A natural orifice transrectal approach for oncologic resection of the rectosigmoid: an experimental study and comparison with conventional laparoscopy.

BACKGROUND: A transrectal (TR) approach for natural orifice translumenal endoscopic surgery (NOTES) makes sense for colorectal surgery because the colotomy can be incorporated into subsequent anastomosis. Because cancer is a primary indication for left-sided colon resection, oncologic standards will have to be met by a NOTES procedure. This study aimed to assess whether pure TR rectosigmoidectomy can be performed with strict adherence to oncologic principles compared with a conventional laparoscopically assisted approach (LAP). METHODS: Human male cadavers were allocated to either TR (n = 4) or LAP (n = 2). A simulated sigmoid lesion was created at 25 cm. Transrectal retrograde mobilization of the rectosigmoid was performed using conventional transanal endoscopic microsurgery (TEM) instrumentation. After ligation of the superior hemorrhoidal artery and further mobilization, the specimen was delivered transanally and divided extracorporeally. Using a circular stapler, NOTES colorectal anastomosis was performed. Lymph node yield, adequate resection margins, and operative time were compared with LAP. RESULTS: Transrectal retrograde rectosigmoid dissection was achieved in all attempts (4/4) and showed numbers of lymph nodes (median, 5; range, 3-6) similar to the LAP group (median, 4.5; range, 2-7). One pure TR approach failed to resect the lesion. Three TR procedures required additional mobilization via an abdominal approach to provide adequate margins. The mean length of TR specimens was 16 ± 4 cm compared with 31 ± 9 cm achieved by LAP (p < 0.01). The TR operative time was significantly longer (247 ± 15 vs 110 ± 14 min). CONCLUSION: Lymph node yield during TR rectosigmoidectomy was similar to that achieved by the LAP approach. However, conventional TEM instrumentation alone did not permit adequate colon mobilization. This indicates a need for flexible instrumentation or other technical solutions to perform true NOTES colectomies.

Cervical adenoid basal tumors comprised of adenoid basal epithelioma associated with various types of invasive carcinoma: clinicopathologic features, human papillomavirus DNA detection, and P16 expression.

Adenoid basal tumors are uncommon cervical lesions that some pathologists consider invasive carcinomas but others consider "epitheliomas" due to their low-grade histological appearance and rarely documented malignant behavior. We report the clinicopathologic features of 10 tumors comprised of both typical low-grade adenoid basal tumors (epitheliomas) intimately associated with invasive carcinomas having infiltrative growth, increased cytological atypia and mitotic activity, and various types of differentiation, including adenoid basal/squamous, pure squamous, adenoid cystic, and small cell neuroendocrine. Tumors were evaluated for the presence of human papillomavirus (HPV) DNA and immunohistochemical p16 expression. The patients in the study group ranged in age from 45 to 81 years (mean, 65 years). Most of the patients presented with abnormal cervicovaginal smears. The initial diagnosis was made on specimens obtained by cervical biopsy, laser electrocautery excision procedure (LEEP), or cone biopsy in 8 patients. Two 2 patients were incidentally diagnosed in hysterectomy specimens. All 10 patients had squamous intraepithelial lesions (9 high-grade, 1 low-grade). In all cases diagnosed in LEEP or cone biopsy specimens, the invasive carcinoma component was present in the excisional specimen and extended to the margins. Seven patients diagnosed on excisional or biopsy specimens who underwent hysterectomy had residual tumor in the cervix, ranging from microscopic foci to deeply invasive. No lymph node metastases were identified in 4 patients who were staged. Seven patients with follow-up were alive without evidence of disease after follow-up intervals of 8 to 84 months (mean, 45 months; median, 29 months). One patient with a component of small cell carcinoma died of other causes without evidence of disease at 18 months. HPV 16 DNA was detected in both the adenoid basal epithelioma and invasive carcinoma components in 9 tumors by in situ hybridization, and HPV 33 was detected by polymerase chain reaction in 1 tumor. All tumors expressed p16 diffusely. Adenoid basal tumors are high-risk HPV-related tumors that can be comprised of both a low-grade adenoid basal tumor, which can be designated as epithelioma, and invasive carcinomas of various types. The invasive component is usually evident in the excisional biopsy specimen, allowing for recognition of a tumor that needs further management.

Human monocytic ehrlichiosis presenting as acute appendicitis during pregnancy.

Human monocytic ehrlichiosis (HME) is caused by Ehrlichia chaffeensis, an obligate intracellular bacterium that infects mononuclear phagocytic cells. We report a unique case of HME diagnosed in a woman who presented with abdominal pain and acute appendicitis during early pregnancy and whose condition progressively deteriorated to adult respiratory distress syndrome.

Noninvasive and invasive micropapillary (low-grade) serous carcinoma of the ovary: a clinicopathologic analysis of 135 cases.

Reports describing the behavior of micropapillary serous carcinomas (MPSCs) of the ovary have focused on those that are noninvasive. There are only very limited data on the behavior of those that are invasive. To further characterize the behavior of MPSCs, invasive versus noninvasive primary tumors were distinguished based on the presence or absence of destructive infiltrative growth. To qualify for inclusion, invasive MPSCs, like the noninvasive tumors, were required to display a micropapillary architecture and low-grade nuclei. A total of 135 cases of MPSC were identified: 96 noninvasive and 39 invasive. On follow-up, survival for 10 patients with stage I noninvasive and invasive MPSCs was 100%, and survival for women with stage II and III noninvasive and invasive MPSCs with noninvasive implants was 80%. In contrast, the 5-year and 10-year survival for patients with stage II and III noninvasive MPSCs with invasive implants was 85% and 55%, respectively. The 5-year and 10-year survival for women with invasive MPSCs and invasive implants was 55% and 45%, respectively. The median time from diagnosis to death for women with noninvasive and invasive MPSCs with invasive implants was 60 months (range 33-240 months). The indolent behavior of these low-grade carcinomas distinguishes them from conventional serous carcinomas, which are high-grade aggressive neoplasms. Five of six patients with small (<5 mm) MPSCs in whom follow-up was available presented with high stage disease. Of these five women, three are alive and well and two are alive with disease (one with invasive and one with noninvasive implants). Nearly three fourths of noninvasive MPSCs were associated with atypical proliferative serous tumors, adenofibromas, or both, and 62% of invasive MPSCs were associated with noninvasive MPSCs, atypical proliferative serous tumors, and adenofibromas, alone or in combination. In addition to the frequent mixtures of these tumor components, transitions between them were common. These data in conjunction with recent molecular genetic studies strongly suggest that MPSCs (low-grade carcinomas) arise from atypical proliferative serous tumors unlike conventional serous carcinomas (high-grade carcinomas), which appear to develop de novo. The findings provide further support for the hypothesis that there are distinct pathways of carcinogenesis for low-grade and high-grade serous carcinoma of the ovary.

Diagnostic criteria and behavior of ovarian seromucinous (endocervical-type mucinous and mixed cell-type) tumors: atypical proliferative (borderline) tumors, intraepithelial, microinvasive, and invasive carcinomas.

Ovarian endocervical-type (müllerian) mucinous tumors and tumors composed of a mixture of endocervical-type mucinous, serous, endometrioid, squamous, and indifferent cells with abundant eosinophilic cytoplasm reported to date have been primarily limited to borderline and microinvasive types, with only one report of a disease-related death. The clinicopathologic features of 54 endocervical-type and mixed cell-type mucinous tumors, defined as tumors with papillary architecture resembling serous tumors but containing endocervical-type mucinous epithelium, were evaluated. Thirty-four tumors (64%) were classified as atypical proliferative (borderline) tumors based on the absence of stromal invasion and the absence of micropapillary architecture measuring >5 mm. Five tumors (9%) qualified as intraepithelial carcinoma based on the presence of marked cytologic atypia or a complex cribriform growth pattern involving the epithelium covering the surface of papillae or lining cystic spaces. Eight tumors (15%) with stromal invasion < or =5 mm were classified as microinvasive carcinoma. Seven tumors (13%) with either stromal invasion (five tumors) or micropapillary architecture measuring >5 mm (two tumors) were classified as carcinoma. Sixteen tumors (30%) were bilateral, and endosalpingiosis was identified in 41% of cases. Serous-type differentiation was present in all cases. Of the 29 patients with atypical proliferative tumors, intraepithelial carcinomas, and microinvasive carcinomas for whom follow-up was available, there were no disease-related deaths. In contrast, of the seven patients whose tumors had either stromal invasion or micropapillary architecture >5 mm, two stage III patients died of disease (one with frank invasion and one with a micropapillary tumor that lacked stromal invasion). One other stage III patient with a noninvasive micropapillary carcinoma was alive with disease at 84 months. The remaining four patients (three stage I and one stage III) were alive with no evidence of disease. In summary, most endocervical-type atypical proliferative tumors are stage I and benign. The presence of either intraepithelial carcinoma or microinvasion has no adverse effect on behavior. Rare endocervical-type mucinous tumors demonstrate histologically malignant features and aggressive behavior that warrant designation as carcinoma. As with serous tumors, micropapillary architecture without frank invasion in endocervical-type mucinous tumors is associated with disease recurrence and death when presenting as advanced-stage disease. All the tumors in this study were composed of a heterogeneous population of cells, consisting mainly of serous (ciliated) and endocervical-type mucinous cells. In addition, they all contained endometrioid-type cells, hobnail cells, and indifferent cells with abundant eosinophilic cytoplasm to a varying degree. Accordingly, it appears that tumors that feature endocervical-type mucinous cells are rarely if ever pure but almost invariably of mixed cell type. Despite containing mucinous epithelium, the papillary architecture, serous-type differentiation, association with endosalpingiosis, frequent bilaterality, size, and clinical behavior of endocervical-type mucinous tumors closely resemble serous tumors. We therefore recommend the term "seromucinous" for these tumors, which acknowledges both their serous and mucinous features.

Clinical significance of Her-2/neu overexpression in uterine serous carcinoma.

OBJECTIVE: To evaluate the clinico-pathologic characteristics and survival outcome associated with overexpression of Her-2/neu in patients with uterine serous carcinoma (USC). METHODS: Twenty-five patients with a confirmed pathologic diagnosis of USC and available paraffin embedded tissue samples treated at the Johns Hopkins Medical Institutions from 1/1/1992 through 12/31/2000 were identified retrospectively. Her-2/neu expression was evaluated by immunohistochemistry using HercepTest (DAKO). Clinical data were abstracted from medical records. Clinico-pathologic characteristics associated with Her-2/neu overexpression like staging, histology, lymph-vascular space involvement, and myometrial invasion were evaluated using logistic regression analysis and Fisher's exact test. Analyses of overall survival time were performed using the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: Twelve (48%) of the 25 USC cases demonstrated Her-2/neu overexpression. There was a significant difference in Her-2/neu overexpression and surgical staging (81.8% vs. 28.6%, P = 0.01). Survival analysis according to primary tumor characteristics revealed that overexpression of Her-2/neu was significantly associated with a worse survival outcome (HR = 6.58, 95%CI: 1.36-31.89, P = 0.02). CONCLUSIONS: Her-2/neu overexpression is associated with advanced surgical stage USC and poor survival outcome. These data may be useful in guiding the clinical management of patients with USC and have potential implications for the development of novel treatment strategies.