Mixed histology bladder cancer as a complication of clam ileocystoplasty

Abstract

A 58-year-old woman with a previous clam ileocystoplasty was referred to the urology department for the investigation of haematuria. CT urogram showed a large left-sided soft tissue mass arising from the bladder. Histological analysis of the shavings from transurethral resection revealed a G3pT2 transitional cell carcinoma and T4N1Mx adenocarcinoma. The patient was referred to oncology for the discussion of palliative chemotherapy; however, in the interim she deteriorated and was admitted to hospital with a post-renal acute kidney injury. A right-sided nephrostomy was inserted relieving her obstruction and she subsequently made a good recovery. This case report illustrates the difficulties in the long-term follow-up of patients having undergone what is now a rarely performed procedure. In the absence of regular cystoscopic follow-up post ileocystoplasty, malignancy may present late and with complications from advanced disease.

Background

Clam ileocystoplasty was undertaken as a surgical management option for urge incontinence when conservative and medical management failed. However, with the advent of intravesical botulinum toxin injection and sacral neuromodulation, clam ileocystoplasty is performed less frequently.

This procedure aims to surgically improve functional bladder capacity and is usually accomplished by a lower midline incision. The operative steps involve an ileal segment with its mesentery being detached from the rest of the bowel and laid open at the antimesenteric side. The bladder is opened at its superior aspect to resemble a clam and the ileal segment is then anastomosed to the defect created (figure 1).

Figure 1.

Schematic depicting the key operative steps in an ileocystoplasty procedure. Figure kindly provided by Miss Jaissie Ngan, independent illustrator.

Malignancy is a known but rare complication following ileocystoplasty and most published data are confined to case reports, case series and retrospective cohort studies. A systematic review of case reports documents an incidence of 0.9%–5.5% in those undergoing ileocystoplasty with an average onset of 15 years post operation.¹

Follow-up with cystoscopy is controversial, and the frequency and time from operation this should occur is widely debated.² There is currently no recognised surveillance protocol in the UK for evaluating these patients. Given the long latency period between index operation and development of cancer, many patients are lost to follow-up and are not investigated until the development of symptoms.

We present a case of mixed histology bladder cancer which by the time the patient presented with symptoms was late stage and associated with complications. This case demonstrates the sequelae of patients with previous ileocystoplasty.

Case presentation

A 58-year-old woman was referred by the general practitioner (GP) to our urology department for the investigation of visible haematuria. Relevant history from the patient was that she had had a clam ileocystoplasty more than 25 years earlier for intractable urge incontinence. Her non-urological diagnoses included hypertension, hypercholesterolaemia, previous hysterectomy for heavy bleeding, depression and oesophagitis with hiatus hernia.

She presented with a 3-month history of visible blood in the urine associated with left loin and groin pain that had not responded to four courses of antibiotics. General examination was unremarkable with no evidence of cachexia. Her performance status was 0.

Investigations

Baseline blood tests revealed haemoglobin (Hb) 135 g/L, white cell count (WCC) 10.3×10⁹/L, platelet (Plt) count 296×10⁹/L, sodium (Na) 136, potassium (K) 5.3, creatinine (Cr) 86, urea (Ur) 3.8 and estimated glomerular filtration rate (eGFR) 57.

CT urogram was arranged which showed a large left-sided soft tissue bladder mass inseparable from the vaginal vault (figure 2A). Furthermore, the bladder mass was obstructing the left vesicoureteric junction causing moderate hydronephrosis and hydroureter (figure 2B). The left kidney was smaller than the right and had reduced contrast enhancement with no contrast at all within the left collecting system. There were several enlarged local lymph nodes adjacent to the bladder mass.

Figure 2.

(A) CT urogram coronal section showing the bladder mass invading the vaginal vault. (B) CT urogram coronal section showing a small left kidney with hydronephrosis.

Following this, an MRI pelvis was performed for local staging and a dimercaptosuccinic acid (DMSA) scan to assess the split function of the kidney. MRI pelvis revealed a 3×1.5 cm left lateral bladder wall lesion with extravesical extension into the vaginal vault and further right-sided bladder wall thickening suggestive of a multifocal lesion (figure 3A, B). The common iliac and external iliac nodes were involved. The DMSA scan showed a split function of right kidney 99% and left kidney 1% (figure 4A, B).

Figure 3.

(A) MRI pelvis coronal section showing the left lateral bladder wall tumour with extravesical spread and involvement of the vaginal vault. (B) MRI pelvis axial sections showing the left lateral bladder wall tumour with extravesical spread and involvement of the vaginal vault.

Figure 4.

(A) Dimercaptosuccinic acid scan showing normal homogenous uptake of tracer in the right kidney only and no focal scarring. (B) Split function according to the geometric mean measures the right kidney at 99% and left kidney at 1%.

The patient subsequently underwent transurethral resection of bladder tumour. On examination under anaesthesia, a bladder mass was seen fixed to the left side of the pelvis. This was a solid tumour with no papillary features and infiltrated the trigone. Neither ureteric orifice could be seen. The lesion could not be completely resected.

The histology report came back as showing combined transitional cell carcinoma and adenocarcinoma of at least pT2 (figure 5A, B). There was lymphovascular and perineural invasion. The tumour cells showed positive staining with the urothelial marker GATA-3 and negativity with the colorectal marker CDX-2. After discussion at the urology multidisciplinary team (MDT) meeting, the cancer was staged as a G3pT2 transitional cell carcinoma and T4N1Mx adenocarcinoma. Subsequent CT thorax did not reveal metastatic spread to the lungs.

Figure 5.

(A) Histology (H&E at 10× magnification) showed high-grade solid transitional cell carcinoma (lower image) invading the fibres of the muscularis propria (upper image). (B) There were separate fragments exhibiting invasive adenocarcinoma.

Outcome and follow-up

Following MDT discussion, the patient was swiftly referred to the regional clinical oncology team for discussion of non-curative chemotherapy. However in the interim, she was admitted with a 3-hour history of confusion and hallucinations.

An initial arterial blood gas showed a metabolic acidosis with pH 7.13, PCO₂ 4.70, bicarbonate 11.8 and lactate 0.50.

Blood tests revealed Hb 95, WCC 8.3, Plt 335, international normalised ratio 1.0, Na 126, K 7.4, Cr 805, Ur 33.6, eGFR 4, calcium (Ca) 2.28, alkaline phosphatase 111, albumin 29, magnesium 1.00 and C reactive protein 113.2. Given the background history and the blood tests, the clinical picture was consistent with acute kidney injury most likely post-renal in origin. The patient was treated with calcium gluconate, insulin dextrose and salbutamol nebulisers for the initial management of hyperkalaemia. Calcium resonium and sodium bicarbonate were also started for the continuing management of hyperkalaemia and acidosis.

Ultrasound of the urinary tract was undertaken which showed bilateral hydronephrosis, but because the patient only had a single functioning right kidney, nephrostomy was only performed on the right. CT head did not reveal any evidence of metastases as a cause for her confusion. Over the next few days, she improved clinically and her biochemical markers normalised (figure 6). She was discharged after the ninth day when stable.

Figure 6.

Trend of blood tests from admission to discharge. GFR, glomerular filtration rate.

Discussion

Clam ileocystoplasty has been performed for multiple reasons including for urge incontinence refractory to maximal medical therapy as in our case presented above. The principle is to improve functional bladder capacity and decrease maximal detrusor pressure by inserting a segment of opened-up ileum to the superior wall of the bladder. Tuberculous cystitis is rare in the UK, but clam ileocystoplasty has been commonly undertaken for this indication in other parts of the world where inflammation causes a chronically shrunken bladder.

Since the majority of existing literature on ileocystoplasty comes from case reports and single centre studies, the true risk of malignant transformation is not known. However, a systematic review of case reports documents an incidence of 0.9%–5.5%.¹ It appears the most common tumour type is adenocarcinoma, and the next most common is transitional cell carcinoma, with tumours tending to occur at the anastomotic site.^{3 4} There have also been case reports of carcinoid tumour, sarcoma and small cell carcinoma.^5–7

Malignancy has also been seen to occur with other bowel segments used for augmentation such as the stomach and colon. In addition, urinary diversions, for example, ureterosigmoidostomy, have an established malignancy risk with a multicentre analysis finding the prevalence to be 2.6% and a systematic review quoting an incidence of up to 15%.^{8 9}

In urinary diversion, the proposed mechanism is the nitrosamine theory where mixing of the urinary and faecal streams promotes carcinogenesis due to in vivo bacterial-mediated formation of N-nitroso compounds.¹⁰ However, the nitrosamine theory cannot explain the development of malignancy where there is no mixing of the urinary and faecal streams such as in ileocystoplasty.

There are no nationally recognised pathways for monitoring of patients post ileocystoplasty. Some authors have suggested annual cystoscopy after 10 years from the index operation and others after 15 years.^{11 12} On the other hand, some do not recommend routine cystoscopy at all as it is unclear whether it is cost effective due to the long latency period and lack of robust data on incidence.^{13 14} Other methods such as urinary cytology and tumour markers are probably unhelpful due to mucous production by glandular tissue from bowel and the non-specificity of markers.

This case illustrates the difficulties faced with follow-up post ileocystoplasty. Our patient presented more than 25 years following her index operation with advanced disease. While follow-up cystoscopy after 10–15 years is probably the best practice, the difficulty lies in identifying those at risk as many will have lost contact with their primary operative centre. All patients with a background of urinary tract reconstruction and new visible haematuria should have rapid workup with cystoscopy and CT urogram. In addition, all patients undergoing such augmentation should be carefully counselled about the risk of late malignancy and more especially of the need for late surveillance.

Learning points.

• In the absence of regular cystoscopic follow-up, malignancy may not be detected until late and may present with complications and/or inoperable disease.

• All patients undergoing clam ileocystoplasty should be carefully counselled about the risk of late malignancy.

• New-onset visible haematuria in the context of urinary tract reconstruction is an indication for urgent investigation including flexible cystoscopy and imaging.

• There is no routine pathway for cystoscopic follow-up in UK; however, 3–5 yearly after 15 years from index operation may represent a more cost effective solution than annual cystoscopy.