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Sawabata et al.                                                                                                                                                   Circulating tumor cells after lung-cancer biopsy

           Pulmonary wedge resection is also a crucial diagnostic   fixed  tumor  cells. [16]   ScreenCell  Cyto is designed
                                                                                           ®
           technique for pulmonary nodules that may indicate lung   for cytological studies and the filter allows a fast and
           cancer. This procedure also may potentially dislodge   regular filtration, preserving the CTC morphology and
           tumor cells from the surgical margin to the body, even   microcluster  structures. Blood samples  were diluted
           when  a specimen  of pulmonary  wedge  resection   with the (LC/CC) ScreenCell  (ScreenCell, Westford,
                                                                                        ®
           contents histologically  malignant  negative  surgical   MA)  dilution  buffers  for  fixed  cells.  At  the  end  of
                                                                                   ®
           margin. [6,7]  Malignant-positive results in the surgical   filtration, the ScreenCell  Cyto filter was released onto
           margin have been reported to be an indicator of poor   a  standard microscopy glass  slide; a  7  mm  circular
           prognosis in a retrospective  study.  Furthermore, it   coverslip  was  then  laid  down  on  the  filter  with  the
                                           [8]
           has been  reported  that malignant  surgical  margins   appropriate mounting medium.
           of  pulmonary wedge resection for  lung cancer was
           a negative prognostic predictor in a subset analysis   Peripheral blood (3 mL) was collected into an EDTA
           included in a multicenter prospective study of limited   tube pre-  and  post-FFB.  Tumor  cells in two  blood
           pulmonary  resection for compromised  lung  cancer   samples from  each patient  were simultaneously
           patients. [9]                                      extracted using the method.  These extracted cells
                                                              were stained using a hematoxylin and eosin method
           TBB  is also an important method in diagnosing     and observed with a conventional microscope. Tumor
           lung  cancer. However, there have  been  reports   cells were classified using three categories: no tumor
           demonstrating  a prognostic  disadvantage  for biopsy   cells detected (N), single cell or less than four cells (S),
           using  FFB. [10,11]  An observational  study revealed  that   and clustered cells (C).
           patients who were diagnosed with lung cancer using
           a trans-pleural technique had a statistically (P = 0.04)   RESULTS
           better 5-year survival  rate than patients  diagnosed
                     [10]
           using TBB.  This phenomenon was also reported in   FFB-TBB was carried out under localized anesthesia
           a study using propensity score matched analysis.    using  radiography  to  confirm  that  a  sampling  device
                                                         [11]
           These results may mean  that an intervention  in a   reaches hits at  a lesion. Samples for  cytology and
           cancer lesion using  TBB  may dislodge cancer cells   pathology were  collected from  a  lesion. Cytological
           from the lesion to the circulating blood.          diagnosis  of malignancy  was achieved  in only  four
                                                              cases, while all lesions revealed a pathological
           There are also studies revealing that manipulation   diagnosis, which is the result of manipulation that FFB-
           during lung cancer surgery has the potential to dislodge   TBB made while  contacting  a cancer  lesion.  There
           cancer cells into the circulating blood, which is reported   was no complication during and after FFB-TBB and all
           to be aprognostic  indicator  of poor  outcomes. [12-15]    patients were discharged without event.
           Above all, detecting cluster circulating  tumor cell
           (CTC) is speculated the best a strong predictor of early   Patient/tumor characteristics and status of CTC in each
           recurrence.  FBB also manipulates the area of lung   patient are shown in Table 1. There were five males
                     [13]
           cancer during biopsy; thus, CTCs might be dislodged   and one female with a median age of 63 years, (range
           from the lesion to the circulating blood as the same   59-78 years). According to CT findings, all lesions were
           manner as surgical manipulation. For that reason we   solid  and  tumor  size  on  CT  findings  was  a  median
           assessed the status  of  CTC before and after  FFB   2.5 cm (range 2.1-3.5 cm). Tumor invasiveness status
           biopsy to diagnose lung cancer.                    in pathological diagnosis was “invasive” in all cases.
                                                              Clinical  stage was clinical  -- stage IA in four cases,
           METHODS                                            stage IB  in one case and stage IIIA in one case.
                                                              Singular  or cluster CTCs were  detectable  as shown
           This investigation was approved by the institutional   in  Figure 1.  The CTC counts at pre- and post-FFB
           review board of the Hoshigaoka Medical Center and all   procedures  are shown  in Table 1. In one case CTC
           patients provided their informed consent to participate   was detectable before FFB. This case was stage IIIA
           in this study.                                     with mediastinal lymphadenopathy.  In  an analysis of
                                                              all cell categories, no tumor cell was detected at pre-
           Among 6 patients with non-small  cell lung cancer   FFB; at post-FFB a tumor cell was detected in three
           (NSCLC) who underwent  FFB  to diagnose  a lesion   cases (50.0%). No tumor cell was detected at pre-FFB,
           pathologically, CTCs were extracted from a peripheral   while CTCs were detected at post-FFB in two cases
           vein at pre-FFB and at post-FFB using a size selection   (33.3%) and CTCs  were detected at  pre-FFB,  while
           method [ScreenCell  Cyto (ScreenCell,  Westford,   numerous CTCs were detected at post-FFB in one
                              ®
           MA)]:  using  a  micro-pore  film  that  extracts  formalin-  case (17.7%). In analysis of singular cells, no tumor
                           Journal of Cancer Metastasis and Treatment ¦ Volume 3 ¦ January 23, 2017        17
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