Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care.

CONTEXT: Low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites); however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria. OBJECTIVE: To determine the pathological diagnostic concordance for appendix neoplasia and related lesions during patient referral to an academic medical center specialized in treating patients with PMP. DESIGN: The anatomic pathology laboratory information system was searched to identify cases over a two-year period containing appendix specimens with mucinous neoplasia evaluated by an outside pathology group and by in-house slide review at a single large academic medical center during patient referral. RESULTS: 161 cases containing appendix specimens were identified over this period. Forty-six of 161 cases (28.6%) contained appendiceal primary neoplasia or lesions. Of these, the originating pathologist diagnosed 23 cases (50%) as adenocarcinoma and 23 cases (50%) as LAMN; however, the reference pathologist diagnosed 29 cases (63.0%) as LAMN, 13 cases (28.3%) as adenocarcinoma, and 4 cases (8.7%) as ruptured simple mucocele. Importantly, for cases in which the originating pathologist rendered a diagnosis of adenocarcinoma, the reference pathologist rendered a diagnosis of adenocarcinoma (56.5%, 13 of 23), LAMN (39.1%, 9 of 23), or simple mucocele (4.3%, 1 of 23). The overall diagnostic concordance rate for these major classifications was 71.7% (33 of 46) with an unweighted observed kappa value of 0.48 (95% CI, 0.27-0.69), consistent with moderate interobserver agreement. All of the observed discordance (28.3%) for major classifications could be attributed to over-interpretation. In addition, the majority of LAMN cases (65.5%) had potential diagnostic deficiencies including over-interpretation as adenocarcinoma and lacking or discordant risk stratification (i.e. documentation of extra-appendiceal neoplastic epithelium). CONCLUSIONS: Appendiceal mucinous lesions remain a difficult area for appropriate pathological classification with substantial discordance due to over-interpretation in this study. The findings highlight the critical need for recognition and application of diagnostic criteria regarding these tumors. Recently published consensus guidelines and a checklist provided herein may help facilitate improvement of diagnostic concordance and thereby reduce over-interpretation and potential overtreatment. Further studies are needed to determine the extent of this phenomenon and its potential clinical impact.

Haemodynamic changes during hyperthermic intra-thoracic chemotherapy for pseudomyxoma peritonei.

PURPOSE: Hyperthermic intra-thoracic chemotherapy (HITOC) combined with cytoreductive surgery (CRS) is a novel approach in the management of pseuodmyxoma peritonei with thoracic extension. The haemodynamic effects of hyperthermic chemotherapy present an anaesthetic challenge. Here, we describe the haemodynamic changes seen during HITOC. MATERIALS AND METHODS: A retrospective case note review of adult patients undergoing CRS with HITOC from 2009 to 2016. Intra-operative haemodynamics were measured using the LIDCOrapidTM brand of invasive cardiac output (CO) monitor. Intravenous fluids, vasopressor requirements and urine output (UO) were recorded. RESULTS: Four patients were included in the study. Mean heart rate (HR) peaked at 20 min following commencement of HITOC. The difference between HR at time 0 and at peak was minimal. There was minimal change in CO, and stroke volume variation (SVV) remained stable. Vasopressor dose was minimally changed throughout surgery. Average UO during HITOC was 142.5 ± 109.6 mls at 60 min. Mean fluid requirements during HITOC was 586.2 ± 441.2 mls. No significant change occurred in pH or base excess (BE). CONCLUSIONS: Significant haemodynamic instability including cardiac asystole has been reported during HITOC. The application of hyperthermic agents to the thorax results in vasodilatation, cardiac warming and compression of mediastinal vessels. Measurement of haemodynamic variables allowed careful titration of intravenous fluid therapy to CO and stroke volume, allowing for haemodynamic stability. This has not been described elsewhere.

Pseudomyxoma peritonei: natural history and treatment.

Pseudomyxoma peritonei (PMP) is an uncommon disease characterised by mucinous ascites, classically originating from a ruptured low grade mucinous neoplasm of the appendix. The natural history of PMP revolves around the "redistribution phenomenon", whereby mucinous tumour cells accumulate at specific sites with relative sparing of the motile small bowel and to a lesser extent other parts of the gastrointestinal tract. Peritoneal tumour accumulates due to gravity and at the sites of peritoneal fluid absorption, namely, the greater and lesser omentum and the under-surface of the diaphragm, particularly on the right. The optimal treatment is complete macroscopic tumour excision termed cytoreductive surgery (CRS) combined with Hyperthermic Intra-Peritoneal Chemotherapy (HIPEC). Total operating time for complete CRS and HIPEC for extensive PMP is around 10 h and generally involves bilateral parietal and diaphragmatic peritonectomies, right hemicolectomy, radical greater omentectomy with splenectomy, cholecystectomy and liver capsulectomy, a pelvic peritonectomy with, or without, rectosigmoid resection and bilateral salpingo-oophorectomy with hysterectomy in females. A unique feature of low grade PMP, which differs from other peritoneal malignancies, includes slow disease progression, which may be asymptomatic until advanced stages. Additionally, very extensive disease with a high "PCI" (Peritoneal Carcinomatosis Index) may still be amenable to complete excision and cure. In cases where complete tumour removal is not feasible, maximum tumour debulking can still result in long-term survival in PMP. PMP is challenging, complex but nevertheless the most rewarding peritoneal malignancy amenable to cure by CRS and HIPEC.

Adenocarcinoma mucinoso de quiste gigante de uraco asociado a pseudomixoma peritoneal / Mucinous adenocarcinoma arising in a giant urachal cyst associated with pseudomyxoma peritoneal

El pseudomixoma peritoneal originado en el adenocarcinoma mucinoso de uraco, es una condición extremadamente rara. Tras estudio de la literatura, se han publicado hasta la actualidad, 36 observaciones. Se publica el caso, en un hombre de 51 años de edad, asintomático, que presentó como hallazgo en TAC de abdomen tras litotricia, una masa en la pared anterior dependiente del uraco. En la laparotomía, se encontró una masa quística de 10x8 cm, bilobulada y rota, conteniendo un fluido mucinoso espeso. Este mismo fluido estaba presente en la cavidad peritoneal. Se extirpó la tumoración y se extrajo la mayor cantidad posible de líquido libre. La histología reveló un adenocarcinoma mucinoso de uraco asociado a pseudomixoma peritoneal. Después de la primera intervención se decidió una segunda operación. Se realizó cirugía citorreductora y quimioterapia intraperitoneal hipertérmica. El paciente está asintomático y libre de enfermedad a los 6 meses de la segunda intervención. Se discuten los aspectos relacionados con la embriología, epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de esta patología

Pseudomyxoma peritonei arising from mucinous adenocarcinoma of the urachus is an extremely rare condition. We identified 36 previous cases published to date.We report the case in a 51-year-old man, asymptomatic, presented as a finding on CT abdomen review after lithotripsy, a mass in the anterior wall urachal dependent. At laparotomy, the cystic mass, 10x8 cm, was could be completely separated from the bladder and was excised. It was smooth-walled and filled with thick mucinous fluid. A large volume of pseudomyxoma peritonei was present. Histology revealed an adenocarcinoma mucinous of the urachus associated with pseudomyxoma peritonei. After the first intervention was decided to reoperate the patient. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy was performed. The patient was well, with no tumour recurrence, at 6 months follow-up. We discuss aspects of embryology, epidemiology, clinical manifestations, diagnosis and treatment of this complex pathology

Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects.

Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1-2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as the secreted mucins of relevance in PMP. Development of mucin-targeted therapies could be a promising avenue for future research which is addressed in this article.

Pseudomyxoma peritonei: biological features are the dominant prognostic determinants after complete cytoreduction and hyperthermic intraperitoneal chemotherapy.

OBJECTIVE: To investigate outcome and prognostic factors in patients with pesudomyxoma peritonei (PMP) treated by complete cytoreduction and hyperthermic intraperitoneal chemotherapy. BACKGROUND: After comprehensive treatment, prognosis of PMP is predominantly dependent on the completeness of cytoreduction. Once complete cytoreduction is achieved, additional factors predicting long-term outcome are still poorly understood. METHODS: From a prospective database, we selected 102 patients undergoing complete cytoreduction (residual tumor nodules < or =2.5 mm) and closed-abdomen hyperthermic intraperitoneal chemotherapy with mitomycin-C and cisplatin. Previously, 22 patients had systemic chemotherapy. PMP was histologically classified into disseminated peritoneal adenomucinosis, peritoneal mucinous carcinomatosis (PMCA), and intermediate/discordant group. Twenty-one patient-, tumor-, and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. The following immunohistochemical markers were tested: cytokeratin (CK)-7, CK-20, CDX-2, MUC-2, and MUC-5AC. RESULTS: Operative mortality was 1%. Seventy-eight patients were diagnosed with disseminated peritoneal adenomucinosis, 24 with PMCA, none with intermediate/discordant group. For the overall series, median follow-up, 5-year OS, and PFS were 45 months (range 1-110), 84.4%, and 48.3%, respectively. In most cases, CK20, CDX-2, and MUC-2 were diffusely positive, whereas CK-7 and MUC-5AC were variably expressed. At multivariate analysis, previous systemic chemotherapy and PMCA correlated to both worse OS and PFS, elevated serum CA125 only to worse PFS. CK20, CDX-2, and MUC-2 expression correlated to prognosis at univariate analysis. CONCLUSIONS: After complete cytoreduction and hyperthermic intraperitoneal chemotherapy, prognosis of PMP is primarily dependent on pathologic and biologic features. MUC-2, CK-20, and CDX-2 may be related to the disease biology. Understanding PMP molecular basis may facilitate personalized treatment.

Mucoceles apendiculares / Mucocele of the appendix

Introducción. Los mucoceles apendiculares son una entidad infrecuente; representan sólo el 0,25% de todas las apendicectomías y un 8% de todos los tumores apendiculares. Material y métodos. Describimos 27 casos de mucoceles apendiculares tratados entre enero de 1978 y diciembre de 2006 en el Hospital Donostia. Resultados. La edad media ± desviación estándar de los pacientes fue de 54,4 ± 21,7 años (rango, 17-88). De los 27 pacientes, 15 (55,5%) eran varones y 12 (44,5%) mujeres. Fueron intervenidos de urgencia 17 pacientes (62,9%). Resultaron hallazgos operatorios en el curso de intervenciones por otra razón en 7 (25,9%) ocasiones; 3 pacientes fueron operados con diagnóstico de tumoración abdominal no filiada (11,1%). La causa principal de intervención de urgencia fue el dolor en la fosa ilíaca derecha, 14 (82,2%); obstrucción intestinal, 1 (5,8%); diagnóstico de endometriosis, 1 (5,8%), y diagnóstico de piosalpinx, 1 (5,8%). Se intervino a 3 pacientes por presentar seudomixoma peritoneal pasados 24, 36 y 41 meses. El último caso se encuentra bien tras peritonectomía y pasados 78 meses. Hemos encontrado una incidencia global de 11 casos (40,7%) de neoplasias isocronas o metacronas de otra localización en estos pacientes. Conclusiones. Recomendamos el seguimiento de todos los pacientes con mucocele apendicular porque a veces se asocian a neoplasias de otra localización y riesgo de seudomixoma peritoneal, incluso en fases más avanzadas del seguimiento (AU)

Introduction. Mucoceles of the appendix are infrequent entities and are found in only 0.25% of all appendectomies and 8% of all appendicular tumors. Material and methods. We describe 27 cases of mucocele of the appendix treated at Donostia Hospital between January 1978 and December 2006. Results. The mean age of the patients was 54.4 ± 21.7 years (range: 17­88). Of the 27 patients, 15 (55.5%) were males and 12 (44.5%) were females. Emergency surgery was performed in 17 patients (62.9%). Mucoceles were identified as operative findings during surgery for other reasons in seven patients (25.9%). Three patients (11.1%) underwent surgery because of a diagnosis of abdominal tumor. The main reason for emergency surgery was lower right abdominal pain in 14 patients (82.2%), intestinal obstruction in one (5.8%), a diagnosis of endometriosis in one (5.8%) and a diagnosis of pyosalpinx in one (5.8%). Three patients underwent surgery due to pseudomyxoma peritonei after 24, 36 and 41 months' follow-up. The third patient is asymptomatic after peritonectomy and a follow-up of 78 months. We found an overall incidence of 11 cases (40.7%) presenting with synchronous or metachronous neoplasms from other locations. Conclusions. We recommend monitoring of all patients with mucocele of the appendix, because these masses can sometimes be associated with neoplasms in other locations and there is a risk of pseudomyxoma peritonei even after a long follow-up (AU)

Hemodynamic and cardiovascular problems during modified hyperthermic intraperitoneal perioperative chemotherapy.

BACKGROUND/AIMS: Cytoreductive surgery and hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) significantly improves patients survival with peritoneal carcinomatosis especially in low-grade tumor e.g. ovarian and appendiceal adenocarcinoma, peritoneal pseudomyxoma and grade I gastric and colorectal cancer. METHODOLOGY: During a period of nine years, hemodynamic and cardiac functions combined with urinary output during hyperthermic intraoperative intraperitoneal chemotherapy were prospectively measured in 60 patients. RESULTS: Statistically significant hemodynamic and cardiac parameters were characterized by an increased heart rate and cardiac output as well as decreased systemic vascular resistance associated with an increased body temperature and decreased effective circulating volume. The tendency of urinary output was to decrease as the therapy progressed. CONCLUSIONS: HIPEC induces a hyperdynamic circulatory state requiring increased intravenous fluid administration, which avoids changes because of increased intra-abdominal pressure. Documented by normal blood pressure and adequate urinary output hemodynamic and intravenous fluids, titrated to frequent urinary output determination, can achieve cardiac stability.