Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study.

BACKGROUND: Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP. METHODS: Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed. RESULTS: Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (p = 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively). CONCLUSION: These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.

The Pathologic Peritoneal Cancer Index (PCI) Strongly Differs From the Surgical PCI in Peritoneal Metastases Arising From Various Primary Tumors.

BACKGROUND: The surgical peritoneal cancer index (sPCI) is calculated based on a subjective evaluation of the extent of peritoneal disease during surgery. The pathologic PCI (pPCI) may be a more accurate and objective method for determining the PCI. This study aimed to compare the sPCI and pPCI and to study the potential pitfalls and clinical implications of using the pPCI. METHODS: This prospective study (July to December 2018) included all patients undergoing cytoreductive surgery (CRS). The pPCI was calculated for each patient and compared with the sPCI. The impact of potential confounding factors on the difference between pPCI and sPCI was evaluated. RESULTS: Among 191 patients undergoing CRS at four centers, the pPCI and sPCI were concordant for 37 patients (19.3%). The pPCI was lower than the sPCI for 125 patients (65.4%) and higher for 29 patients (15.1%). The concordance between the two groups was maximum for gastric cancer (38.8%) and colorectal cancer (27.6%) and least for mesothelioma (6.7%) and rare primary tumors (5.6%) (p = 0.04). The difference was 0 to 3 points for 119 patients (62.3%), 4 to 5 points for 27 patients (14.1%), and more than 5 points for 45 patients (23.5%). The rate of concordance was not influenced by the use of neoadjuvant chemotherapy (NACT) (p = 0.4), but the difference was greater when NACT was used (p = 0.03). CONCLUSIONS: The pPCI strongly differs from the sPCI for patients undergoing CRS for peritoneal disease and may provide a more accurate evaluation of the peritoneal disease extent. Further studies are needed to determine its prognostic value compared with sPCI, and consensus guidelines are needed for calculating it.

Prognostic impact of combined progression index based on peritoneal grading regression score and peritoneal cytology in peritoneal metastasis.

AIMS: The peritoneal regression grading score (PRGS) and peritoneal cytology (PC) assess response to chemotherapy in peritoneal metastasis (PM) in a setting of palliative treatment by pressurized intraperitoneal aerosol chemotherapy (PIPAC). Progression has been defined as an increase of PRGS between first and third PIPAC procedures (iPRGS). iPRGSand positive peritoneal cytology were not associated with prognostic impact. These results may be explained by a lack of statistical power. Also, it is not known whether the mean or the highest PRGS among taken peritoneal biopsies bears the highest clinical value. We therefore conducted the largest prospective study to investigate the prognostic impact of PGRS, PC, and their combination, designated as combined progression index (CPI). METHODS AND RESULTS: Patients with PM who underwent >3 PIPAC (n = 112) between December 2016 and February 2019 were prospectively included. A significant difference in OS and PFS according to CPI (used highest value of PRGS) was found (OS: CPI-, 83.3, 95% CI [49.8; NA] vs. CPI+, 48.1, 95% CI [38.5; 66.4] months; and PFS (respectively, 59.7, 95% CI [43.0; 96.0] vs. 33.7, 95% CI [30.4; 44.2] months). PRGS or PC had no independent prognostic impact. CPI+ was an independent predictor of worse prognosis, in OS (HR = 5.24, 95% CI [2.07; 13.26]), and PFS (HR = 4.41, 95% CI [1.40; 13.88]). CONCLUSIONS: The CPI based on highest PRGS and PC was found to be independently associated with a worse prognosis for OS and for PFS in the setting of peritoneal metastasis. These results indicate that it should be of interest to systematically take peritoneal fluid for cytological examination and to implement the CPI in the therapeutic decision-making process in the context of PIPAC.

Risk of Omental Metastases in Patients Undergoing Cytoreductive Surgery for Colorectal Peritoneal Metastases.

BACKGROUND: Complete cytoreductive surgery of macroscopic tumor is a potentially curative treatment for patients with colorectal peritoneal metastases. OBJECTIVE: This study aims to determine the risk of microscopic tumor involvement of the greater omentum in patients with normal-looking omentum at the time of cytoreductive surgery for colorectal peritoneal metastases. DESIGN: This was a cohort study. SETTINGS: The prospective BIG-RENAPE database (NCT02823860) was analyzed. PATIENTS: All patients who underwent a complete cytoreductive surgery with greater omentectomy for colorectal peritoneal metastases at a single institution between January 2005 and December 2017 were included. MAIN OUTCOME MEASURE: Data regarding involvement of the greater omentum were extracted from surgical and pathological records. RESULTS: Of 337 patients who underwent cytoreductive surgery for colorectal peritoneal metastases, 241 (71.51%) presented macroscopic omental invasion. Among the 96 patients who underwent a complete cytoreductive surgery with no macroscopic evidence of disease in the greater omentum during surgical exploration, 17 patients (17.70%) had microscopic evidence of tumor in the omentum. Patients with pathological evidence of omental tumor involvement were more likely to have a higher peritoneal cancer index (median 9 vs 4, p = 0.006). LIMITATIONS: No survival analysis could be provided regarding the impact of omentectomy. CONCLUSION: In patients with a normal-looking omentum during surgery for colorectal peritoneal metastases, microscopic tumor was present in 17%. Routine greater omentectomy should be considered in these patients to ensure complete cytoreduction. See Video Abstract at http://links.lww.com/DCR/B262.ClinicalTrials.gov Identifier: NCT02823860 RIESGO DE METÁSTASIS OMENTALES EN PACIENTES SOMETIDOS A CIRUGÍA CITORREDUCTORA, POR METÁSTASIS PERITONEALES COLORRECTALES: La cirugía citorreductora completa del tumor macroscópico, es un tratamiento potencialmente curativo, en pacientes con metástasis peritoneales colorrectales.Determinar el riesgo de afectación tumoral microscópica del epiplón mayor, en pacientes con epiplón de aspecto normal, al momento de la cirugía citorreductora por metástasis peritoneales colorrectales.Este fue un estudio de cohorte.Se analizó la base de datos prospectiva BIG-RENAPE (NCT02823860).Se incluyeron a todos los pacientes sometidos a una cirugía citorreductora completa con omentectomía mayor, por metástasis peritoneales colorrectales, de una sola institución, entre enero de 2005 y diciembre de 2017.Se extrajeron los datos de la afectación del epiplón mayor, de los registros quirúrgicos y patológicos.De 337 pacientes sometidos a cirugía citorreductora por metástasis peritoneales colorrectales, 241 (71.51%) presentaron invasión omental macroscópica. Entre los 96 pacientes sometidos a cirugía citorreductora completa, sin evidencia macroscópica de enfermedad en el epiplón mayor, durante la exploración quirúrgica, 17 pacientes (17,70%) tuvieron en el epiplón, evidencia microscópica de tumor. Los pacientes con evidencia patológica de afectación del tumor omental, fueron más propensos a tener un índice de cáncer peritoneal más alto (mediana 9 frente a 4, p = 0,006).No se pudo obtener ningún análisis de supervivencia, sobre el impacto de la omentectomía.En pacientes con epiplón de aspecto normal, durante la cirugía por metástasis peritoneales colorrectales, estuvo presente el tumor microscópico, en el 17% de los casos. Se debe considerar una omentectomía mayor de rutina en estos pacientes, para asegurar una citorreducción completa. Consulte Video Resumen http://links.lww.com/DCR/B262.Identificador de ClinicalTrials.gov: NCT02823860.

The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens.

OBJECTIVE: Diffuse malignant peritoneal mesothelioma (DMPM), represents 30% of all malignant mesothelioma, and is characterised by a difficult diagnosis and different presentations. Immunohistochemistry has improved the diagnostic sensitivity and specificity in the differential diagnosis between metastatic adenocarcinoma and malignant mesothelioma, and loss of BRCA-1-associated protein 1 (BAP1) expression is correlated with BAP1 somatic or constitutional genetic defects. Furthermore, cyclin-dependent kinase inhibitor 2A (CDKN2A) is frequently lost in DMPM. In the present study, we assessed the value of integrating BAP1 in the panel of antibodies used for the diagnosis of DMPM in cytological samples. Since p16 fluorescent in situ hybridisation (FISH) assay could constitute an additional useful adjunct, results of BAP1 immunostaining and p16 FISH assays have been compared. METHODS: Forty-eight DMPM patients and 71 peritoneal carcinomatosis patients were included. BAP1 immunohistochemical and CDKN2A FISH techniques were performed on tissue specimens of DMPM (n = 48) and peritoneal carcinomatosis (n = 71) then on cell-block of DMPM (n = 16), peritoneal carcinomatosis (n = 25) and peritoneal benign effusion (n = 5). RESULTS: Loss of BAP1 expression was observed in 56.3% of DMPM while none of the peritoneal carcinoma specimens showed BAP1 loss of expression. CDKN2A loss was observed in 34.9% DMPM and 2.1% peritoneal carcinoma. Although BAP1 immunostaining was successful in 100% of cytological DMPM samples, CDKN2A deletion status could be obtained for 75% of DMPM cases. CONCLUSION: BAP1 immunostaining represents an objective and reproducible diagnostic biomarker for peritoneal mesothelioma in effusion cytology specimens and should be preferred to CDKN2A FISH analysis on these precious samples.

Acute Renal Colic Due to Immunoglobulin Free Light Chain Kidney Stones: A Case Report of an Unusual Complication of Multiple Myeloma.

Kidney failure is common in patients with a monoclonal gammopathy, most frequently due to hypercalcemia or myeloma cast nephropathy. Immunoglobulin crystallization is an uncommon phenomenon that also results in kidney injury. We report the case of a 74-year-old man with recurrent renal colic and acute kidney injury. He presented with κ light chain Bence-Jones proteinuria, hypogammaglobulinemia, anemia, and high plasma κ light chain level, leading to the diagnosis of κ light chain multiple myeloma. One calculus was collected and its analysis revealed a unique protein structure consisting of κ immunoglobulin free light chain. Genetic sequencing of the κ light chain identified a subgroup of variable domain previously identified as prone to crystallization. Eight cycles of cyclophosphamide-bortezomib-dexamethasone chemotherapy resulted in a partial hematologic response and kidney recovery without recurrence of renal colic. This rare case of urinary light chain nephrolithiasis highlights the importance of genetic and molecular analysis of the immunoglobulin variable domain to better understand the wide spectrum of monoclonal gammopathies.

The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinomas and pseudomyxoma peritonei.

The vermiform appendix is the primary site of several distinctive benign and malignant neoplasms. Some can produce the clinical syndrome of pseudomyxoma peritonei (PMP). A consensus on their terminology was reached by an international panel of pathologists and clinicians working under the auspices of the Peritoneal Surface Oncology Group International (PSOGI), and this review discusses the application of the PSOGI classification to routine reporting. We discuss diagnosis and differential diagnosis together with implications for patient management, covering low-grade appendiceal mucinous neoplasms, high-grade appendiceal mucinous neoplasms, serrated polyps, adenomas and adenocarcinomas. We do not cover goblet cell tumours or neuroendocrine neoplasms in this paper.

FDG-PET/ceCT is useful to predict recurrence of Pseudomyxoma peritonei.

PURPOSE: Pseudomyxoma peritonei (PMP) is a rare peritoneal neoplasm originating from appendicular tumours. There is no consolidated data available in the literature about the precise role of [(18)F] fluorodesoxy-D-glucose Positron Emission Tomography / contrast enhanced Computed Tomography (FDG-PET/ceCT). The aim of this study was to evaluate the correlation between preoperative FDG-PET/ceCT (qualitative and semi-quantitative assessment) and progression free survival (PFS) of patients treated for PMP. METHODS: All patients scheduled for PMP treatment by cytoreductive unicentric surgery, intraperitoneal chemotherapy (HIPEC), and who underwent a FDG-PET/ceCT between February 2008 and January 2014, were included. No previous treatment was performed (except biopsy or appendectomy). FDG-PET/ceCT was interpreted by two nuclear physicians in consensus. Positive FDG-PET/ceCT scans were further labelled in diffuse disease and poly/mono focal disease. SUVmax was measured based on post-operative reports. The Peritoneal Cancer Index (PCI) and Completeness of CytoReduction Score (CCR) were assessed after surgery. RESULTS: Fifty-six patients were included in this study, with a mean age of 56-years-old and a mean follow-up of 29.3 months. SUVmax, with a cut-off at 2.02, was predictive for the PFS on multivariate analysis. No differences were observed between diffuse disease and focal disease on PFS for progression free survival, PCI, and SUVmax (p = 0.1). Post-operative CCR was not significantly correlated with SUVmax or FDG-PET/ceCT qualitative assessment. CONCLUSION: SUVmax on preoperative FDG-PET/ceCT was an independent predictive factor for PFS in PMP. Further studies are needed to explore if FDG-PET/ceCT could potentially predict post-operative CCR.

[BRCA1 associated protein 1 (BAP1) expression in pleural diffuse malignant mesothelioma: A comparative cytological and histological analyses on 50 patients]. / Apport de l'expression protéique de BRCA1 associated protein 1 (BAP1) dans le diagnostic des mésothéliomes malins diffus pleuraux : une analyse cytologique et histologique comparative sur une série de 50 patients.

INTRODUCTION: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD. MATERIALS AND METHODS: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis. RESULTS: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation. DISCUSSION AND CONCLUSION: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect.

Bowel endometriosis: preoperative diagnostic accuracy of 3.0-T MR enterography--initial results.

PURPOSE: To prospectively determine the accuracy of 3.0-T magnetic resonance (MR) enterography in the preoperative assessment of deep infiltrating endometriosis (DIE) lesions located in the bowel above the rectosigmoid junction. MATERIALS AND METHODS: Institutional review board approval for this study was obtained, and each patient gave written informed consent. Over 18 months, patients with known pelvic DIE who were scheduled for surgery were recruited. Consecutive patients suspected of having bowel endometriosis above the rectosigmoid junction underwent 3.0-T MR enterography. Two blinded readers independently performed a systematic analysis of nine bowel segments above the rectosigmoid junction. MR images were compared with surgical and pathologic findings. Efficacy parameters were calculated with 95% confidence intervals (CIs). Interobserver agreement was assessed with κ statistics. RESULTS: Among the 43 patients enrolled in this study, 33 underwent surgery and were included in the final analyses. Sixteen (48%) patients had bowel DIE lesions located above the rectosigmoid junction at surgery and histopathologic examination. Twenty-six lesions were analyzed, including four ileal, two ileocecal, three cecal, three appendicular, and 14 sigmoid colon lesions. For the diagnosis of these lesions, MR imaging showed sensitivities of 92% (95% confidence interval [CI]: 81.7, 100) for reader 1 and 96% (95% CI: 87.1, 100) for reader 2 and specificities of 100% (95% CI: 98.8, 100) for both readers. The κ value was 0.97. CONCLUSION: These results show 3.0-T MR enterography is accurate in the preoperative diagnosis and mapping of bowel DIE lesions located above the rectosigmoid junction. Online supplemental material is available for this article.

Pathological response to neoadjuvant chemotherapy: a new prognosis tool for the curative management of peritoneal colorectal carcinomatosis.

PURPOSE: The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). METHODS: A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. RESULTS: Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. CONCLUSIONS: Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.

[The RENAPE network: towards a new healthcare organization for the treatment of rare tumors of the peritoneum. Description of the network and role of the pathologists]. / Réseau RENAPE : vers une nouvelle organisation des soins pour le traitement des tumeurs rares du péritoine. Description du réseau et rôle des pathologistes.

As part of the national 2009-2013 Cancer Plan, and with the support of the National cancer Institute and the French ministry of health, the National network for the treatment of rare peritoneal malignancies (RENAPE) has been organized. Its main objective is to optimize the framework for the healthcare management and treatment of rare peritoneal malignancies. This specific organization covers the whole national territory including clinical expert and specialized structures and should lead to an appropriate treatment based on expertise and proximity. Within the RENAPE network, the RENA-PATH group gathers the pathologists actively involved in the management of rare peritoneal malignancies. The actions of RENA-PATH are focused primarily on the harmonization of pathological diagnostic criteria, reporting of new cases in the RENAPE registry and histology reviewing.

[Peritoneal pseudomyxoma: an overview emphasizing pathological assessment and therapeutic strategies]. / Mise au point sur le pseudomyxome péritonéal. Aspects anatomo-pathologiques, et implications thérapeutiques.

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

[Peritoneal malignant mesothelioma: review and recent data]. / Mésothéliome malin péritonéal : mise au point et données actuelles.

Peritoneal malignant mesothelioma is a rare tumor, less common than its pleural counterpart. It develops from the mesothelial cells overlying peritoneum and preferentially occurs in male, with an average age ranging from 47 to 60.5 years. Asbestos whose impact is less strong than in pleural mesothelioma, SV 40 virus, chronic peritonitis could be implicated as factors favoring the development of peritoneal mesothelioma. Clinical symptoms are not specific, and the imagery remains little or not contributive. The 2004 WHO classification recognizes 3 different types, which differ in terms of presentation and prognosis: diffuse epithelioid mesothelioma (the most common), sarcomatoid mesothelioma and biphasic mesothelioma. Many variants are described within these groups. Immunohistochemistry is mandatory to affirm or disprove peritoneal malignant mesothelioma diagnosis, based on a panel of antibodies divided in positive markers and negative markers. Indeed an accurate diagnosis is necessary to define a therapeutic strategy more and more frequently based on the combination of radical surgery and hyperthermic intra peritoneal chemotherapy. Such an approach significantly improves the prognosis of these aggressive diseases.

Intraperitoneal cytokine level in patients with peritoneal surface malignancies. A study of the RENAPE (French Network for Rare Peritoneal Malignancies).

BACKGROUND: Prognosis of peritoneal surface malignancies is influenced by the adequacy of surgical and chemotherapeutic treatment and by tumor spread at the time of diagnosis. By promoting morphological changes in the mesothelium, inflammatory cytokines reflect tumor biology and could be evaluated as biomarkers. Our objective was to evaluate intraperitoneal levels of IL-6, IL-8, IL-10, TNF-alpha, and sICAM in patients with pseudomyxoma peritonei and peritoneal mesothelioma. METHODS: Serum and peritoneal fluid samples were prospectively collected in patients managed for peritoneal surface malignancies including pseudomyxoma peritonei (PMP), mesotheliomas, and other rare primitive peritoneal cancers (cancer group) and patients who underwent intraperitoneal laparoscopic surgical procedures for benign diseases (noncancer group). Samples were analyzed for IL-6, IL-8, IL-10, TNF-alpha, and sICAM concentrations. Correlations were assessed with tumor spread related clinical scores. RESULTS: In both patient groups, intraperitoneal cytokine levels were higher than serum levels. Cancer patients had significantly higher intraperitoneal cytokine levels than noncancer patients. Peritoneal levels tended to increase in cancer patients with free tumor cells in peritoneal fluid. They were significantly higher in patients with tumor implants ≥2 cm and/or patients with peritoneal carcinomatosis index (PCI) >19. Furthermore, patients with malignant pseudomyxoma peritonei (grades II and III) had higher levels than patients with nonmalignant disease (grade I). CONCLUSIONS: Assessment of intraperitoneal IL-6, IL-8, IL-10, TNF-alpha, and sICAM levels can be performed in patients with peritoneal surface malignancies. They can be considered as both diagnostic and prognostic biomarkers that could be used as useful adjuncts for therapeutic decision making.

Ocular sarcoidosis: when should labial salivary gland biopsy be performed?

PURPOSE: To assess the usefulness of a labial salivary gland biopsy (LSGB) in subsets of patients with uveitis. METHODS: A retrospective study of 115 consecutive patients with uveitis for whom a LSGB had been done because of suspected ocular sarcoidosis (n = 86) or unexplained uveitis (n = 29). Eighty-six patients had a suspicion of ocular sarcoidosis because of ocular features (n = 67), an elevated angiotensin converting enzyme (ACE) (n = 29), or because of CT findings (n = 32) suggestive of sarcoidosis. The biopsy results were analyzed together with their ophthalmological features and the results of other relevant examinations, such as the serum levels of ACE and a chest radiography or a CT scan. RESULTS: Six of the 115 patients (5.2 %) with uveitis had sarcoid granulomas on the LSGB. At the end of the study, 32 patients had proven sarcoidois while 22 patients were considered as having either indeterminate or presumed sarcoidosis, according to the criteria of Abad et al. A raised ACE (p = 0.016) and a compatible radiology (p = 0.033) were related to a positive LSGB test, but not to the features of uveitis. Granulomas were only found in the LSGB of the patients with an elevated ACE or compatible CT scans. CONCLUSIONS: In this study, the LSGB sensitivity (18.75 %) in the patients with proven sarcoidosis appears to be lower than in other reports. Our results suggest that this investigation is a possible method of tissue diagnosis in patients with raised ACE and/or CT scan pattern compatible with sarcoidosis, and should not be performed in patients with unexplained uveitis or because of their ophthalmological features.

Progression following neoadjuvant systemic chemotherapy may not be a contraindication to a curative approach for colorectal carcinomatosis.

OBJECTIVE: The objective of this retrospective study was to evaluate the influence of neoadjuvant systemic chemotherapy on patients with colorectal carcinomatosis before a curative procedure. BACKGROUND: Peritoneal carcinomatosis (PC) from colorectal cancer may be treated with a curative intent by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The role of perioperative systemic chemotherapy for this particular metastatic disease remains unclear. METHODS: One hundred twenty patients with PC from colorectal cancer were consecutively treated by 131 procedures combining CRS with HIPEC. The response to neoadjuvant systemic chemotherapy was assessed on data from previous explorative surgery and/or radiological imaging. RESULTS: Ninety patients (75%) were treated with neoadjuvant systemic chemotherapy in whom 32 (36%) were considered to have responded, 19 (21%) had stable disease, and 19 (21%) developed diseases progression. Response could not be evaluated in 20 patients (22%). On univariate analysis, the use of neoadjuvant systemic chemotherapy had a significant positive prognostic influence (P = 0.042). On multivariate analysis, the completeness of CRS and the use of adjuvant systemic chemotherapy were the only significant prognostic factors (P < 0.001 and P = 0.049, respectively). Response to neoadjuvant systemic chemotherapy had no significant prognostic impact with median survival of 31.4 months in patients showing disease progression. CONCLUSIONS: In patients with PC from colorectal cancer without extraperitoneal metastases, failure of neoadjuvant systemic chemotherapy should not constitute an absolute contraindication to a curative procedure combining CRS and HIPEC.

5-hmC loss is another useful tool in addition to BAP1 and MTAP immunostains to distinguish diffuse malignant peritoneal mesothelioma from reactive mesothelial hyperplasia in peritoneal cytology cell-blocks and biopsies.

The differentiation between reactive mesothelial hyperplasia (RMH) and diffuse malignant peritoneal mesothelioma (DMPM) is challenging especially when applied on peritoneal small samples. The use of BRCA-associated protein 1 (BAP1) and methylthioadenosine phosphorylase (MTAP) immunostains is familiar to identify malignant mesothelial proliferation. Recently, nuclear 5-hydroxymethylcytosine (5-hmC) was reported to be a new recognition tool of pleural mesothelial malignancy on surgical specimens. However, application of 5-hmC immunostaining has not yet studied in peritoneal specimens from small biopsies or cytology cell-blocks. The aim was to assess the diagnostic accuracy of this new marker combination to distinguish DMPM from RMH in biopsies and cell-blocks. Seventy-five cases were analyzed; among which, 38 were of cytological specimens including 6 RMH and 32 DMPM, and 37 tissue biopsies with 7 RMH and 30 DMPM. BAP1, MTAP, and 5-hmC immunostains were performed on all cases. RMH cases exhibited a retained staining with all immunostains. Among DMPM, BAP1 was lost in 71.8% of cytology cell-blocks and 66.7% of biopsies. MTAP was lost in 40.6% of cytology cell-blocks and 33.3% of biopsies. 5-hmC was lost in 40.6% of cytology cell-blocks and 30% of biopsies. The combination of BAP1, MTAP, and 5-hmC showed the best accuracy in differential diagnosis between RMH and DMPM (sensitivity = 0.84, specificity = 1 in cytology cell-blocks; sensitivity = 0.90, specificity = 1 in biopsy). The best diagnostic combination in peritoneal cytology effusion fluids and biopsies samples provided by BAP1, MTAP, and 5-hmC should be applied on a diagnostic step-wise algorithm by pathologists involved into the management of DMPM, because of their therapeutic implications.

Sarcoidosis: A Clinical Overview from Symptoms to Diagnosis.

Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25-50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren's syndrome, lupus pernio, Heerfordt's syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.