Systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC): A case report of a multimodal treatment for peritoneal metastases of pancreatic origin

Introduction: Pancreatic ductal adenocarcinoma (PDAC) with peritoneal metastases (PM) has a dismal prognosis and palliative systemic chemotherapy, which represents the standard treatment option, has significant pharmacokinetics limitations and low efficacy. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new method of drug delivery that is expected to maximize exposure of peritoneal nodules to antiblastic agents. A combination of systemic chemotherapy and PIPAC may be valuable. Presentation of case: A 55 years old male affected by PDAC with synchronous PM underwent a multimodal treatment comprising systemic chemotherapy and PIPAC without any procedural-related adverse events. Tumor genomic profiling evaluation from peritoneal biopsies addressed further tailored systemic chemotherapy. Discussion: The presented case illustrates the possibility of adding PIPAC to systemic chemotherapy with a fair tolerance profile and good quality of life while allowing monitoring of therapy-response and tailoring of the antiblastic treatment

Pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin or oxaliplatin for peritoneal metastasis from pancreatic adenocarcinoma and cholangiocarcinoma

Background: Systemic chemotherapy for pancreatic adenocarcinoma (PDAC) and cholangiocarcinoma (CC) with peritoneal metastases (PM) is affected by several pharmacological shortcomings and low clinical efficacy. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is expected to maximize exposure of peritoneal nodules to antiblastic agents. This study aims to evaluate safety and efficacy of PIPAC for PM of PDAC and CC origin. Methods: This is a retrospective analysis of consecutive PDAC and CC cases with PM treated with PIPAC at two European referral centers for peritoneal disease. We prospectively recorded from August 2016 to May 2019 demographic, clinical, surgical, and oncological data. We performed a feasibility and safety assessment and an efficacy analysis based on clinical and pathological regression. Results: Twenty patients with PM from PDAC (14) and CC (six) underwent 45 PIPAC administrations. Cisplatin–doxorubicin or oxaliplatin were administered to eight and 12 patients, respectively. We experienced one intraoperative complication (small bowel perforation) and 18 grade 1–2 postoperative adverse events according to Common Terminology Criteria for Adverse Events version 4.0. A pathological regression was recorded in 50% of patients (62% in the cisplatin–doxorubicin cohort and 42% in the oxaliplatin one). Median survival from the first PIPAC was 9.7 and 10.9 months for PDAC and CC, respectively. Conclusion: PIPAC resulted feasible and safe without relevant toxicity issues, with both cisplatin–doxorubicin and oxaliplatin. The pathological response observed supports the evidence of antitumoral activity. Despite the study limitations, these outcomes are encouraging, recommending PIPAC in prospective, controlled trials in the palliative setting or the first line chemotherapy for PM from PDAC and CC

Corded and hyalinized endometrioid carcinoma: Summary of clinical, histological, immunohistochemical and molecular data

Corded and hyalinized endometrioid carcinoma (CHEC) represents a potential pitfall for pathologists. This study aimed to provide a complete overview of all clinicopathological and molecular features of CHEC. Electronic databases were searched for all published series of CHEC. Clinical, histological, immunohistochemical and molecular data about CHEC were extracted and pooled. Six studies with 62 patients were identified; mean age was 49.8 years (range 19–83). Most cases showed FIGO stage I (68%), low grade (87.5%), and a favorable outcome (78.4%), with “no specific molecular profile” (NSMP). A subset of cases showed high-grade features (12.5%), p53 abnormalities (11.1%) or mismatch repair (MMR) deficiency (20%) and occurred at an older age (mean age>60 years). Common features of CHEC were: superficial localization of the corded component (88.6%), squamous/morular differentiation (82.5%), nuclear β-catenin accumulation (92%), partial/total loss of CKAE1/AE3 (88.9%), estrogen receptor (95.7%) and e-cadherin (100%), stromal changes such as myxoid (38.5%), osteoid (24%) and chondroid (4.5%), CTNNB1 mutations (57.9%), and POLE-wild-type (100%); 24.4% of cases showed lymphovascular space invasion. A minority of cases (16.2%) showed poor outcome despite a low-grade, NSMP phenotype; the molecular basis for the aggressiveness of these cases is still undefined. Further studies are necessary in this field

Recent Advances in Cervical Cancer Management: A Review on Novel Prognostic Factors in Primary and Recurrent Tumors

Background: Several pathological parameters, including tumor size, depth of stromal invasion, lympho-vascular space invasion and lymph node status, have been proposed as prognostic predictors in cervical cancer. However, given the high mortality and recurrence rate of cervical cancer, novel parameters that are able to provide additional prognostic information are needed in order to allow a better prognostic stratification of cervical cancer patients. Methods: A search was conducted on PubMed to identify relevant literature data regarding prognostic factors in cervical cancer. The key words “cervical cancer”, “prognostic factors”, “pathology”, and “outcome” were used. Results: The novel pathological grading system based on tumor budding and cell nest size appeared the most relevant prognostic factor in primary neoplasms. Moreover, other potentially useful prognostic factors were tumor size, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes. Prognostic factors related to advanced-stage cervical cancer, including lymph-nodes status, endometrial and cervical involvement as well as distant metastases, were also taken into consideration. Conclusions: According to our findings, tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance and tumor-infiltrating lymphocytes appeared the most relevant factors included in the pathology report

ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid

Gene Expression Profiling of Pancreas Neuroendocrine Tumors with Different Ki67-Based Grades.

Pancreatic neuroendocrine tumors (PanNETs) display variable aggressive behavior. A major predictor of survival is tumor grade based on the Ki67 proliferation index. As information on transcriptomic profiles of PanNETs with different tumor grades is limited, we investigated 29 PanNETs (17 G1, 7 G2, 5 G3) for their expression profiles, mutations in 16 PanNET relevant genes and LINE-1 DNA methylation profiles. A total of 3050 genes were differentially expressed between tumors with different grades (p < 0.05): 1279 in G3 vs. G2; 2757 in G3 vs. G1; and 203 in G2 vs. G1. Mutational analysis showed 57 alterations in 11 genes, the most frequent being MEN1 (18/29), DAXX (7/29), ATRX (6/29) and MUTYH (5/29). The presence and type of mutations did not correlate with the specific expression profiles associated with different grades. LINE-1 showed significantly lower methylation in G2/G3 versus G1 tumors (p = 0.007). The expression profiles of matched primaries and metastasis (nodal, hepatic and colorectal wall) of three cases confirmed the role of Ki67 in defining specific expression profiles, which clustered according to tumor grades, independently from anatomic location or patient of origin. Such data call for future exploration of the role of Ki67 in tumor progression, given its involvement in chromosomal stability

Risk factors for pancreas and lung neuroendocrine neoplasms: a case-control study.

Neuroendocrine neoplasia (NEN) has been displaying an incremental trend along the last two decades. This phenomenon is poorly understood, and little information is available on risk factor for neuroendocrine neoplasia development. Aim of this work is to elucidate the role of potentially modifiable risk factors for pancreatic and pulmonary NEN. We conducted a case-control study on 184 patients with NEN (100 pancreas and 84 lung) and 248 controls. The structured questionnaire included 84 queries on socio-demographic, behavioral, dietary and clinical information. Increased risk was associated with history of cancer ("other tumor", lung OR = 7.18; 95% CI: 2.55-20.20 and pancreas OR = 5.88; 95% CI: 2.43-14.22; "family history of tumor", lung OR = 2.66; 95% CI: 1.53-4.64 and pancreas OR = 1.94; 95% CI: 1.19-3.17; "family history of lung tumor", lung OR = 2.56; 95% CI: 1.05-6.24 and pancreas OR = 2.60; 95% CI: 1.13-5.95). Type 2 diabetes mellitus associated with an increased risk of pancreatic NEN (OR = 3.01; 95% CI: 1.15-7.89). Besides site-specific risk factors, there is a significant link between neuroendocrine neoplasia and cancer in general, pointing to a shared cancer predisposition

hemangioma of the umbilical cord with associated amnionic inclusion cyst two uncommon entities occurring simultaneously

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