Abdominosacral resection for locally recurring rectal cancer

AIM To investigate feasibility and outcome of abdominalsacral resection for treatment of locally recurrent rectal adenocarcinoma.METHODS A population of patients who underwent an abdominalsacral resection for posterior recurrent adenocarcinoma of the rectum at the National Cancer Institute of Milano, between 2005 and 2013, is considered. Retrospectively collected data includes patient characteristics, treatment and pathology details regarding the primary and the recurrent rectal tumor surgical resection. A clinical and instrumental follow-up was performed. Surgical and oncological outcome were investigated. Furthermore an analytical review of literature was conducted in order to compare our case series with other reported experiences.RESULTS At the time of abdomino-sacral resection, the mean age of patients was 55(range, 38-64). The median operating time was 380 min(range, 270-480). Sacral resection was performed at S2/S3 level in 3 patients, S3/S4 in 3 patients and S4/S5 in 4 patients. The median operating time was 380 ± 58 min. Mean intraoperative blood loss was 1750 m L(range, 200-680). The median hospital stay was 22 d. Overall morbidity was 80%, mainly type Ⅱ complication according to the ClavienDindo classification. Microscopically negative margins(R0) is obtained in all patients. Overall 5-year survival after first surgical procedure is 60%, with a mediansurvival from the first surgery of 88 ± 56 mo. The most common site of re-recurrence was intrapelvic.CONCLUSION Sacral resection represents a feasible approach to posterior rectal cancer recurrence without evidence of distant spreading. An accurate staging is essential for planning the best therapy.

Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer

Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis.

Histopathological landscape of rare oesophageal neoplasms

The landscape of neoplastic pathology of the oesophagus is dominated by malignancies of epithelial origin,in particular by oesophageal adenocarcinoma and oesophageal squamous cell carcinoma.However,several other histopathological variants can be distinguished,some associated with peculiar histopathological profiles and prognostic behaviours and frequently underrecognized in clinical practice.The aim of this review is to provide a comprehensive characterization of the main morphological and clinical features of these rare variants of oesophageal neoplastic lesions.

Update on Therapeutic Strategy in Lung Carcinoids

An estimated 25% to 30% of all neuroendocrine tumors (NETs) have their origin in the bronchial tree and into the lungs. Although lung NETs account for less than 1% of all pulmonary malignancies, the incidence of these neoplasms has risen precipitously since the mid 1970s. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), high-grade large-cell neuroendocrine carcinoma (LCNEC) and small-cell carcinoma (SCLC). Surgery is the treatment of choice for typical and atypical carcinoid lung NETs with loco-regional disease. At diagnosis up to 64% of patients with atypical carcinoid lung NETs present with lymph node metastases, and 5-year survival ranges from 61% to 88%. In contrast, lymph node metastases are present in fewer than 15% of typical carcinoid lung NETs, and 5-year survival exceeds 90%. To date, there is no recognized standard of treatment for advanced carcinoid lung NETs. In recent years only two trials reported intriguing results regarding lung NETs: a phase 2 retrospective study of dacarbazine derivative temozolomide and the phase 3, RADIANT-2 trial in advanced NETs. Successful management requires a multidisciplinary team management. This review is restricted to typical/atypical NETs.

Decellularized extracellular matrix as scaffold for cancer organoid cultures of colorectal peritoneal metastases

Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood, and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional (3D) nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. The ex vivo 3D model, obtained by combining patient-derived decellularized ECM with organoids to mimic the metastatic niche, could be an innovative tool to develop new therapeutic strategies in a biologically relevant context to personalize treatments.

Orbital lesions,an exceedingly rare site of neuroendocrine tumor metastasis

Neuroendocrine tumors are rare neoplasms arising primarily in the gastrointestinal tract and lung.The liver is the most common site of metastases,but these tumors can rarely metastasize to atypical sites.Surgery is the only curative approach while the optimal medical treatment is debated.From this perspective,a multidisciplinary approach for each single case becomes very important.In this report we describe the case of a male affected by a single intraorbital metastasis from a midgut well differentiated neuroendocrine tumor.The patient refused surgical removal and therefore he was at first treated with stereotactic radiotherapy and systemic treatment with a somatostatin analog(SSA).After achieving a stable disease for four months he underwent primary tumor resection.Six years after the initial diagnosis,the patient is currently stable and receiving SSA at standard dose.