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 cecum^2,3). 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.

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.

Laboratory tests, pathologic findings, and chemotherapeutic agents shown in Table 2.

One of the four patients received prednisolone (12 mg/day) together at the onset of appendicitis, and one received steroids in previous chemotherapy.

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 involved^6,7).

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 abdomen^9,10), 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 investigators^10–12) 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.

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.