Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

Mucinous appendiceal neoplasms and pseudomyxoma peritonei: Morphological and clinical findings, differential diagnosis, and prognosis

Background: Low-grade appendiceal mucinous neoplasms (LAMN) of the appendix have bland cytological features and well-differentiated morphology. Despite this, they may cause a pseudomyxoma peritonei (PMP) disease characterized by mucinous deposits in the peritoneal cavity and may exhibit malignant behavior. Aims and Objectives: In this study, we evaluated the clinical course and histopathological findings of LAMN. The rate of progression to PMP, factors affecting its development, and the clinical course of cases with PMP were investigated. Materials and Methods: Twelve thousand and forty-seven cases who underwent appendectomy were reviewed, and 71 mucinous lesions cases whose slides are in our archive were included in the study. Histopathological findings were re-evaluated. Morphological findings that guide the differential diagnosis, the clinical course of the patients, and factors affecting PMP development were determined. Results: The cases were divided into group 1 non-neoplastic (9.9%), group 2 benign (18.3%), group 3 LAMN (60.6), and group 4 malignant neoplasms (11.3%). Age, gender, appendix diameter, gross appearance, epithelial characteristics, and presence of microcalcification were significantly different between the patient groups. The presence of mucin in the ileocecal region was found to be significant in the development of PMP. It was observed that the additional procedure performed after the appendectomy did not prevent a recurrence. Conclusion: LAMNs are lesions with characteristic findings and different behaviors. The only method to distinguish from the lesions included in the differential diagnosis is to interpret the histopathological findings correctly. Additional operations after appendectomy do not contribute to preventing recurrence.

Mucocele of the appendix: what to expect / Mucocele do apêndice: o que esperar

Abstract Mucoceles of the appendix are rare and can have quite variable imaging and clinical presentations, sometimes mimicking an adnexal mass. The underlying cause can be neoplastic or non-neoplastic. The typical imaging appearance of a mucocele of the appendix is that of a cystic structure with a tubular morphology. This structure is defined by having a blind-ending and being contiguous with the cecum. Radiologists should be familiar with key anatomical landmarks and with the various imaging features of mucoceles of the appendix, in order to provide a meaningful differential diagnosis of a lesion in the right lower abdominal quadrant. In addition, a neoplastic mucocele can rupture, resulting in pseudomyxoma peritonei, which will change the prognosis dramatically. Therefore, prompt diagnostic imaging is crucial.

Resumo Mucoceles do apêndice são raras e podem ter uma apresentação clínica e imagiológica bastante variável, por vezes mimetizando patologia anexial. As causas subjacentes podem ser neoplásicas ou não neoplásicas. O aspecto de imagem típico de mucoceles do apêndice é o de uma estrutura de natureza cística com morfologia tubular. Esta estrutura deverá terminar "em fundo cego" e ser contígua com o ceco. Os radiologistas devem estar familiarizados com os pontos anatômicos de referência e com as diferentes características imagiológicas de mucoceles do apêndice, de modo a fornecer um adequado diagnóstico diferencial de uma lesão localizada no quadrante abdominal inferior direito. Para além disso, uma mucocele neoplásica pode sofrer ruptura, resultando em pseudomixoma peritoneal, o que altera drasticamente o prognóstico. Assim, o diagnóstico por imagem em tempo útil é crucial.

Epidemiological Study of New Cases of Peritoneal Metastases / 肿瘤防治研究

Peritoneal metastases (PM) are defined as the primary or secondary occurrence/progression of malignant tumor in peritoneum. PM were previously thought to be a terminal disease without effective treatment, with short survival and poor prognosis. With the change in the understanding of PM, the oncology communities regard it as a curable regional cancer metastasis, and create a comprehensive treatment technology system with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as the core, and establish professional PM treatment centers based on this. The professional PM treatment centers have significantly prolonged the survival of patients, and some patients can even achieve clinical cure. However, in China, there are very few professional PM treatment centers, but the number of PM patients is huge, and most of the patients can't receive professional treatment, resulting in poor survival and prognosis. Based on the cancer statistics in 2015 published by China National Cancer Center Registry and clinical outcome literature on peritoneal metastasis, this paper uses clinical epidemiology methodology to calculate the number of newly diagnosed patients with peritoneal metastasis, to estimate the number of specialized peritoneal cancer centers required, to provide data support for the promotion of professional treatment technology system for PM in our country, and to boost the development of peritoneal oncology.

Pseudomixoma peritoneal primario de origen ovárico / Primary pseudomyxoma peritonei originated from ovaries

Resumen ANTECEDENTES: El pseudomixoma peritoneal es muy raro; se caracterizada por ascitis mucinosa e implantes peritoneales relacionados con la rotura y diseminación del contenido de un tumor mucinoso. En 80 al 90% de los casos el tumor primario es apendicular y el ovario es una localización realmente excepcional. CASO CLÍNICO: Paciente de 49 años que acudió a consulta debido a un dolor abdominal. En las pruebas de imagen se visualizó una tumoración anexial izquierda y se advirtieron hallazgos sugerentes de pseudomixoma peritoneal. En la cirugía, la masa ovárica se objetivó parcialmente fragmentada, con el apéndice aumentado de tamaño y extensos implantes peritoneales; además de gran cantidad de mucina libre en la cavidad peritoneal. El análisis anatomopatológico determinó la existencia de un adenocarcinoma mucinoso en el ovario afectado, con inmunohistoquímica positiva para CK7+ y CK20+, múltiples implantes de mucina y el apéndice sin daño. Por lo anterior se diagnosticó: pseudomixoma peritoneal de origen ovárico. Luego de dos intervenciones quirúrgicas no se consiguió la citorreducción completa. La paciente permaneció estable durante siete años, momento en el que fue evidente el avance de los síntomas de la enfermedad, circunstancia que la condujo a la muerte. CONCLUSIÓN: Determinar el origen de un pseudomixoma peritoneal sigue siendo un reto pues, con frecuencia, tanto el apéndice como los ovarios se afectan simultáneamente. Por ello, la apendicectomía y la exploración bilateral de los ovarios deben ser prácticas de rutina. El análisis extenso de las muestras y la inmunohistoquímica pueden facilitar la catalogación de estos infrecuentes tumores.

Abstract BACKGROUND: Pseudomyxoma peritonei is very rare; it is characterized by mucinous ascites and peritoneal implants related to rupture and dissemination of the contents of a mucinous tumor. In 80 to 90% of cases the primary tumor is appendicular and the ovary is a truly exceptional location. CLINICALCASE: A 49 year old female patient presented for consultation due to abdominal pain. Imaging tests showed a left adnexal tumor and findings suggestive of pseudomyxoma peritonei. At surgery, the ovarian mass was partially fragmented, with an enlarged appendix and extensive peritoneal implants; in addition to a large amount of free mucin in the peritoneal cavity. The anatomopathological analysis determined the existence of a mucinous adenocarcinoma in the affected ovary, with positive immunohistochemistry for CK7+ and CK20+, multiple mucin implants and an undamaged appendix. Therefore, a diagnosis was made: pseudomyxoma peritoneum of ovarian origin. After two surgical interventions she did not achieve complete cytoreduction. The patient remained stable for seven years, at which time the symptoms of the disease became evident and led to her death. CONCLUSION: Determining the origin of a pseudomyxoma peritonei remains a challenge as often both the appendix and ovaries are affected simultaneously. Therefore, appendectomy and bilateral ovarian exploration should be routine practice. Extensive specimen analysis and immunohistochemistry can facilitate cataloging of these infrequent tumors.

Efficacy and safety in the use of intraperitoneal hyperthermia chemotherapy and peritoneal cytoreductive surgery for pseudomyxoma peritonei from appendiceal neoplasm: A systematic review

Abstract The objective of this systematic review is to provide efficacy and safety data in the application of Intra-Abdominal Hyperthermia Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS) in patients with Peritoneal Pseudomyxoma (PMP) of origin in the cecal appendix. The databases Medline and Central Cochrane were consulted. Patients with PMP of origin in the cecal appendix, classified as low grade, high or indeterminate, submitted to HIPEC and CRS. The results were meta-analyzed using the Comprehensive Metanalysis software. Twenty-six studies were selected to support this review. For low-grade PMP outcome, 60-month risk of mortality, Disease-Free Survival (DFS), and adverse events was 28.8% (95% CI 25.9 to 32), 43% (95% CI 36.4 and 49.8), and 46.7% (95% CI 40.7 to 52.8); for high-grade PMP, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 55.9% (95% CI 51.9 to 59.6), 20.1% (95% CI 15.5 to 25.7) and 30% (95% CI 25.2 to 35.3); PMP indeterminate degree, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 32.6% (95% CI 30.5 to 34.7), 61.8% (95% CI 58.8 to 64.7) and 32.9% (95% CI 30.5 to 35.4). The authors conclude that the HIPEC technique and cytoreductive surgery can be applied to selected cases of patients with PMP of peritoneal origin with satisfactory results.

Clinicopathological analysis and surgical strategy of primary appendiceal neoplasms / 中华胃肠外科杂志

Objective: To investigate the clinicopathological features, surgical methods and prognosis of primary appendiceal neoplasms. Methods: A descriptive case series study was performed. Clinical data of patients diagnosed with primary appendiceal neoplasms in Peking University First Hospital from 2006 to 2017 were retrospectively analyzed. Patients who underwent surgery and were confirmed as appendiceal neoplasms by postoperative pathology were included. Cases of cecal tumor invading the appendix and other organ tumors implanting in the appendix and cases of recurrent appendix tumors were excluded Pathological classification was based on the 4th edition of the WHO classification of digestive tract tumors (2010 edition), and the efficacy of operation methods of low grade appendiceal mucinous neoplasm (LAMN) were analyzed. Results: A total of 115 patients were enrolled, including 52 males and 63 females with a median age of 59 (51, 71) years. Clinical symptoms usually manifested as dormant pain in the right lower quadrant, migrating right lower abdominal pain, fever and bloating. Twenty-four cases were accidentally discovered during surgery, and 21 cases were found by physical examination. The preoperative diagnosis rate of CT and ultrasound was 40.2% (43/107) and 25.5% (24/94) respectively. The postoperative pathological types contained 83 cases of LAMN, 12 cases of mucinous adenocarcinoma, 9 cases of appendiceal neuroendocrine neoplasms (aNEN), 2 cases of mucinous adenocarcinoma with signet ring cells, 3 cases of serrated adenoma, 2 cases of goblet cell carcinoid, 2 cases of lymphoma, 1 case of leiomyoma and 1 case of schwannomas. All the patients underwent surgical resection, including 41 cases of appendectomy, 21 cases of partial cecectomy, 48 cases of right hemicolectomy, and 5 cases of combined organ resection due to appendiceal tumor infiltration or dissemination. Eighteen cases were diagnosed with pseudomyxoma peritonei (PMP) during operation. A total of 98 patients were enrolled for follow-up. The median follow-up time was 58 (5-172) months. The 5-year disease-free survival (DFS) rate was 84.5% and 5-year overall survival (OS) was 88.2%. Multivariate analysis revealed that high-grade malignancy tumors (HR=25.881, 95% CI: 2.827-236.935, P=0.004) and PMP formation (HR=42.166, 95% CI: 3.470-512.439,P=0.003) were independent risk factors for prognosis. Patients undergoing right hemicolectomy presented longer operation time, more blood loss and higher morbidity of complication as compared to those undergoing appendectomy and partial cecectomy (all P<0.05), while no significant differences in 5-year DFS (P=0.627) and 5-year OS (P=0.718) were found. Conclusions: Primary appendiceal neoplasms usually have no typical features, accompanied with low preoperative diagnosis rate. The common pathological types are LAMN, mucinous adenocarcinoma and aNEN. Appendectomy or partial cecectomy for LAMN may achieve satisfactory prognosis. High-grade malignancy tumors and PMP formation are independent risk factors for prognosis.

Pseudomyxoma peritonei: two case study and literatures review

Pseudomyxoma peritonei (PMP) is a rare neoplastic illness with unique clinical and pathologic patterns. This disease characterized by being chronic, indolent, and relapsing. It is diagnostically challenging and very vague disease. It characterized by huge amounts of thick mucinous ascites with multiple omental and peritoneal implants that is gradually fill the abdominal and pelvic cavities. The most common clinical features are progressive abdominal distention with increase in the abdominal girth. Diagnosis of Pseudomyxoma peritonei (PMP) is usually difficult due to its vague symptoms especially in the early stages. Ultrasound examination is very useful and generally has pictures similar to that of CT scan images. Treatment of Pseudomyxoma peritonei (PMP) is cytoreductive (debulking) surgery to remove the mucin and the tumor implants in the peritoneal cavity. This is followed by intraoperative hyperthermic peritoneal chemotherapy (HIPEC). Recurrence of pseudomyxoma peritonei (PMP) patients is quite common as particularly when the disease is diagnosed and treated in the late stage.

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei: a single-center experience with 854 patients / 中国肿瘤临床

Pseudomyxoma peritonei (PMP) is a rare clinical syndrome. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is gradually being accepted as the standard treatment for PMP. At Aerospace Hospital, we have been treating patients with PMP since 2008 and performing total peritoneal resection since 2016. This study summarizes the experience at our center and collates past data. Methods: We performed a retrospective analysis of a prospectively maintained database of all patients who had undergone CRS and HIPEC for PMP at our center. Clinical data, such as the surgical approach, completeness of cytoreduction, and surgical complications, were collected. The results from follow-up were analyzed to simultaneously evaluate the clinical value of CRS+HIPEC and peritonectomy procedures. Results: A total of 854 consecutive patients with PMP were included in the study. Their mean age was 50 years. The median modified peritoneal cancer index (PCI) was 29. Of the patients, 25.5% under-

The many faces of pseudomyxoma peritonei: a radiological review based on 30 cases / As múltiplas faces do pseudomixoma peritonial: uma revisão radiológica baseada em 30 casos

Abstract Objective: To determine the most common imaging features of pseudomyxoma peritonei (PMP), as well as the histologic subtypes of the primary tumors. Materials and Methods: We reviewed 30 cases of women with pathologically confirmed PMP. Only computed tomography scans were available. All cases were retrospectively studied by four radiologists, working independently. We identified the most common imaging findings, the predominant primary site of the disease, and the growth pattern. The most common sites of recurrence were also analyzed. Results: The most common computed tomography finding was peritoneal/omental nodules (including "omental caking"), followed by visceral scalloping and non-mucinous ascites. The most common site of the primary tumor was the appendix (in 63.3%), followed by the ovaries (in 16.6%), and 16.6% of the tumors were of undetermined origin. There was one case of synchronous appendiceal and ovarian tumors. Low-grade mucinous neoplasm was the most common histologic subtype, accounting for 84.2% of the appendiceal tumors and 40% of the ovarian tumors. Conclusion: Although PMP is a relatively rare entity, radiologists must be aware of its possible imaging findings, common locations, and possible patterns of recurrence. The origin of the primary tumor should also be investigated. Future studies are needed in order to determine which preoperative imaging findings predict surgical outcomes and to characterize the main findings of radiological recurrence.

Resumo Objetivo: Determinar as características de imagem mais frequentes do pseudomixoma peritonial (PMP), bem como os subtipos histológicos dos tumores primários. Materiais e Métodos: Foram revisados 30 casos confirmados patologicamente de PMP em mulheres. Somente a tomografia computadorizada estava disponível. Todos os casos foram estudados de forma independente e retrospectiva por quatro radiologistas. Os autores relataram os achados de imagem mais frequentes, a localização predominante da doença primária e o padrão de crescimento. Os locais de recorrência mais comuns também foram analisados. Resultados: Os achados tomográficos mais frequentes foram nódulos peritoniais/omentais (incluindo "bolo omental"), seguidos por scalloping visceral e ascite não mucinosa. Os padrões de localização mais comuns do PMP também foram documentados. A grande maioria dos tumores primários foi de origem apendicular (63,3%), seguida de origem ovárica (16,6%) e indeterminada (16,6%). Houve um caso síncrono de tumor apendicular e ovário. A neoplasia mucinosa de baixo grau foi o subtipo histológico mais frequente, representando 84,2% dos tumores do apêndice e 40% dos tumores primários ovarianos. Conclusão: Embora o PMP continue sendo uma entidade relativamente rara, o radiologista deve estar ciente de seus possíveis achados de imagem, locais comuns e possíveis padrões de recorrência. A investigação do tumor primário também deve ser encorajada. Futuros estudos são necessários para prever o resultado cirúrgico da imagem pré-operatória e caracterizar os principais achados de recorrência radiológica.

MSCT preoperative evaluation on peritoneal cancer index of patients with pseudomyxoma peritonei / 中国医学影像技术

Objective: To investigate the value of MSCT in preoperative assessing operitoneal cancer index (PCI) in patients with pseudomyxoma peritonei (PMP). Methods MSCT data of histopathologically proved PMP in 108 patients were retrospectively analyzed. MSCT-PCI scores were evaluated and compared with intraoperative PCI scores, 0-8 was assigned to the omentum area, the liver area, the small omental sac area, the spleen area, the descending colon area, the left iliac area, the pelvic area, the right iliac area and the ascending colon area, respectively, whereas 9 to 12 were assigned to the small intestine area. The consistency between MSCT-PCI scores and the intraoperative PCI scores in different regions and MSCT-PCI scores in different regions between different observers were analyzed. The efficacy of MSCT in diagnosing PMP in different regions was calculated. Results Among 108 patients, the consistency between MSCT-PCI and intraoperative PCI scores in 1-3 regions was good, of 0, 4-9 regions was moderate, while of the 10-12 regions was fair. The consistency of MSCT-PCI scores in 0, 4 and 7 regions between 2 observers was better, of 1-3, 5, 8-10 regions was good, of 6, 11, 12 regions was moderate. The sensitivity of MSCT in diagnosis of PMP in 0-12 regions was 92.63% (88/95), 97.94% (95/97), 95.83% (92/96), 95.79% (91/95), 89.69% (87/97), 95.00% (95/100), 96.08% (98/102), 96.12% (99/103), 94.90% (93/98), 87.78% (79/90), 88.89% (80/90), 86.17% (81/94) and 85.71% (84/98); the specificity was 84.62% (11/13), 100% (11/11), 91.67% (11/12), 84.62% (11/13), 100% (11/11), 87.50% (7/8), 83.33% (5/6), 100% (5/5), 100% (10/10), 83.33% (15/18), 83.33% (15/18), 85.71% (12/14) and 80.00% (8/10); and the accuracy was 91.67% (99/108), 98.15% (106/108), 95.37% (103/108), 94.44% (102/108), 90.74% (98/108), 94.44% (102/108), 95.37% (103/108), 96.30% (104/108), 95.37% (103/108), 87.04% (94/108), 87.96% (95/108), 86.11% (93/108) and 85.19% (92/108). Conclusion MSCT can accurately assess PCI of PMP, therefore providing references for clinical development of treatment plan.

Establishment of patient derived xenograft model of high-grade mucinous carcinoma peritonei accompanied with signet ring cells and identification of biological characteristics / 中华肿瘤杂志

Objective@#To establish the patient derived xenograft (PDX) model of pseudomyxoma peritonei (PMP), and identify the key characteristics of tumor biology of this model, in order to provide a reliable model for studying the pathological mechanisms and new therapeutic strategies of PMP.@*Methods@#PMP tumor tissue was obtained from surgery and cut into pieces after washing. Then tumor pieces were implanted subcutaneously in BAL B/c-nu mice for 6 stable passages. In the 7th passage, tumor tissue was implanted orthotopically into abdomen. Subcutaneous tumor and orthotopic tumor were then homogenized to make tumor cell suspension, implanted into abdomen of 10 BAL B/c-nu mice through midline laparotomy, 100 μl for each. The key experimental parameters including body weight changes in the observation period, experimental peritoneal cancer index (ePCI) score at the autopsy, histopathological and immunohistochemical characteristics, and gene expression profiles by high-throughput whole-genome exon sequencing were detected and recorded.@*Results@#The successful rate of established orthotopic PDX model of human PMP was 100% (10/10). The animals showed smooth body weight increases after tumor inoculation until day 27, then the body weight began to decrease steadily. Widespread tumor dissemination of PMP tumor through the whole abdomen was found by autopsy, including the diaphragm, liver, spleen, stomach, kidney, parietal peritoneum, bowel and mesenterium. Gelatinous ascites was also observed in abdominopelvic cavity. The ePCI score ranged from 5 to 9, with a 8 of median ePCI. Histopathological studies showed peritoneal mucinous carcinomatosis accompanied with signet ring cells (PMCA-S), obvious tumor cell atypia and parenchymal invasion.Immunohistochemistry showed the expressions of MUC1, MUC2, MUC5AC, CEA, CA199, CK20, CDX-2 and Ki-67 were positive, MUC6, CK7 and p53 were negative. Whole-exome sequencing identified that the most significant genetic alteration is the exon10 missense mutation c. 1621A>C of KIT gene, the mutation abundance was 89.7%.@*Conclusion@#PDX model of PMCA-S is successfully established, which displays the characters of high-degree malignancy, high proliferation and strong aggressiveness.

A single-center clinical analysis of 65 cases of pseudomyxoma peritonei from appendiceal origin in the early stage / 中华肿瘤杂志

Objective@#To analyze the efficacy and safety of cytoreduction surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) in the early stage.@*Methods@#The clinical data, including pathological features, recurrence and survival of 65 PMP patients in the early stage underwent CRS combined with HIPEC in Aerospace Center Hospital from January, 2011 to December, 2018 were retrospectively analyzed.@*Results@#65 patients with early stage PMP underwent CRS+ HIPEC. Among these patients, 25 were males and 40 were females, and the mean age was 52.5 years. The median peritoneal cancer index was 3 (0-16). The score of completeness of cytoreduction (CC) of 63 patients (96.9%) was 0, and 2 patients (3.1%) was 1. No perioperative death occurred, the incidence of surgical complications above grade 3 was 3.1%. Three patients relapsed during the follow-up period, including 1 patient with low-grade PMP, 1 patient with high-grade PMP, and 1 patient with high-grade PMP accompanied by signet ring cell. The 5-year disease-free survival rate of the whole group was 92.4%.@*Conclusions@#PMP patients in the early stage treated by CRS combined with HIPEC can achieve benefit and safety. A close long-term follow-up is necessary.

Diagnosis and treatment of pseudomyxoma peritonei of extra-appendiceal origin:analysis of 34 cases / 中国肿瘤临床

Objective: To investigate the clinicopathological features and treatment strategy of pseudomyxoma peritonei (PMP) of ex-tra-appendiceal origin. Methods: Clinical data of 34 patients diagnosed with PMP of extra-appendiceal origin who were treated by cy-toreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in the Aerospace Center Hospital from September 2011 to February 2019 were retrospectively analyzed. Clinical and imaging features were summarized and the Log-rank test was used for survival analysis. Results: The clinical manifestations of the 34 patients with PMP of extra-appendiceal origin were mainly abdomi-nal distension (58.8%) and abdominal pelvic mass (52.9%), which are very similar to those of appendiceal PMP. The incidence of main complications after CRS and HIPEC was 14.7%. During the follow-up period of a median of 12 months (range 1-46 months), 9 patients died, and the 1-and 3-year overall survival rates were 69.6% and 53.5%, respectively. In the univariate analysis, peritoneal cancer in-dex (PCI)>20, no HIPEC, and non-radical surgery were significant risk factors for poor prognosis, while gender, age, origin, and patho-logical type did not show significant correlations. Conclusions: The clinical features of PMP of extra-appendiceal origin are not differ-ent to those of PMP originating from the appendix. It is difficult to ascertain the primary lesion before the operation; however, regard-less of the origin, CRS combined with HIPEC is always a safe and effective treatment choice.

Clinicopathological analysis of ovarian pseudomyxoma peritonei / 中国肿瘤临床

Objective: To analyze the clinicopathological characteristics of ovarian pseudomyxoma peritonei (PMP). Methods: Clinical and pathological data from a total of 272 PMP patients diagnosed at Beijing Shijitan Hospital from January 2010 to January 2019 were collected from a database and retrospectively analyzed to study the origin of PMP tumors. Pathological slides marked with antigens were further studied using immunohistochemical staining, including CK7, CK20, CEA, Villin, CDX2, SATB2, CA125, ER, PR, MUC1, and MUC2. Results: Among the 272 PMP patients studied, the tumors of 245 (90.1%) originated from the appendix, while the remaining 27 (9.9%) originated from non-appendix tissues, including 5 (1.8%) from the ovaries. Ovarian cases included two ovarian teratomas, two ovarian mucinous cystadenomas, and one borderline ovarian mucinous cystadenoma. Histopathological analysis of peritoneal me-tastases further revealed two acellular mucins, two low-grade mucinous carcinoma peritonei, and one high-grade mucinous carcinoma peritonei, while immunohistochemistry revealed positive staining for CK20, CEA, Villin, and CDX2; SATB2 was also found to be partially positive in teratomas with mucinous tumors: negative in two cases and partially positive in one case. Conclusions: The occurrence of ovarian PMP is rare. Its precise diagnosis demands for a serial section of the whole appendix or suspected tissue to exclude any appen-diceal mucinous neoplasms, as well as the combination of a comprehensive analysis of its clinical signs and symptoms, imaging find-ings, surgical findings, histopathological characteristics, and immunohistochemistry.

Pathological prognostic factors of pseudomyxoma peritonei / 中华病理学杂志

Objective@#To analyze the pathological features of pseudomyxoma peritonei (PMP) in correlation with the survival status and independent prognostic factors.@*Methods@#One-hundred and fifty-five PMP specimens were collected at Beijing Shijitan Hospital, Capital Medical University, from 2012 to 2018. Conventional histopathological evaluation was performed to document the primary tumor site, histopathological type, lymph nodes metastasis, tumor emboli in the blood and lymph vessels, nerve invasion and cellular density. The immunohistochemical parameters including Ki-67, p53, MMR-related protein, MUC2 and MUC5AC were analyzed. Clinical follow-up data were reviewed to correlate with pathological prognostic factors using Kaplan-Meier estimator and Cox proportional hazards regression model for univariate and multivariate analysis.@*Results@#Among 155 PMP patients, there were 77 males and 78 females. There were 98 cases (63.2%) of low-grade peritoneal mucinous carcinomatosis, 49 cases (31.6%) of high-grade peritoneal mucinous carcinomatosis, 8 cases (5.2%) of high-grade mucinous carcinoma peritonei with signet ring cells; only 15 cases (9.7%) with lymph node metastasis; 18 cases (11.6%) with tumor emboli in the blood and lymph vessels; 8/126 (6.3%) were positive dMMR; 100 cases (64.5%) had Ki-67 label index <50%, and 56 cases(36.1%) presented with mutant type p53. Univariate analysis revealed 11 survival-related pathological parameters including gender, age, primary tumor site, histopathological type, lymph node metastasis, tumor emboli in the blood and lymph vessels, nerve invasion, cellular density, Ki-67 label index rate, p53 and dMMR. Multivariate analysis identified 4 independent prognostic factors including the histopathological type (HR 59.78, P<0.01), lymph node metastasis (HR 3.74, P=0.028), nerve invasion (HR 7.81, P=0.007) and dMMR (HR 9.82, P<0.01).@*Conclusions@#Histopathological type is the most important prognostic factor of PMP with dMMR as an independent molecular prognostic indicator.

Spectrum of computed tomography manifestations of appendiceal neoplasms: acute appendicitis and beyond

Appendiceal neoplasms are rare and often only discovered incidentally during surgery performed for acute appendicitis. Computed tomography (CT) has been demonstrated to be a reliable technique for accurately establishing the preoperative diagnosis of appendiceal neoplasms that manifest as acute appendicitis through the presence of certain imaging findings. Other manifestations of appendiceal neoplasms include appendiceal mass, mucocoele, localised abscess formation, ileus, increasing abdominal girth from pseudomyxoma peritonei, and intussusception. This pictorial essay illustrates varied CT findings of neoplasms of the appendix, with emphasis on the more commonly encountered manifestations of these tumours.

Peritoneal carcinomatosis treated with cytoreductive surgery and intraperitoneal chemotherapy / Carcinomatose peritoneal tratada com cirurgia citoreductiva e quimioterapia intraperitoneal

ABSTRACT Introduction: To evaluate the combined treatment with cytoreductive surgery and intraperitoneal chemotherapy for peritoneal carcinomatosis arising from colorectal cancer, pseudomyxoma peritonei and mesothelioma. Methods: Data were obtained from 73 patients with peritoneal carcinomatosis arising from colorectal cancer (52.1%), pseudomyxoma peritonei (41.1%) or mesothelioma (6.8%) between 2002 and 2011. We reported the morbidity grade (II, III and IV), mortality and survival rates of the candidates after cytoreductive surgery and intraperitoneal chemotherapy. Results: 41 (56.2%) women participated, and the median age was 50 years. Thirty-nine patients (53.4%) underwent complete cytoreductive surgery and intraperitoneal chemotherapy. Patients who underwent a complete cytoreduction received intraperitoneal chemotherapy with mitomycin C, from which only 16/39 (41%) had hyperthermic intraperitoneal chemotherapy (41-42 °C). The overall morbidity rate was 23.3% and the grade III/IV complication rate was 12.3%. The overall mortality rate was 5.5%. The univariate analysis showed that cytoreductive surgery and intraperitoneal chemotherapy (p = .029), a blood transfusion (p = .002) and the operative time (p = .001) were significant for the occurrence of postoperative complications. Patients with peritoneal carcinomatosis from colorectal cancer who underwent complete cytoreductive surgery and intraperitoneal chemotherapy had overall survival rates of 81.3%, 12.5% and 12.5% at 1, 3 and 5 years, respectively. Patients with peritoneal carcinomatosis from pseudomyxoma peritonei who underwent complete cytoreductive surgery and intraperitoneal chemotherapy had overall survival rates of 84.2%, 77.7% and 77.7% at 1, 3 and 5 years, respectively. Conclusion: The combined treatment for peritoneal carcinomatosis may be performed safely with acceptable morbidity and mortality in a specialized unit setting. Although over half of patients underwent normothermic intraperitoneal chemotherapy, our results were comparable to results from others centers.

RESUMO Introdução: O objetivo foi avaliar o tratamento combinado da cirurgia citorredutora e quimioterapia intraperitoneal em pacientes com carcinomatose peritoneal secundária ao câncer colorretal, pseudomixoma peritoneal e mesotelioma. Métodos: Foram obtidos dados de 73 pacientes com carcinomatose peritoneal secundária ao cirurgia citorredutora (52.1%), pseudomixoma peritoneal (41,1%) ou mesotelioma (6,8%). Foram avaliados o grau de morbidade, a taxa de mortalidade e as taxas de sobrevida após a cirurgia citorredutora e quimioterapia intraperitoneal. Resultados: 41 (56,2%) pacientes do sexo feminino participaram, com média de idade de 50 anos. 39 pacientes (53,4%) foram submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal. Todos esses receberam Mitomicina C, sendo 16/39 (41%) quimioterapia intraperitoneal hipertérmica (41-42°C). A morbidade global foi 23,3%, com taxa de mortalidade global de 5,5%. A análise univariada mostrou que câncer colorretal e quimioterapia intraperitoneal (p = .029), transfusão sanguínea (p = .002) e tempo operatório (p = .001) foram associados com complicações pós-operatórias. Pacientes com carcinomatose peritoneal secundária ao cirurgia citorredutora submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal tiveram sobrevida global de 81,3%; 12,5% e 12,5% em 1, 3 e 5 anos, respectivamente. Os pacientes com pseudomixoma peritoneal que foram submetidos a cirurgia citorredutora completa e quimioterapia intraperitoneal tiveram sobrevida global de 84,2%; 77,7% e 77.7% em 1, 3 e 5 anos, respectivamente. Conclusão: O tratamento combinado para carcinomatose peritoneal é seguro quando realizado em centros terciários com experiência no procedimento. Embora mais da metade dos pacientes tenham sido submetidos a quimioterapia intraperitoneal normotérmica após a cirurgia citorredutora completa, os resultados podem ser comparados a de outros centros que utilizam exclusivamente a quimioterapia hipertérmica.

Pseudomyxoma peritonei originating from appendix tumors / Pseudomixoma peritoneal com origem em tumores do apêndice

ABSTRACT Background: Appendix tumors represent about 1% of all gastrointestinal neoplasia, in other words they are quite rare. However, there is a specific type of appendiceal neoplasms (mucinous adenocarcinoma) that spreads to the peritoneum and in almost 20% of the cases, resulting in a disease called pseudomyxoma peritonei. Although, it is a very rare condition, it is nonetheless a very severe one and therefore it is crucial to know how to correctly diagnose and treat it. Objective: This study provides updated data on how to diagnose, classify and treat pseudomyxoma peritonei that originates from appendix tumors. Methods: A bibliographic research was performed on PubMed database, including articles published since 2000, as well as, cross-referencing with the initial research. Discussion: In the past, patients diagnosed with pseudomyxoma peritonei would only undergo palliative measures, so their overall survival rate was greatly reduced. Over the years pseudomyxoma peritonei treatment has evolved and patients are now undergoing treatment which is a combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. This new therapy has allowed an increase of survival chances of up to 5 years in those patients with values between 53% and 88%, depending on the type of tumor. Conclusion: Despite the great progress we have witnessed in recent years, which have led to a large increase in survival rates, more research needs to be done, on what to do when the disease is in an unresectable stage. Finding a less aggressive therapy than cytoreductive surgery + hyperthermic intraperitoneal chemotherapy will be an important step forward.

RESUMO Introdução: As neoplasias do apêndice são bastante raras, representando atualmente cerca de 1% de todas as neoplasias gastrointestinais. O adenocarcinoma mucinoso é um dos subtipos de neoplasia do apêndice e caracteriza-se por metastizar para o peritoneu, em 20% dos casos, facto que se manifesta sob a forma de uma doença designada por Pseudomixoma Peritoneal. Apesar de ser uma condição muito rara, a sua extrema gravidade justifica a importância de a saber diagnosticar e tratar corretamente. Métodos: Foi realizada uma pesquisa bibliográfica na base de dados PubMed, incluindo artigos publicados desde 2000 bem como artigos de pesquisa cruzada com os iniciais. Discussão: No passado, os doentes diagnosticados com Pseudomixoma Peritoneal eram apenas submetidos a medidas paliativas, pelo que a sua sobrevida era muito reduzida. Ao longo dos anos o tratamento do Pseudomixoma Peritoneal foi evoluindo sendo agora os doentes submetidos a uma combinação de cirurgia citoredutiva e quimioterapia hipertérmica intraperitoneal. Esta nova terapêutica tem permitido aumentar a sobrevida aos 5 anos destes pacientes para valores entre os 53% e os 88%, dependendo do tipo de tumor. Conclusões: Apesar dos grandes avanços que se têm verificado, e que culminaram com um grande aumento das taxas de sobrevivência, devem ser feitos mais estudos que encontrem novas abordagens para quando o tumor já é diagnosticado num estado irressecável, bem como terapêuticas menos invasivas.

Pseudomyxoma peritonei in a pediatric patient: A case report and literature review / Pseudomixoma peritoneal em paciente pediátrico: relato de caso e revisão de literatura

Summary Introduction: Pseudomyxoma peritonei (PMP) is a rare clinical condition, with an incidence of 1-2 cases per million, characterized by the dissemination of mucinous implants on the peritoneal surface and progressive gelatinous ascites. Although it usually presents an indolent behavior, its non-specific clinical presentation contributes to many cases remaining undiagnosed until a laparotomy is performed. With late diagnosis, performed after a long period of clinical deterioration and disease progression, it is common to find complications such as the formation of intestinal fistulas and obstruction. Method: Review of the medical record and search for references in the Medline, Lilacs, SciELO and MD Consult databases. Results: There are rare case reports found in the literature demonstrating atypical PMP presentations. Our report is that of a 17-year-old adolescent with a sporadic tumor diagnosed in a primary site in the transverse colon, contrary to data commonly found in the literature that mention a more frequent occurrence in women in the fifth decade of life and with a primary site in the ovary and appendix. The development of mucinous adenocarcinoma is rare in the pediatric population, and topography in the transverse colon and non-familial sporadic pattern are unusual. Conclusion: The case reported not only raises awareness about the atypical presentations of the disease, but also emphasizes the use of imaging examinations for diagnosis, which has an important impact on prognosis and survival if performed timely.

Resumo Introdução: O pseudomixoma peritoneal (PMP) é uma condição clinica rara, com incidência de 1-2 casos por milhão, caracterizada pela disseminação de implantes de natureza mucinosa pela superfície peritoneal e acúmulo progressivo de ascite gelatinosa. Embora apresente geralmente um comportamento indolente, a apresentação clínica inespecífica contribui para que muitos casos permaneçam sem diagnóstico até a realização de laparotomia. Com o diagnóstico tardio, realizado após um longo período de deterioração clínica e progressão de doença, é comum encontrar complicações, como a formação de fístulas e obstruções intestinais. Método: Revisão do prontuário médico e pesquisa bibliográfica nas bases de dados Medline, Lilacs, SciELO e MD Consult. Resultados: São raros os relatos de caso encontrados na literatura que demonstram apresentações atípicas do PMP. O presente estudo apresenta o caso de um adolescente com 17 anos ao diagnóstico e sítio primário no colón transverso com tumor esporádico, contrário aos dados comumente encontrados na literatura, que referem acometimento mais comum em mulheres na quinta década de vida e com sítio primário em ovário e apêndice. O desenvolvimento de adenocarcinoma mucinoso é raro na população pediátrica e a topografia no cólon transverso e padrão esporádico não familial também são pouco usuais. Conclusão: O caso relatado alerta para as apresentações atípicas da doença e enfatiza o uso de exames de imagem para o diagnóstico, que, se realizado precocemente, impacta de maneira importante o prognóstico e a sobrevida.