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Mura et al.                                                                                                                                                                            The peritoneal metastases from GC

           the EpCAM antigen is expressed; on the contrary the   treatment algorithm of advanced GC. [76]
           peritoneal mesenchymal cells do not express it.  The
                                                     [69]
           rationale is strong, more evidence on results is needed.  The  identification  of  patients  at  risk  of  peritoneal
                                                              recurrence and the diagnosis  of intra-peritoneal  free
           In a randomised study, a clinical effect was obtained   cancer  cells  are probabilly  two aspects of the same
           after intraperitoneal  infusion  of catumaxomab    problem. The majority of patients with positive cytology
           in patients with symptomatic malignant  ascites    on peritoneal  washing  develop  PC, although  it also
           secondary  to EpCAM+ carcinomas, 66 out of 258     may occur in patients with negative cytological results.
           notably from GC.  Heiss and coll randomly assigned   These observations indicate that conventional cytology
                          [69]
           the patients to paracentesis alone, or to paracentesis   lacks sensitivity for the detection of residual cancer cells
           plus intraperitoneal catumaxomab. Puncture-free    and the prediction of peritoneal spread. Many reports
           survival  was  significantly  longer  in  the  group  treated   have emphasized the clinical significance of molecular
           with catumaxomab compared to  that  in the  control   diagnosis using reverse transcriptase-polymerase
           group (46 vs. 11 days, P < 0.0001) but median overall   chain reaction analysis for more sensitive detection of
           survival was similar between the two groups: 72 days   GC cells in peritoneal  washing. Fujiwara  analyzed
                                                                                                   [77]
           in the catumaxomab group vs. 68 days in the control   the survival of 123 patients with serosa-invading GC.
           group (n.s). [69]                                  The prognosis of the 29 patients with positive cytology
                                                              in the peritoneal  washing was very poor,  and most
           Elias  and  his  team from Gustave Roussy  Institute   of them died within 1 year after surgery. Among the
           (Villejuif, France), with long-date experience in HIPEC   93 patients with negative cytology (CY0), 49 had a
           for  PC, recently proposed a randomized  phase II   positive  genetic  diagnosis  and  a  significantly  poorer
           study, combining complete cytoreductive surgery with   prognosis  than those with  negative  genetic  results.
           intraperitoneal  immunotherapy.  The main inclusion   More than half of the patients with positive PCR and
                                       [70]
           criteria of the protocol are PC of minimum or moderate   CY0  developed peritoneal  recurrence  after surgery,
           extension and macroscopic resection of all the lesions:   while almost all patients with negative PCR and CY0
           they just match the experience-based indications for   had no peritoneal recurrence after  surgery.   These
                                                                                                     [77]
           HIPEC in PC from GC.   As requested for HIPEC,     results have been confirmed by many studies. All the
                                 [54]
           the complete  resection  of all  macroscopic  disease   authors  concluded  that molecular  diagnosis  based
           before starting the intra-peritoneal administration  of   on peritoneal washing  is useful to predict peritoneal
           catumaxomab is necessary. The immunotherapy could   recurrence  for patients  with serosal  invasion  of GC;
           therefore efficiently treat microscopic residual disease.  PCR positivity has significant correlation with overall
                                                              survival and with peritoneal recurrence rate. [78-81]  Up 2
           DIAGNOSIS OF INTRA-PERITONEAL FREE                 patients of 3 with negative cytology can be positive to
           CANCER CELLS AND IDENTIFICATION                    PCR detection; in other terms, when surgeons perform
           OF PATIENTS AT RISK OF PERITONEAL                  R0 surgery (i.e.  no macroscopic, microscopic and
           RECURRENCE                                         cytologic residual disease) for advanced GC, there is
                                                              high probability that it’s not true.
           The methods of detecting peritoneal free cancer cells
           represent an area in evolution.  It’s well known that   Molecular biological techniques are anyway time- and
           the positive  peritoneal  cytology is according  to the   labour-intensive, and without yet diffuse application in
           depth in  invasion of  the gastric wall, and that  it  has   clinical practice. A new rapid gene detection system,
           a prognostic value. [71,72]  In the same way, it’s well   One-step nucleic acid amplification has been recently
                                                                       [82]
           known that cumulative  risk of peritoneal  recurrence   proposed.  It shows  potential for routine  use in
           is  based  on  the  infiltration  of  the  gastric  serosa.    the clinical laboratory because of  its  simplicity and
                                                         [73]
           Cytological examination of peritoneal washing at the   rapidity.  On  the  other hand, the  molecular detection
           time of primary tumor resection is frequently positive.   of intraperitoneal GC cells is not only an independent
           Free peritoneal cells are associated with an average   prognostic  factor, but also provides valuable  clinical
           survival of 4 months vs. 21 months for patients with   information for choosing the appropriate treatment for
           negative cytology. [71,74]                         cytology-negative patients: such patients are potential
                                                              candidate to intraperitoneal therapy, such as HIPEC,
           According  to the 7th edition of the  American  Joint   immunotherapy or both.
           Committee on Cancer positive cytology in the absence
           of visible peritoneal  implants is considered  as M1   CONCLUSION
           disease.   Peritoneal  washing  for  cytology  (better
                   [75]
           during a staging laparoscopy) is mandatory in staging/  The peritoneal metastatic spread of GC leads to PC, a
            370                                                            Journal of Cancer Metastasis and Treatment ¦ Volume 2 ¦ September 18, 2016
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