Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy by laparoscopy via a single-port approach for low-grade peritoneal malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a long and complex procedure. A minimal invasive approach is rarely performed. The feasibility of laparoscopic CRS and HIPEC via a single port (SP) approach is unknown. The aim of this study was to assess the feasibility of CRS and HIPEC with a SP approach. METHODS: This study is IDEAL stage I-IIa. Patients with low grade and limited peritoneal malignancy were included in a tertiary care cancer center. Intra- and post-operative adverse events were recorded and classified according to medical and surgical dedicated classifications. The main objective measurement to assess feasibility was the conversion to open or multiport surgery. RESULTS: A total of 12 highly selected patients were assessed. The median operating time was 240 min (range, 180-360) and two near miss events were reported. Two conversions to open and multiport surgery occurred. The median comprehensive complication index was 0 (range, 0-42.6) with two severe adverse events (Clavien-Dindo or CTC-AE ≥ 3). The median length of stay was 8.5 days (range, 5-13). CONCLUSION: CRS and HIPEC via a laparoscopic SP approach are feasible and safe in the short term. The next step should be a prospective development study.

Single-port endoscopic mesocolic and mesorectal excision using an extraperitoneal approach.

BACKGROUND: The extraperitoneal rectal dissection via a transanal approach facilitates the mesorectal dissection. The retroperitoneal approach for mesocolic excision may also offer some similar advantages. To complete the lymphadenectomy of extraperitoneal mesorectal resection, we developed an innovative approach for upper rectal and mesocolic excision via an exclusive retroperitoneal dissection using a single-port access at the site of the future stomy. METHODS: This study was a prospective pilot study and was conducted between 2013 and 2015 at two oncologic centers. Five consecutive patients, with ano-rectal cancer requiring permanent stoma, underwent this procedure. RESULTS: The bowel was never touched or mobilized to perform the lymphadenectomy, and no Trendelenburg was required. The median operative duration was 300 min (range 205-310). The quality of the surgical plane was classified as good (mesorectal) in the five patients. The median circumferential and distal margins were, respectively, 5 mm (range 1-20) and 20 mm (range 5-25). The median number of harvested lymph nodes was 11 (range 5-18). No laparotomy or multiport laparoscopy was required. There was no death. Two patients had perineal wound dehiscence (one minor and one major). CONCLUSIONS: The mesocolic excision via a retroperitoneal approach is feasible, completes naturally the transanal mesorectal excision and may confer several advantages including no morbidity of small bowel manipulation or Trendelenburg position. Further studies are required to analyze this approach.

[Urachus adenocarcinoma case report and review of literature]. / Adénocarcinome de l'ouraque: à propos d'un cas clinique et revue de la littérature.

This article describes the case of a 38-year-old patient with a urachus tumor treated surgically by resection and chemotherapy. When the chemotherapy was stopped, a peritoneal carcinomatosis appeared. We are conducting a review of the literature regarding the diagnosis and treatment of urachus tumors.

Model predicting the ypN0 status after good response to chemoradiotherapy in rectal cancer.

BACKGROUND: The purpose of this study was to identify the predictive factors for ypN0 status in tumors with good pathologic response to chemoradiotherapy (CRT). METHODS: A retrospective chart review was conducted on patients at two tertiary cancer center who underwent rectal resection after good response to CRT between 2000 and 2013. RESULTS: No preoperative treatment (oxaliplatin use, radiotherapy boost of 5,4 Gy, delay CRT-surgery) impacted on the ypN status. In the multivariate analysis, only a ypT<3 (HR 7.5 [2,9-19.5]) was significant and no lymphovascular invasion (HR 8,9 [1.6-49.8]) was limited to significance.The best model predicting the ypN0 status used only the ypT status<3. The major part (92.2%) of patients with ypT0-2 tumors had no LN invasion. CONCLUSION: The risk of lymph node involvement metastases was only 7.8% for the patients with an ypT0-2 status. A fullthickness transanal resection coud be the futur treatment of these patients.

Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey.

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.

HPV Prevalence and Prognostic Value in a Prospective Cohort of 255 Patients with Locally Advanced HNSCC: A Single-Centre Experience.

Background. HPV is a positive prognostic factor in HNSCC. We studied the prevalence and prognostic impact of HPV on survival parameters and treatment toxicity in patients with locally advanced HNSCC treated with concomitant chemoradiation therapy. Methods. Data on efficacy and toxicity were available for 560 patients. HPV was detected by PCR. Analysis was performed using Kaplan-Meier survival curves, Fisher's test for categorical data, and log-rank statistics for failure times. Results. Median follow-up was 4.7 years. DNA extraction was successful in 255 cases. HPV prevalence was 68.6%, and 53.3% for HPV 16. For HPV+ and HPV-, median LRC was 8.9 and 2.2 years (P = 0.0002), median DFS was 8.9 and 2.1 years (P = 0.0014), and median OS was 8.9 and 3.1 years (P = 0.0002). Survival was different based on HPV genotype, stage, treatment period, and chemotherapy regimen. COX adjusted analysis for T, N, age, and treatment remained significant (P = 0.004). Conclusions. Oropharyngeal cancer is increasingly linked to HPV. This study confirms that HPV status is associated with improved prognosis among H&N cancer patients receiving CRT and should be a stratification factor for clinical trials including H&N cases. Toxicity of CRT is not modified for the HPV population.

High expression of inhibitory receptor SHPS-1 and its association with protein-tyrosine phosphatase SHP-1 in macrophages.

SHPS-1 (or SIRP) is a member of the immunoglobulin (Ig) superfamily abundantly expressed in neurons and other cell types. Within its cytoplasmic domain, it possesses at least two immunoreceptor tyrosine-based inhibitory motifs, which are targets for tyrosine phosphorylation and mediate the recruitment of SHP-2, an Src homology 2 (SH2) domain-containing protein-tyrosine phosphatase. Since other immunoreceptor tyrosine-based inhibitory motifs-containing receptors have critical roles in the negative regulation of hemopoietic cell functions, we wanted to examine the expression of SHPS-1 in cells of hematological lineages. By analyzing a panel of hemopoietic cell lines, evidence was provided that SHPS-1 is abundantly expressed in macrophages and, to a lesser extent, in myeloid cells. No expression was detected in T-cell or B-cell lines. Expression of SHPS-1 could also be documented in normal ex vivo peritoneal macrophages. Further studies showed that SHPS-1 was an efficient tyrosine phosphorylation substrate in macrophages. However, unlike in non-hemopoietic cells, tyrosine-phosphorylated SHPS-1 in macrophages associated primarily with SHP-1 and not SHP-2. Finally, our analyses allowed us to identify several isoforms of SHPS-1 in mouse cells. In part, this heterogeneity was due to differential glycosylation of SHPS-1. Additionally, it was caused by the production of at least two distinct shps-1 transcripts, coding for SHPS-1 polypeptides having different numbers of Ig-like domains in the extracellular region. Taken together, these findings indicate that SHPS-1 is likely to play a significant role in macrophages, at least partially as a consequence of its capacity to recruit SHP-1.

A reporter gene assay for high-throughput screening of G-protein-coupled receptors stably or transiently expressed in HEK293 EBNA cells grown in suspension culture.

We describe in detail a robust, sensitive, and versatile functional assay for G-protein-coupled receptors (GPCRs) expressed in human embryonic kidney (HEK) 293-EBNA (Epstein-Barr virus nuclear antigen) (designated 293E) cells. The ability to grow these cells in suspension, in conjunction with the use of the secreted form of the human placental alkaline phosphatase (SEAP) as the reporter enzyme transcriptionally regulated by 5-cyclic AMP (cAMP) response elements (CREs) (Chen et al., Anal. Biochem. 226, 349-354 (1995)), makes this CRE-SEAP assay potentially attractive for high-throughput screening (HTS). A 293E clonal cell line, stably transfected with the CRE-SEAP plasmid, was initially characterized with compounds known to activate intracellular signal transduction pathways similar to those activated by GPCRs. Forskolin and cAMP analogues were potent at inducing SEAP expression but calcium ionophores (A23187 and ionomycin) were without effect. The forskolin response was also potentiated by the protein kinase C activator phorbol myristate acetate as well as the phosphodiesterase inhibitor isobutylmethylxanthine. Previously established cell lines expressing the G(alphas)-coupled DP or the G(alphaq)-coupled-EP(1) prostanoid receptors were stably transfected with the reporter gene construct and clones were selected based on their ability to secrete SEAP upon agonist challenge. Pharmacological characterization of the DP and EP(1) receptors displayed a similar rank order of potency for several known prostanoids and related compounds to that previously reported using classical binding assays or other functional assays. The CRE-SEAP assay was also used to characterize the EP(1) receptor antagonists SC-51322, SC-51089, and AH6809. In summary, we have established a reporter gene assay for GPCRs that couple to both G(alphas) and G(alphaq) and is amenable to HTS of both agonists and antagonists.