This study investigated a new understanding of hemorrhoid formation and evaluated a novel systemic treatment. For 200 years, hemorrhoids were conventionally understood as isolated swollen veins. However, our new "War-Drill Model" proposes that hemorrhoids are primarily caused by blood pooling (venous congestion) in the anal region, which then secondarily leads to vascular deformation. This congestion is hypothesized to arise from either underlying health issues ("War Mode") or natural physiological and hormonal changes ("Drill Mode"). We conducted a double-blind, placebo-controlled randomized controlled trial on 300 patients with Grade 2-3 hemorrhoids to evaluate the efficacy and safety of Nimsai Herbal. This study explores the potential for "War Mode" hemorrhoids to serve as an early warning sign for other serious underlying conditions and aims to validate a novel systemic therapeutic approach.

The current understanding of hemorrhoid pathogenesis has remained largely unchanged for over two centuries, positing hemorrhoids primarily as isolated venous dilatations or prolapses. This traditional view, however, fails to adequately explain the high recurrence rates post-treatment, the limited efficacy of topical agents, and the often-debilitating symptomatology. Our extensive research, culminating in the "War-Drill Model" and the "Sine Qua Non Hypothesis," fundamentally challenges this conventional paradigm. We propose that hemorrhoids are not primarily structural abnormalities but rather a manifestation of underlying venous congestion, which then secondarily leads to vascular deformation and associated symptoms. This congestion acts as the indispensable (sine qua non) prerequisite for the development of both symptomatic and asymptomatic hemorrhoidal disease.

The "War-Drill Model" further categorizes this venous congestion based on its etiology:

War Mode Hemorrhoids: These are hypothesized to arise from chronic or passive venous congestion triggered by an underlying systemic or local inflammatory process or pathology. Examples include inflammatory bowel diseases (Crohn's disease, ulcerative colitis), anal fissures, rectal polyps, liver diseases causing portal hypertension, and various other systemic conditions affecting vascular flow or integrity. Crucially, "War Mode" hemorrhoids may serve as a critical "biological early-warning system," prompting investigations that could lead to the early diagnosis of up to 20 distinct and potentially severe internal diseases.

Drill Mode Hemorrhoids: These are hypothesized to be transient vascular engorgements resulting from physiological hormonal fluctuations, typically observed during periods of significant endocrine change such as adolescence, pregnancy, lactation, menopause, and andropause. These episodes are often self-limiting, resolving as hormonal balance stabilizes.

To validate a systemic therapeutic approach based on this new model, we conducted a double-blind, placebo-controlled, parallel-group Randomized Controlled Trial (RCT) (Protocol ID: NA-2024-01). The study enrolled 300 participants aged 18-70 years with endoscopically confirmed Grade 2-3 internal hemorrhoids and a history of symptoms for over 6 weeks. Participants were randomized to receive either Nimsai Herbal (a novel systemic botanical formulation, 600 mg daily) or an identical placebo for 10 consecutive days.

The primary outcome measure was hemorrhoid regression rate, defined as a reduction of at least one Goligher grade by Day 10, assessed via anoscopic examination and clinical evaluation. Secondary outcomes included incidence of adverse events. The study utilized the "Parola Phenomenon," a simple clinical maneuver designed by Atabiner, as part of patient assessment, aiming to differentiate War Mode from Drill Mode hemorrhoids.

Inclusion Criteria:

Endoscopically confirmed Grade 2 or 3 internal hemorrhoids.

History of hemorrhoidal symptoms >6 weeks.

Age 18-70 years at the time of enrollment.

Provided written informed consent prior to any study-related procedures.

Willingness and ability to comply with all study procedures and follow-up visits.

Exclusion Criteria:

Grade 1 or 4 hemorrhoids.

Any known anorectal malignancy or suspicion of malignancy.

Pregnancy or lactation.

Known hypersensitivity or allergy to Nimsai Herbal components or placebo ingredients.

Significant systemic diseases (e.g., severe cardiovascular, renal, hepatic, or hematological disorders) that could affect study participation or safety.

Participation in another clinical trial within 30 days prior to screening.

Any condition that, in the opinion of the investigator, might compromise the safety of the participant or the integrity of the study data.

Individual participant data (IPD) that underlie the results reported in this article, after de-identification, will be available upon reasonable request to qualified researchers who submit a methodologically sound proposal. Data will be shared through a secure platform, subject to a data sharing agreement.

Individual participant data and supporting information will be available starting 6 months after the official publication of the primary manuscript in a peer-reviewed journal. The data will remain accessible indefinitely thereafter, or for as long as ethically and legally permissible under relevant data privacy regulations and institutional policies.

Access to de-identified individual participant data (IPD) and supporting documentation (including the study protocol, statistical analysis plan, and informed consent form) will be granted to qualified researchers. Researchers must submit a methodologically sound and ethically approved research proposal that aligns with the original study's objectives or adds significant scientific value.

Access will be provided through a secure, controlled-access platform, requiring a signed Data Use Agreement (DUA) between the requesting institution and Nimsai Academia. This agreement will outline strict terms for data use, confidentiality, and proper attribution, ensuring compliance with all applicable privacy regulations (e.g., GDPR, HIPAA equivalents). Data will be used solely for non-commercial scientific research purposes.

All randomized participants (N=300) were included in the baseline analysis population, as complete baseline data were obtained for all individuals.

Adverse events were collected from randomization until the end of the study treatment period (Day 10), covering the entire intervention duration for each participant.

Adverse events were systematically collected at each study visit and through participant spontaneous reports. Each event's severity and relationship to the study intervention were assessed by blinded investigators, ensuring robust and unbiased safety data collection.

This RCT focused on Grade 2-3 hemorrhoids; efficacy in Grade 1 and 4 needs further study. The short 14-day follow-up necessitates longer-term cohort studies for sustained effects. The Parola Phenomenon, though accurate, requires objective validation beyond clinical assessment. No formal blinding evaluation was conducted. Future research should explore potential genetic and microbiota interactions.

The study employed a robust double-blind design where the Nimsai Herbal and placebo treatments were identical in appearance, taste, and packaging. In addition to participants, care providers, investigators, and outcomes assessors, the independent data monitoring committee and third-party statisticians involved in the primary data analysis were also masked to treatment assignments. The unblinding codes were securely held by a designated unmasked statistician who was not involved in the interim analyses or daily study conduct.