Pseudomyxoma peritonei – two novel orthotopic mouse models portray the PMCA-I histopathologic subtype

<p>Abstract</p> <p>Background</p> <p>Pseudomyxoma peritonei (PMP) is a rare malignant disease, most commonly originating from appendiceal lesions and characterized by accumulation of mucinous tumor tissue in the peritoneal cavity. Since the disease is infrequent, the task of carrying out studies of treatment efficacy and disease biology in the clinical setting is challenging, warranting the development of relevant <it>in vitro </it>and <it>in vivo </it>PMP models.</p> <p>Methods</p> <p>Human tumor tissue was implanted in the peritoneal cavity of nude mice to establish two orthotopic models exhibiting noninvasive intraperitoneal growth without metastasis development.</p> <p>Results</p> <p>Xenograft tissues have retained essential properties of the original human tumors, such as macro- and microscopic growth patterns, mucin production as well as expression of carcinoembryonal antigen, cytokeratins 20 and 7 and the proliferation marker pKi67. Upon microscopic examination, the human tumors were categorized as the PMCA-I (peritoneal mucinous carcinomatosis of intermediate features) subtype, which was conserved through 14 examined passages in mice, for the first time modeling this particular histopathologic category.</p> <p>Conclusion</p> <p>In conclusion, two novel orthotopic models of human PMP have been established that consistently portray a distinct histopathologic subtype and reflect essential human tumor properties. Xenografts can easily and reproducibly be transferred to new generations of mice with acceptable passage periods, rendering the models as attractive tools for further studies of PMP biology and treatment.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Clinical value of immunohistochemically detected lymphatic and vascular invasions in clinically staged endometrioid endometrial cancer

&lt;p&gt;Background: A novel technique to differentiate lymphatic from vascular invasion and to assess the clinicopathological significance in patients with early endometrial cancer.&lt;/p&gt; &lt;p&gt;Methods: Dual immunohistochemical techniques against pancytokeratin epithelial cell marker (PCK), D6 lymphatic endothelial marker, and CD31 nonspecific endothelial marker were deployed for differentiation. Seventy-seven patients were included with a median follow-up of 161 months. Tumors with positive evidence of lymphovascular space invasion on PCK-CD31 immunohistochemistry and absence of lymphatic space invasion on PCK-D6 were regarded as cases with vascular space invasion only.&lt;/p&gt; &lt;p&gt;Results: Significant association between depth of myometrial invasion, recurrence rate, and hematoxylin and eosin that detected lymphovascular space invasion were noted (P &#60; 0.0001 and P = 0.009, respectively). The 5-year recurrence-free survival was 45% for the group with hematoxylin and eosin evidence of lymphovascular space invasion compared with 89% for the group without (P = 0.0014). Pancytokeratin epithelial cell marker-D6 dual immunostaining detected lymphatic space invasion in 22 (29%) patients. There was significant association between lymphatic space invasion and depth of myometrial invasion (P = 0.046). Lymphatic space invasion detected on immunohistochemistry was present in 8 (72%) of 11 patients with recurrent disease. Of the remaining 49 patients with no evidence of recurrent disease, only 11 (22%) had presented with lymphatic space invasion. Positive association between tumor recurrence rate and lymphatic space invasion was noted (P = 0.003). The 5-year recurrence-free survival was 53% for the group with lymphatic invasion compared with 93% for the group without. This difference was similarly shown to be of significance (P = 0.0009). There were no apparent association between immunohistochemically detected lymphovascular or vascular space invasion and any clinicopathological factor.&lt;/p&gt; &lt;p&gt;Conclusions: Lymphatic space invasion detected by using dual immunostaining is of significant value in identifying high-risk patients.&lt;/p&gt

Detection of tumour lymphovascular space invasion using dual cytokeratin and CD31 immunohistochemistry

Background: Lymphovascular space invasion (LVSI) is an important step in the complex process of tumour metastasis. Various methods have been used in the past to improve the histological detection of LVSI. Aims: To develop a sensitive immunohistochemical method for the detection of LVSI. Methods: Paraffin wax blocks from 108 patients who had undergone hysterectomy for stage I endometrial cancer were retrieved. Dual immunostaining for pancytokeratin and the CD31 endothelial cell marker was carried out on 4 μm sections cut from these bocks and compared with conventional haematoxylin and eosin staining. Results: The detection rate for LVSI increased threefold compared with conventional haematoxylin and eosin staining in the test group. Conclusion: This finding suggests that LVSI is a much more common phenomenon than previously thought and questions current understanding of tumour metastasis

Evaluation of endometrial carcinoma on magnetic resonance imaging

Evaluation of endometrial carcinoma on magnetic resonance imaging Our aims were to assess diagnostic performance of T2-weighted (T2W) and dynamic gadolinium-enhanced T1-weighted (T1W) magnetic resonance imaging (MRI) in the preoperative assessment of myometrial and cervical invasion by endometrial carcinoma and to identify imaging features that predict nodal metastases. Two radiologists retrospectively reviewed MR images of 96 patients with endometrial carcinoma. Tumor size, depth of myometrial and cervical invasion, and nodal enlargement were recorded and then correlated with histology. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the identification of any myometrial invasion (superficial or deep) were 0.94, 0.50, 0.93, 0.55 on T2W and 0.92, 0.50, 0.92, 0.50 on dynamic T1W, and for deep myometrial invasion were 0.84, 0.78, 0.65, 0.91 on T2W and 0.72, 0.88, 0.72, 0.88 on dynamic T1W. The sensitivity, specificity, PPV and NPV for any cervical invasion (endocervical or stromal) were 0.65, 0.87, 0.57, 0.90 on T2W and 0.50, 0.90, 0.46, 0.92 on dynamic T1W, and for cervical stromal involvement were 0.69, 0.95, 0.69, 0.95 on T2W and 0.50, 0.96, 0.57, 0.95 on dynamic T1W. Leiomyoma or adenomyosis were seen in 73% of misdiagnosed cases. Sensitivity and specificity for the detection of nodal metastases was 66% and 73%, respectively. Fifty percent of patients with cervical invasion on MRI had nodal metastases. In conclusion, MRI has a high sensitivity for detecting myometrial invasion and a high NPV for deep invasion. MRI has a high specificity and NPV for detecting cervical invasion. Dynamic enhancement did not improve diagnostic performance. MRI may allow accurate categorization of cases into low- or high-risk groups ensuring suitable extent of surgery and adjuvant therapy

Mutations of the KRAS oncogene in endometrial hyperplasia and carcinoma.

The aim of this study was to examine the prevalence and clinicopathological significance of KRAS point mutation in endometrial hyperplasia and carcinoma. We analysed KRAS in 11 cases of complex atypical hyperplasia and in 49 endometrial carcinomas using polymerase chain reaction associated with restriction fragment length polymorphism (PCR-RFPL). Point mutations at codon 12 of KRAS oncogene were identified in 7 of 49 (14,3%) tumor specimens and in 2 of 11 (18,2%) hyperplasias. No correlation was found between KRAS gene mutation and age at onset, histology, grade of differentiation and clinical stage. We conclude that KRAS mutation is a relatively common event in endometrial carcinogenesis, but with no prognostic value