Keywords
colorectal neoplasms - colorectal surgery - syndromes - acute kidney injury - electrolyte
disturbance - chronic diarrhea
Background
Originally described in 1954, McKittrick-Wheelock syndrome (MKWS) is a rare syndrome
characterized by a triad of conditions, including acute kidney failure and an electrolytic
disorder associated with chronic diarrhea due to an underlying large distal colorectal
tumor, most commonly a villous adenoma.[1]
[2]
[3] A hypersecretory state secondary to a large villous adenoma is responsible for most
of the syndrome's signs and symptoms, and its cause is due to the secretion of a large
amount of fluid which overwhelms the reabsorption capacity of the colorectal mucosa.[4]
Without proper management, the mortality rate of this condition can reach 100%.[5] However, a correct diagnosis associated with immediate treatment can completely
reverse the symptoms. The recommended management includes the surgical removal of
the tumor.[6]
In view of the clinical severity of this syndrome and its relatively uncommon association
with malignant tumors, the present work describes a rare case of a 62-year-old man
diagnosed with rectal adenocarcinoma associated with MKWS.
Case Report
A 62-year-old man presented with a 2-year history of mucoid diarrhea, which occurred
up to 10 times per day and was preceded by abdominal pain. He denied hematochezia
and weight loss. He reported that, 3 months before, he started having migratory cramps
and nausea. He also had a history of smoking (20 cigarettes per day for 25 years;
quit 20 years ago) and use of alcohol (quit 2 years ago). He was admitted to an emergency
service due to complaints of nausea and migratory cramps associated with the chronic
diarrhea. He had a heart rate of 150 bpm and a blood pressure of 90/65 mmHg. Laboratory
tests revealed a potassium level of 2.8 mEq/L, a calcium level of 11.1 mg/dL, a sodium
level of 127 mEq/L, a urea level of 226 mg/dL, a creatinine level of 4.3 mg/dL, a
hemoglobin level of 18.8 g/dL, and a red blood cell count of 56.7%. The patient was
diagnosed with electrolyte disturbance, dehydration and acute renal failure (ARF).
He remained hospitalized for five days, and was referred to a specialist for further
care.
A digital rectal examination revealed a tumor 6 cm from the anal margin. Flexible
sigmoidoscopy showed a polypoid lesion of the villous surface, characterized by lateral
growth and located from the first Houston valve to the rectosigmoid transition. The
histopathology revealed a tubulovillous adenoma with high-grade dysplasia.
An abdominal computed tomography (CT) scan showed parietal, endophytic, asymmetric
and irregular thickening of the upper rectum, extending 112 mm craniocaudally, associated
with a stretched lumen due to the presence of liquid material ([Figure 1]). A tridimensional endorectal ultrasound scan showed an area of mixed echogenicity
occupying approximately 85% of the circumference of the middle and lower rectum. No
growth beyond the mucosa and no spread of metastases to nearby lymph nodes were identified
(uTis uN0). Longitudinally, the lesion measured more than 6 cm, and its lower extremity
was 37 mm above the posterior plane of the puborectal muscle.
Fig. 1 Abdominal CT scan showing a large rectal tumor. (A) Sagittal view. (B) Axial view.
Considering the typical clinical presentation and the findings of acute kidney injury
and electrolyte disturbances associated with the patient's rectal neoplasia, MKWS
was diagnosed. An open low anterior resection of the rectum was performed with a colonic
J-pouch and a diverting loop ileostomy ([Figure 2]). In the postoperative period, he developed a pelvic abscess which had to be drained
through an exploratory laparotomy. Closure of the ileostomy was performed after 18
months, and the patient remained asymptomatic, with normalization of the renal function
and electrolytes, and without signs of tumor recurrence. The histopathological results
revealed an invasive rectal adenocarcinoma with submucosal invasion (pathological
staging pT1pN0).
Fig. 2 Macroscopic appearance of the rectal tumor.
Discussion
The case herein reported draws attention to a rare and potentially deadly condition
that is typically associated with large distal colorectal adenomas, although it may
also occur in the presence of underlying adenocarcinomas.[7]
First described in 1954, MKWS is characterized by a long latent phase of mucous diarrhea
followed by an acute phase of severe electrolyte disturbance, dehydration, and prerenal
acute kidney failure secondary to a hypersecretory adenoma.[8]
Although the exact pathophysiology of the depletion syndrome has not been completely
explored, studies[4]
[7]
[9]
[10] have shown that the large surface area of the tumor probably leads to an increase
in the secretion of fluid, mainly because of the overexpression of prostaglandin E2
(it has been reported that cyclooxygenase 2 [COX-2] expression is significantly higher
in tubulovillous adenomas), which overwhelms the ability of the remaining normal colorectal
mucosa to reabsorb the extra fluid. The distal location of the tumor makes it difficult
for an adequate compensatory reabsorption mechanism to occur, causing watery diarrhea
and volume depletion.
McKittrick-Wheelock syndrome is an uncommon disease that usually affects elderly men
and initially manifests as chronic watery diarrhea, with a median stool frequency
of 10 times within 24 hours. A long duration of symptoms is another characteristic
feature of this syndrome, and patients commonly have symptoms for more than 24 months.[8] With the progression of the electrolytic disorder, which is worsened by fluid loss
through the diarrhea, MKWS can lead to acute kidney failure, severe hyponatremia,
and hypokalemia, and patients usually present with a history of multiple hospital
admissions.[1]
It has been indicated that more severe syndromes can develop with larger and more
distal adenomas, and severe cases may present with complications such as azotemia
and coma. The diagnostic delay can be very harmful, and can provoke chronic renal
failure and/or cardiac arrhythmias.[1]
[2]
McKittrick-Wheelock syndrome is frequently related to a villous adenoma; however,
rarely, it can be secondary to malignant tumors. Malik et al.7 (2016) reviewed the features of 35 cases of MKWS, and reported that 22 had a villous
adenoma, 8 cases had an underlying adenocarcinoma, 1 case had a hyperplastic polyp,
and 1 case had a neuroendocrine tumor of the rectum with liver metastasis.[7]
Important steps in the management include thorough history taking and physical examination.
Because it is a rare condition, there may be a delay in the diagnosis, and other diagnoses
are usually considered first. However, to avoid patients reaching the decompensation
stage, some studies[8]
[9]
[11] suggest that clinicians who identify large tumors on endoscopy should promptly ask
for recent renal function and electrolyte laboratory values and consider this syndrome
as a differential diagnosis.
Recommendations at admission include aggressive fluid resuscitation to match the losses
through the rectum. The early use of flexible sigmoidoscopy may also reveal a definitive
diagnosis in 99% of cases, and a CT of the abdomen and pelvis can be a useful tool
as part of the preoperative workup once renal function has been established. In terms
of medical management, indomethacin and octreotide have been used to reduce fluid
losses while awaiting surgery.[7]
[8]
[12]
Surgical alternatives are most effective when treating the underlying disease, and
an anterior resection is the most commonly used approach. Complete removal of the
lesion prevents the progression of the tumor and resolves the depletion syndrome.
Some authors[13]
[14] have reported successful outcomes obtained with laparoscopic rectal resections and
intersphincteric rectal resections.
Despite its low incidence, especially when associated with malignancy, MKWS is an
important disease of which all clinicians must be aware. It should be included in
the differential diagnoses of chronic diarrhea associated with an electrolytic disorder,
mostly because the correct diagnosis and proper management enables the complete reversal
of symptoms and can be life-saving in most cases.
