Case report of perforation of an ileal neobladder after treatment of rectal cancer with bevacizumab and comment on mechanisms of intestinal perforation associated with bevacizumab.

WHAT IS KNOWN AND OBJECTIVE: Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) that has activity in several types of malignancies. One of the uncommon adverse effects is spontaneous bowel perforation. In patients who have undergone cystectomy, a loop of small bowel is often used to create a neobladder. We report the first case of ileal neobladder perforation associated with bevacizumab. CASE SUMMARY: We describe a 38-year-old male with metastatic rectal cancer who was receiving treatment with bevacizumab when he presented with acute abdominal pain. Radiographic evaluation revealed perforation of his ileal neobladder. WHAT IS NEW AND CONCLUSION: We describe the first report of ileal neobladder perforation in the setting of bevacizumab therapy. Although bowel perforation is a well-documented adverse effect of bevacizumab, this case suggests that displaced bowel tissue is still susceptible to these effects. We comment on what is known about bevacizumab-associated intestinal perforation.

Merkel cell carcinoma: review of 22 cases with surgical, pathologic, and therapeutic considerations.

BACKGROUND: Merkel cell carcinoma is a primary small blue cell tumor of the skin with a proclivity to metastasize. Surgery and radiation therapy have defined roles in the primary treatment of Merkel cell carcinoma. Systemic chemotherapy can produce good response rates but does not have a primary role in the management of nondisseminated Merkel cell carcinoma patients. METHODS: Twenty-two patients were identified over the last 10 years in a retrospective analysis of tumor registries from the 6 hospitals of the ScrippsHealth facilities. Hospital and clinic charts as well as pathology specimens were reviewed. RESULTS: Eight patients underwent Mohs' surgery with permanent tissue technique. None of these patients had a subsequent local recurrence. Six patients received adjuvant radiation therapy, only one of whom developed a disease recurrence within a radiation port. Systemic chemotherapy was given to seven patients. One patient did not accept further treatment after a punch biopsy. CONCLUSIONS: Merkel cell carcinoma is an aggressive primary neoplasm of the skin, the histologic diagnosis of which can be difficult. Mohs' surgical technique combined with radiation therapy provides excellent local control. Systemic treatment is associated with high response rates, but to the authors' knowledge durable responses are uncommon.

Physicians and gumshoes: prescription for bad medicine, or the man who didn't like doctors.

Raymond Chandler, the creator of legendary detective Philip Marlowe and the recipient of increasing literary admiration over the past 40 years, used numerous physicians as minor characters in his novels and short stories. The presence of physicians as minor characters in Chandler's work, though unnoticed by previous critics, is illustrative both of the writer's personal antipathy towards medical doctors and larger societal forces which left medical charlatans free to open "clinics." Chandler's own chronic health problems and those of his wife Cissy may have contributed to the writer's negative attitude toward medicine and health care, though little is known of Chandler's personal interactions with physicians prior to his death in 1959.

2-chlorodeoxyadenosine administration to patients with the myeloid blast phase of chronic myelogenous leukemia.

Three patients with chronic myelogenous leukemia (CML) in myeloid blast phase received 2-chlorodeoxyadenosine (2-CdA) at 0.7 mg/kg per course over 5 days every 2-4 weeks for 7, 2 and 5 courses. Each patient had a decrement in their white blood cell count, and in the absolute number and percentage of circulating immature cells following 2-CdA administration. Two patients achieved hematologic responses of 14 and 3 months and survived 19 and 6 months, respectively, while the non-responder died 2 months later. 2-CdA-induced anemia and thrombocytopenia, generally mild and reversible, were observed in all patients. Given the dismal results and considerable toxicities that follow multiagent induction chemotherapy for CML in myeloid blast phase, 2-CdA therapy may represent a reasonable therapeutic alternative, although confirmation is required in larger numbers of patients.

Prophylactic antibiotics eliminate bacteremia and allow safe outpatient management following high-dose chemotherapy and autologous stem cell rescue.

This study examines the effectiveness of prophylactic ciprofloxacin and rifampin following high-dose chemotherapy and autologous stem cell rescue (HDC/ ASCR). Specific endpoints included the incidence of fever, clinically documented infection, bacteremia, and readmission rates from an outpatient bone marrow transplant setting following infection or fever. A group of 97 patients receiving 134 cycles of HDC/ASCR were studied. Patients were given ciprofloxacin 750 mg p.o. twice daily and rifampin 300 mg p.o. twice daily beginning on the day of stem cell reinfusion (24-48 h after completion of high-dose chemotherapy). Most patients were either discharged to an outpatient setting following completion of their chemotherapy or received all of their chemotherapy in an outpatient setting. Febrile neutropenia was treated with empirical antibiotics in an outpatient setting unless it was complicated by hypotension, renal failure, severe mucositis or other problems. The median duration of neutropenia (absolute neutrophil count below 500/mm3) was 7 days. Neutropenic fever occurred in 62% of patients but clinically documented bacterial infection occurred in only 2 (1.5%) patients during their neutropenic period. No bacteremia was noted. Readmission to the hospital following fever or infection occurred in 26% of patients maintained in the outpatient setting. There were no deaths from a bacterial infection in this study although 1 patient (0.7%) died from aspergillosis. Prophylactic ciprofloxacin and rifampin is a well-tolerated and highly effective combination that effectively decreases the risk of both gram-positive and gram-negative bacterial infection following HDC/ASCR. It facilitates outpatient management of myelosuppressed patients receiving autologous stem cell rescue.

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy.

PURPOSE: This study was designed to evaluate the absolute bioavailability (F value) of 2-chlorodeoxyadenosine (cladribine; 2-CdA) after multiple oral administrations, and the intersubject variability after oral and 2-hour intravenous (IV) administration schedules in patients with malignancy. PATIENTS AND METHODS: Patients with advanced malignancies were eligible. There were two treatment cycles; during cycle 1, patients received 2-CdA solution at 0.28 mg/kg/d orally under fasting conditions for 5 consecutive days concomitantly with omeprazole, and 4 weeks later during cycle 2 patients received 2-CdA as a 2-hour IV infusion of 0.14 mg/kg/d for 5 consecutive days. Serial blood samples for 2-CdA plasma levels were obtained after drug administrations on days 1 and 5 during each treatment cycle. RESULTS: Ten patients completed cycles 1 and 2. The F value of oral 2-CdA measured on days 1 and 5 was 37.2% and 36.7%, respectively. For both oral and IV multiple administrations, there was no significant accumulation in maximum concentration (Cmax), and the intersubject variabilities (coefficient of variation [CV], approximately 40%) in Cmax and area under the concentration-time curve from 0 to 24 hours [AUC(0-24)] values were comparable for both routes on days 1 and 5. A three-compartment open model was applied to the plasma concentration data after oral and IV administrations and resulted in good agreement between observed and simulated concentration-time profiles. Neutropenia was the principal adverse event observed when 2-CdA was administered orally and IV. CONCLUSION: The F value of 2-CdA after oral administration was approximately 37% and there were no cumulative differences in bioavailability observed on multiple dosing of the drug. The absorption and disposition characteristics of oral 2-CdA were linear and predictable with this dosing regimen.

Acute myelogenous leukemia presenting with bulky lymphadenopathy. Case report and literature review.

We report a patient with acute myeloid leukemia (AML) presenting with generalized lymphadenopathy, clinically stimulating aggressive non-Hodgkin's lymphoma. This patient presented with anemia and bulky lymphadenopathy in the oropharyngeal (Waldeyer's ring), submandibular, supraclavicular and inguinal nodal regions. Lymph node biopsy was initially suggestive of a T-cell lymphoblastic lymphoma, based on morphologic features together with positive immunohistochemical staining for CD7 and CD43 (Leu 22). Definitive diagnosis of AML was established when a more detailed immunophenotypic analysis showed expression of the myeloid markers CD13 and CD33, and by the demonstration of rare Auer rods and positive peroxidase staining in bone marrow blast cells. Although this is a rare presentation, AML must always be considered in the clinical and pathologic differential diagnosis of aggressive non-Hodgkin's lymphoma.

Two unusual presentations of müllerian adenosarcoma: case reports, literature review, and treatment considerations.

Müllerian adenosarcomas of the uterus usually present as pedunculated endometrial masses in postmenopausal women with vaginal bleeding. Extraendometrial variants (originating in the ovary, adnexa, or myometrium) are much less common, and they tend to present at a more advanced stage due to their location. The sarcomatous portion of müllerian adenosarcoma can vary from low grade to very high grade and the clinical behavior of the tumors can be indolent or aggressive. We present two cases, one of which originated in the adnexa and the other in an apparent focus of uterine adenomyosis. These cases illustrate the difficulty of correct diagnosis and treatment.

Prolactin-secreting pituitary carcinoma with implants in the cheek pouch and metastases to the ovaries. A case report and literature review.

BACKGROUND: Prolactin-secreting pituitary carcinomas are uncommon, locally destructive neoplasms that rarely metastasize outside the central nervous system. The authors report a case of a prolactin-secreting tumor that initially presented as the empty sella syndrome. Two recurrences along transsphenoidal surgery tracts in cheek pouches were followed by distant metastases later in the abdomen and pelvis. Only 10 previous cases of either extracranial or intracranial metastases from prolactin-secreting pituitary carcinomas have been reported. No metastases below the diaphragm have been reported previously. METHODS: The patient's cheek pouch implants, lymph node metastases, ovarian metastases, and uterine metastases were studied with prolactin-specific immunohistochemistry. RESULTS: Long term treatment with bromocriptine, several debulking surgeries, extensive local radiation therapy (external beam and proton beam), and cytotoxic chemotherapy had little impact. Tamoxifen, however, may have slowed tumor growth. CONCLUSION: Tamoxifen may have efficacy in the treatment of prolactin-secreting pituitary carcinomas.

The optimal management of hairy cell leukaemia.

Hairy cell leukaemia is an uncommon B cell chronic lymphoproliferative disorder characterised by circulating lymphocytes displaying prominent cytoplasmic projections. Therapy is initiated for severe cytopenias or recurrent infections. Splenectomy, the first standard treatment, is now less commonly used as primary treatment. Interferon-alpha (IFN alpha) induces partial responses in most patients but complete responses in only a few. Adverse effects from IFN alpha are common but not life-threatening. The ability of two newer purine analogues, pentostatin (2'-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine), to induce long-lasting complete remissions in the majority of patients has revolutionised the treatment of this disease. Cladribine is emerging as the treatment of choice because of its favourable toxicity profile, brief duration of treatment, high percentage of unmaintained complete remissions and low incidence of relapse.

Isolated cerebral mucormycosis: case report and therapeutic considerations.

Cerebral mucormycosis (without associated involvement of and invasion from the nasal sinuses and turbinates) is an extremely rare opportunistic infection of the central nervous system. We report the case of an intravenous drug abuser (who was negative for the human immunodeficiency virus) who presented with hemiparesis on the right side, slurred speech, altered mental status, and an unsteady gait. Imaging studies revealed a large left-side basal ganglia lesion. A stereotactic biopsy obtained a tissue sample that revealed wide, nonseptated hyphal fragments with granulomatous inflammation. The patient was treated with 3 gm of amphotericin B during a 5-month period. The patient had no residual neurological dysfunction after treatment. Open surgical resection was not employed. This case suggests that stereotactic biopsy followed by long-term amphotericin B therapy, in lieu of open surgical resection, represents a viable treatment option for this rare disorder.

Polyoma virus-induced murine odontogenic tumors.

Neonatal mouse pups were injected subcutaneously with polyoma virus to induce odontogenic tumors. This treatment resulted in a spectrum of tumors that arose in organs dependent upon epithelial-mesenchymal interactions for their organogenesis, which included the teeth, salivary glands, thymus, and lacrimal glands. In addition, several odontogenic tumors with a histologic resemblance to ameloblastoma were identified and analyzed with respect to the presence of markers specific for various stages of ameloblast differentiation. Immunodetection analyses of the odontogenic tumors identified fibronectin and laminin, typical of basement membrane organization during early tooth organogenesis. These same tumors failed to express amelogenin, a gene whose expression is limited to differentiated ameloblasts. In contrast, a 47 kDa enamelin-like polypeptide was identified with the use of an antienamelin antibody. These data were interpreted to suggest that the polyoma virus truncated the differentiation pathway for these odontogenic tissues at an early stage of their development and retained the expression of basement membrane components and the enamelin-like polypeptides, yet excluded expression of amelogenin gene products. This observation suggests that polyoma viral transformation may dysregulate odontogenic tissue interactions and produce tumors composed of cells arrested at a specific stage in their development.