The relation between seroma fluid and local recurrence after conservative breast surgery

The relation between seroma fluid and local recurrence after conservative breast surgery

TarekA. El-Fayoumi,MD; Haytham Fayed,MD

Department of General  Surgery, Alexandria University, Alexandria, Egypt.

Objectives: After conservative management  of breast cancer, two third are at risk of local relapse, a risk which is largely reduced by radiotherapy. Seroma formation after mastectomy typically delays recovery and adds to morbidity.

Aim  of  the  work:  This  study aims  at  collection  of  the  seroma  fluid  after  conservative breast surgery and detection of malignant cells in the drained fluid and its relation with local recurrence.

Methods: Twenty three patients with early breast cancer were included  in the  study and after conservative breast surgery. Seroma fluids were collected from the drain for detection of malignant cells then these patients were followed for twelve to twenty four months for detection oflocalrecurrence

Results:  There was a high significance in local recurrence associated  with cases showing malignant second samples compared with those with negative one (X2=29.076, p=O.OOO).

Conclusions: Persistent  presence of malignant  cells in the postoperative  drained fluid in females with early breast cancer is predictive for local recurrence. However long terms follow up and an increase in the number of the studied cases is recommended to confirm these results.

Introduction:

After     conservative     management      of breast cancer, two third are at risk of local relapse, a risk which is largely reduced by radiotherapy.l,2 Seroma formation after mastectomy   typically  delays  recovery  and adds to morbidity.3 Prognostic factors that influence breast cancer varies from many different  clinical  and  histopathological criteria; definitely lymph nodes condition remains the most reliable one upon which depends further adjuvant therapy.4  The main target in surgical management of breast cancer is to obtain maximum chance of cure and to prevent   local   recurrence.!   Most   common sites of local recurrence after mastectomy  is the skin  of the  previous  mastectomy,  axilla and less commonly internal mammary, supraclavicular   and  infraclavicular   nodes.5

There   is  no   obvious   mechanism   that   is accused  in local recurrence  but some  claim that improper surgical technique by leaving residual tumor tissue or implanting malignant

cells  from   blood   vessels   and  lymphatics which are        opened during   surgery             are concerned, however this is not common after conservative  breast  surgery  as  this  is  done by lumpectomy  and detection  of free safety margin  by  intra  operative  frozen  section.6

Drains are channels that collect  body fluids and blood after many operations.7   Draining the axillary field and the site of lumpectomy after  breast  conserving  surgery  is  a  way to collect postoperative secretions for cytological detection of malignant  cells. The proper way of drainage is by active suction drain in order to avoid any residual fluids or cell collection. This study aims at collection of the seroma fluid after conservative  breast surgery and  detection  of malignant  cells  in the drained fluid and its relation with local recurrence.8

Patients and  methods:

The  study  included  twenty  three  female patients  with  early  breast cancer  who  were

candidates for breast conservative surgery admittedto Surgical OncologyUnitAlexandria Main University Hospital. After taking their consent  for the surgical  plan of management, patients  were subjected to history,  clinical examination, laboratory investigations, mammography, ultrasonography of both breasts  and cytological estimation and metastatic work out. Then breast conservative surgery was done for all patients with an intraoperative frozen section for detection of a histopathological negative  safety  margin  and for diagnosis of clinically suspicious cases with a non-  conclusive fine needle  aspiration cytology.   Then,  closure  of  the  lumpectomy site was performed followed by axillary dissection through a separate incision  then  a Redivac negative suction drain was applied. Postoperative collection and estimation of the volume  of the  drained  fluid  was  performed. The drain was removed  when the output was less  than   30  ml/day.9  Patients   were   given

100  mg  oral  Sudan  III  in  a  piece  of  butter

-a dye  with  high  affinity  to  stain  fat  cells usually  between the 3rd and 5th postoperative nights  when  the  discharge was  less  bloody and still of moderate amount- and the  color of  the   drainage   was  observed   for   change into orange.10 The drainage  duration,  daily amount and total amount were measured. Five ml samples  of the drainage  were taken  on the

1st postoperative day and the day of drain removal   then  the   sample   was   centrifuged and stained  with  H and  E and submitted for cytological examination. The second samples were considered more reliable,  as persistent presence  of  malignant cells  in the  samples lower the probability of false results.  Follow up was done every three month for two years for morbidity,  mortality and recurrence with correlation between the malignant cells in the drained fluid and local recurrence. Statistical analysis  was  done  using  SPSS,  five  percent was the level of statistical significance.

Results:

The mean  age  of the  studied  female patients  ranged  from  25 to  71  years  with  a mean of 49.69 ± 8.97 years. Breast  mass was a constant  complaint.  The  mean  duration of

symptoms was  4.04  ±  2.61  months  (range from 1-12 months) the physical signs are presented  in Table (1).  92.1% of cases  were diagnosed  preoperative  by  fine   needle   as being malignant while the rest of cases  were diagnosed during  intraoperative lumpectomy and  frozen  section.  After  performing breast conserving surgery  for all cases,  the mean duration of drainage was 6.61± 2.75 days with an average  of 4 -13 days and a mean of daily output  of77.78 ± 31.95  ml  with an average of  40  -  160  ml  and  a mean  total  output  of

550.67  ± 361.33  ml with an average  of 120-

1420  ml.  Pathological examination revealed node  negative  in 30.3%  of cases.  Naked  eye appearance of the drained fluid varied in color from   serous,   serosanguinuous  and   orange after the oral intake of Sudan III in all patients. However,     microscopically           revealed                    that majority of cells were inflammatory composed mainly  of neutrophils with  lymphocytes and histiocytes. Fat  cells  also  were  significantly higher in the second axillary  samples than the first presenting 96.6% and 89.9% respectively (X2 = 35.528,  p = 0.000).  Malignant cells  in the form  of clusters  of viable  epithelial  cells with large  pleomorphic hyperchromic nuclei and  acidophilic  cytoplasm were  present   in

14.6%  of  cases  from  the  first  samples  and

20.2%  had  malignant first  axillary samples. Only   15.7%   showed   persistent  malignant second    samples:     4.5%    breast     samples and   11.2%   axillary   samples.   There   was  a statistically  significant  difference    between the  lower  malignant second  samples  and the first  one  (X2 = 17.100,  p = 0.000).   None  of the  nodal   negative   patients   had  malignant cells  in  the  fluid  drained.  Also  cases  with malignant  second   samples   had   significant more  higher  mean  number  of involved   and dissected lymph  nodes  (7.86  ± 3.13  Vs  1. 56

± 1.99)   (t  = 9.819,   p  = 0.000)   and   (24.36

± 4.634 Vs 11.59 ± 3.03) (t = 13,21, p = 0.000)

respectively.

A   range   of   follow    up   24-48   months showed local  recurrence in  10.1%  of cases:

66.7% axillary  and 33.3%  breast with a mean duration of recurrence 41.22± 9.52 month, tumor  characteristics and its relation  to local recurrence are presented in Table (1).  There

Table I: local recurrence and its relation with clinical and  histopathological features of the tumor.

was a high significance in local recurrence associated with cases showing malignant second samples compared with those with negative  one (50%  Vs 2.7%) (X2 = 29.076, p = 0.000).

Discussion:

The prediction of local recurrence after surgical management of breast cancer is difficult   despite   the    clinical   knowledge about the  disease.  Early  diagnosis,  the number of microscopic  and macroscopic lymph node affection, proper staging and histopathological   type   and   grade,   proper

surgical  management  with  the  proper selection of the adjuvant therapy are the feasible  predictive  factors.6  The  old  belief that the more extensive surgical excision and aggressive  radiotherapy  the  more  curability is  not  nowadays  the  rule,  this  is  because during  operation  opening  of  blood  vessels and  lymphatics   allow  field  contamination with lymph and blood harboring malignant cells  and  that  local  recurrence  occur  from this cause rather than inadequate surgical remova1.6 The present study included twenty three patients  in which we tried to trace the malignant   cells   after   conservative   breast

surgery  by  taking  drain  samples  from  the breast  and  axilla  with  special  precautions in  the  technique  as  they  were  transmitted freshly  to  the  pathological  examination  for detection  of malignant  cells.  We considered the second samples as more reliable - the first sample  was  discarded  as it was  considered as operative field wash out from the shaded and floating malignant cells which may result from transgression  of malignant tissue- they were  taken  long  duration  postoperative  on the day of drain removal in ordered to give chance for the floating cells to clear, then after that  time  the  discharge  may  be  associated with  continuous  source  of viable  malignant cells. The color of drained fluid turned from serous  to serosanguinuous  into orange  after oral  admission  of  Sudan  III  which  is  due to  staining  of fat  cells.  Definitely  these  fat cells are from the crashed lymphatic vessels contained   in  the   lymphatic  fluid  that  are the  main  source  of  postoperative  discharge which  might  contain  malignant  cells.  In  a study done by Boolsen et alll they found that the  drained  fluid  collected  postoperative  is not an accumulation  of serum  but exudates. Another study by Bonnema et all2 comparing the composition of the drained fluid with the constituents  of  blood and  peripheral  lymph and  found  that  after the  first postoperative day  the  drainage  changed  into  lymph  like fluid. These two studies support the theory of the leakage of lymphatic as a probable source of malignant cells in the drainage. Vujicic et al6 reported the presence  of malignant cells in   the  postoperative   seroma   but  without talking about local recurrence, this study was performed on 142 female patients with breast cancer  treated  by  radical  mastectomy,  the aspirated  seroma  on the sixth  postoperative day where malignant cells in 22.5% of cases and  appeared  as  isolated  cells,  with  some noted  degenerative   changes.   In  our  study malignant  cells  were  detected  in  15.7%  of cases  in  the  form  of  groups  of  malignant epithelial  cells, this may be attributed to the fresh  sample  taken from  the  draining  tubes rather than puncturing old seroma fluid after six  days.  Puncturing  the seroma  may  yield only the separated, floating, degenerating and

nonresident cells, but malignant cells forming groups might be deeply seated, stuck to the seroma wall or laying inside septations.

The larger the number of involved lymph

nodes the  more  the  malignant  cells  studied in the lymphatics released in the axilla when dissected and significantly correlating with malignant second samples. Also the number of dissected lymph nodes reflects the radicality in the axillary dissection and consequently more lymphatic vessels injured and more lymphatic  vessels  postoperative,  this theory is  also  supported  by  absence  of  malignant cells in the drainage when the patient is node negative.

A study  done by Madyl3  comparing  two

groups of patients with early breast cancer where twenty did breast conservative surgery and the other twenty did modified radical mastectomy they found that the incidence of malignant cells in axillary  drainage  was the same in both groups, there was an incidence of  malignant  cells  and  axillary  recurrence in six cases due to lymphatic leak from the interrupted  axillary lymphatic vessels during dissection. Dissection is associated with transection  of  some  lymphatics  of  the  arm and  the  arm  movements  act  as  pump  that forces lymph, probably with malignant cells, into empty axillary fossae.l4

The malignant second sample was significantly correlating the local recurrence. This relation  could be explained  by the fact that the radicality in surgery or adjuvant therapy does not sterilize the field from malignant   cells.   Residual   malignant   cells might  become  dormant  and  suppressed  by the immune system, it becomes compromised allowing a chance for these cells to proliferate into local recurrence  which may explain its late occurrence  in this  study.  In conclusion persistent presence of malignant  cells in the postoperative  drained fluid in females with early breast cancer is predictive for local recurrence.  However  long terms  follow  up and an increase in the number of the studied cases is recommended to confirm these results

Reference

1-   Whipp E, Beresford M, Sawyer E, Halliwell