Subtotal colectomy with Deloyers colo-anal anastomosis for refractory ulcerative colitis: A case report

Abstract

BACKGROUND

Ulcerative colitis (UC) is a chronic inflammatory bowel disease often requiring advanced therapies, with up to 40% of patients experiencing non-response to anti-tumor necrosis factor agents. Tofacitinib offers rapid symptom improvement, but its long-term high-dose use and role in post-operative management are poorly documented. Subtotal colectomy with colo-anal anastomosis using Deloyers procedure is an uncommon alternative to standard proctocolectomy with ileal pouch-anal anastomosis.

CASE SUMMARY

We report the management of a patient with refractory extensive UC using prolonged high-dose tofacitinib followed by function-preserving subtotal colectomy. A 47-year-old male with extensive UC, refractory to 5-aminosalicylic acid and azathioprine, presented with severe disease activity. After primary non-response to infliximab, tofacitinib 10 mg twice daily was initiated, escalated to 10 mg thrice daily with a 5-aminosalicylic acid enema due to partial response. After four months, clinical remission was achieved, but endoscopy revealed a striking differential healing pattern, with endoscopic healing in the right colon (Mayo Endoscopic Score 0-1) but persistent severe inflammation distally (Mayo Endoscopic Score 3). Subtotal colectomy with Deloyers procedure was performed, followed by tofacitinib 10 mg twice daily post-operatively. At six-month follow-up, the patient was asymptomatic with only mild endoscopic erythema and histologic diversion colitis but no active UC.

CONCLUSION

This case highlights the novel use of prolonged high-dose tofacitinib, achieving differential mucosal healing, and function-preserving subtotal colectomy with post-operative tofacitinib to manage refractory UC. It underscores the importance of addressing clinical-endoscopic discordance and suggests a tailored medical-surgical approach for complex UC.

Key Words: Ulcerative colitis; Tofacitinib; Function-preserving subtotal colectomy; Clinical-endoscopic discordance; Differential healing; Case report

Core Tip: We report a rare case of refractory ulcerative colitis displaying “differential healing” following prolonged high-dose tofacitinib (10 mg thrice daily) rescue therapy. While the distal colon remained severely inflamed despite clinical remission (clinical-endoscopic discordance), the proximal colon achieved complete mucosal healing. This unique segmental response facilitated a function-preserving subtotal colectomy with Deloyers colo-anal anastomosis, avoiding a permanent stoma or ileal pouch. This case highlights a novel medical-surgical strategy leveraging differential healing to preserve colonic function and quality of life in complex scenarios.

INTRODUCTION

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with a rising global incidence[1]. While many patients are managed with conventional therapies, 10%-15% develop moderate-to-severe disease requiring advanced treatments such as anti-tumor necrosis factor (anti-TNF) agents[2]. However, primary non-response or secondary loss of response to anti-tumor necrosis factors remains a significant clinical challenge, requiring therapy with different mechanisms of action[3]. The modern therapeutic landscape for UC now includes anti-integrins (vedolizumab), interleukin-12/23 and interleukin-23p19 inhibitors (ustekinumab, risankizumab), and Janus kinase (JAK) inhibitors, including tofacitinib, which is notable for demonstrating symptom improvement within 3 days of initiation, a critical factor in severe disease[3-5].

Despite these options, challenges like clinical-endoscopic discordance - where symptomatic remission masks ongoing mucosal inflammation - and the need for unconventional strategies in refractory cases persist[3]. The use of high-dose tofacitinib [10 mg thrice daily (TID)] has been described as short-term salvage therapy in acute severe UC, but its role in the long-term outpatient setting is less well-documented[4]. Similarly, function-preserving subtotal colectomy is rarely employed for UC driven by inflammation alone, with most literature focusing on its use for concomitant malignancy[6].

We present the case of a 47-year-old male with refractory extensive UC managed with a unique, sequential medical-surgical strategy. This report details the use of prolonged, high-dose tofacitinib leading to a differential healing pattern, followed by a successful function-preserving segmental colectomy with post-operative tofacitinib maintenance. This case provides valuable insights into managing clinical-endoscopic discordance and showcases a novel approach addressing the unique challenge of differential mucosal healing in severe UC.

CASE PRESENTATION

Chief complaints

Bloody diarrhea (6-7 times/day), abdominal cramping, and weight loss.

History of present illness

The patient presented to the hospital with severe symptoms including frequent bloody stools (5-6 times/day), abdominal cramping, and weight loss. Due to the severity of the flare, he was referred to our center for advanced therapy.

History of past illness

The patient had an 8-year history of extensive UC. The disease was refractory to conventional maintenance therapies, including 5-aminosalicylic acid (5-ASA) and azathioprine. Notably, the patient had a history of corticosteroid dependence but was naïve to biologic therapy prior to this referral.

Personal and family history

The patient had no family history of inflammatory bowel disease.

Physical examination

Physical examination revealed pallor and mild left lower quadrant tenderness.

Laboratory examinations

Initial labs showed moderate anemia [hemoglobin (HGB) 83 g/L], hypoalbuminemia (29.8 g/L), and severe inflammation [C-reactive protein (CRP) 50.4 mg/L; fecal calprotectin (FC) > 800 μg/g]. Infectious etiologies were ruled out.

Imaging examinations

Endoscopic evaluation revealed severe active pancolitis (Mayo Endoscopic Subscore 3) (Figure 1).

Figure 1 Baseline colonoscopic findings. Initial colonoscopic evaluation revealing severe active pancolitis (Mayo Endoscopic Score 3) with diffuse erythema, friable mucosa, and deep ulcerations prior to biologic therapy. The terminal ileum was endoscopically normal with no evidence of inflammation, and random biopsies from the ileum and colon showed features consistent with ulcerative colitis without granulomas or other findings suggestive of Crohn’s disease.

FINAL DIAGNOSIS

The patient fulfilled Truelove and Witts criteria for severe UC (bloody stool ≥ 6/day, HGB < 105 g/L, CRP > 30 mg/L), with a Full Mayo Score of 12.

TREATMENT

He received induction therapy with infliximab (5 mg/kg) and azathioprine (2 mg/kg/day). After four doses, he remained symptomatic with elevated inflammatory markers (CRP: 70 mg/L, FC > 800 μg/g). Endoscopic evaluation revealed severe active pancolitis [Mayo Endoscopic Score (MES 3)].

Due to primary non-response and unavailable therapeutic drug monitoring (TDM), therapy was switched to tofacitinib 10 mg twice daily (BID). Four months post-tofacitinib initiation, he showed clinical improvement, with bloody stool frequency reduced to 2-3 episodes/day and CRP decreased to 38 mg/L (Table 1). Due to a partial response, tofacitinib was escalated to 10 mg TID with adjunctive 5-ASA enema. After four months, this regimen induced clinical remission and improved biochemical markers (HGB: 125 g/L, FC: 317 μg/g). However, a follow-up endoscopy revealed a differential healing response: Mucosal healing in the right colon (MES 0-1) but persistent severe distal disease involving the rectum and the sigmoid colon (MES 3) (Figure 2A).

Figure 2 Endoscopic and gross pathological evidence of differential mucosal healing post-tofacitinib therapy. A: Follow-up colonoscopy illustrating a heterogeneous healing pattern: Mucosal remission in the right colon (Mayo Endoscopic Score 0-1) contrasted with persistent severe inflammation in the distal segments, including the rectum and sigmoid colon (Mayo Endoscopic Score 3); B: Gross specimen of the resected colorectum demonstrating severe inflammation, mural thickening, and extensive ulceration in the sigmoid colon and rectum, confirming the extent of medically refractory disease.

Table 1 Summary of clinical, biochemical, and endoscopic parameters over time.

Parameter	At referral	After infliximab	After 4 months of standard dose tofacitinib	After 4 months of high-dose tofacitinib	6 months post-surgery
Clinical symptoms	Bloody diarrhea (6-7/day)	Not improved	Improved	Clinical remission	Asymptomatic
Hemoglobin (g/L)	83	83	109	125	138
Albumin (g/L)	29.8	31.3	30	36.0	45.0
CRP (mg/L)	50.4	70.0	38	9.5	1.9
Fecal calprotectin (μg/g)	> 800	> 800	> 800	317	Not assessed
MES	3 (pancolitis)	3 (pancolitis)	3 (distal)/2 (proximal)	3 (distal)/0-1 (proximal)1	No active UC
Full Mayo Score	12	12	9	61	0-1

¹The Full Mayo Score of 6 despite clinical remission reflects this discordance, driven by the severe distal Mayo Endoscopic Score while stool frequency and rectal bleeding subscores had normalized.

This table illustrates the patient’s clinical-endoscopic discordance: Significant improvement in symptoms and biochemical markers during high-dose tofacitinib contrasted with persistently severe distal inflammation (Mayo Endoscopic Score 3), ultimately necessitating surgery. CRP: C-reactive protein; MES: Mayo Endoscopic Score.

Based on this refractory distal disease, a decision for surgery was made. After a two-month pre-operative de-escalation of tofacitinib to 10 mg BID, he underwent surgery approximately 19 months after his initial referral. A laparoscopic subtotal colectomy with proctectomy and a Deloyers procedure was performed, creating a right-sided colo-anal anastomosis and a diverting loop ileostomy. The resected specimen confirmed severe end-stage disease distally (Figure 2B). The proximal resection margin in the transverse colon demonstrated quiescent colitis with mucosal healing, characterized by mild chronic inflammation, restored crypt architecture, and absence of active inflammation, dysplasia, or malignancy. This histological confirmation validated the endoscopic assessment of differential healing and supported the safety of anastomosis at this level. Post-operatively, tofacitinib 10 mg BID was restarted to maintain inflammatory control in the preserved colon.

OUTCOME AND FOLLOW-UP

The patient’s recovery was excellent. At six months post-surgery, while still diverted, he was asymptomatic with normalized labs (HGB: 138 g/L, CRP: 1.9 mg/L). Colonoscopy showed only mild erythema (Figure 3A), and biopsies confirmed diversion colitis without active UC (Figure 3B). Ileostomy reversal was successfully performed shortly thereafter. Two weeks following ileostomy reversal, maintenance therapy with tofacitinib 5 mg BID was reinitiated. At the most recent follow-up (2 months post-reversal), the patient reported excellent functional outcomes: 3-4 formed bowel movements daily, complete fecal continence with no episodes of urgency or incontinence, no nocturnal bowel movements, and return to full occupational and social activities. The patient expressed high satisfaction with the surgical outcome and quality of life, preferring the current status over his pre-operative condition. Formal quality of life assessment using validated instruments was not performed, which we acknowledge as a limitation.

Figure 3 Postoperative endoscopic and histopathological findings at six months following subtotal colectomy. A: Colonoscopy of the remaining colon shows a patent colo-anal anastomosis and only mild, diffuse erythema; B: Corresponding histopathology (hematoxylin and eosin stain) of biopsies reveals features consistent with diversion colitis, including chronic inflammation and glandular atrophy, with a complete absence of neutrophils, indicating no evidence of active ulcerative colitis.

DISCUSSION

Clinical-endoscopic discordance, where up to 45% of UC patients in clinical remission exhibit active endoscopic inflammation, is a well-recognized challenge[7]. Our case provides a compelling clinical illustration: Despite clinical remission on high-dose tofacitinib, objective markers confirmed persistent severe mucosal inflammation. More strikingly, this case demonstrated a pattern of ‘differential healing’, with mucosal recovery in the proximal colon while the distal segments remained severely inflamed. This regional heterogeneity may be explained by the proximal-to-distal gradient of submucosal fibrosis described in UC. A study of 89 colectomy specimens demonstrated that submucosal fibrosis and muscularis mucosae thickness (142.8 μm vs 48.6 μm in involved vs uninvolved segments; P < 0.001) increase significantly toward the distal colon[8]. Crucially, this fibrosis correlates with the severity and chronicity of mucosal injury rather than active inflammation alone.

In our patient with an 8-year disease history and longstanding pancolitis, the rectosigmoid region, as the site of disease onset and longest inflammatory exposure, likely accumulated the greatest degree of structural remodeling. This fibrotic microenvironment, characterized by increased wall stiffness, submucosal collagen deposition, and muscularis mucosae hypertrophy, may impair mucosal drug penetration and vascular perfusion, creating tissue resistance to systemic therapies including JAK inhibition. Conversely, the proximal colon, with presumably less chronic injury and preserved tissue architecture, retained the capacity for mucosal healing. This hypothesis aligns with the emerging concept of UC as a progressive disease, wherein cumulative inflammatory burden leads to irreversible structural damage[9], and underscores the importance of early, sustained disease control to prevent such refractory outcomes.

Following primary non-response to infliximab within the context of the therapeutic landscape in Vietnam, influenced by accessibility, cost considerations, and the unavailability of TDM, tofacitinib was selected over ustekinumab. This decision was informed by evidence from network meta-analyses showing comparable end-of-induction efficacy[2], but a more rapid onset of action for JAK inhibitors, a critical factor in severe disease[5]. An unconventional regimen of tofacitinib 10 mg TID was initiated for four months. Given the persistence of inflammation in the distal colon, a topical 5-ASA was adjunctively administered alongside tofacitinib, consistent with the suggestion from a recent American Gastroenterological Association guideline on moderate-to-severe UC[10].

This prolonged high-dose use in an outpatient setting is a novel approach, distinguishing this case from prior studies focused on short-term acute severe UC salvage therapy[11-13], and deviates from the standard 10 mg BID induction regimen established in the pivotal OCTAVE trials[14]. The standard 10 mg BID tofacitinib induction regimen yielded a partial symptomatic response. When subsequent alternatives, including combination therapy with ustekinumab or total colectomy with ileal pouch-anal anastomosis (IPAA), were declined by the patient, the decision was made to escalate to a high-dose 10 mg TID regimen. This decision involved a careful risk-benefit analysis, weighing the remission benefits against the known risks of high-dose JAK inhibition, such as an increased risk of herpes zoster and venous thromboembolism (VTE) as observed in the UC clinical trial program[15]. To mitigate the known risks of high-dose JAK inhibition, particularly VTE, a rigorous pre-escalation safety assessment was conducted. The patient was confirmed to have a low thrombotic risk profile (non-smoker, no personal or family history of VTE). We maintained strict vigilance for adverse events, treating this high-dose regimen as a time-limited ‘rescue’ bridge to a definitive surgical solution rather than a long-term maintenance strategy. No complications from high-dose tofacitinib were observed. The dose was then de-escalated to 10 mg BID for two months prior to surgery. This decision was based on the clinical principle of minimizing immunosuppression before major surgery to reduce complication risks, a concept supported by current guidelines[3,4]. While British guideline states that advanced therapies can be continued peri-operatively, they also highlight the limited safety data for JAK inhibitors and cite studies noting risks such as VTE in this setting, justifying a cautious approach of dose reduction[4].

A distinctive and patient-centered aspect of this case lies in the surgical strategy adopted. While total proctocolectomy with IPAA remains the standard approach for medically refractory UC, it is associated with considerable trade-offs, including altered bowel habits, pouchitis, and long-term impact on quality of life[3,4]. In contrast, our decision to pursue a function-preserving subtotal colectomy was driven by the unique endoscopic finding of differential healing - marked mucosal recovery in the right colon (MES 0-1) and persistently severe disease in the distal colon (MES 3). Preoperative computed tomography imaging revealed a relatively short mesentery and a long, narrow pelvic girdle, suggesting that achieving a tension-free IPAA would have required extensive mesenteric lengthening procedures, with potential compromise of vascular integrity[16]. This anatomical constraint further supported the choice of a Deloyers procedure, which enabled a tension-free colo-anal anastomosis using the well-healed proximal colon[17]. Beyond anatomical constraints, this approach was preferred over standard IPAA to maximize functional preservation. By maintaining the well-healed proximal colon, the Deloyers procedure preserves native water absorptive capacity and avoids common IPAA-associated complications such as pouchitis and nocturnal seepage, thereby offering the potential for superior quality of life[17,18]. This potential advantage is supported by the high cumulative incidence of pouchitis after IPAA, reported in up to 72% of patients at 10 years, which can significantly impair quality of life through recurrent symptoms and the need for ongoing treatment[19]. The decision to pursue this non-standard, function-preserving approach relied heavily on shared decision-making. We engaged in extensive counseling with the patient regarding the trade-offs between total proctocolectomy with IPAA vs subtotal colectomy. The discussion explicitly covered the risks of the preserved colon, including the potential for disease recurrence in the remnant segment, the necessity of indefinite cancer surveillance, and the requirement for continued medical therapy (tofacitinib). The patient prioritized the potential for superior bowel function and the avoidance of pouch-related complications, providing informed consent for this personalized strategy. While literature on segmental or subtotal colectomy for UC primarily focuses on cases involving colorectal neoplasia, its application here - purely for inflammatory control - introduces a valuable perspective[6]. Notably, a recent review found no significant difference in reoperation rates between segmental colectomy and total proctocolectomy, though the quality of evidence was low[6].

The success of this non-standard surgery depended on effective post-operative medical management. Tofacitinib was continued to leverage its systemic JAK inhibition against the risk of inflammatory recurrence in the preserved colon, which could necessitate completion colectomy[15]. Our patient’s excellent outcome, with histology confirming diversion colitis without active UC and successful ileostomy reversal at 6 months, is particularly noteworthy. Indeed, Lincango et al's review[6] reinforce this concern, cautioning that low-quality evidence and reinterventions driven by colitis flares warrant a careful approach to this surgical option. No prior studies, to our knowledge, have reported tofacitinib use to prevent UC recurrence after a function-preserving subtotal colectomy, suggesting a novel application for JAK inhibitors.

We acknowledge several limitations. Most notably, the follow-up period is limited to eight months. While the patient achieved clinical and endoscopic remission in the preserved segment, this duration is insufficient to deem this strategy a proven long-term solution. Continued long-term observation is required to assess the durability of remission and the risk of disease recurrence in the remaining colon. Nevertheless, this report serves as a preliminary communication demonstrating the feasibility and short-term safety of this tailored medical-surgical approach. We are committed to ongoing surveillance with colonoscopy and plan to report extended follow-up outcomes in a subsequent publication. Additionally, the unavailability of TDM for infliximab, which precluded dose optimization and prompted an empirical switch to a different therapeutic class, represents a limitation in the initial management pathway. Furthermore, cross-sectional imaging such as computed tomography or magnetic resonance enterography for objective assessment of transmural inflammation and bowel wall thickening was not performed during medical management. Such imaging might have revealed differential mural changes correlating with the observed endoscopic healing pattern and provided insight into the degree of submucosal fibrosis across colonic segments, which has been shown to influence treatment response[8]. A further limitation is the off-label use of high-dose tofacitinib, which, despite serving as a successful bridge to surgery, represents a deviation from standard protocols. Selection bias is possible, as this surgical approach was chosen for a patient who had already demonstrated a favorable response in the preserved colonic segment. As a single case, these findings are not generalizable but may inform future studies.

CONCLUSION

In conclusion, this case offers several important lessons. It reinforces the indispensability of objective monitoring over clinical symptoms. It presents a novel report on the prolonged, high-dose use of tofacitinib, which resulted in a differential healing pattern. The differential healing likely reflects the progressive fibrotic remodeling in chronically inflamed segments, which may impair tissue responsiveness to systemic therapies. This finding enabled a successful function-preserving subtotal colectomy with colo-anal anastomosis - a departure from standard surgical practice. The excellent short-term post-operative outcome, maintained with tofacitinib, suggests this tailored medical-surgical strategy can be a viable option in highly selected patients, though long-term data are needed to confirm its persistence. Future research, ideally involving multicenter data, is necessary to determine the reproducibility, long-term durability, and safety of this tailored approach in a broader patient population.