The continuum of stem cell transdifferentiation: possibility of hematopoietic stem cell plasticity with concurrent CD45 expression.

Recent years have seen a surge of scientific research examining adult stem cell plasticity. For example, the hematopoietic stem cell has been shown to give rise to skin, respiratory epithelium, intestinal epithelium, renal epithelium, liver parenchyma, pancreas, skeletal muscle, vascular endothelium, myocardium, and central nervous system (CNS) neurons. The potential for such stem cell plasticity seems to be enhanced by stressors such as injury and neoplasia. Interestingly, recent studies have demonstrated that hematopoietic stem cells may be able to adopt certain nonhematopoietic phenotypes, such as endothelial, neural, or skeletal muscle phenotypes, without entirely losing their initial hematopoietic identity. We propose that transdifferentiation can, in certain conditions, be a partial rather than a complete event, and we encourage further investigation into the phenomenon of a stem cell simultaneously expressing phenotypic features of two distinct cell fates.

Hematopoietic stem cells give rise to perivascular endothelial-like cells during brain tumor angiogenesis.

Bone marrow (BM) cells have recently been shown to give rise to skeletal, hepatic, cardiac, neural, and vascular endothelial tissues. However, it has been shown that this is the result of cell fusion rather than transdifferentiation of hematopoietic stem cells (HSC). For this study, we established a mouse model of brain tumor growth to investigate the differentiation potential of HSC into endothelial cells during brain tumor-induced angiogenesis. Nontransgenic (GFP(neg)) recipient mice were lethally irradiated, and their hematopoietic cells were subsequently repopulated by transplantation of a single green fluorescent protein (GFP)-expressing HSC. Rat glioma (RT-2/RAG) cells were then injected into the striatum of the chimeric mice 6-8 weeks post-transplantation. The animals were sacrificed 3-9 days after tumor implantation, and the mobilization, temporal-spatial distribution, and lineage-specific marker expression profile of the GFP(+) cells within the growing tumor were analyzed. We saw that GFP(+) cells gave rise to elongated, CD34(+)/Flk-1(+) cells that incorporated into the endothelium of tumor blood vessels. However, all GFP(+) cells were also CD45(+), and the presence of CD45 on the HSC-derived endothelial-like cells supports the hypothesis that the hematopoietic cells were recruited into the tumor milieu. The fact that we failed to demonstrate the expression of von Willebrand factor in these cells argues against a true endothelial identity. Nevertheless, the recruitment of HSC-derived endothelial-like cells was an extremely rare event in normal brain parenchyma, and, thus, the permissive influence afforded by the growing tumor appeared to enhance the perivascular tropism and acquisition of an endothelial phenotypes by a population of HSC-derived cells.

Initial nonoperative management for periappendiceal abscess.

PURPOSE: Our goal was to compare initial operative and nonoperative management for periappendiceal abscess complicating appendicitis. METHODS: This study is a retrospective review of 155 consecutive patients with appendicitis complicated by periappendiceal abscess treated between 1992 and 1998. Eighty-eight patients were treated initially nonoperatively, and 67 patients were treated operatively. All patients had localized abdominal tenderness and either computed tomography or intraoperative documentation of an abscess. RESULTS: Our patient population consisted of 107 males and 48 females, with an average age of 33 (range, 16-75) years. Age, gender, comorbidity, white blood cell count, temperature, and heart rate did not differ significantly between groups. For the initial nonoperative management group, the failure rate was 5.8 percent and the appendicitis recurrence rate was 8 percent after a mean follow-up of 36 weeks. The response to treatment of the initial nonoperative group and the initial operative group was compared by length of stay (9 +/- 5 days vs. 9 +/- 3 days; P = not significant), days until white blood cell count normalized (3.8 +/- 4 days vs. 3.1 +/- 3 days; P = not significant), days until temperature normalized (3.2 +/- 3 days vs. 3.1 +/- 2 days; P = not significant), and days until a regular diet was tolerated (4.7 +/- 4 days vs. 4.6 +/- 3 days; P = not significant). Complication rate was significantly lower in the nonoperative group (17 vs. 36 percent; P = 0.008). CONCLUSIONS: Initial nonoperative management of appendicitis complicated by periappendiceal abscess is safe and effective. Patients undergoing initial nonoperative management have a lower rate of complications, but they are at risk for recurrent appendicitis.

Can perforated appendicitis Be diagnosed preoperatively based on admission factors?

The optimal initial treatment for selected patients with perforated appendicitis may be nonoperative. For this reason it is important to be able to diagnose perforated appendicitis preoperatively. The purpose of this study was to determine the accuracy of diagnosing perforated appendicitis using only admission factors. The study population was comprised of 366 adult patients who underwent appendectomy for presumed appendicitis during 1997. Admission factors associated with perforated appendicitis were determined using univariate and multivariate analyses. These variables were then used to formulate a rule for the diagnosis of perforated appendicitis. Sensitivity and specificity were calculated for this rule. The admission factors analyzed were sex, race, age, days of pain, temperature, heart rate, symptoms, physical examination findings, and laboratory findings. Multivariate regression analysis revealed days of pain, temperature, and localized tenderness outside the right lower quadrant to be significant (P <0.05). Using two or more days of pain, a temperature of >/=101 F (38.3 C), or localized tenderness outside the right lower quadrant as criteria to indicate perforation, we achieved a sensitivity of 86% and a specificity of 58% for distinguishing perforated from nonperforated appendicitis. We concluded that (1) perforated appendicitis cannot reliably be distinguished from nonperforated appendicitis based on admission factors, and (2) two or more days of pain, localized tenderness outside the right lower quadrant, and a temperature of >/=101 F (38.3 C) define a group of patients with appendicitis who have a high incidence of perforation.

Patterns of recurrence in anal canal carcinoma.

HYPOTHESIS: The initial modality of treatment of anal canal carcinoma (ACC) influences the pattern of recurrence of disease. DESIGN: A retrospective analysis comparing patterns of recurrence in patients with ACC undergoing either surgery or chemoradiotherapy as their initial therapeutic intervention. Anal margin cancers and adenocarcinomas were excluded. SETTING: A university-affiliated urban medical center. PATIENTS: Eighty-one patients were given a diagnosis of ACC between February 1, 1952, and December 31, 1998. Fifty-one (63%) of the patients initially underwent surgery: abdominoperineal resection in 38 patients (75%) and local excision in 13 patients (25%). Chemoradiotherapy was the initial therapeutic intervention in 30 patients (37%). MAIN OUTCOME MEASURES: The patterns of recurrence (local vs distant disease) and survival were compared between the group that underwent palliative surgery (hereafter referred to as the surgical group) and the group that received chemoradiotherapy (hereafter referred to as the chemoradiotherapy group). RESULTS: The mean follow-up was 40 months. Local recurrence occurred in 7 patients (14%) in the surgical group vs 7 patients (23%) in the chemoradiotherapy group (P =.46). Using Kaplan-Meier actuarial analysis, local recurrence rates for the surgical and chemoradiotherapy groups at 1 year were 0% and 6%, respectively (P =.32), and at 5 years were 17% and 36%, respectively (P =.02). The average (+/-SD) time to local recurrence in the surgical group was 23 +/- 0.7 months and for the chemoradiotherapy group 16 +/- 2.9 months (P =.27). Five (71%) of the 7 patients with local recurrences in the chemoradiotherapy group underwent salvage abdominoperineal resection with 100% disease-free survival at a mean follow-up of 35 months. When patients presenting with metastatic disease were excluded, distant recurrences developed in 7 patients (16%) in the surgical group and 2 (7%) in the chemoradiotherapy group (P =.31). Actuarial 5-year distant recurrence rates for the surgical and chemoradiotherapy groups were 26% and 19%, respectively (P =.65). Five-year survival was 42% in the surgical group and 74% in the chemoradiotherapy group (P =.01). CONCLUSION: There was a higher rate of local recurrence in patients with ACC treated with chemoradiotherapy vs surgical resection as the initial therapeutic intervention. However, when this occurred, abdominoperineal resection was effective salvage therapy and was associated with a 100% disease-free survival at 3 years. Therefore, chemoradiotherapy is justified as the initial treatment for ACC and has an overall 5-year survival that is significantly higher than that attained with initial surgical treatment.

Nonoperative management of perforated appendicitis without periappendiceal mass.

BACKGROUND: Initial nonoperative treatment for patients with periappendiceal mass has been shown to be safe and effective. Our goal was to evaluate the safety and efficacy of initial nonoperative management for perforated appendicitis not accompanied by a palpable mass. METHODS: The study population consisted of 77 patients with appendicitis treated initially nonoperatively between 1992 and 1998. All had localized abdominal tenderness and computed tomography findings of abscess or phlegmon. None had a palpable abdominal mass. Outcome parameters evaluated were rate of failure, complication, and recurrence. RESULTS: There were 49 males and 28 females with a mean age of 35 years (range 16 to 75). Initial nonoperative management was successful in 95% of patients. Complications occurred in 12% of patients. Recurrent appendicitis developed in 6.5% of patients after an average follow-up of 30 weeks. CONCLUSIONS: Perforated appendicitis patients with localized abdominal tenderness and abscess or phlegmon can safely and effectively be treated in an initial nonoperative fashion.

Computed tomography scanning for the diagnosis of perforated appendicitis.

The optimal initial treatment for perforated appendicitis may be nonoperative. For this reason it is important to be able to reliably distinguish between acute and perforated appendicitis. CT scanning has been shown to be highly accurate for the diagnosis of appendicitis, but it has not been specifically evaluated for perforated appendicitis. Our objective was to evaluate CT for the diagnosis of perforated appendicitis. Our study population comprised 84 patients who underwent appendectomy between 1993 and 1997 and who had CT scanning performed preoperatively. Medical records were reviewed retrospectively. CT scans were reviewed in a blinded fashion. CT findings were correlated with pathologic and clinical factors. Sixteen patients with acute appendicitis, 59 patients with gangrenous or perforated appendicitis, and 9 patients with normal appendices or other diagnoses were evaluated. For patients with pathologic documentation of appendicitis, CT findings that independently predict perforation or gangrene included abscess (P<0.001), phlegmon (P<0.001), extraluminal gas (P = 0.01), and terminal ileal wall thickening (P = 0.03). CT findings of an abscess, extraluminal gas, or phlegmon have a sensitivity of 92 per cent, specificity of 88 per cent, positive predictive value of 96 per cent, and negative predictive value of 74 per cent for perforated or gangrenous appendicitis. We conclude that CT can reliably distinguish between acute and perforated appendicitis.