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Background: Early diagnosis of Peritoneal metastasis (PM) is clinically significant regarding optimal treatment selection and avoidance of unnecessary surgical procedures. Cytopathology plays an important role in early screening of PM. We aimed to develop a deep learning (DL) system to achieve intelligent cytopathology interpretation, especially in ascites cytopathology., Methods: The original ascites cytopathology image dataset consists of 139 patients' original hematoxylin-eosin (HE) and Papanicolaou (PAP) Staining images. DL system was developed using transfer learning (TL) to achieve cell detection and classification. Pre-trained alexnet, vgg16, goolenet, resnet18 and resnet50 models were studied. Cell detection dataset consists of 176 cropped images with 6573 annotated cell bounding boxes. Cell classification data set consists of 487 cropped images with 18,558 and 6089 annotated malignant and benign cells in total, respectively., Results: We established a novel ascites cytopathology image dataset and achieved automatically cell detection and classification. DetectionNet based on Faster R-CNN using pre-trained resnet18 achieved cell detection with 87.22% of cells' Intersection of Union (IoU) bigger than the threshold of 0.5. The mean average precision (mAP) was 0.8316. The ClassificationNet based on resnet50 achieved the greatest performance in cell classification with AUC = 0.8851, Precision = 96.80%, FNR = 4.73%. The DL system integrating the separately trained DetectionNet and Classificationnet showed great performance in the cytopathology image interpretation., Conclusions: We demonstrate that the integration of DL can improve the efficiency of healthcare. The DL system we developed using TL techniques achieved accurate cytopathology interpretation, and had great potential to be integrated into clinician workflow.

Background: Malignant peritoneal mesothelioma (PeM) is a rare and fatal cancer that originates from the peritoneal lining of the abdomen. Standard treatment of PeM is limited to cytoreductive surgery and/or chemotherapy, and no effective targeted therapies for PeM exist. Some immune checkpoint inhibitor studies of mesothelioma have found positivity to be associated with a worse prognosis., Methods: To search for novel therapeutic targets for PeM, we performed a comprehensive integrative multi-omics analysis of the genome, transcriptome, and proteome of 19 treatment-naïve PeM, and in particular, we examined BAP1 mutation and copy number status and its relationship to immune checkpoint inhibitor activation., Results: We found that PeM could be divided into tumors with an inflammatory tumor microenvironment and those without and that this distinction correlated with haploinsufficiency of BAP1. To further investigate the role of BAP1, we used our recently developed cancer driver gene prioritization algorithm, HIT'nDRIVE, and observed that PeM with BAP1 haploinsufficiency form a distinct molecular subtype characterized by distinct gene expression patterns of chromatin remodeling, DNA repair pathways, and immune checkpoint receptor activation. We demonstrate that this subtype is correlated with an inflammatory tumor microenvironment and thus is a candidate for immune checkpoint blockade therapies., Conclusions: Our findings reveal BAP1 to be a potential, easily trackable prognostic and predictive biomarker for PeM immunotherapy that refines PeM disease classification. BAP1 stratification may improve drug response rates in ongoing phases I and II clinical trials exploring the use of immune checkpoint blockade therapies in PeM in which BAP1 status is not considered. This integrated molecular characterization provides a comprehensive foundation for improved management of a subset of PeM patients.

Introduction: The pathological classification of PMP of appendiceal origin has prognostic and treatment implications. Our goals were to • Classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological features. • Compare the reproducibility of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor., Patients and Methods: A retrospective analysis of patients undergoing CRS and HIPEC or debulking surgery was done. All the tumors were re-classified according to the PSOGI classification. LGMCP was further classified into three histological subgroups and the impact on survival was evaluated., Results: From Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n = 89) or debulking surgery (n=12). The median PCI was 28 (3-39) and 74.1% patients had CC-0/1 resections. Of the 76.2% patients who had LGMCP, 4 patients (5.1%) were classified as group 1, 54 (70.1%) as group 2 and 19 patients (24.6%) as group 3. At a median follow up of 21 months, the disease free survival was not reached, 30 months and 14 months for groups 1, 2 and 3 respectively (p = 0.09). There was no difference in overall survival. Using the WHO classification, there was a discordance in the grade of the primary tumor and the peritoneal lesions in 19.8% and conflicting terminology was used in 62% of patients., Conclusions: The subgroups of LGMCP described here are prognostically different though this needs further prospective evaluation in larger series. The PSOGI classification is more uniformly reproducible and should be preferred to the WHO classification., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: In subtypes of non-endometrioid endometrium cancers (non-ECC), it is not clear whether the omentectomy is a part of debulking if visual assessment is normal. Recently, the ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group in their report titled "Endometrial Cancer: diagnosis, treatment and follow-up" recommended that omentectomy be performed in the serous subtype, but not in carcinosarcoma, undifferentiated endometrial carcinoma or clear cell. In this study, the question is whether omentectomy should be a part of a staging procedure in patients with non-ECC. Besides, the sensitivity and specificity of the visual assessment of omentum were analyzed., Methods: Patients diagnosed with non-ECC in 2 gynecological oncology clinics between 2005 and 2015 were retrospectively reviewed. Occult (absence of visible lesions) and gross (presence of visible lesions) omental metastasis rates of histological subtypes were analyzed., Results: We identified 218 patients with non-ECC. Thirty-four of them (15.1%) had omental metastases and 44.1% of these metastases (n = 15) were occult metastases. The sensitivity of the surgeon's visual assessment of an omentum (positive or negative) was 0.55. The highest rate of omental metastasis was found in carcinosarcoma followed by serous, mixed subtypes, and clear-cell (20.4, 17.3, 16.6, 10.0%, respectively). Adnexal metastasis was the only factor associated with occult omental metastasis (p = 0.003)., Conclusion: Omental metastases occur too often to omit omentectomy during surgical procedures for non-ECC regardless of histological subtypes, and visual assessment is insufficient in recognizing the often occult metastases. Omentectomy should be a part of the staging surgery in patients with non-ECC., (© 2017 S. Karger AG, Basel.)

The roles of histologic characterization and staging are to provide reproducible metrics for cancer classification with which to direct the most appropriate clinical care and to yield the most stable reliable system to allow both prospective and retrospective data analysis. Both the histologic and staging classifications of malignant ovarian/tubal/peritoneal cancers have recently changed. The World Health Organization sponsored a review and reclassification of the pathology of cancers of the ovaries, fallopian tubes, and peritoneum, and published these updates in 2014. In so doing, they codified the two-tiered grading system that has been in use in serous ovarian cancers for nearly a decade. In parallel, FIGO reviewed and updated the surgical staging system, applied to all histotypes of ovarian, tubal, and peritoneal cancers, also published in 2014. In both cases, the changes made are meant to encompass a better understanding of disease, but both have important merits and drawbacks. Changes in staging complicate analysis of retrospective data against current data. Though in some aspects controversial, the changes overall are meant to represent a better biologic understanding of disease that we hope will lead to an improvement in patient care and directed therapy., (Published by Oxford University Press on behalf of the European Society for Medical Oncology 2017. This work is written by US Government employees and is in the public domain in the US.)

Histologic subtype is recognized as a prognostic factor in malignant pleural mesothelioma. Specifically, epithelial morphology is associated with a better prognosis than other subtypes, and the same association is observed in peritoneal malignant mesothelioma. Recently, prognostic differences based on morphologic subtypes of epithelial peritoneal malignant mesothelioma were reported. Herein, we report the interobserver variability across four pathologists at three institutions. The authors independently reviewed 67 cases of malignant peritoneal epithelioid mesotheliomas and subclassified them according to their epithelial subtype: papillary, tubulopapillary, trabecular, micropapillary, solid and/or pleomorphic. The cases were also evaluated by each author for several other histopathologic parameters including depth of invasion, nuclear grade, lymphocytic host response, mitotic count/index, presence of lymphovascular invasion, and stromal desmoplasia. The interobserver agreement for histopathologic parameters was highest for mitotic rate (κ=0.36) and primary epithelial subtype (κ=0.32). The interobserver variability for solid subtype pattern was moderate (κ=0.49). We found that the interobserver variability for most histopathologic parameters is poor., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Tumor stage, residual postoperative tumor, histological type and grading are considered among the main prognostic parameters in the consensus-based recommendations in the new S3 guidelines for diagnosis, treatment and clinical follow-up of malignant tumours of the ovary. Based on the 2014 update of the WHO Classification of Tumours of the Female Reproductive Organs this article summarizes the most significant changes. For example now the same TNM and FIGO classification applies for tumours of the ovary, peritoneum or fallopian tube. Noninvasive implants of serous borderline tumours are now named implants. In contrast, invasive implants are regarded as low-grade serous carcinoma. By presenting the current background information, we want to provide a basis for discussion, regarding more detailed consensus recommendations for pathologists and clinicians in the future.

Introduction: Pelvic high-grade serous carcinomas (HGSCs) include carcinoma of ovary, fallopian tube, and peritoneum. Five-year survival, irrespective of the stage, is between 35-40%. Most patients are diagnosed in advanced stages of the disease. The new revised and expanded dualistic model of ovarian carcinogenesis shows that type II tumors are composed for the most part of high-grade serous ovarian carcinoma, carcinosarcoma, undifferentiated carcinoma and can be further subdivided into morphologic and molecular subtypes. Many type II carcinomas develop from STIC predominantly in the distal portion of the fallopian tube and it is very likely the point of the origin of a significant subset of the pelvic high-grade serous carcinomas., Objective: To provide an overview of major changes in our understanding of the origin of ovarian cancer, that led to the revision of FIGO (International Federation of Gynecology and Obstetrics) classification and its unification for the ovary, fallopian tube and peritoneum. We summarize the new classification, main changes compared to the former one and their clinical impact., Methods: For this review, we have used the results of studies and review articles on the subject published in English up to October 2016. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords ("serous tubal intraepithelial carcinoma" or "high-grade serous ovarian carcinoma" or "FIGO ovarian cancer staging 2014"). We retrieved and assessed potentially relevant studies, and checked the reference lists of all papers of interest to identify additional relevant publications., Conclusion: The origin of most cases of pelvic HGSC (carcinoma of ovary, the fallopian tube, and peritoneum) is expected in the fallopian tube epithelium. The main changes in the revised FIGO classification for extrauterine pelvic serous carcinomas were subdivision of stages IC, III and IV and elimination of the stage IIC, based on new knowledge and prognostic data. A prerequisite for the proper treatment of patients is to perform adequate surgical and pathological staging, including determining the grade of carcinoma. These factors, coupled with appropriately performed operation with zero postoperative residuum (R0), are the most important prognostic factors for patients with carcinoma of the ovary, fallopian tube, and peritoneum.

Background: The impact of histopathologic features on oncologic outcomes for patients with peritoneal metastases from goblet cell carcinoid (GCC) undergoing multimodality therapy, including cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), is unknown., Methods: This study prospectively analyzed 43 patients with GCC undergoing CRS-HIPEC between 2005 and 2013. Pathology slides were re-reviewed to classify GCC into histologic subtypes according to the Tang classification. Kaplan-Meier survival curves and multivariate Cox-regression models identified prognostic factors affecting oncologic outcomes., Results: The 43 patients in this study underwent 50 CRS-HIPEC procedures for peritoneal metastases from GCC, and the majority received neoadjuvant and/or adjuvant systemic chemotherapy. The GCC demonstrated an aggressive phenotype with frequent lymph node and peritoneal metastases without systemic dissemination. The majority of the patients had Tang B GCC. The estimated median overall survival times after surgery for the patients with Tang A, B, and C GCC were respectively 59, 22, and 13 months. In a multivariate Cox-regression analysis, poor survival was associated with patients who had Tang B or C GCC, those undergoing incomplete macroscopic resection, and those with symptoms at the time of CRS-HIPEC. The patients with Tang A GCC demonstrated oncologic outcomes similar to those with intermediate-grade (American Joint Committee on Cancer [AJCC] grade 2) disseminated mucinous appendiceal neoplasms, whereas the patients with Tang B and C GCC demonstrated survival rates similar to or worse than those with high-grade (AJCC grade 3) disseminated mucinous appendiceal neoplasms., Conclusions: Tang classification is an independent prognostic factor for poor survival after multimodality therapy for GCC. Patients with Tang C GCC demonstrate limited survival and are not ideal candidates for a surgical approach.

Objective: This study aimed to evaluate the prognostic significance of revised International Federation of Gynecology and Obstetrics (FIGO2013) staging classification for cancer of the ovary, fallopian tube, and peritoneum in patients exhibiting high-grade serous histology., Methods: Clinical records of patients with high-grade serous carcinoma who underwent primary surgery between 2007 and 2012 were reviewed retrospectively. Patients were reclassified according to the FIGO2013 criteria. Progression-free survival (PFS) and overall survival (OS) were calculated for each stage using Kaplan-Meier estimates and compared with the log-rank test., Results: In total, 125 patients were included in the analysis. The distribution of the study cohort according to the revised classification was as follows; stage I, 6 patients; stage II, 9 patients; stage III, 85 patients; and stage IV, 25 patients. Median follow-up time was 36 months (95% confidence interval [CI], 3-110). The median PFS and OS were 14 months (95% CI, 12.4-15.6) and 60 months (95% CI, 47.0-72.9), respectively. Both PFS and OS were significantly different among stages I, II, III, and IV (P < 0.01). Subgroup analyses for stage III disease also revealed significant differences in survival. The median PFS for stages IIIA1, IIIB, and IIIC was 56, 46, and 16 months, respectively (P < 0.01), and the median OS was 104, 95, and 60 months, respectively (P = 0.03). The outcomes of patients with stage IV disease differed slightly but nonsignificantly according to new substages. The median PFS for stages IVA and IVB was 12 and 6 months, respectively (hazard ratio, 1.16; 95% CI, 0.48-2.79; P = 0.72), and the median OS was 41 and 24 months, respectively (hazard ratio, 1.62; 95% CI, 0.58-4.55; P = 0.35). The study sample was insufficient in size for subgroup analyses in stages I and II., Conclusions: The revised FIGO2013 staging system is highly prognostic for discriminating outcomes of patients with high-grade serous carcinoma across stages I to IV, in subgroups of stage III, but not in subgroups of stage IV.

Purpose: We evaluated the 7th edition of the American Joint Committee on Cancer (AJCC) staging classification in terms of overall survival (OS) in patients with PMP treated with cytoreductive surgery (CRS)/hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: A total of 208 PMP patients treated with CRS/HIPEC were identified from a prospective database. Patients with peritoneal mucinous carcinomatosis (PMCA) were retrospectively staged at time of diagnosis according to AJCC staging classification. Patients with disseminated peritoneal adenomucinosis (DPAM) were evaluated in a separate group., Results: Median follow-up was 5.2 years. Of 208 patients, 124 had PMCA and 84 patients had DPAM. According to the AJCC staging classification 47 lymph node (LN) negative patients with well-differentiated PMCA, were classified as a stage IVA. 77 patients with either moderately or poorly differentiated PMCA irrespective of LN status, or well-differentiated PMCA with positive LN were classified as stage IVB. 84 patients with DPAM, constituted a separate group. OS of stage IVA and IVB patients was 100, 90, 67, and 91, 50, and 27 for 1, 3, and 5 years, respectively (p < 0.001). OS of DPAM patients was 96, 90, and 88 % for 1, 3, and 5 years, respectively (p = 0.025 comparing to IVA). PFS was estimated for IVA and IVB PMCA patients who were considered disease free after CRS/HIPEC and was 78, 52, and 43 % in the IVA patients and 65 %, 15 %, and 0 in the IVB group at 1, 3, and 5 years, respectively (p = 0.004). The adjusted HR for AJCC stages (IVA/IVB) was 3.7 (95 % confidence interval 2.0-6.7) (p < 0.001)., Conclusions: The 7th edition of the AJCC staging classification is a simple, reproducible, and valid classification for staging patients with PMCA undergoing CRS/HIPEC.

Background: Peritoneal surface malignancies (PSMs) are usually staged using Sugarbaker's Peritoneal Cancer Index (PCI) and completeness of cytoreduction score (CC-s). Although these staging tools are essential for selecting patients and evaluating outcome after cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), both scoring models lack some anatomic information, thus making staging laborious and unreliable. Maintaining Sugarbaker's original concepts, we therefore developed a computerized digital tool, including a new anatomic scheme for calculating PCI and CC-s corresponding closely to patients' real anatomy. Our new anatomic model belongs in a web-based application known as the PSM Staging System, which contains essential clinical and pathological data for the various PSMs currently treated., Methods: The new digital tool for staging PSM runs on a personal computer or tablet and comprises male and female colored anatomic models for the 13 endoabdominal regions, with borders defined according to real anatomic landmarks. A drag-and-drop tool allows users to compute the PCI and CC-s, making it easier to localize and quantify disease at diagnosis and throughout treatment, and residual disease after CRS., Conclusions: Once tested online by registered users, our computerized application should provide a modern, shareable, comprehensive, user-friendly PSM staging system. Its anatomic features, along with the drag-and-drop tool, promise to make it easier to compare preoperative and postoperative PCIs, thus improving the criteria for selecting patients to undergo CRS plus HIPEC. By specifying the size, site, and number of residual lesions after CRS plus HIPEC, our digital tool should help stratify patients into outcome classes.

Introduction: Molecular pathological research has contributed to improving the knowledge of different subtypes of ovarian cancer. In parallel with the implementation of the new FIGO staging classification, the WHO classification was revised. The latter is mainly based on the histopathological findings and defines the actual type of tumor. It has, therefore, also an important impact on prognosis and therapy of the patient., Materials and Methods: The new WHO Classification of Ovarian Cancer published 2014 by Robert Kurman and co-authors is summarized. The major changes compared to the hitherto existing classification are presented., Results: The new classification eliminates the previous focus of mesothelial origin of ovarian cancer. Instead, it features a discussion of tubal carcinogenesis of hereditary and some other high-grade serous carcinomas. The previously assumed pathogenesis pathway may be correct for some, but not for all, serous cancers. The new classification was established to classify ovarian cancer in a more consistent way. The earlier transitional cell type of ovarian cancer has been removed while seromucinous tumors have been added as a new entity. The role of some borderline tumors as one possible step in the progression from benign to invasive lesions is incorporated. The article summarizes the essential updates concerning serous, mucinous, seromucinous, endometrioid, clear-cell, and Brenner tumors., Conclusion: The new WHO classification takes into account the recent findings on the origin, pathogenesis, and prognosis of different ovarian cancer subtypes. The tubal origin of hereditary and some non-hereditary high-grade serous cancers is mentioned in contrast to the hitherto theory of mesothelial origin of tumors. Seromucinous tumors represent a new entity.

Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.

"Invasive micropapillary serous carcinoma" has been proposed as a synonym for low-grade serous carcinoma by some expert pathologists. In contrast, Singer and colleagues reported that some serous carcinomas with conspicuous invasive micropapillary pattern (SC-IMPs) can show high-grade nuclear atypia. However, the molecular features of such tumors have not been well documented. The aim of this study was to demonstrate and emphasize the fact that high-grade serous carcinoma confirmed by immunohistochemistry and molecular analysis can show conspicuous invasive micropapillary pattern. We selected 24 "SC-IMPs" and investigated: (1) their morphologic features; (2) the immunostaining pattern of p53 protein; and (3) KRAS/BRAF/TP53 gene mutations. The 24 SC-IMPs were subdivided into low-grade and high-grade tumors based primarily on the nuclear atypia, with the mitotic rate used as a secondary feature: low grade (n=5) and high grade (n=19). Low-grade SC-IMPs were characterized by low-mitotic activity, absence of abnormal mitosis, presence of serous borderline tumor, occasional BRAF mutation, and infrequent TP53 mutation. High-grade SC-IMPs were characterized by high-mitotic activity, presence of abnormal mitosis, conventional high-grade serous carcinoma, frequent TP53 mutation, and lack of KRAS/BRAF mutation. We demonstrated that high-grade serous carcinoma confirmed by aberrant p53 immunostaining and molecular analysis can show conspicuous invasive micropapillary pattern, validating Singer and colleague's report. Serous carcinoma with conspicuous invasive micropapillary pattern should not be readily regarded as low-grade serous carcinoma. Nuclear grade is the most important diagnostic feature in the SC-IMPs.

Objective: The Japanese classification of peritoneal metastases from colorectal cancer is easy to use for general surgeons in routine clinical practice. However, the objectivity of this classification has not been determined. This study aimed to clarify the objectivity of the Japanese classification of peritoneal metastases from colorectal cancer., Methods: The data of patients with Stage IV colorectal cancer between 1991 and 2007 in 16 hospitals, who were members of the Japanese Society for Cancer of the Colon and Rectum, were investigated. The size, number and extent (nine areas) of peritoneal metastases according to the Japanese classification (P1, P2 and P3) were investigated using Akaike's information criterion., Results: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 had hematogenous metastases. The minimum Akaike's information criterion was obtained with the cutoff value of one area for P1 metastasis and two or more areas for P2 metastasis (P < 0.0001). When P2 metastasis was compared with P3 metastasis, the cutoff value of the number of peritoneal metastases was 10., Conclusions: The present study proposes a revision that would give objectivity to the present Japanese classification as follows: P1 is defined as peritoneal metastases 20 mm or smaller confined to one area; P2 is defined as 10 or fewer peritoneal metastases disseminated in two or more areas, or peritoneal metastases confined to one area but the size is >20 mm and P3 is defined as >10 peritoneal metastases disseminated in two or more areas., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

During recent years paramount changes have occurred in the pathogenesis of ovarian cancer and recent clinical studies identified new prognostic factors. Consequently, the FIGO has established a new staging system collectively covering carcinomas derived from the ovaries, the fallopian tubes and primary peritoneal cancers as well as malignant ovarian germ cell and sex-cord stromal tumors. The new staging system started on 01 January 2014. Major changes occurred in the FIGO IC/T1c stage with surgical spill (FIGO IC1/T1c1) versus capsule ruptured before surgery or tumor on ovarian or fallopian tube surface (FIGO IC2/T1c2) versus malignant cells in the ascites or peritoneal washings (FIGO IC3/T1c3). The regional lymph node metastases were subcategorised using a cut-off value of 10 mm as the largest dimension of the metastatic deposits. Distant metastases (excluding peritoneal metastases) were substaged as FIGO IVA/M1a in cases of cytologically or histologically proven pleural involvement and as FIGO IVB/M1b in cases of parenchymal metastases and metastases in extra-abdominal organs (including lymph nodes outside the peritoneal cavity and the inguinal lymph nodes).

Background and Objectives: Autofluorescence imaging (AFI) is mainly used to detect (pre)cancerous colorectal and pulmonal lesions. This is the first report establishing the feasibility of AFI in patients with peritoneal carcinomatosis (PC)., Methods: This is a prospective analysis of 10 patients undergoing conventional white-light laparoscopy (WL) and AFI for PC of different gastrointestinal tumors and 1 ovarian cancer. Before taking biopsies, suspicious peritoneal lesions were first detected by WL and then investigated by AFI. The intraoperative findings were photographed and then correlated with histological results., Results: Conventional WL and AFI evaluation was successful in all patients. A total of 38 biopsies were taken. The neoplasm detection rate under WL was 66% and increased to 86% when using AFI. The positive tumor detection rate was slightly higher in low AF lesions (83 vs 88%) and higher in tumor nodules (94%) than in flat peritoneal lesions (75%). For tumor nodules, the sensitivity was 94%, and the specificity was 100%. For flat lesions, the sensitivity was 75% and specificity 50%., Conclusions: We demonstrate the feasibility and effectiveness of AFI in patients with PC.

Background: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis., Methods: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum., Results: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection., Conclusions: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

Background: Preoperative detection of small peritoneal metastases is difficult, and a convenient method is required to decide the nature of procedures subsequent to initial exploratory surgery. The aim of this study was to validate the Japanese classification of peritoneal metastasis from colorectal cancer., Methods: This retrospective study analyzes data from a multi-center registry. Factors affecting the extent of peritoneal metastasis, macroscopic radical resection and prognosis were analyzed using data from patients with colorectal cancer and synchronous peritoneal metastasis. Peritoneal metastasis was classified depending on extent into three groups (P1-P3)., Results: Among 60,176 patients with colorectal surgery, 3,075 (5.1 %) had synchronous peritoneal metastasis. Tumor location on the right side (P < 0.0001), histological grade (P = 0.0014) and distant metastasis (P < 0.0001) were associated with the extent of peritoneal metastasis. Gender (P = 0.041), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis according to the present classification (P < 0.0001) and the period when the patient underwent the operation (operative period; P < 0.0001) were independently associated with macroscopic radical resection. Cox proportional hazards model disclosed that gender (P = 0.0046), tumor location (P = 0.032), age (P = 0.048), histological grade (P < 0.0001), lymph node metastasis (P < 0.0001), distant metastasis (P < 0.0001), extent of peritoneal metastasis (P < 0.0001), and macroscopic radical resection (P < 0.0001) were independent prognostic factors., Conclusions: Macroscopic radical resection was an independent prognostic factor even without hyperthermic intraperitoneal chemotherapy. The referral of patients without distant metastasis to centers with experienced peritoneal surgeons might be a potential option if the peritoneal metastasis is unresectable in general hospitals.

Pseudomyxoma peritonei is a clinical entity characterized by a gelatinous ascite associated with mucinous tumor deposits spreading on peritoneal surface and potentially invading abdominal organs. It is considered as a tumor process linked, in most of cases, to a mucinous appendiceal neoplasm. Pseudomyxoma peritonei may benefit from a therapeutic strategy combining cytoreductive surgery and intra-peritoneal chemotherapy, which has led to a major prognosis improvement. Different classifications are available and the last one corresponds to the WHO 2010 version, which individualizes pseudomyxoma peritonei in two classes: low grade and high grade mucinous carcinoma. The very low frequency of this entity and its specific therapeutic strategy need specific health care centres, as well as physicians and pathologists collaborating through dedicated networks. The aim of this article is to summarize the pathology, causes, mechanisms and therapeutic approaches of pseudomyxoma peritonei, as well as their interfaces with dedicated networks., (Copyright © 2014. Published by Elsevier Masson SAS.)

The nomenclature and classification of pseudomyxoma peritonei (PMP) is confusing and controversial. Numerous classification systems have been proposed, none of which are easily reproducible or a useful guide for treatment. Patients with PMP of appendiceal origin were identified from our institution's database. Kaplan-Meier analyses were performed based on a proposed new PMP classification, a three-tiered grading system designated PMP1, PMP2, and PMP3. These results were compared with the established schemes by Ronnett and Bradley et al. There were 211 patients included in the analysis with a mean age of 51 ± 12 years at diagnosis. For PMP1, 86 patients (40.8%) included cases with abundant extracellular mucin and columnar nonstratified epithelium without dysplasia or atypia. For PMP3, 50 patients (23.7%) consisted of PMP with any percentage of signet ring cells (SRCs), For PMP2, 75 patients (35.5%) included all other patients. The mean age (± standard deviation) for PMP 1, 2, and 3 were 51 ± 12, 51 ± 12, and 51 ± 10 years, respectively (P = 0.90). The three groups had similar sex distribution (P = 0.24) and resection status (P = 0.47). Kaplan-Meier analyses showed median survivals of 120, 88, and 40 months and 5-year survival rates of 85.7, 63.05, and 32.2 per cent (P < 0.0001) for PMP 1, 2, and 3, respectively. Three distinct categories, PMP1, 2, and 3, were identified, which provide better stratification in terms of overall survival and represent differences in tumor biology that may impact treatment recommendations.

Opinion Statement: Pseudomyxoma peritonei and peritoneal carcinomatosis derived from appendiceal epithelial tumors are controversial entities from classification to treatment. For the former entity, multiple classification systems have been attempted to distinguish indolent from more aggressive subtypes. The treatment of the low grade variants is managed with serial cytoreduction surgery, with data indicating possible, but unproven, benefit from heated intraperitoneal chemotherapy (HIPEC). There is no consensus on the role of cytoreduction and HIPEC for the management of the more aggressive histologic variants and peritoneal carcinomatosis. Currently, we believe systemic chemotherapy is the standard of care for patients with the high grade variants and peritoneal carcinomatosis.

Purpose: Five prognostic factors had been previously identified in patients with metastatic colorectal cancer (MCRC) who received irinotecan-based second-line chemotherapy. Patients were classified into three prognostic groups based on significant differences in median overall survival (OS). This study is conducted to validate this classification in an external validation cohort., Methods: This retrospective study included 193 patients of an external validation cohort who received irinotecan-based second-line chemotherapy after first-line oxaliplatin-based chemotherapy, with or without bevacizumab at three institutions., Results: Three of the five predefined factors (poorly differentiated adenocarcinoma, LDH ≥400 IU/L, progression-free survival of first-line therapy <6 months) remained highly significant in the validation cohort, although two (performance status 2 and peritoneal metastasis) were associated with borderline significance. The distribution of the three prognostic groups (low risk = no factors, intermediate risk = 1 factor, high risk = 2 or more factors) was low risk (n = 68; 35 %), intermediate risk (n = 80; 41 %), and high risk (n = 45; 23 %). The median OS of each group were 19.8, 11.0, and 7.9 months, respectively, with significant differences between groups, as found in the previous cohort., Conclusion: The previous prognostic classification of patients with MCRC who received irinotecan-based second-line chemotherapy was validated in another independent cohort. Validation in prospective studies is warranted.

Aim: To assess the clinicopathologic features and its relationship with prognosis of pseudomyxoma peritonei (PMP) in Chinese patients., Methods: The clinicopathologic features and follow-up data of 92 patients with PMP were reviewed and retrospectively analyzed. The cases were categorized into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). The log-rank test was used to analyze survival for each group and various clinicopathological parameters. Multivariate Cox proportional-hazard models were constructed to determine the important factors associated with survival., Results: The median age at diagnosis was 51.9 years (range: 22-76 years). The median follow up was 124 mo. The 3-, 5- and 10-year survival rates were 74.0%, 67.4% and 49.1%, respectively. There were 49 (53.2%) patients with DPAM, 26 (28.3%) with PMCA-I and 17 (18.5%) with PMCA. Patients with DPAM, PMCA-I/D and PMCA exhibited statistically significant difference in survival (P = 0.001). The 3 year survival for DPAM, PMCAI/D and PMCA was 97.0%, 80.0% and 67.0%, respectively; the 5 year survival was 80.0%, 67.0% and 50.0%, respectively; and the 10 year survival was 65.0%, 28.0% and 14.0%, respectively. Survival rate was significantly lowest in patients < 40 age years of age (P = 0.011). Appendiceal tumor and extra-ovarian parenchymal organ involvement were significantly related to overall survival. Patients with appendiceal mucinous adenocarcinoma (MACA) showed the significantly poorer prognosis (P = 0.011). Multivariate analysis showed that pathological classification, age, appendiceal tumor were significant related to overall survival., Conclusion: The clinical process "PMP" should be pathologically classified into DPAM, PMCA and PMCA-I/D. Pathological classification, age, appendiceal MACA are survival independent predictors in Chinese patients with PMP.

Mucinous neoplasms of the appendix are rare tumors, some of them characterized by an enigmatic discrepancy between a benign morphologic appearance and an aggressive biologic potential, associated with a poor prognosis and high mortality. The clinical picture of pseudomyxoma peritonei is, with few exceptions, caused by mucinous appendiceal neoplasms and differs in many aspects from usual peritoneal carcinomatosis. The controversy regarding terminology, diagnostic criteria, classification and therapy of these tumors has lasted for decades. The revised edition of the World Health Organization Classification of Tumors of the Digestive System proposes a uniform reporting system for mucinous appendiceal neoplasms and the peritoneal disease associated with it, thereby creating a comparable basis for pathological diagnosis, clinical therapy and further scientific studies.

Aim: Current classification systems of large bowel cancer only refer to metastatic disease as M0, M1 or Mx. Recurrent colorectal cancer primarily occurs in the liver, lungs, nodes or peritoneum. The management of each of these sites of recurrence has made significant advances and each is a subspecialty in its own right. The aim of this paper was to devise a classification system which accurately describes the site and extent of metastatic spread., Method: An amendment of the current system is proposed in which liver, lung and peritoneal metastases are annotated by 'Liv 0,1', 'Pul 0,1' and 'Per 0,1' in describing the primary presentation. These are then subclassified, taking into account the chronology, size, number and geographical distribution of metastatic disease or logoregional recurrence and its K-Ras status., Conclusion: This discussion document proposes a classification system which is logical and simple to use. We plan to validate it prospectively., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

Context: Appendiceal mucinous neoplasms are considered enigmatic tumors of unpredictable biologic potential. Their importance lies in their potential to spread to the peritoneum and viscera in the form of gelatinous mucin deposits. Extra-appendiceal spread of these tumors is the most common etiology of pseudomyxoma peritonei , which is a descriptive term encompassing a number of neoplastic and nonneoplastic peritoneal disorders. Many studies aimed at evaluating the biologic importance of appendiceal mucinous neoplasms and pseudomyxoma peritonei have employed inconsistent histologic criteria for their diagnosis and descriptive terminology for their classification. As a result, appendiceal mucinous neoplasms and associated peritoneal disease represents one of the most confusing and controversial areas in gastrointestinal pathology., Objectives: To summarize the literature regarding the biologic potential of appendiceal mucinous neoplasms and pseudomyxoma peritonei and to discuss the similarities and differences between proposed systems for their classification., Data Sources: Literature review and case-derived material., Conclusions: Many studies have contributed to an increased understanding of the natural progression of mucinous neoplasms of the appendix and peritoneum, and the adoption of a uniform reporting system, as advocated by the American Joint Committee on Cancer and the World Health Organization, will facilitate clear communication among pathologists and clinical colleagues.

Background: Previous studies revealed serosal invasion as one of the most important predictors of peritoneal micrometastasis. However, even for cancers with serosal invasion, the macroscopic serosal appearance is highly heterogeneous. The aim of the present study was to propose a macroscopic serosal classification (MSC) and to investigate the validity of this classification as a predictor of peritoneal recurrence., Materials and Methods: Clinicopathologic features including MSC of 1528 patients with pT3/pT4a stage gastric cancers who underwent potentially radical surgery were retrospectively reviewed. MSC was classified as reactive type, nodular type, tendonoid type, and color-diffused type according to the macroscopic serosal appearance., Results: There were significant differences in tumor size, location, Bormann type, Lauren grade, lymphatic and/or blood vessels invasion (LBVI), width of serosa changes, depth of invasion, number of nodes metastasis, lymph node metastasis ratio, pN stage, and peritoneal cytology between patients with different types of serosa. Multivariate analysis revealed MSC, as well as depth of invasion, Lauren grade, and pN stage, significantly predicted the presence of peritoneal-free cancer cells. Both MSC and peritoneal cytology significantly correlated with patient survival. However, only MSC significantly predicted peritoneal recurrence on multivariate analysis, but peritoneal cytology did not, indicating MSC was more sensitive than cytologic examination. Further investigation suggested MSC and pN stage were also independent predictors of peritoneal recurrence for patients with negative peritoneal cytology., Conclusions: The MSC sensitively predicts the presence of peritoneal micrometastasis for pT3/pT4a-stage gastric cancer patients who underwent potentially radical surgery. Consequently, it might be considered a good indicator to guide perioperative adjuvant therapy for patients with high risk of peritoneal recurrence.

Background: Unlike novel molecular-targeted therapies for metastatic gastrointestinal stromal tumors (GIST), conventional treatments for peritoneal sarcomatosis (PS) are mostly ineffective. As with carcinomatosis of epithelial origin, a rationale base supports an aggressive locoregional treatment of PS, but the use of CRS and HIPEC in this setting is still controversial. We assessed the outcome of clinically and pathologically homogeneous subsets of patients with PS uniformly treated by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)., Methods: A prospective database of 37 patients who underwent CRS and close-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C was reviewed. PS originated from GIST (pre-imatinib era) in 8 patients, uterine leiomyosarcoma (ULS) in 11, retroperitoneal liposarcoma (RPLP) in 13, and other sarcoma in 5., Results: CRS was macroscopically complete in 28 patients (75.7%). Operative mortality was 3.7% and morbidity 21.6%. After median follow-up of 104 (range, 1-131) months, peritoneal disease progression occurred in 16 patients, distant metastases in 5, and both in 13. For all patients, median overall survival was 26.2 months; 7 patients were alive at 46-130 months (ULS, n = 4; RPLP, n = 2; GIST, n = 1). RPLP had the best overall survival (median, 34 months) but 100% peritoneal relapse; GIST had dismal overall, local-regional-free and distant-free survival; ULS had the higher proportion of long survivors and best local-regional-free survival., Conclusions: Overall, results of CRS and HIPEC did not compare favorably to those of conventional therapy. In a subgroup analysis, the combined approach did not change GIST and RPLS natural history. The interesting results with ULS may warrant further investigations.

In humans, mesothelioma has been linked to asbestos exposure, especially crocidolite and amosite asbestos, which contain high amounts of iron. Previously, we established a rat model of iron-induced peritoneal mesothelioma with repeated intraperitoneal injections of iron saccharate and an iron chelator, nitrilotriacetate. Here, we analyze these mesotheliomas using array-based comparative genomic hybridization (aCGH) and gene expression profiling by microarray. Mesotheliomas were classified into two distinct types after pathologic evaluation by immunohistochemistry. The major type, epithelioid mesothelioma (EM), originated in the vicinity of tunica vaginalis testis, expanded into the upper peritoneal cavity and exhibited papillary growth and intense podoplanin immunopositivity. The minor type, sarcomatoid mesothelioma (SM), originated from intraperitoneal organs and exhibited prominent invasiveness and lethality. Both mesothelioma types showed male preponderance. SMs revealed massive genomic alterations after aCGH analysis, including homozygous deletion of CDKN2A/2B and amplification of ERBB2 containing region, whereas EMs showed less genomic alterations. Uromodulin was highly expressed in most of the cases. After 4-week treatment, iron deposition in the mesothelia was observed with 8-hydroxy-2'-deoxyguanosine formation. These results not only show two distinct molecular pathways for iron-induced peritoneal mesothelioma, but also support the hypothesis that oxidative stress by iron overload is a major cause of CDKN2A/2B homozygous deletion.

Background: This study aimed to validate an easy to use practical classification of peritoneal metastasis arising from colorectal cancer., Patients and Methods: Data from 2,134 consecutive patients who underwent resection for colorectal cancer at a single institution were reviewed. Peritoneal metastasis was classified depending on extent into three groups (P1-P3). The macroscopic radical resection rates and survival of patients with colorectal cancer complicated with peritoneal metastasis were analyzed., Results: Of the 2,134 patients, 116 (5.4%) had peritoneal metastasis. Among them, 20 (17.2%) underwent macroscopic radical resection. Tumor location on the right side was associated with more extensive peritoneal metastasis (p = 0.010). Male gender (p = 0.0027), liver metastasis (p = 0.0021), and P3 peritoneal metastasis were independent risk factors for noncurative resection. The Cox proportional hazards model showed that gender (p = 0.031), operation period (p = 0.031), and macroscopic radical resection for colorectal cancer and peritoneal metastasis (p = 0.031) were independent prognostic factors., Conclusions: Being female with left colon cancer complicated with P1 or P2 peritoneal metastasis is a good indicator for macroscopic radical resection if liver metastasis is absent. The present classification helped to determine surgical indication for patients with colorectal cancer complicated with synchronous peritoneal metastasis in routine clinical practice., (Copyright © 2010 S. Karger AG, Basel.)

This retrospective study was performed to clarify whether or not ovarian metastasis from colorectal cancer should be classified into peritoneal metastasis. We compared patient background data and prognosis between patients with ovarian metastasis (ovarian group, n=16) and female patients with peritoneal metastasis without involving ovaries (peritoneal group, n=22) treated between 1998 and 2008. The two groups did not significantly differ in terms of other clinicopathological factors evaluated. The median overall survival period was 13.8 months for the ovarian group and 16.7 months for the peritoneal group (p=0.96). The 3-year overall survival rate was 48.6%, 46.9%, and 11.5% for patients with ovarian metastasis only (P2), those with minute peritoneal metastasis without involving ovaries (P1), and those with multiple (numerous) peritoneal metastasis without involving ovaries (P3) (p=0.13), respectively. These results suggest that it is valid to classify ovarian metastasis as peritoneal metastasis. However, further collection of data may be needed to conclude that solitary ovarian lesion(s) would be classified into P2.

Malignant peritoneal mesotheliomas arise mainly in male patients and the median age of initial diagnosis is about 56 years. Epitheloid subtype predominates in peritoneal mesotheliomas. Asbestos exposure is the best-known and most common risk factor associated with the development of both pleural and peritoneal mesotheliomas and, therefore, about 90% of cases can be assessed as asbestos-associated. Patients with peritoneal mesotheliomas have distinctly higher asbestos burden of the lungs than patients with pleural mesotheliomas. The mean latency period between exposure and diagnosis of peritoneal mesothelioma ranges from 35 to 40 years and is comparable to that of pleural mesothelioma. Mesothelioma of the tunica vaginalis testis also belongs to the group of peritoneal mesotheliomas. No significant evidence exists for the classification of well-differentiated papillary mesothelioma, solitary fibrous tumor, adenomatoid tumor, primary peritoneal serous borderline tumor, and benign multicystic mesothelioma as asbestos-associated tumors. Except malignant mesotheliomas, the induction of other abdominal tumors is independent of an exposure to asbestos dust.

Serous carcinoma of the ovary has been traditionally graded as well-differentiated, moderately differentiated, and poorly differentiated (ie, a 3-tier system). A new 2-tier system grades serous carcinomas into low or high grade. Recent morphologic and molecular studies have shown that invasive well-differentiated serous carcinoma, referred to by us as "invasive low-grade micropapillary serous carcinoma," is clearly distinct from high-grade serous carcinoma from the standpoint of pathogenesis and clinicopathologic features. As high-grade serous carcinoma is histologically heterogeneous, the goal of this study was to determine, based on molecular and drug resistance data, whether further subclassification of high-grade serous carcinomas into additional grades (moderately and poorly differentiated) has biologic validity. One hundred eleven ovarian and peritoneal high-grade serous carcinomas further subclassified as moderately and poorly differentiated types using the International Federation of Gynecology and Obstetrics (FIGO) grading system were analyzed for TP53 mutations and in vitro extreme drug resistance to 10 chemotherapeutic drugs. Seventy-six and 35 cases were subclassified as moderately and poorly differentiated, respectively. A TP53 mutation was present in 84% of moderately and 70% of poorly differentiated types of high-grade serous carcinomas, respectively (P=0.21), and there were no significant differences in the frequency of extreme drug resistance for each of the 10 drugs tested (P values ranging from 0.14 to >0.99). Although additional investigation is warranted, this study suggests that subclassification of high-grade serous carcinoma into moderately and poorly differentiated is not relevant. Accordingly, they can be simply classified as high-grade serous carcinoma.

Objective: The objective of our study was to illustrate various CT findings of peritoneal mesotheliomas, to review their clinicopathologic features, and to discuss the differential diagnoses., Conclusion: The clinicopathologic features of peritoneal mesotheliomas vary among the subtypes such as malignant mesotheliomas, cystic mesotheliomas, and well-differentiated papillary mesotheliomas, and accordingly, there is a spectrum of CT appearances.

Objective: To clarify the various diagnostic connotations of pseudomyxoma peritonei (PMP) and to study their prognostic implications., Methods: Clinicopathologic features and follow-up data of 40 patients with PMP diagnosed in The General Hospital of PLA were retrospectively reviewed. The cases were histologically classified into 3 subcategories: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and PMCA with intermediate or discordant features (PMCA-I/D). The survival rate was calculated using Kaplan-Meier method and the difference was statistically analyzed., Results: Twelve of the 40 patients died on follow up. The duration of survival ranged from 2 to 348 months (medium = 37.5 months). In general, the 3-year, 5-year and 10-year survival rates were 79.0%, 69.4% and 53.0%, respectively. The mean age of the patients at the time of diagnosis was 50.3 years (age range = 22 to 76 years). The male-to-female ratio was 1:1. The age and sex of patients, frequency of operation and presence of ovarian involvement did not correlate with duration of survival. On the other hand, the presence of appendiceal tumor, parenchymal invasion of abdominal viscera, cellularity, architecture, nuclear atypia and mitotic activity of the peritoneal lesion significantly correlated with survival. There was also significant difference in survival between DPAM, PMCA-I/D and PMCA subcategories (P = 0.018). The difference in survival rate between PMCA-I/D and PMCA subgroups however was not statistically significant (P = 0.096). The outcome of DPAM was significantly better when compared with the combined group of PMCA-I/D and PMCA (P = 0.006)., Conclusions: In general, the 10-year survival rate of PMP was low, despite the relatively benign-looking or low-grade pathologic appearance. Peritoneal lesions with higher cellularity, conspicuous nuclear atypia and higher mitotic activity are associated with a lower survival rate. The prognosis was even worse in the presence of appendiceal carcinoma or parenchymal invasion of abdominal viscera. It is thus advisable to subclassify PMP into DPAM, PMCA and PMCA-I/D, due to the difference in prognostic implication.

Aims: CDX-2 is a highly sensitive and specific marker of intestinal epithelial cells and their neoplastic counterparts. CDX-2 status in pseudomyxoma peritonei (PMP) has been barely reported. The aim of this study was to investigate the clinicopathological features of 42 cases of PMP with a special emphasis on CDX-2., Methods and Results: All patients were treated by cytoreduction. Immunohistochemistry was performed for CDX-2, MUC-2, MUC-5AC, cytokeratin (CK) 7 and CK20. Statistical correlation was evaluated for age, sex, completeness of cytoreduction and histological subtype with overall and progression-free survival (OS and PFS). PMP consisted of 32 cases of disseminated peritoneal adenomucinosis and 10 cases of peritoneal mucinous carcinomatosis. The appendix evaluated in 25 cases showed two mucinous adenocarcinomas and 21 low-grade appendiceal mucinous neoplasms. CDX-2 was diffusely positive in 40 cases, with the remaining two cases being focally positive. All cases demonstrated diffuse reactions to CK20 and MUC-2, and variable reactions to MUC-5AC, while CK7 was variably positive in 38 cases. Five-year OS was 97%. Histological type was significantly correlated with PFS (P=0.02)., Conclusions: CDX-2 is diffusely and strongly positive in PMP. This is a useful marker to confirm an appendiceal origin of PMP, particularly when used in conjunction with CK7, CK20, MUC-2 and MUC-5AC.

Pseudomyxoma peritonei is a clinical term for gelatinous ascites, usually secondary to an appendiceal tumor. The pathologic classification of pseudomyxoma peritonei and its associated appendiceal tumors has been plagued with controversy and confusing terminology. In an effort to clarify this, we reviewed the pathology of 101 patients, all treated at our institution from 1993 to 2005, with pseudomyxoma peritonei of appendiceal origin. All patients were uniformly treated with our standardized protocol. This is the largest pathologic series solely devoted to appendiceal neoplasia with gelatinous ascites. The cases were assigned, according to previously published criteria, to the categories of disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), or PMCA with intermediate (well differentiated) features (PMCA-I), with the exception that any case with a signet-ring cell component was considered as PMCA and not PMCA-I. By histologic category, 58 patients had DPAM, 23 were PMCA, and 20 were PMCA-I.One-year, 3-year, and 5-year survival outcomes were not significantly different between DPAM and PMCA-I. DPAM and PMCA-I also exhibited a roughly equal incidence of parenchymal (beyond the serosa) organ invasion. Survival outcomes were significantly worse for PMCA, compared with PMCA-I and DPAM. After reviewing our data and the literature, mucinous carcinoma peritonei-low grade was applied to the low-grade histology of pseudomyxoma peritonei, including those cases referred to by some as DPAM in the same category as PMCA-I. Cases that are moderately differentiated to poorly differentiated are classified as mucinous carcinoma peritonei-high grade.

Introduction: With the aim of identifying metastases-related genes in gastric cancer, we performed a broad analysis of differential gene expression between low-metastatic parental cell lines and established highly metastatic sublines., Materials and Methods: We established novel cell lines, AZ-H5c, NUGC-3H5, and TMK-1H7, with a high potential of liver metastasis, and AZ-P7a, NUGC-3P4T, and TMK-1P4a, with a high potential of peritoneal metastasis. These cell lines were derived from low-metastatic parental AZ-521, NUGC-3, and TMK-1 cell lines, respectively. Furthermore, to investigate different levels of gene expression implicated in metastatic potentials in gastric cancer, we investigated approximately 2000 expressed genes in each cell line using a DNA microarray., Results: Varieties of genes were up-regulated or down-regulated in highly metastatic liver and peritoneal cell lines. Fifty-eight genes, including the transferrin receptor, ras-related rho, and osteopontin, and 22 genes, including apolipoprotein E and inhibin A-submit, were up-regulated and down-regulated in two or three liver metastatic sublines. On the other hand, 19 genes, the transferrin receptor, c-fos, and RANTES, and 26 genes, including MAC25, PISSLRE, and RNA polymerase, were up-regulated and down-regulated in two or three peritoneal metastatic sublines., Conclusion: How gene expression is implicated in gastric cancer metastasis has never been thoroughly explained, and further studies are necessary to understand the involvement of genes in cancer metastasis more thoroughly. We hope that our highly metastatic liver and peritoneal experimental models are helpful for further study and gene therapy of human gastric cancer.

Pseudomyxoma peritonei is an overused and underspecified condition that has garnered much attention in the historic literature. In recent years, this condition has been convincingly linked to appendiceal mucinous neoplasms, yet there has been insufficient attention to the histologic characteristics, classification, and differential diagnostic considerations of these neoplasms when encountered by the surgical pathologist. This review provides a coherent approach to the diagnosis and classification of appendiceal mucinous tumors and the peritoneal implants associated with the pseudomyxoma peritonei syndrome with emphasis on differential diagnostic considerations and recommendations for the final pathology report.

Aims and Background: Peritoneal mesothelioma is a rare disease with a universally fatal outcome when managed in a traditional palliative manner. New approaches to treatment using cytoreductive surgery and intraperitoneal chemotherapy suggest that long-term survival is possible in selected patients. Early recognition of this disease process with an orderly surgical approach will begin to optimize treatment., Methods: Thirty-three patients with malignant peritoneal mesothelioma had CT scans available for review. A Z-score was used to evaluate the incidence of cancer at a particular anatomic site as compared to a general incidence of disease at all sites. CT was analyzed by abdominopelvic anatomic sites (16), abdominopelvic regions (9), and for presence versus absence of disease in the chest. Interpretative CT findings (class 0-III) were determined for these 33 patients., Results: Eight of 33 patients had pleural abnormalities. In an analysis of 16 abdominopelvic anatomic sites, the vesical or rectal uterine pouch was involved in 97% and the greater omentum in 91%. These anatomic sites were the only ones with a positive Z-score of >1. In the analysis of 9 abdominopelvic regions, the central and pelvic regions had Z-scores >2 for large volume disease >5 cm. For CT interpretative findings class I, class II and class III was determined in approximately one-third in each category. Sixty-six percent of the patients had ascites by CT., Conclusions: Malignant peritoneal mesothelioma by CT evaluation predominates in tumor mass within the central and pelvic portions of the abdomen. Minimal, moderate, and extensive small bowel enlargements were seen in roughly one-third of the patients. With the use of the Z-score and interpretative small bowel findings a radiologic characterization of this disease for primary radiologic diagnosis is possible.