Acute Appendicitis in Patients with Acute Leukemia
Article information
Abstract
The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immunesuppression. Leukemic patients, who presented significant RLQ pain, had been indicated for operation, despite having advanced disease or having had received chemotherapy or steroids.
Four adult leukemia patients, complicated by acute appendictis, were reviewed. Two patients were in induction chemotherapy, one receiving salvage chemotheapy due to relapse and the other was in conservative treatment. Two patients were acute myelocytic leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had aleukemic leukemia. All patients underwent appendectomy and recovered without complication. Our experience supports the theory that the surgical management of appendicitis in acute leukemia is the most effective way, in spite of leukopenia.
INTRODUCTION
At present, advanced leukemic chemotherapy and improved general supportive care have led to prolonged survival of patients with acute leukemia. With the prolonged survival, there are increasing complications related to the disease process and to the chemotherapy used to treat the disease1). The prolonged survival has resulted in an increasing frequency of acute abdominal pain such as appendicitis, in conjunction with the tendency of the necrotizing enteropathy of the ileum, appendix or cecum2,3). Diagnosis or surgical consultation may be delayed because typical signs and symptoms of acute intra-abdominal infection sometimes are deficient in leukemic patients4). So the decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes of abdominal pain.
Appendectomy is accepted as the treatment of choice for presumed uncomplicated appendicitis also in patients with acute leukemia5).
We present 4 cases of acute appendicitis in adult leukemia, one of them was periappendiceal abscess.
PATIENTS
There were men and one woman ranging in age from 22 to 71. Two patients were AML, one ALL, and the other had aleukemic leukemia. Two patients developed symptoms during induction chemotherapy, one during salvage chemotherapy, and the other was in conservative treatment because of poor performance status and old age. Preoperative CBC was absolute granulocytopenia in all patients and relative thrombocytopenia, except one. Preoperative and intraoperative infusion of blood and platelets were required for three patients.
Table 1 lists the patients with their signs and symptoms presented at the onset of appendicitis.
Signs and Symptoms and their Relationship to the Status of Leukemia
Laboratory tests, pathologic findings, and chemotherapeutic agents shown in Table 2.
WBC counts, Pathologic findings and Chemotherapeutic agents before Onset of Symptoms
One of the four patients received prednisolone (12 mg/day) together at the onset of appendicitis, and one received steroids in previous chemotherapy.
CASE REPORTS
Case 1
The patient, a twenty-two-old woman with acute lymphocytic leukemia, had induction chemotherapy, with intravenous vincristine (2mg, weekly), adriamycin (45mg/M2×3days) and oral prednisolone (60mg/M2, daily). A week later, fever and right lower quadrant pain developed, but she denied diarrhea, nausea and vomiting and there was no rebound tenderness. Radiography of the small bowel revealed no pathological findings. On complete blood count, leukocyte count was 1500/mm3, with 29% of neutrophils, 62% of lymphocytes %, 7% of monocytes. The hemoglobin was 7.8 mg/dl, hematocrit 22.8%, platelet 68,000/mm3. Liver function test (SGOT and SGPT) was three to five times higher than normal and hepatitis B virus surface antigen (HBsAg) was negative. Blood cultures were negative at three times. Bone marrow aspiration revealed a remitted state of ALL.
As appendicitis was suspected, explosive laparatomy was done immediately. The appendix was perforated and had abscess formation. Biopsy results showed acute suppurative inflammation with periappendiceal abscess formation, but there was no evidence of leukemic involvement. After surgery, the patient made an eventful recovery.
Case 2
The patient, a thirty-three-year-old man, who was diagnosed as hybrid leukemia which further defined AML, had induction chemotherapy, intravenously vincristine (2mg, weekly), adriamycin (45mg/M2×3days), L-asparginase (6000 IU/M2×12days) and oral prednisolone (60 mg/M2×four weeks). On the fifth day, sudden spiking fever, RLQ pain and tenderness developed. On complete blood count, leukocyte count was 700/mm3, 83% of lymphocytes, 10% of neutrophils, 7% of band forms.
Operation was performed and biopsy results were acute gangreous inflammation and leukemic infiltration of the appendix.
Case 3
The patient, a twenty-nine-year-old man with acute myelogenous leukemia (M1), admitted for salvage chemotherapy due to relapse, received scheduled mitoxantrone (10mg/M2×5 days) and etoposide (100mg/M2×5 days). On the twelfth day, he complained of RLQ pain with fever, RLQ rebound and positive Rovsing sign. On complete blood count, leukocyte count was 700/mm3, with 98% of lymphocytes, 2% of monocytes. Hemoglobin was 10.0mg/dl, hematocrit 27.5%, platelet 47,000/mm3. Ultrasonographic findings were regional ileus in RLQ, but not visualized appendix. Operation was performed immediately and biopsy result was acute inflammatory change. No surgical complications were noted.
Case 4
The patient, a seventy-one-year-old man with aleukemic leukemia, had not received chemotherapy due to poor performance status and old age, and supportive care was done for a year. He complained of sudden onset of RLQ pain and tenderness and was operated on under the diagnosis of acute appendicitis. The biopsy resulted in acute suppurative inflammation.
DISCUSSION
Now that aggressive chemotherapy and advanced general supportive care improve survival, more patients with leukemia are likely to present intra-abdominal disease, not necessarily related to the underlying hematologic malignancy, which may require surgical intervention. The disease is more commonly reported in children, but is being increasingly reported in adult patients1).
It is thought that chemotherapy may damage the gastrointestinal tract by destroying the rapidly dividing mucosal cells which, when coupled with neutropenia, allows bacterial invasion of the bowel wall. The invasive infection leads to necrosis of various layers of the bowel wall. The process has a predilection for the terminal ileum and cecum, but any segment of the bowel can be involved6,7).
Intra-abdominal disease in leukemic patients seems to be most frequenlty associated with the use of cytosine arabinoside and anthracycline8), although it has been reported following a variety of other chemotherapeutic regimens. Our patients had received adriamycin, etoposide, mitoxantrone and vincristine.
The diagnosis of acute appendictis may also be complicated by chemotherapeutic agents, whose effects may mask the signs and symptoms or whose toxic effect may mimic the acute surgical abdomen9,10), and differential diagnosis is so difficult that a necrotizing enteropathy of the ileocecal lesion not limited to the appendix may occur. Diagnosis of neutropenic colitis, termed typhiltis, without pathologic examination is speculative and the differentiation from appendicitis is unclear. Typhlitis and appendicitis appear to be equally common in young leukemic patients with right lower quadrant pain and signs of peritoneal irritation. The preoperative differentiation between these two problems is difficult and one cannot be secure in recommending nonoperative treatment. The role of surgical management in appendicitis is clear, the role of surgical therapy in typhilitis is less well defined11).
Several investigators10–12) have pointed out the difficulty in diagnosing intra-abdominal catastrophies. Signs suggesting an acute abdomen, such as abdominal pain, nausea, vomiting and melena, are frequent in leukemic patients and are also frequent symptoms of antileukemic drug foxicity. In addition, the frequent use of steroids may mask serious surgical complications. All of our patients had RLQ pain and tenderness, but had not peritoneal irritation signs and symptoms, for example, rebound tenderness, nausea and vomiting, excepts for one. We think that the typical signs and symptoms of acute appendicitis are not present due to severe neutropenia.
Preoperative barium enema study may be helpful in differentiating appendicitis from other entities but any rectal manipulation such as colonoscopy or contrast enemas are contra-indicated in severely neutropenic patient13). Alexander et al14) reported characteristic echogenic thickening of the bowel mucosa on ultrasonography to be helpful in the diagnosis of the disease process. We performed ultrasonography in two cases, but did not find abnomalities in the appendix.
Zeulzer and Flatz12) indicated that the succcess of surgical procedures in patients with acute leukemia and surgical complications depends on the presence of hematological remission.
Appendectomy is also accepted as the treatment of choice for presumed uncomplicated appendicitis in patients with acute leukemia, but the management of perforative appendicitis with abscess formation remains controversial4). The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Vaughan et al15) advocated close surveillance, early surgical consultation and early operative intervention in patients with acute leukemia and intra-abdominal complications, even in the presence of granulocytopenia and thrombocytopenia. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immuno-suppression4). This principle may be correct as a general rule, but is not always true in individual instances. Leukemic patients who presented significant right lower quadrant symptoms and signs of peritoneal irritation had sufficient indications for operation, despite having advanced disease or having received chemotherapy or steroids9). Our patients underwent appendectomy as soon as the diagnosis was suspected, although they had not peritoneal irritation signs. When needed, infusions of red blood cells, platelets and antibiotics were given, but granulocytes infusion was not given. The role of broad spectrum antibiotics has contributed significantly to the support of the patient during the postoperative period until marrow recovery occurs, and is probably the reason for the increasing proportion of patients who survive and recover from surgery16).
Although occurring infrequently, appendicitis is associated with a high mortality rate in leukemic patients17). In a recent review of the results of the intra-abdominal operations in cases of acute and chronic leukemia, the overall surgical mortality was 29%, and the difference between mortality associated with emergency procedures and with elective operations (55% vs 8%) was statistically significant15). All of our patients were operated on as an emergency procedure, and all patients recovered without considerable complication.
CONCLUSION
In this review, four patients with acute leukemia developed acute appendicitis, and appendectomy was performed on three of them and appendectomy and removal of periappendiceal abscess was performed on one. Although the symptoms and signs are mild and not typical, early diagnosis and surgical intervention is the effectively way of dealing with acute appendicitis in acute leukemia.
Case 1. Appendix biopsy: Infiltration of mononuclear cells, lymphocytes and monocytes in the subserosal and mucular layer, suggesting reactive appendicitis (A: H and E, Original magnification, ×100, B: H and E, Original Magnification, ×400).
Case 2. Appendix biopsy: Acute gangrenous inflammation and leukemic infiltration with immature leukemic cells (A: H and E, Original Magnification, ×100, B: H and E, Original Magnification, ×400).