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PubMed1987

Right lower quadrant pain in young patients with leukemia. A surgical perspective.

A retrospective review of cecal and appendiceal complications occurring in young patients with acute leukemia since 1969 was performed. The objective of this study was to determine the relative incidence of appendicitis and typhlitis among patients with acute leukemia who had operation or autopsy in this institution as well as to determine the risks of operative intervention. Fifteen patients with these complications were identified among the 400 patients with acute leukemia seen during this time period. Signs and symptoms of an acute abdomen were present despite immunosuppression. The incidence of sepsis at the time of presentation was 53%. Preoperative risk factors identified most frequently were coagulopathy and organ failure resulting from sepsis. Postoperative morbidity (25%) and mortality rates (8%) were related to the development of infectious complications. Appendicitis occurred in eight of the 15 patients studied, whereas typhlitis or its complications was found in seven patients. No preoperative factors could be found to differentiate typhlitis from appendicitis on clinical examination. It is suggested that operation can be safely performed in neutropenic patients who have acute right lower quadrant pain and signs of peritoneal irritation and may be the only effective way of differentiating appendicitis from typhlitis.

Abdomen, Acute↗

PubMedDate not supplied

Sometimes it really is appendicitis: case of a CML patient with acute appendicitis.

We report on the case of a 24-year-old white man with a history of chronic leukemia treated with unrelated bone marrow transplantation and chemotherapy who was correctly diagnosed with appendicitis rather than typhlitis. The approach to diagnosing an acute abdomen in the leukemic patient is discussed, with particular focus on appendicitis vs. typhlitis. A focused CT scan proved to be instrumental in making the correct diagnosis of appendicitis in our patient. The literature on this topic for the past 30 years is reviewed. The purpose of our report is to demonstrate that despite the recent trend toward diagnosing RLQ pain as typhlitis which requires medical management, there are still instances where it 'really is' appendicitis. Appendicitis, therefore, must always be ruled out in the leukemic patient.

Acute Disease↗

PubMed1978

Escherichia coli and diarrhoea in the rabbit.

An outbreak of severe diarrhoea and death in young rabbits was associated with many nonenterotoxigenic Escherichia coli in the caecum. The severe clinical, pathological and bacteriological features of the diesase, acute diarrhoea associated with typhlitis and many E. coli in the caecum, could be reproduced either by the intraintestinal inoculation of many bacteria recovered aerobically or anaerobically from the caecum of these rabbits or by the intestinal inoculation of large numbers of a serogroup of E. coli, 0153, recovered from the caecum. Further experiments showed that this serogroup of E. coli, as well as a nonenteropathogenic serotype recovered from human faeces, would cause typhlitis and diarrhoea if inoculated in large numbers into the jejunum; pathological changes also were seen in the liver and kidney. Similar changes also could be induced by intravenous inoculation of a freeze-thaw (endotoxic) extract prepared from these strains. Any factor that allows rapid multiplication of E. coli in the rabbit caecum may be followed by absorption of endotoxin and subsequent typhlitis and so metimes by severe diarrhoea; this effect is seen in some field cases of diarrhoea in the rabbit.

Animals↗

PubMed1988

[Necrotizing enteritis during the therapeutic induction phase in leukemia. Value of surgical treatment].

A case of typhlitis in a 3,5 year old girl, during induction therapy for acute lymphoblastic leukemia is reported. This typhlitis, or necrotizing enterocolitis involving the coecum and right colon resulted in stercoral peritonitis during the neutropenic phase. After surgery, the patient had a favorable outcome with complete recovery. Knowledge about this uncommon but severe complication of hemopathies leads to follow clinical, microbiologic and radiologic rules of prophylaxis and screening. Typhlitis requires early treatment by supportive care and surgical cure if necessary.

Child, Preschool↗

PubMed1988

The pathology of chronic Drechslera campanulata toxicosis in inbred rats.

Cultures on autoclaved maize of the phytopathogenic fungus, Drechslera campanulata, were incorporated into diets and fed to male inbred BDIX rats. In a pilot trial, a diet containing 30% D. campanulata culture material killed 5 out of 5 rats in 15-25 days. Lesions included gastric corpus erosions, gastrorrhagia and ulcerative typhlitis. Diets containing 5% or 10% culture material induced erosive to ulcerative typhlitis and oedema and hyperplasia of the ileocaecal lymph nodes in 40 out of 40 rats. Other changes included: mass loss; normocytic, hyperchromic anaemia; leukocytosis with neutrophilia; reductions in plasma proteins, creatinine, calcium and cholesterol; elevated serum enzymes; hepatosis, nephrosis and mycoplasma-like interstitial pneumonia. No lesions were present in control rats, and their profiles were normal. Ulcerative typhlitis induced by D. campanulata in rats resembles that seen in chronic piperonyl butoxide intoxication as well as that due to single treatments of indomethacid, although small intestinal ulcers are more frequent in the latter. Overgrowth of intestinal flora may be involved in ulcer pathogenesis. The pathology of drechsleratoxicosis in rats is compared to that in sheep and goats where necrotic lesions in the forestomach and, to a lesser extent, in the caecum are characteristic findings.

Animals↗

PubMed1992

Acute appendicitis in children with leukemia and other malignancies: still a diagnostic dilemma.

Of 6,099 children treated for malignancy, 16 (ages 3.5 to 18 years) developed acute appendicitis between 1962 and 1989. Fourteen had leukemia (ALL 10, AML 4). One each had rhabdomyosarcoma and Ewing's sarcoma. Active malignancy at diagnosis was noted in 10, 4 of whom had severe neutropenia (absolute neutrophil count less than 500/mm3). Of all the leukemics (2,794/6,099), abdominal pain during induction was a frequent complaint. The incidence of appendicitis, however, was low (0.5%). Nine of the 16 patients presented classically, facilitating prompt diagnosis and treatment. Six diagnoses were delayed. Three of these patients presented atypically with vague, nonlocalized pain, abdominal distention, lack of abdominal guarding, fever, dehydration, diarrhea, and unusual symptoms such as upper gastrointestinal bleeding. In each of these 6 patients the appendix was ruptured. Delays led to complications and deaths. Three patients required perioperative transfusions to treat excessive bleeding and two patients with ruptured appendicitis developed wound abscesses. Two patients died; in one, ruptured appendix was diagnosed only at autopsy. The other patient died of uncontrolled sepsis. Typhlitis occurring during induction chemotherapy may present similarly and is the main differential diagnosis. Typhlitis will usually improve with medical treatment alone. Nausea and vomiting (13/16), right lower quadrant pain (13/16), guarding (14/16), tachycardia (12/16), fever (10/16), and rebound tenderness (10/16) were the most frequent signs and symptoms of appendicitis. Persistent localized abdominal pain and guarding, lack of improvement with medical treatment, clinical deterioration, and the development of a mass were our indications for laparotomy. Despite major improvements in therapy, there is still a 37.5% error rate in our ability to accurately diagnose appendicitis in pediatric cancer patients.

Acute Disease↗

PubMed2005

Salmonella enterica serovar Typhimurium pathogenicity island 2 is necessary for complete virulence in a mouse model of infectious enterocolitis.

Salmonella species cause a wide range of disease in multiple hosts. Salmonella enterica serovar Typhimurium causes self-limited intestinal disease in humans and systemic typhoid-like illness in susceptible mice. The prevailing dogma in murine S. enterica serovar Typhimurium pathogenesis is that distinct virulence mechanisms-Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2)-perform distinct roles in pathogenesis, the former being important for invasion and intestinal disease and the latter important for intracellular survival and systemic persistence and disease. Although evidence from bovine infections has suggested that SPI2 has a role in ileal disease, there is no evidence that SPI2 is important for inflammation in a disease that more closely recapitulates human colitis. Using S. enterica serovar Typhimurium strains that lack functional type III secretion systems, we demonstrate that SPI2 is essential for complete virulence in murine infectious enterocolitis. Using a recently characterized murine model (M. Barthel,S. Hapfelmeier, L. Quintanilla-Martinez, M. Kremer, M. Rohde, M. Hogardt, K. Pfeffer, H. Russmann, and W. D. Hardt, Infect. Immun. 71:2839-2858, 2003), we demonstrate that SPI1 mutants are unable to cause intestinal disease 48 h after infection and that SPI2-deficient bacteria also cause significantly attenuated typhlitis. We show that at the peak of inflammation in the cecum, SPI2 mutants induce diminished intercellular adhesion molecule 1 expression and neutrophil recruitment but that wild-type and mutant Salmonella are similarly distributed in the lumen of the infected organ. Finally, we demonstrate that attenuation of intestinal inflammation is accompanied by resolution of typhlitis in the mutant, but not wild-type, infections. Collectively, these results indicate that SPI2 is needed for enterocolitis, as well as for systemic disease.

Animals↗

PubMed2005

Colonic rupture in a patient on combination chemotherapy for metastasized carcinoma of the esophagogastric junction. Case report and review of the literature.

BACKGROUND: Cecal perforation due to neutropenic colitis is a known and described side effect of many chemotherapy regimens. We present a case of a patient with gastric adenocarcinoma who developed spontaneous cecal perforation during chemotherapy without the classic pattern of typhlitis. CASE REPORT: A 58-year-old woman was on chemotherapy for an adenocarcinoma of the gastric junction, when she developed a cecal perforation. There was neither evidence for leucopenia nor for typhlitis. Laparotomy was performed and cecostomy was established using the perforated bowel. Postoperative course was uneventful. The patient died from tumor progression 8 months after the diagnosis was made. CONCLUSION: There is no evidence for a connection between this event and chemotherapy treatment but neither can it be excluded. Even if unusual, colon toxicity could be a potential life-threatening complication associated with more drugs than usually thought.

Adenocarcinoma↗

PubMed1987

Right lower quadrant pain in the immunocompromised patient: CT findings in 10 cases.

Ten immunosuppressed patients with right lower quadrant pain were examined by CT. Underlying conditions responsible for immunosuppression included acute myelogenous leukemia (n = 2), acute lymphocytic leukemia (n = 2), aplastic anemia (n = 2), AIDS (n = 3), and cystic fibrosis combined with prolonged steroid therapy for bronchospasm (n = 1). CT suggested the diagnosis of typhlitis (n = 7), intramural hemorrhage (n = 1), ileal perforation (n = 1), and appendiceal abscess (n = 1). The diagnosis of typhlitis was established by clinical evaluation in five patients, by colonoscopy in one patient, and by autopsy in another patient. The single cases of intestinal hemorrhage, ileal perforation, and appendiceal abscess were confirmed by exploratory laparotomy. It is difficult to make an accurate diagnosis of acute abdominal conditions in the immunosuppressed patient. Symptoms and physical findings are often suppressed as a result of steroid or immunosuppressive therapy. CT, being noninvasive, is useful in the evaluation of persistent right lower quadrant pain in the immunocompromised patient.

Adolescent↗

PubMed1984

Endogenous development and pathogenicity of Eimeria angusta in the ruffed grouse, Bonasa umbellus.

Oocysts of Eimeria angusta were recovered from the cecum of a captive ruffed grouse which died of coccidial typhlitis. Five experimental passages were made in grouse over a 2-yr period. Prepatent period was 6.5-7.0 days; sporulation time at 22 C was 54-60 hr. Endogenous stages were not found in grouse killed 1 and 2 days after inoculation (DAI). A few immature schizonts were in cecal epithelium 4 DAI. Developing and mature schizonts, and undifferentiated gamonts were in cecal epithelium 5 DAI. Developing micro- and macrogamonts, but no oocysts, were present 6.5 DAI. Fibrinohemorrhagic typhlitis, associated with large numbers of gamonts and oocysts in the epithelium, was found 9 DAI. Cecal glands were hypertrophic and there was a heavy mixed inflammatory cell reaction. Diarrhea, depression and reduced feed intake occurred 7-10 DAI with most severe signs and greatest oocyst passage 8 or 9 DAI. Most infected birds lost weight 5-8 or 9 DAI, but none died.

Animals↗

PubMed1978

Equine myositis and septicemia caused by Acinetobacter calcoaceticus infection.

Myositis and septicemia caused by Acinetobacter calcoaceticus were diagnosed in a mare. The infection was characterized clinically by ventral swelling and edema, diarrhea, listlessness, and rectal temperature of 39.4 C. The mare was treated symptomatically for 2 days but died on the 3rd day. Conditions seen at necropsy were myositis, enteritis, typhlitis, colitis, and hepatitis. Lymph nodes were moderately enlarged throughout the body. Gross lesions in musculature were edema, scarring, petechiae, and an occasional exxhymosis. The enteritis was catarrhal, with excessive mucus and moderate hyperemia. The typhlitis and colitis were hemorrhagic. The swollen liver had a diffuse mottled pale and red pattern. Microscopic lesions in skeletal muscle consisted of petechiation, necrosis, scarring, and edema. Cardiac muscle was also scarred and necrotic, but edema was not prominent. Periacinal necrosis was found in the liver. Acinetobacter calcoaceticus was isolated from myocardium and liver.

Acinetobacter Infections↗

PubMed1989

Evaluation of right hemicolectomy for unexpected cecal mass.

Ileocecal mass is occasionally encountered unexpectedly by surgeons operating for presumed appendicitis. A five-year retrospective study was performed to review the management of this problem. Thirteen patients were identified who had had right hemicolectomy performed for unexpected mass in which neoplasm, diverticular disease, or inflammatory bowel disease could not be differentiated from severe appendicitis at laparotomy. Seven patients (group 1) had a final pathologic diagnosis of appendiceal phlegmon. The other patients (group 2) had Crohn's disease, typhlitis, or neoplasm. Right hemicolectomy was performed with a morbidity of 7% and mortality of 7% in all patients. This procedure is acceptable for unexpected cecal mass.

Appendectomy↗

PubMed1997

Abdominal ultrasound findings during and after treatment of childhood acute lymphoblastic leukemia.

BACKGROUND: The treatment of acute leukemia in childhood has been increasingly successful. Concurrently, severe leukemia-related gastrointestinal complications have become more common. METHODS: We evaluated the findings of the abdominal ultrasound (US) examinations of 52 children with acute lymphoblastic leukemia (ALL) who had severe clinical symptoms indicating infection or abdominal complication during chemotherapy treatment or after the cessation of such treatment and assessed the impact of these findings on patients' subsequent treatment and survival. RESULTS: Our study presents ten cases of typhlitis with a prevalence of 9%, all of which were rapidly diagnosed by US and had a favourable outcome. We also found focal intra-abdominal parenchymal lesions in six children, five of them due to fungal infection and one due to leukemic infiltration. Several other intra-abdominal pathologies significant for the patients' treatment are also reported. DISCUSSION: We believe that abdominal US is a useful, rapid, safe, and accurate imaging method for children with ALL suspected to suffer from leukemia- or chemotherapy-related gastrointestinal complications. More invasive imaging methods are seldom needed. CONCLUSIONS: According to our results, abdominal US gives the necessary information in most of the cases and provides prompt diagnosis, which may prevent possible fatal complications.

Abdomen↗

PubMed1995

Safety and efficacy of l-leucovorin rescue following high-dose methotrexate for osteosarcoma.

High-dose methotrexate with leucovorin rescue (HDMTX-LCV) is an important component of regimens used in the treatment of osteosarcoma. As of this writing the commercially available form of leucovorin is a racemic mixture of d- and l-diastereoisomers; the l-isomer is the active component. This study describes the efficacy and safety of l-leucovorin in HDMTX-LCV regimens. Fifteen patients with osteosarcoma who were enrolled into or treated according to Pediatric Oncology Group protocols 8759 and 8651 received l-leucovorin (7.5 mg every 6 hours) in place of d,l-leucovorin following high-dose methotrexate. Safety data were collected for 1 week after each course or until any toxicities resolved. The mean number of l-leucovorin doses per course was 16.2 and the mean total dose per course was 126 mg. Adverse experiences were generally mild or moderate and occurred in 54 (60%) of 90 courses of l-leucovorin therapy. One l-leucovorin patients, who had inadequate methotrexate rescue, developed severe typhlitis. There were no instances of severe, acute methotrexate toxicity. Myelosuppression was seen but, in general, was not severe. These results support the conclusion that l-leucovorin effectively rescues patients from the toxicity of high-dose methotrexate.

Adolescent↗

PubMed1986

Management of the ileocecal syndrome. Neutropenic enterocolitis.

Neutropenic enterocolitis, also known as typhlitis or ileocecal syndrome, is a recognized complication of the treatment of hematologic malignancies and usually is fatal. The pathologic findings consist of bowel-wall ulcerations and necrosis with bacterial or fungal invasion. These findings are usually limited to the ileum, cecum, ascending colon, and appendix. The syndrome occurs in a select patient population who generally have 1) a hematologic malignancy, 2) neutropenia, 3) thrombocytopenia, 4) a recent course of chemotherapy, and 5) a recent course of antibiotics. This syndrome also can arise spontaneously in patients with aplastic anemia or cyclic neutropenia. The clinical presentation consists of a high fever and right-sided abdominal pain with evidence of peritoneal irritation. Recommended therapy is right hemicolectomy.

Child↗

PubMed2001

Effect of low and high doses of Salmonella enteritidis PT4 on experimentally infected chicks.

Chicks (1-d-old, three groups, each containing 50 chicks) were inoculated with 2 x 10(2) and 2 x 10(8) CFU of Salmonella enteritidis; the third group were kept as uninoculated control. Five birds from each group were euthanized at intervals from 6 h to 4 weeks post-inoculation (pi). In the low-dose group S. enteritidis was isolated from 60% cecal samples at 18 h pi, and from 20% of livers at 3 d pi. Individual variation in the frequency of S. enteritidis recovery was observed in this group. The clearance of salmonella from the organs was faster in the low-dose group, and salmonella was not isolated from the liver and cecum at 21 and at 27 d pi, respectively. However, in the high-dose group, S. enteritidis was isolated from all ceca and 80% of liver 6 h pi, and salmonella was detected in the cecum and liver throughout the experiment. Serous typhlitis and unabsorbed yolk sac were the most prevalent lesions in both groups. Granulomatous nodules in the cecum were found occasionally in some cases in both inoculated groups, which can play a role as reservoirs in carrier chicks.

Animals↗

PubMed2004

Feasibility and pharmacokinetic study of infusional dexrazoxane and dose-intensive doxorubicin administered concurrently over 96 h for the treatment of advanced malignancies.

PURPOSE: Dexrazoxane administration prior to short infusion doxorubicin prevents anthracycline-related heart damage. Since delivery of doxorubicin by 96-h continuous intravenous infusion also reduces cardiac injury, we studied delivering dexrazoxane and doxorubicin concomitantly by prolonged intravenous infusion. METHODS: Patients with advanced malignancies received tandem cycles of concurrent 96-h infusions of dexrazoxane 500 mg/m2 and doxorubicin 165 mg/m2, and 24 h after completion of chemotherapy, granulocyte-colony stimulating factor (5 microg/kg) and oral levofloxacin (500 mg) were administered daily until the white blood cell count reached 10,000 microl(-1). Plasma samples were analyzed for dexrazoxane and doxorubicin concentrations. RESULTS: Ten patients were enrolled; eight patients had measurable disease. Two partial responses were observed in patients with soft-tissue sarcoma. The median number of days of granulocytopenia (<500 microl(-1)) was nine and of platelet count <20,000 microl(-1) was seven. Six patients received a single cycle because of progression (one), stable disease (four), or reversible, asymptomatic 10% decrease in cardiac ejection fraction (two). Principal grade 3/4 toxicities included hypotension (two), anorexia (four), stomatitis (four), typhlitis (two), and febrile neutropenia (seven), with documented infection (three). One death from neutropenic sepsis occurred. Dexrazoxane levels ranged from 1270 to 2800 nM, and doxorubicin levels ranged from 59.1 to 106.9 nM. CONCLUSIONS: These results suggest that tandem cycles of concurrent 96-h infusions of dexrazoxane and high-dose doxorubicin can be administered with minimal cardiac toxicity, and have activity in patients with recurrent sarcomas. However, significant non-cardiac toxicities indicate that the cardiac sparing potential of this approach would be maximized at lower dose levels of doxorubicin.

Adult↗

PubMed2005

Phase I study of the combination of topotecan and irinotecan in children with refractory solid tumors.

PURPOSE: We have shown in xenograft studies that the antitumor activities of topotecan and irinotecan are highly schedule- and dose-dependent, with a high frequency of response at low, protracted dose schedules. Preclinical and clinical data suggest that topotecan and irinotecan have different antitumor activities and mechanisms of resistance, and non-overlapping toxicities, providing a rationale for their combination. Combining both agents may increase the amount of camptothecin delivered to the tumor, without additive toxicity. METHODS: We conducted a phase I study in children with refractory solid tumors to determine the maximum tolerated dose (MTD) of irinotecan when administered with a targeted systemic exposure (TSE) of topotecan and to define the dose-limiting toxicity (DLT) of this combination. Irinotecan was administered IV over 60 min followed by topotecan over 30 min daily for 5 days for two consecutive weeks. We initially fixed the topotecan-TSE to 80+/-10 ng*h/ml and investigated the ability to escalate irinotecan (starting dose 16 mg/m2/d). Topotecan and irinotecan pharmacokinetics were determined. RESULTS: Eleven patients (median age 10 years) were enrolled. Owing to DLT, irinotecan was de-escalated to 12 (level -1; n = 3) and 9 (level -2; n = 3) mg/m2/day, and topotecan-TSE was reduced to 60+/-10 ng*h/ml (level -3; n = 2). DLTs were neutropenia (n = 8), typhlitis (n = 5), and skin rash (n = 1). MTD could not be reached. Median (range) irinotecan and topotecan lactone systemic clearances were 50.3 (16.6-76.2) l/h/m2 and 27.6 (14.7-55.9) l/h/m2, respectively. The pharmacokinetics profile of each agent was similar to that seen in previous single agent studies. One patient with neuroblastoma and one with rhabdomyosarcoma had a partial and a complete response, respectively. CONCLUSION: Despite promising antitumor activity, the combination of topotecan and irinotecan given on a protracted schedule does not warrant further development in children due to unacceptable toxicity.

Adolescent↗