hypertension, Pelvic Congestion, Sleep Apnea, Hypothyroidism, Marfan Syndrome, Cirrhosis, Myeloproliferative Neoplasms, BPH, Rectal Varices, Pelvic Tumors, Chronic Venous Insufficiency, FLT4/VEGF-C Polymorphisms, Obesity, Chronic Hypoxia) will enable physicians to adopt a more comprehensive diagnostic approach. In patients with complaints of anal swelling, not only hemorrhoids but also other potential underlying diseases in this list will be considered, and the possibility of early diagnosis will be increased. This list is a dynamic resource that can be continuously updated with new information from internal medicine and other specialties.
In conclusion, Nimsai Academia's Combat-Drill Model is a revolutionary step in our understanding of hemorrhoid pathogenesis. This theory is not only a scientific advancement but will also create a significant global public health impact by enabling millions of people to reach the correct diagnosis, avoid unnecessary treatments, have underlying serious diseases diagnosed early, and develop more conscious health behaviors by overcoming the feeling of shame. The adoption of this theory by the medical community and its integration into clinical practices is of vital importance for the health of humanity.
Hemorrhoids Research Team
Nimsai Herbal
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