Appendiceal Mucinous Adenocarcinoma Research Articles

Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade.

AIMTo investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma (MAA).METHODSTwo hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression.RESULTSThere were 201 (75.8%) well-, 45 (16.9%) moderately- and 19 (7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival (OS), 94%, 71% and 30% respectively (P < 0.001) as well as the 5-year disease-free survival (DFS) 66%, 21% and 0%, respectively (P < 0.001). Independent predictors of DFS included tumor grade (HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement (HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score (HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index (PCI) (HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade (HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI (HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction (HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low (6%) and high (40%) risk groups.CONCLUSIONOur data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well- and poorly-differentiated MAA. The three-tier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms.

Intrathoracic Chemoperfusion Decreases Recurrences in Patients with Full-Thickness Diaphragm Involvement with Mucinous Appendiceal Adenocarcinoma.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is the preferred treatment for selected patients with mucinous appendiceal adenocarcinoma. Frequently, the hemidiaphragms are infiltrated with tumor, requiring partial diaphragm resection (DR) in order to obtain complete cytoreduction (CC-0). The clinical significance of diaphragmatic invasion and the optimum management to prevent transmission of disease from abdomen to chest is largely unknown. This was a retrospective review of 78 patients with mucinous appendiceal adenocarcinoma undergoing cytoreduction and partial DR at a single institution between 2010 and 2014. Partial DR was necessary in 31 (39.7%) patients in order to obtain CC-0. DR was not associated with increased morbidity or poor survival. Of the 31 patients who had a DR, 26 (83.9%) were treated with thoracoabdominal chemoperfusion. The remaining five (16.1%) patients had the diaphragm closed prior to HIPEC. Thoracoabdominal chemoperfusion was not associated with increased 30-day grade III/IV morbidity or respiratory complications. Overall, five (20%) patients with a DR developed thoracic recurrence. There were two (8%) thoracic recurrences in the 26 patients treated with thoracic chemoperfusion compared with three (60%) in the five patients who had their diaphragm closed prior to HIPEC (p=0.002). In univariate analysis histology, CC-0 and thoracoabdominal chemoperfusion were associated with thoracic disease-free survival; however, none of these were significant on multivariate analysis. DR is not associated with increased morbidity and should be performed, if needed, to obtain a CC-0. Following DR, patients remain at significant risk of developing thoracic recurrence. Thoracoabdominal chemoperfusion reduces this risk without increasing morbidity.

Hyperthermic Intraperitoneal Chemotherapy Following Cytoreductive Surgery Improves Outcome in Patients With Primary Appendiceal Mucinous Adenocarcinoma: A Pooled Analysis From Three Tertiary Care Centers.

Appendiceal mucinous neoplasms (AMN) are a rare heterogeneous group of diseases. In the absence of randomized trials, AMN management is controversial. The goal of this study was to evaluate the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery on survival in AMN patients. Patient data including demographics, pathology, type of therapy, and outcomes were collected from Emory University, the Ohio State University, and Wayne State University databases. One of the three centers did not use HIPEC. Statistical analysis evaluating overall survival (OS) of AMN patients was performed. Between 1990 and 2010, 163 AMN patients were identified. Histology showed 60 patients had diffuse peritoneal adenomucinosis, 88 had peritoneal mucinous carcinomatosis (PMCA), and 15 had PMCA with indeterminate or discordant features. Complete surgical resection was achieved in 76 patients. HIPEC was used in 79 patients. The median OS was 77 months for patients who received HIPEC compared with 25 months for patients who did not (p < .001). In multivariable analysis, histopathologic subtype (p < .001), complete surgical resection (p < .001), and HIPEC (p < .001) were independent predictors for improved OS. A survival advantage for AMN patients treated at HIPEC-treating centers was observed (p = .0026). After adjusting for HIPEC therapy, no significant survival difference was observed between the non-HIPEC-treating center and the HIPEC-treating centers (p = .094). The addition of HIPEC to cytoreductive surgery likely provides a survival advantage and should be considered in the treatment strategy for AMN.

A mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix

Appendiceal mucinous tumors (AMTs) are classified as low-grade appendiceal mucinous neoplasms (LAMNs) or mucinous adenocarcinomas (MACs), although their carcinogenesis is not well understood. As somatic activating mutations of GNAS are considered to be characteristic of LAMNs while TP53 mutations have been shown to be specific to MACs, MACs are unlikely to result from transformation of LAMNs. However, emerging evidence also shows the presence of GNAS mutations in MACs. We examined 16 AMTs (11 LAMNs and 5 MACs) for genetic alterations of GNAS, KRAS, BRAF, TP53, CTNNB1, and TERT promoter in order to elucidate the possibility of a shared genetic background in the two tumor types. Extensive histological examination revealed the presence of a low-grade component in all cases of MAC. GNAS mutations were detected in two LAMNs and in one MAC, although the GNAS mutation in this MAC was a nonsense mutation (Q227X) expected not to be activating mutation. TP53 mutations were detected in three LAMNs; they were frequently detected in MACs. KRAS mutations were detected in three LAMNs and three MACs, and CTNNB1 mutations were detected in two LAMNs. KRAS mutation and activating mutation of GNAS occurred exclusively in AMTs. BRAF and TERT mutations were not detected. Overexpression of p53 was observed in only two MACs, and p53 immunostaining clearly discriminated the high-grade lesion from a low-grade component in one. These findings suggest that p53 overexpression plays an important role in the carcinogenesis of AMTs and that, in addition to mutations of GNAS, KRAS and TP53 alterations might be shared by AMTs, thus providing evidence for the possible progression of LAMNs to MAC.

Comprehensive genomic profiling of cancer of the appendix to reveal new routes to targeted therapies.

608 Background: Cancers of the appendix are rare forms of malignancy that include two major mucin producing tumors, mucinous adenocarcinoma (MA) and goblet cell carcinoid (GCC). There is no clear standard of care for management of these malignancies. We queried whether comprehensive genomic profiling (CGP) of MA and GCC would reveal differences in the pattern of genomic alterations (GA) of these two subtypes of appendiceal cancer and serve as a guide for targeted therapies for this disease. Methods: DNA was extracted from 40 microns of FFPE sections from 20 clinically advanced appendiceal carcinomas (9 GCC and 11 MA). Comprehensive genomic profiling was performed on hybridization-captured, adaptor ligation based libraries to a high mean coverage depth of &gt;600X for 3,230 exons of 182 cancer-related genes, plus 37 introns from 14 genes frequently rearranged in cancer. The results were evaluated for all classes of GA including base substitutions, short insertions and deletions, copy number alterations and fusions/rearrangements. Clinically relevant GAs were defined as GAs linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: Base substitutions in KRAS were seen in 73% of MA and 11% of GCCs. TP53 mutations were seen in 64% of MA and 22% of GCCs. MYC (36%), SMAD4 (27%), and APC (27%) mutations were found in MA but were absent in GCC. Other GA of low frequency, but clinically relevant in both subsets included ERBB2, GNAS, ARID1A, PIK3CA, NRAS, CTNNB1, BRCA1, BRAF, KDR, PTEN, MCL1, IDH1, FBXW7, and RICTOR. Conclusions: KRAS and TP53 mutations are common in appendiceal MA, but rare in appendiceal GCCs. This confirms the differences in biology and has implications regarding the use of targeted therapies such as anti-EGFR antibody treatments. The high frequency of clinically relevant genomic alterations uncovered in this study that can potentially serve as targets for therapies, either approved or in clinical trials, raises hope that CGP can lead to improvement in outcomes for patients with this aggressive form of malignancy.

The role of systemic chemotherapy in adenocarcinomas of the appendix: Analysis of the National Cancer Database.

668 Background: Adenocarcinomas of the appendix represent a heterogeneous disease depending upon the presence of mucinous histology, histologic grade, and stage. We sought to explore the interplay of these factors with systemic chemotherapy in a large population dataset. Methods: Patients in the National Cancer Data Base (NCDB) with mucinous, non-mucinous and signet-ring cell type appendiceal neoplasms from 1985-2006 were selected and American Joint Committee on Cancer (AJCC) 7thedition stage was derived. Multivariable cox proportional hazards regression models to predict death using the available variables age, sex, histology, grade, stage, chemotherapy and surgery were developed. Results: 11,881 patients met our inclusion criteria: 50.3% mucinous, 40.5% non-mucinous and 9.2% signet ring cell. 5-yr OS was similar for mucinous (53.6%) and non-mucinous (46.2%), but differences in stage distribution existed with stage IV disease in 26.2% of mucinous vs. 10.6% of non-mucinous cases, p&lt;0.0001. 5-yr OS stratified by grade was similar across stage I-III disease but not for stage IV disease. Median OS for stage IV mucinous and non-mucinous histology was 6.4 and 2.3 for well differentiated (p&lt;0.0001), 2.5 and 1.0 for moderately differentiated (p&lt;0.0001), and 1.5 and 0.8 for poorly differentiated (p&lt;0.0001), respectively. In multivariable modeling for stage I-III disease, adjuvant chemotherapy improved OS for both mucinous and non-mucinous histologies: HR of 0.78 (0.68-0.89; p=0.0002) and 0.83 (0.74-0.94;p=0.002) respectively. For stage IV disease systemic chemotherapy was significant for non-mucinous 0.72 (0.64-0.82; p&lt;0.0001) but not mucinous 0.95 (0.86-1.04;p=0.2), though this was grade dependent. Median OS for chemotherapy vs. no chemotherapy was 6.4 vs. 6.5 yrs (P=1.0) for mucinous well differentiated and 1.6 vs. 1.0 yrs (P=0.0007) for mucinous poorly differentiated. Conclusions: Adjuvant chemotherapy demonstrated a significant OS benefit regardless of histology. However, for stage IV disease the benefit of systemic chemotherapy varied by histology and grade, with well differentiated mucinous appendiceal adenocarcinomas deriving no survival benefit from systemic chemotherapy.

Pseudomyxoma Peritonei a Classical Case with Cytological and Histopathological Co-relation

Pseudomyxoma peritonei is an uncommon disease characterized by abundant extracellular mucin in the peritoneum, reactive fibrosis, neovascularization, and inflammation. We present a case report of a 58 year old male patient who presented with massive abdominal enlargement leading to pseudomyxoma peritonei arising from low grade appendiceal mucinous adenocarcinoma

Primary appendiceal mucinous adenocarcinoma: A case report

Primary appendiceal mucinous adenocarcinoma: A case report

Mucinous Appendiceal Adenocarcinoma Presenting as Sister Mary Joseph Nodule: Case Report and Brief Review of Literature

Sister Mary Joseph nodule is a rare form of umbilical metastasis. Often, this is the only initial presenting sign for an underlying internal malignancy and is usually associated with poor prognosis. Although the gastrointestinal tract is the most common primary site, the majority of these metastases are from gastric and colorectal sites. We report a case of Sister Mary Joseph nodule in a patient with no GI complaints. Further evaluation led to the diagnosis of primary mucinous adenocarcinoma of the appendix. Primary mucinous adenocarcinoma of the appendix is a very rare tumor type that can give rise to umbilical metastases. To the best of our knowledge, only 3 cases of adenocarcinoma of the appendix metastasizing to the umbilicus have been reported in the medical literature.

Molecular profiling of appendiceal epithelial tumors using massively parallel sequencing to identify somatic mutations.

Some epithelial neoplasms of the appendix, including low-grade appendiceal mucinous neoplasm and adenocarcinoma, can result in pseudomyxoma peritonei (PMP). Little is known about the mutational spectra of these tumor types and whether mutations may be of clinical significance with respect to therapeutic selection. In this study, we identified somatic mutations using the Ion Torrent AmpliSeq Cancer Hotspot Panel v2. Specimens consisted of 3 nonneoplastic retention cysts/mucocele, 15 low-grade mucinous neoplasms (LAMNs), 8 low-grade/well-differentiated mucinous adenocarcinomas with pseudomyxoma peritonei, and 12 adenocarcinomas with/without goblet cell/signet ring cell features. Barcoded libraries were prepared from up to 10 ng of extracted DNA and multiplexed on single 318 chips for sequencing. Data analysis was performed using Golden Helix SVS. Variants that remained after the analysis pipeline were individually interrogated using the Integrative Genomics Viewer. A single Janus kinase 3 (JAK3) mutation was detected in the mucocele group. Eight mutations were identified in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes among LAMN samples. Additional gene mutations were identified in the AKT1 (v-akt murine thymoma viral oncogene homolog 1), APC (adenomatous polyposis coli), JAK3, MET (met proto-oncogene), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), RB1 (retinoblastoma 1), STK11 (serine/threonine kinase 11), and tumor protein p53 (TP53) genes. Among the PMPs, 6 mutations were detected in the KRAS gene and also in the GNAS, TP53, and RB1 genes. Appendiceal cancers showed mutations in the APC, ATM (ataxia telangiectasia mutated), KRAS, IDH1 [isocitrate dehydrogenase 1 (NADP+)], NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog], PIK3CA, SMAD4 (SMAD family member 4), and TP53 genes. Our results suggest molecular heterogeneity among epithelial tumors of the appendix. Next generation sequencing efforts have identified mutational spectra in several subtypes of these tumors that may suggest a phenotypic heterogeneity showing mutations that are relevant for targeted therapies.

Primary appendiceal mucinous adenocarcinoma mimicking bladder carcinoma: A case report and review of the literature

Primary appendiceal mucinous adenocarcinoma is a rare entity, while appendiceal carcinoma invading the urinary bladder is even rarer. The current study presents the case of a 54-year-old male with primary appendiceal mucinous adenocarcinoma, without gastrointestinal symptoms, presenting only with signs of bladder irritation. Abdominal computed tomography scans demonstrated a mass at the right anterior level of the bladder. During intraoperative exploration, the mass was detected to connect and adhere to the ileocecal junction, and normal appendix tissues were not found. The frozen section revealed a mucinous adenocarcinoma of the appendix and the patient immediately underwent a subsequent hemicolectomy. The present case indicates that a diagnosis of a primary appendiceal mucinous carcinoma must considered by radiologists and clinicians for patients who do not exhibit gastrointestinal symptoms, but show involvement of the nearest organs and the bladder wall.

Beyond acute appendicitis: imaging and pathologic spectrum of appendiceal pathology

While acute appendicitis is a common and important clinical problem, a variety of other disease processes can affect the appendix. Simple and perforated appendicitis, tip appendicitis, and stump appendicitis share a common clinical presentation including anorexia, right lower quadrant pain, and fever. By imaging, most cases of acute appendicitis exhibit luminal dilation, wall thickening, and periappendiceal inflammatory stranding. In tip appendicitis, these changes are isolated to the distal appendix, often with an obstructing appendicolith. Perforated appendicitiscan exhibit mural discontinuity, periappendiceal abscess, and/or extraluminal appendicoliths. After appendectomy, the appendiceal remnant or "stump" can become inflamed, often necessitating repeat surgery. Inflammatory bowel disease can involve the terminal ileum, secondarily involving the appendix, or may primarily involve the appendix. Patient symptoms can be chronic in such cases, and mucosal hyperenhancement is a pronounced imaging feature. In asymptomatic patients without appendiceal inflammation, the appendix can be dilated by intraluminal material such as inspissated succus in cystic fibrosis or mucus from benign appendiceal mucocele. Finally, neoplasms such as typical appendiceal carcinoid tumor and mucinous adenocarcinoma can involve the appendix. Carcinoids are often small and incidentally discovered at pathologic examination, while malignant mucinous adenocarcinoma tends to present with advanced disease including pseudomyxoma peritonei. Cecal cancers can also obstruct the appendiceal lumen and cause acute appendicitis; an astute radiologist can recognize this prospectively and facilitate definitive resection (right hemicolectomy) at the time of surgery. Attention to mural features, cecal configuration, and periappendiceal inflammation is essential to the correct prospective diagnosis of complicated appendicitis and less common appendiceal pathologies.

Invasive mucinous adenocarcinoma associated with adjacent sessile serrated lesion of the appendix vermiform: a case report.

Although the definition of sessile serrated lesion (SSL) of colon is controversial and the risk of progression to malignancy is also under investigation at present, SSL is generally described as a polyp characterized by a serrated architecture. It is estimated to represent a feature of a new cancerization pathway, coined “serrated neoplasia pathway,” particularly in right-sided colon adenocarcinomas. On the other hand, in appendix, the role of this pathway remains uncertain, probably because very few cases of appendiceal adenocarcinoma associated with SSL were reported, and furthermore, immunohistochemical examination was rarely carried out. We herein report an interesting case of invasive appendiceal mucinous adenocarcinoma exhibiting SSL, which was pathologically estimated as a potential precursor lesion, and performed representative immunohistochemistry for both the mucinous adenocarcinoma and SSL in the same specimen. To further elucidate the progression of the appendiceal carcinoma from SSL, both an adequate sectioning of the lesion and systematic immunohistochemical examination of a large number of appendiceal carcinoma cases containing adjacent SSL would be required.

Abstract A11: Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors

Abstract Background: Mucinous ovarian tumors (MOT) have been linked to mucinous colorectal and appendiceal adenocarcinomas. However, recent molecular studies suggest MOT may share more in common with pancreatic mucinous cystic neoplasms (MCN). Commonalities between these seemingly disparate tumors are explored. Methods: Epidemiologic features of MOT and mucinous gastrointestinal tumors were compared using the SEER database. Regional cases of 287 mucinous ovarian tumors were examined against 2,339 age-matched controls to delineate MOT risk factors. A case series of MCN was identified by chart review. Protein expression patterns among tumors were examined using seven immunohistochemical markers. Results: SEER revealed that among GI neoplasms the epidemiology of MCN was most similar to MOT by age, race, and stage. MCN occurred almost exclusively in women, with a sex ratio of 19:1, compared to 1•1:1 and 1•2:1 for mucinous colorectal and appendiceal adenocarcinomas. In the case-control study, appendectomy and cervical conization did not reduce the risk of MOT, while smoking (OR 2•68, 95% CI 1•85-3•89, p&amp;lt;0•001), was associated with an increased risk of MOT. Smoking was similarly common among MCN patients. Histologically, MOT and MCN were CK7+, CK20-, MUC2-, and CDX2-, whereas mucinous colorectal and appendiceal adenocarcinomas were CK7-, CK20+, MUC2+, and CDX2+. Interpretation: Clinical and morphologic similarities between MOT and MCN suggest a common pathogenesis, potentially a shared precursor such as embryologic rests that stopped in the pancreatic buds during migration of the primordial follicles to the gonads during development. This implies mucinous ovarian tumors may originate from primordial follicles, not the ovarian surface epithelium, offering a novel explanation for their pathogenesis. Citation Format: Intidhar Labidi-Galy, Kevin M. Elias, Allison F. Vitonis, Jason L. Hornick, Leona A. Doyle, Michelle S. Hirsch, Daniel W. Cramer, Ronny Drapkin. Common links suggest a shared embryologic origin for pancreatic and ovarian mucinous tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A11.

Coexisting Gastrointestinal Cytomegalovirus and Herpes Simplex Virus Types 1 and 2 with Superimposed Clostridium difficile Colitis

Purpose: The spectrum of morbidity and mortality caused by gastrointestinal cytomegalovirus (CMV) is classically determined by the host's immune response. Although self-limited in immunocompetent patients, multiple comorbidities, including age and malnutrition, can predispose a patient to debilitating opportunistic infections. We present a case of refractory pseudomembranous colitis with underlying gastrointestinal CMV and herpes simplex virus (HSV) infection. A 79-year-old Hispanic female was admitted for persistent diarrhea and vomiting. One month prior to admission, the patient had metastatic appendiceal mucinous adenocarcinoma, which was surgically excised. No chemotherapeutic regimen was initiated, and the patient was started on ampicillin and ciprofloxacin for a urinary tract infection. One week later, the patient described yellow, non-bloody diarrhea, averaging four bowel movements per day. Stool C. diff toxin assay was positive. Although oral metronidazole was prescribed, treatment was ineffective due to vomiting. On admission, the patient complained of fatigue and nausea, but denied fever, chills or abdominal pain. Past medical history was negative, and the patient's social and family history rendered no risk factors for either hereditary or acquired immunodeficiency. On examination, she was lethargic and cachectic. Her abdomen was distended with voluntary guarding but without peritoneal signs. Bowel sounds were present, and rectal exam showed positive fecal occult blood test. Laboratory showed WBC 10.1 K/uL with 14% bands and hemoglobin of 9.5 gm/dL. HIV was undetectable via PCR quantification. The patient was treated with intravenous metronidazole and oral vancomycin, but symptoms persisted. Rifampin was then added but rapidly discontinued as the patient developed hyperbilirubinemia. On hospital day four, a colonoscopy showed pancolitis with pseudomembranes. Biopsies confirmed the impression of C. diffinfection and demonstrated multiple viral inclusions within the epithelial cells. CMV and HSV immunostaining was positive and CMV DNA was detected in the serum via PCR quantification. Intravenous foscarnet was started with noticeable improvement in diarrhea within two days. With the increasing incidence and severity of C. diff-associated diarrhea, many patients develop infections refractory to standard treatment regimens. Whether this is due to resistance or co-infection needs to be determined. This case demonstrates an example of persistent diarrhea, despite appropriate antibiotics for C. diff colitis due to a viral co-infection. We suggest that this type of co-infection may arise in immunocompetent patients and should be taken into consideration when patients present with refractory colitis.

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.

Improving the AJCC/TNM Staging for Adenocarcinomas of the Appendix

Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade in localized disease, and the validity of the American Joint Committee on Cancer AJCC Staging Manual 7th edition's decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known. Patients with adenocarcinoma of the appendix diagnosed between 1988 and 2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage, and grade was calculated, and Cox proportional hazards regression analyses were performed. We analyzed a total of 2469 appendiceal adenocarcinomas, of which 1375 had mucinous histology and 860 had nonmucinous histology. Though overall CSS was similar for mucinous and nonmucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female sex, stage IV disease, and well-differentiated histology were more common for mucinous adenocarcinomas. Histological grade had a strong prognostic impact, especially in patients with stage IV mucinous adenocarcinoma. The adjusted hazard ratios for stage IV moderately and poorly differentiated histological grade were 1.63 [95% confidence interval (CI): 1.14-2.34] and 4.94 (95% CI: 3.32-7.35) for mucinous histology, in comparison with 1.44 (95% CI: 0.82-2.52) and 1.90 (95% CI: 0.95-3.80) for nonmucinous histology, respectively. The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and these data do not support the combination of these 2 histological grades in the recent AJCC Staging Manual 7th edition.

Pseudomyxoma peritonei due to mucinous adenocarcinoma of the appendix

A 60-year-old man was referred for evaluation of long-standing abdominal pain. CT scan of the abdomen showed a fluid-filled dilated appendix with mural calcifications (Fig. A, asterisk) and intraperitoneal low-attenuation mass like nodular formations (Fig. B, arrows) causing scalloping of liver contour (Fig. A, C, arrowheads). The patient underwent appendectomy and peritonectomy followed by uneventful postoperative recovery. Histopathological examination confirmed the radiological suspicion of pseudomyxoma peritonei (PMP) due to appendiceal mucinous adenocarcinoma.

Recurrent peritoneal carcinomatosis in the scrotum in a patient with a history of mucocele of the appendix

Paratesticular metastases are rare entities and a paratesticular metastasis of a mucinous appendiceal adenocarcinoma with peritoneal carcinomatosis has not been reported in the literature in the last 15 years. We present a case of mucinous appendiceal adenocarcinoma that progressed to peritoneal carcinomatosis. Twenty months following surgery and intraperitoneal therapy, the patient presented with testicular pain and swelling. Ultrasound examination raised suspicion for a neoplastic process and pathology confirmed a metastatic mucinous adenocarcinoma of appendiceal origin. Radiologists should be cognizant of potential paratesticular metastases in patients with a known history of malignancy with new testicular pain and swelling.

Improving the AJCC/TNM staging for adenocarcinomas of the appendix: The prognostic impact of histologic grade.

402 Background: Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas; the prognostic impact of grade in localized disease, and the validity of the AJCC Cancer Staging Manual 7th edition decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known. Methods: Patients with adenocarcinoma of the appendix diagnosed between 1988-2007 were identified from the SEER database. Cancer-specific survival (CSS) stratified by histological subtype, stage and grade were calculated; and Cox proportional hazards regression analyses were performed. Results: We analyzed a total of 2,469 appendiceal adenocarcinomas, of which 1,375 had mucinous histology, 860 had non-mucinous histology, and 234 had signet-ring cell histology. Though overall CSS was similar for mucinous and non-mucinous subtypes, differences in stage distribution and stage-stratified CSS were seen. Female gender (57% vs.45%, P&lt;0.01), stage IV disease (48% vs. 25%, P&lt;0.01), and well differentiated histology (31% vs. 14%, P&lt;0.01) were more common in mucinous as compared to non-mucinous adenocarcinomas. While histological grade for stage I-III cases was not statistically significant, it had strong prognostic impact for stage IV disease. The adjusted hazard ratios for stage IV well, moderately and poorly differentiated histological grade were 1 (reference), 1.63 (95%CI: 1.14-2.34) and 4.94 (95%CI: 3.32-7.35) for mucinous, in comparison to 1 (reference), 1.44 (95%CI: 0.82-2.52) and 1.90 (95%CI: 0.95-3.80) for non-mucinous histological subtypes, respectively. Conclusions: The strong prognostic impact of histological grade for mucinous adenocarcinomas is primarily restricted to stage IV disease. Stage IV moderately and poorly differentiated mucinous adenocarcinomas have distinctly different CSS and this data does not support the combination of these two histological grades in the recent AJCC 7th edition.