Disseminated Peritoneal Adenomucinosis Research Articles

Clinical and ultrasound features of pseudomyxoma peritonei and its histopathological subtypes among women seen at a Philippine tertiary hospital: A 10-year review

OBJECTIVES: Pseudomyxoma peritonei (PMP) in women arises from an appendiceal or ovarian pathology and presents either of two histological subtypes of differing prognosis, disseminated peritoneal adenomucinosis (DPAM), or peritoneal mucinous carcinomatosis (PMCA). This study aimed to evaluate the demographic, clinical, and sonographic features among affected women and the differences between the two histological subtypes. METHODS: A retrospective study was conducted involving 36 women with histopathological diagnosis of PMP who had preoperative ultrasound and underwent surgery at the department of obstetrics and gynecology in a tertiary hospital. Demographic and clinical data, ultrasound images and reports, and final histopathology were reviewed. To compare the subtypes, one-way analysis of variance for continuous data and Chi-square/Fisher exact test for categorical data were used, with P < 0.05 indicating statistical significance. RESULTS: Patients were mostly >50 years of age, multigravid, and presented with abdominal distention. Ultrasound examinations consistently showed amorphous, mixed echo or echogenic ascites, peritoneal thickening, and omental caking. Adnexal/ovarian masses were detected in 66.7% of cases. Omental caking was significantly more prevalent in PMCA (83.3%; P = 0.0002), whereas larger ovarian tumors (>20 cm) and papillarities were more common in DPAM (both 92.9%; P = 0.0005). Most patients underwent gynecologic surgery (n = 31; 86.1%), and 14 (38.9%) required readmission due to recurrence. The final histopathology revealed largest tumor involvement of the appendix (n = 13; 36.1%), the ovaries (n = 11; 30.5%), or undetermined (n = 12; 33.3%). CONCLUSIONS: Preoperative diagnosis of PMP is possible based on its clinical and ultrasound features. Although the subtypes are similar in most of these features, certain ultrasound findings may aid in distinguishing them.

Impact of Macroscopic Tumour Consistency and EPIC in Low-grade Appendiceal Neoplasms With Pseudomyxoma Peritonei

Background/Aim: Low-grade appendiceal mucinous neoplasm (LAMN) with pseudomyxoma peritonei (PMP), otherwise known as disseminated peritoneal adenomucinosis (DPAM), is treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) with or without early postoperative intraperitoneal chemotherapy (EPIC). These tumours can vary significantly intraoperatively in terms of macroscopic appearance and consistency, and this may have an effect on survival outcomes. This study examines the differences between soft and hard tumours in terms of shortterm outcomes and long-term survival and whether this can change with the use of EPIC. Patients and Methods: Patients were classified into having macroscopically soft or hard tumours. A comparison of short-term outcomes (major morbidity, mortality, length of ICU stay and length of hospital stay) and long-term outcomes (overall survival) was performed. Survival sub analysis was performed in the patients who received EPIC. Results: Soft tumours behaved differently, with lower morbidity, mortality, shorter ICU stay and hospitalisation. They also demonstrated greater overall survival (86.7% at 5 years, p<0.001). EPIC improved the overall survival for both soft and hard tumours. Conclusion: Tumour consistency has an impact on the outcomes of patients with DPAM and this can be used for prognostication.

Factors influencing long-term survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei originating from appendiceal neoplasms.

BackgroundPseudomyxoma peritonei (PMP) is a rare disease, most commonly of appendiceal origin. Treatment consists of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS–HIPEC). The aim of this study was to identify prognostic factors for recurrence and survival.MethodsThis was an observational study using a prospectively designed database containing consecutive patients with PMP originating from the appendix, undergoing CRS–HIPEC at a tertiary referral centre between 1996 and 2015. Histopathological slides were reassessed. Cox regression was used for multivariable analyses.ResultsOf 225 patients identified, 36 (16·0 per cent) were diagnosed with acellular mucin, 149 (66·2 per cent) had disseminated peritoneal adenomucinosis (DPAM) and 40 (17·8 per cent) had peritoneal mucinous carcinomatosis (PMCA). The 5‐year overall survival (OS) rates were 93, 69·8 and 55 per cent respectively. Recurrence was observed in 120 patients (53·3 per cent), 39 of whom (17·3 per cent) were treated with a second CRS–HIPEC procedure. Factors independently associated with poor disease‐free survival were six or seven affected regions (hazard ratio (HR) 6·01, 95 per cent c.i. 2·04 to 17·73), incomplete cytoreduction (R2a resection: HR 1·67, 1·05 to 2·65; R2b resection: HR 2·00, 1·07 to 3·73), and more than threefold raised carcinoembryonic antigen (CEA) and/or carbohydrate antigen (CA) 19‐9 level (HR 2·31, 1·30 to 4·11). Factors independently associated with poorer OS were male sex (HR 1·74, 1·09 to 2·77), incomplete cytoreduction (R2a resection: HR 1·87, 1·14 to 3·08; R2b resection: HR 2·28, 1·19 to 4·34), and more than threefold raised CEA and/or CA19‐9 level (HR 2·89, 1·36 to 6·16).ConclusionCEA and CA19‐9 levels raised more than threefold above the upper limit identify patients with PMP of appendiceal origin and poorer survival.

Pseudomyxoma Peritonei Revisited: A Case Report

Bleeding after menopause raises suspicion of malignancy; more so, if combined with increased abdominal girth and constitutional symptoms. This is a case of a 74-year-old Gravida 10 Para 8 (8026) who presented with generalized abdominal pain, enlargement, bloatedness and vaginal bleeding. Ultrasound revealed a complex abdominopelvic mass, likely ovarian in origin. Tumor markers CA-125 and CA-199 were elevated. Endometrial curettage with frozen section revealed Leiomyosarcoma. It was followed by exploratory laparotomy revealing gelatinous material in the peritoneum with seeding of mucoid material into the omentum, ovary and appendix. Frozen section of the right ovary revealed Atypical Mucinous Proliferative Ovarian Tumor (APMOT). Final histopathology result of the endometrial curetting revealed adenomatoid tumor of the uterus. Immunohistochemical staining with desmin and caldesmon revealed negative results implicating the absence of leiomyosarcoma. Final histopathology results were consistent with Disseminated Peritoneal Adenomucinosis (DPAM). Immunohistochemical staining with CK20 was positive and CK7 was negative, consistent with metastases from a primary gastrointestinal tumor. Chemotherapy in the form of FOLFOX regimen was contemplated. However, the patient was lost to follow up

Long term survival analysis after hyperthermic intraperitoneal chemotherapy with oxaliplatin as a treatment for appendiceal peritoneal carcinomatosis

Background and objectivesComplete cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) have been proven to lengthen survival in appendiceal peritoneal carcinomatosis (PC-A). The aim of this study was to analyze survival results of this therapy in our institution over the last 10 years. MethodsData was retrospectively reviewed and analyzed. Treatment consisted of CRS plus HIPEC with oxaliplatin. Ronnett's histologic classification was used (peritoneal mucinous carcinomatosis (PMCA), PMCA with intermediate features (PMCA-I) and disseminated peritoneal adenomucinosis (DPAM)). Overall survival (OS) and disease-free survival (DFS) estimates were calculated using Kaplan–Meier survival curves. Results109 patients with PC-A underwent laparotomy with curative intent. Of those, 92 underwent CRS plus HIPEC. Median follow-up was 42 months. The 5 and 10-year OS rates for the HIPEC group were 82.2% and 76.5%. The 5 and 10-year OS estimates for DPAM and PMCA-I subgroups were 100% and 100%, 78.1% and 72.9%, respectively. For the PMCA subgroup, the 3 and 5-year OS were 61.4% and 40.1%, respectively. The 5 and 10-year DFS estimates were 71.9% and 42.7%. ConclusionCRS plus HIPEC with oxaliplatin represent an effective therapeutic approach for PC-A. Long term OS estimates for patients treated at our institution are encouraging.

Long-term outcomes with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from appendiceal cancer: An 18-year experience.

4098 Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have become standard of care for patients with peritoneal carcinomatosis (PC) from appendiceal cancer (AC). We reviewed our experience and outcomes. Methods: A retrospective review of 614 CRS/HIPEC procedures from 1998-2016 was performed. Patient characteristics, surgical variables, and postoperative outcomes of first CRS/HIPEC were analyzed. Results: Two hundred ninety patients with PC from AC underwent 334 CRS/HIPEC’s. Median age at diagnosis and surgery was 52 (22-79) and 53 (23-81) years, respectively; 65% (187) were female. Prior surgical score was 0, 1, 2, and 3 in 20%, 38%, 37%, and 5%, respectively. Prior systemic chemotherapy was reported in 30% of patients. Median time from diagnosis to CRS/HIPEC was 4 months (0-182). Pre-operative tumor markers (CEA, CA-125, CA-19-9) were positive in 48% with one, two, and three positive markers in 21%, 15%, and 13% patients, respectively. Median Peritoneal Cancer Index was 29. Mitomycin-C was the HIPEC agent of choice. Mean operative time was 10 hours (R: 4-19) and median length of stay was 10 days (R: 4-93). Histology included 59% (171) peritoneal mucinous carcinomatosis (PMCA), 41% (119) disseminated peritoneal adenomucinosis (DPAM). Lymph nodes were positive in 47% PMCA. Complete cytoreduction rate was 87% (84% PMCA, 92% DPAM [p = 0.048]). Grade III-V complications occurred in 21%, with one 30-day mortality (0.3%). Overall, median progression-free survival (PFS) was 84 months with 5-year PFS of 56%. Median PFS was 43 months in PMCA and not reached in DPAM. Five year PFS was 40% PMCA and 82% DPAM (p < 0.001). Median overall survival (MOS) was 139 months with 61% 5-year OS. MOS was 53 months in PMCA and not reached in DPAM. Five year OS was 47% PMCA and 85% DPAM (p < 0.001). At 42-month median follow-up, 68% were alive (92 PMCA/103 DPAM) with 84% disease free (72 PMCA/92 DPAM), 28% died of disease (73 PMCA/7 DPAM). Conclusions: CRS/HIPEC is an effective treatment for patients with PC from AC providing meaningful long term survival in low and high grade tumors and should be considered the standard of care.

Early identification of DPAM in at-risk low-grade appendiceal mucinous neoplasm patients: a new approach to surveillance for peritoneal metastasis

BackgroundDisseminated peritoneal adenomucinosis (DPAM) patients often have a history of appendectomy with identification of an incidental mucinous neoplasm (low-grade appendiceal mucinous neoplasm (LAMN)). The rate of developing DPAM is not well established.MethodsTwenty-two patients with incidental LAMN were identified and monitored with cancer markers and CT every 4–6 months. Laparoscopy with peritoneal washing was performed in patients either in the event of radiographic disease or after 12 months in absence of radiographic disease. The rate of detecting peritoneal metastasis was determined for CT scan and laparoscopy.ResultsPeritoneal metastasis was detected in 5 (23 %) patients. Occult disease was detected in four patients at laparoscopy without a detectable disease on CT scan. One patient developed radiographic progression at 6 months confirmed with laparoscopy. Four patients were treated with cytoreductive surgery (CRS)/HIPEC and one with CRS only. The 17 patients with negative laparoscopy remain disease free with a median follow-up of 50 months.ConclusionsThe rate of peritoneal metastasis in incidental LAMN patients was 23 %. Laparoscopy was the primary screening tool identifying occult metastasis. The median PCI of 7 was low, and all the patients underwent R0/R1 resections. This study revealed 1 in every 4.4 patients with LAMN may develop PMP. Longer follow-up and further patient surveillance is warranted.

Significance of epithelial cell clusters in pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterised by distension of the peritoneum by jelly-like ascites. Cytological evaluation of peritoneal fluid is often an initial diagnostic test for possible ovarian and/or appendiceal primary tumours. The present work was conducted to study the usefulness of peritoneal fluid cytomorphology in the early diagnosis of PMP and to evaluate the significance of the presence of epithelial cell (EC) clusters and their prognostic implications. We evaluated the detailed cytological features of 21 cases of PMP retrospectively. Both conventional and liquid-based cytology smears of peritoneal fluid were reviewed, cytological features were compared with histological findings and cases were classified into disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). In our study, the common causes of PMP were primary gastrointestinal malignancies (appendix and colorectal, 57.14%), followed by primary ovarian mucinous neoplasms (28.57%) and synchronous ovarian and appendicular tumours (14.28%). Thick mucinous material was present in all cases (100%). ECs were present in 18 of 21 (85.17%) patients, with mild nuclear atypia in the majority of cases. Histiocytes, mesothelial cells and fibroblast-like, spindle-shaped cells with entrapped mucin were also noted in the background. The cases of PMCA showed greater numbers of EC clusters in cytology smears and these patients had recurrent episodes of PMP. On cytomorphology, high-grade tumours were more cellular and frequently showed EC clusters with moderate to severe atypia, prominent nucleoli and mitosis, and were more prone to PMCA.

The role of cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) in patients with peritoneal carcinomatosis (PC) of appendiceal origin (AO).

707 Background: Peritoneal carcinomatosis of mucinous appendiceal tumor origin is a rare condition which has poor prognosis if treated with limited surgery or systemic chemotherapy. Several publications show that CRS/HIPEC gives a significant survival benefit for patients with PC of AO. However, many patients do not get appropriate treatment. We show data from our 17-year experience using CRS/HIPEC in PC of AO. Methods: Retrospective analysis of a prospective database of 251 patients with PC of AO was performed. Peritoneal cancer index (PCI), completeness of cytoreduction (CC), lymph node (LN) status, and histopathology data was collected. The impact of each variable evaluated by Hazard ratio analysis. Overall survival (OS) estimated by Kaplan-Meier curves. Results: Mean age 53 years (range 23-81). 251 patients underwent 290 CRS/HIPEC procedures. 31 patients had 2, and 4 patients had 3 CRS/HIPEC. A total of 149 patients (59%) had peritoneal mucinous carcinomatosis (PMCA) and 102 (41%) had disseminated peritoneal adenomucinosis (DPAM) (Ronnett classification). Mean follow-up 4.8 years with a median of 4.7 years. Complete cytoreduction was achieved in 84% (89% DPAM, 80% PMCA; p = 0.047). Mean length of surgery 11.3 hours, mean hospital stay 14 days. No in-hospital or 30-day mortality. 73% had PCI > 20 (78% DPAM; 68% PMCA). LN metastasis in 42% with PMCA. OS from date of HIPEC was 93%, 86%, 81% in DPAM and 90%, 60%, 44% in PMCA for 1, 3, and 5 years, respectively. With CC, the 5-year OS was 84% in DPAM and 49% in PMCA. All PMCA patients with incomplete cytoreduction (n = 30) had PCI ≥ 20 (p < 0.001). Hazard ratios were 2.5 (95% confidence interval [95% CI] 1.3-4.5), 3.1 (95% CI 2.0-4.9), 3.6 (95% CI 2.1-6.2), for PCI < 20, complete cytoreduction, and histopathology (DPAM vs. PMCA), respectively. Hazard ratio (for LN status in patients with PMCA was 3.0 (95% CI 1.8-5.1). Conclusions: Meaningful survival could be achieved in PC of AO even with extensive peritoneal disease (PCI > 20). We consider CRS/HIPEC a standard of care for these patients. CRS/HIPEC should be provided in specialized centers by trained surgeons where complete cytoreduction could be frequently accomplished.

Pseudomyxoma Peritonei from a Borderline Mucinous Tumor Arising in an Ovarian Mature Cystic Teratoma: A Rare Case Report

Pseudomyxoma peritonei (PMP) is a rare associated diagnosis of peritoneal carcinomatosis which, classically, has been characterized by a slowly progressive disease process. More recently, Ronnett et al., have histologically classified PMP into the slow growing disseminated peritoneal adenomucinosis (DPAM), the much more aggressive and invasive peritoneal mucinous carcinomatosis (PMCA) and an intermediate group (ID). Recent studies have shown that most cases of PMP arise from ruptured appendiceal tumors with dissemination of mucin producing epithelial cells into the peritoneal cavity. PMP, contrary to popular belief, almost never arises from a ruptured primary ovarian mucinous tumor, corroborated by two of the largest series on ruptured borderline mucinous ovarian neoplasms. A small number of cases have been reported, however, with peritoneal carcinomatosis secondary to rupture of an ovarian mucinous tumor associated with a mature cystic teratoma. These are usually CK7 negative and CK20 positive, and are immunohistochemically consistent with intestinal type of mucinous tumors that arise from intestinal elements of the teratoma. Other malignancies such as squamous cell carcinomas, malignant endodermal sinus tumors and chorio-carcinomas have been shown to arise from a mature teratoma. We present a case report describing one such rare case of DPAM arising from a ruptured borderline mucinous ovarian tumor in the background of a cystic teratoma.

The 7th Edition of the AJCC Staging Classification Correlates with Biologic Behavior of Mucinous Appendiceal Tumor with Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC).

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). 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. Median follow-up was 5.2years. 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 5years, respectively (p<0.001). OS of DPAM patients was 96, 90, and 88% for 1, 3, and 5years, 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 5years, 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). The 7th edition of the AJCC staging classification is a simple, reproducible, and valid classification for staging patients with PMCA undergoing CRS/HIPEC.

Disseminated peritoneal adenomucinosis (DPAM) – A clinicopathological retrospective analysis of 17 patients with emphasis on origin, management, histology and further treatment

Disseminated peritoneal adenomucinosis (DPAM) – A clinicopathological retrospective analysis of 17 patients with emphasis on origin, management, histology and further treatment

Molecular profiles of high-grade and low-grade pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare disease exhibiting a distinct clinical feature caused by cancerous cells that produce mucinous fluid in the abdominal cavity. PMPs originate most frequently from the appendix and less frequently from the ovary. This disease can range from benign to malignant, and histologically, PMP is classified into two types: disseminated peritoneal adenomucinosis (DPAM) representing the milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) representing the aggressive phenotype. Although histological classification is clinically useful, the pathogenesis of PMP remains largely unknown. To elucidate the molecular mechanisms underlying PMP, we analyzed 18 PMP tumors comprising 10 DPAMs and 8 PMCAs. DNA was extracted from tumor and matched non‐tumorous tissues, and was sequenced using Ion AmpliSeq Cancer Panel containing 50 cancer‐related genes. Analysis of the data identified a total of 35 somatic mutations in 10 genes, and all mutations were judged as pathological mutations. Mutations were frequently identified in KRAS (14/18) and GNAS (8/18). Interestingly, TP53 mutations were found in three of the eight PMCAs, but not in the DPAMs. PIK3CA and AKT1 mutations were also identified in two PMCAs, but not in the DPAMs. These results suggested that KRAS and/or GNAS mutations are common genetic features of PMP, and that mutations in TP53 and/or genes related to the PI3K‐AKT pathway may render malignant properties to PMP. These findings may be useful for the understanding of tumor characteristics, and facilitate the development of therapeutic strategies.

Abstract 4825: Association between genetic profiles and histological classifications of 18 Japanese pseudomyxoma peritonei

Abstract Pseudomyxoma peritonei (PMP) is a rare disease occurring in 1-2 / 1000,000 and shows a distinct clinical feature caused by cancerous cells that produce mucin or gelatinous fluid in the abdominal cavity. Tumor cells are the most frequently originated from appendiceal mucinous cancer, and less frequently from mucinous tumors of the ovary. PMP is histologically classified into two types; disseminated peritoneal adenomucinosis (DPAM) showing milder phenotype, and peritoneal mucinous adenocarcinomas (PMCA) exhibiting more aggressive phenotype. Several molecular studies have shown frequent mutations in the KRAS and GNAS genes. However molecular profiles associated with different histological and/or clinical characteristics remain largely unknown. To elucidate molecular mechanisms underlying PMP, we analyzed 18 Japanese PMP tumors comprising of 10 DPAMs and 8 PMCAs. DNA was extracted from tumor tissues and their matched normal samples, and was subjected to amplicon sequencing using Ion AmpliSeq Cancer Panel v2 (Life Technologies) containing 49 cancer-related genes. In the 18 tumors, we identified a total of 42 somatic mutations (34 missense, 1 deletion, 1 insertion, 2 intron, 1 splice site mutations, and 3 synonymous mutations) in 13 genes. Of the 42 mutations, 35 were judged as pathogenic, and the remaining seven as non-pathogenic by the search of public databases and reports, or by in silico analysis. KRAS and GNAS mutations were found in 14 (77.8%) and 8 (44.4%) tumors, respectively. Interestingly, no mutations were detected in APC or CTNNB1. Notably, TP53 mutation was found in 3 of the 8 PMCAs, but not in the 10 DPAMs. Two of the 8 PMCAs carried mutation in either PIK3CA or AKT1. These data suggest that KRAS and/or GNAS mutations play a vital role in the development of both types of PMP, and that inactivation of Wnt signaling pathway may not be involved in the tumorigenesis. Furthermore, mutations in TP53 and/or genes related to PIK3CA-AKT pathway may be associated with malignant properties of PMCA. Further studies will facilitate the elucidation of molecular mechanism underlying PMP, and contribute to the development of effective therapeutic and preventive strategies to this disease. Citation Format: Rei Noguchi, Hideaki Yano, Yoshimasa Gohda, Ryuichiro Suda, Toru Igari, Yasunori Ohta, Naohide Yamashita, Kiyoshi Yamaguchi, Yumi Terakado, Tsuneo Ikenoue, Yoichi Furukawa. Association between genetic profiles and histological classifications of 18 Japanese pseudomyxoma peritonei. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4825. doi:10.1158/1538-7445.AM2015-4825

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: long-term results at St George Hospital, Australia.

Peritoneal carcinomatosis (PC) results from the secondary spread of many intraabdominal tumour types, such as colorectal malignancy (colorectal cancer, CRC), disseminated peritoneal adenomucinosis (DPAM), appendiceal cancer, ovarian carcinoma, sarcoma or from the occurrence of primary peritoneal disease such as peritoneal mesothelioma. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has seen improvements in survival in selected cases of these cancers. Between 1996 and 2014, a prospective database of 675 patients was created for the peritonectomy unit at our hospital. In total, 827 peritonectomy procedures (including redo CRS) were performed for the major subgroups of PC: DPAM 220; appendiceal cancer (peritoneal mucinous adenocarcinoma (PMCA)) 191; CRC 234; diffuse malignant peritoneal mesothelioma (DMPM) 73 and others 109. There were 152 redo-peritonectomy procedures within the total mentioned earlier (CRC 26; DPAM 58; DMPM 18; appendix 40; other 10). The 5-year survivals for DPAM and PMCA were 80% and 42% respectively. The 5-year survivals for appendiceal cancer with peritoneal cancer index (PCI) <10, 10-20 and >20 were 60, 57 and 37% respectively (P = 0.09). The 2- and 5-year survivals for CRC were 56 and 24% respectively. The 5-year survivals for PCI 0-5, 6-10, 11-15 and >15 were 59, 15, 7 and 0% respectively (P = 0.000). The 5-year survival for DMPM with PCI < 10, 10-20 and >20 were 100, 55 and 39% respectively (P = 0.01). CRS in combination with HIPEC provides a chance of long-term survival in selected cases of PC when compared with systemic therapy alone.

Progression of peritoneal adenomucinosis to the scrotum: a rare occurrence treated with cytoreductive surgery and hyperthermic chemoperfusion of the scrotum in two patients

Disseminated Peritoneal Adenomucinosis (DPAM) is an infrequent presentation of appendiceal cancer. Infrequently, umbilical or inguinal hernias could be the first clinical manifestation of this condition; DPAM extension to the scrotum may be anatomically viable. Treatment with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of treatment for DPAM. We hypothesize that these same treatment principles, consisting of CRS with hyperthermic chemoperfusion of the scrotum (HCS), could be applied to the scrotal dissemination of DPAM. We reviewed our Institution's prospective cancer database and identified two cases of DPAM with extension to the scrotum. Their medical records were examined, and close follow-up was performed. Tumor histopathology and cytoreduction scores were evaluated. Tumor progression was monitored on follow-up by physical examination, tumor markers (CEA, CA 125, CA 19.9) and abdomino-pelvic CT scan. Two patients who previously had CRS/ HIPEC for DPAM were successfully treated with HSC. Both patients are alive and free of disease at 88 and 57 months following initial CRS/HIPEC, and 50 and 32 months following CRS/HCS, respectively. Increased awareness by surgeons to the coexistence of inguinal hernia with peritoneal neoplasm and the need for a surgical repair is raised. CRS/HCS may be employed to treat patients with DPAM extension to the scrotum. Successful outcome is dependent on complete cytoreduction of metastatic tumor.

Prognostic significance of single isolated cells with decreased E-cadherin expression in pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) cases can be classified into the prognosis-related subtypes of disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). To investigate the mechanisms of mucinous invasion and the differing prognoses of these two subtypes, we examined the expression levels of proteins involved in cellular adhesion and invasion, including E-cadherin, vimentin, β-catenin, and S100A4, in single isolated tumor cells (SICs) and cohesive cellular strips within mucin pools isolated from DPAM (n = 31) and PMCA (n = 21) patients. In both PMCA and DPAM cases, SICs showed a complete loss of E-cadherin expression, whereas cells in cohesive cellular clusters retained E-cadherin expression. The frequency of high numbers of SICs (>8) in PMCA cases was significantly greater than that in DPAM cases (86% and 26%, respectively) and was correlated with poor progression-free survival (P = 0.019) in a univariate analysis. In both PMP subtypes, strong vimentin expression was identified in most of the SICs but not the cohesive cellular strips. The relatively slow progression of DPAM may be attributable to the smaller number of SICs that lack E-cadherin expression and have increased vimentin expression, whereas the rapid progression of PMCA may be due to larger numbers of these SICs.

Prognostic value of clinical and pathological characteristics in 48 women with pseudomyxoma peritonei

To investigate the clinic-pathological characteristics and prognosis of 48 female cases with peritoneal pseudomyxoma(PMP). The clinicopathologic features and follow-up data of 48 female patients with PMP diagnosed in the General Hospital of People's Liberation Army from Jan.1982 to Dec.2011 were retrospectively reviewed. The relationship between clinic-pathological characteristics and prognosis were analyzed using log-rank test and Cox proportional hazards model. (1) Clinicopathologic features: the mean age of the 48 cases was 58.8 years (range from 24 to 79 years). abdominal distention and abdominal discomfort were the main symptoms. Imaging examinations showed nonspecific abdominal and pelvic lesions in most cases. all the 48 patients underwent laparotomy and cytoreductive surgery (CRS), in which 15(31%) patients with completeness of the cancer resection (CCR) -1, 24(50%) cases with CCR-2, and CCR-3 in 9(19%) cases. Six (12%) cases were treated by intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin, 20(42%) patients were treated with different options postoperative adjuvant chemotherapy. Pathological types: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), which were 22(46%) cases, 9 (19%)cases and 17 (35%)cases, respectively. Appendiceal tumors: 44(92%) cases underwent appendectomy, in which 38 cases presented appendiceal tumors (including 20 cases of low-grade appendiceal mucinous adenoma and 18 cases of appendiceal mucinous adenocarcinoma), 2 cases were diagnosed as appendicitis, 4 cases with unknown pathologic diagnosis. And the other 4(8%) cases, who didn't undergo appendectomy at the first operation, presented peritoneal tumor recurrence and appendiceal mucinous tumors 1, 11, 32 and 85 months after surgery, respectively. Parenchymal organs involved: ovarian involving was happened in 34 (71%) patients including 15 cases with the right ovary involving, 13 cases in both sides, and 6 cases involving the left side. The other parenchymal organs in 10(21%) cases. (2) Prognostic factors: 11 patients died, 31 survived and 6 cases were lost to follow-up. The mean survival time was 99 months(ranged from 1 to 312 months). The 3-year, 5-year and 10-year survival rates were 73.3%, 68.0% and 46.6%, respectively. Univariate statistical analysis showed that age, pathological type and parenchymal involvement were significantly relationship with the survival time (all P < 0.05). But the operation times, appendiceal tumor type, ovarian involvement, CCR, intraperitoneal HIPEC and post-operative adjuvant chemotherapy were not significantly correlate with survival time (all P > 0.05). Multivariate analysis showed that age and pathologic type were independent prognostic factors(P < 0.05). No specific clinical features presented in PMP. CRS with HIPEC should the recommended treatment. Both ovaries exploration and appendectomy should be carried out routinely in CRS. The 10-year overall survival of PMP is low. Age, pathological type and parenchymal organs involvement other than ovarian are correlated with the prognosis. And the pathological type and age are independent prognostic factors of PMP.

Antibiotic Treatment Decreases Microbial Burden Associated with Pseudomyxoma Peritonei and Affects β-Catenin Distribution

Pseudomyxoma peritonei is an understudied cancer in which an appendiceal neoplasm invades the peritoneum and forms tumor foci on abdominal organs. Previous studies have shown that bacteria reside within pseudomyxoma peritonei tumors and mucin. Thus, we sought to analyze the effect of antibiotics on bacterial density and β-catenin expression within pseudomyxoma peritonei samples. The study included 48 patients: 19 with disseminated peritoneal adenomucinosis (DPAM) and 29 with peritoneal mucinous carcinomatosis (PMCA). Fourteen patients were given antibiotics (30 mg lansoprazole, 1 g amoxicillin, and 500 mg clarithromycin) twice a day for 14 days. One week after completion of therapy, surgery was conducted and specimens were harvested for pathology, bacterial culture, ISH, and immunohistochemistry. ISH showed the presence of bacteria in 83% of the patient samples, with a higher Helicobacter pylori density observed in PMCA versus DPAM. PMCA patients treated with antibiotics had a significantly lower bacterial density and decreased β-catenin levels in the cytoplasm, the cell nuclei, and mucin-associated cells. Although not significant, similar trends were observed in DPAM patients. Cell membrane β-catenin was significantly increased in both DPAM and PMCA patients receiving antibiotics. Bacteria play an important role in pseudomyxoma peritonei. Antibiotic treatment improved the histopathology of tissue, particularly in PMCA patients. In PMCA, antibiotics decreased bacterial density and were associated with a significant β-catenin decrease in the cytoplasm, cell nuclei, and mucin along with a small membrane increase. These results suggest that antibiotics offer potential protection against cell detachment, cellular invasion, and metastasis.

Carbohydrate antigen 19-9 (CA 19-9) is an independent prognostic indicator in pseudomyxoma peritonei post cytoreductive surgery and perioperative intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) is characteristically divided into two histopathological subtypes; disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous carcinomatosis (PMCA). The latter is associated with a worse prognosis. However, even within the DPAM group, there is a considerable variation in outcome. In this study we investigate the role of baseline serum tumor markers CA 19-9, CEA and CA-125 in further stratifying survival. Over 16 years, 218 patients with PMP were treated with cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) at our institution. A CA-125 level of >35 U/L, CA 19-9 of >40 U/mL and CEA of >3 ng/mL were considered positive or elevated outside the laboratory reference range. The impact of clinicopathologic and treatment-related variables on overall survival (OS) was analyzed with the Kaplan Meier method. Survival curves were compared using the log-rank test. Variables deemed significant by univariate analyses were entered into multivariate analysis using the Cox proportional hazards model. Within the DPAM group, the 5-year survival of patients who were CA 19-9 positive versus those with normal values were 58% and 90% respectively (P<0.001). Other variables found to negatively impact on OS in univariate analyses were completeness of cytoreduction (CC) score 2/3 (P<0.001), peritoneal cancer index (PCI) >25 (P<0.001) and male gender (P=0.017). In the Cox regression model, only CA 19-9 positivity was found to be an independent prognostic factor for OS (P=0.034). In addition to marker positivity, the absolute level of CA 19-9 was also prognostically significant. In patients with CA 19-9>1,000 U/mL, the 5-year survival was 23%, in contrast to 90% in patients with CA 19-9<100 U/mL (P<0.001). In the PMCA cohort, only CC-score was found to be associated with OS (P<0.001). Our study provides relevant prognostic information for the DPAM subtype in staging and prioritizing surgery; as even in apparently indolent disease, some patients have poorer survival. CA 19-9 elevation may also be useful in identifying patients who would potentially benefit from adjuvant therapy and/or closer post-operative surveillance. The potential role of CA 19-9 in mediating tumor cell adhesion and disease progression in PMP should be further investigated to deepen our understanding of the disease's inherent biological behavior. If a true relationship exists, CA 19-9 may be a conceivable target for immunotherapy.