Research ArticleClinical Studies

Factor Analysis of Intraoperative Bleeding Loss and its Impact on Prognosis in Breast Cancer

KOJI TAKADA, SHINICHIRO KASHIWAGI, NOZOMI IIMORI, RIKA KOUHASHI, AKIMICHI YABUMOTO, WATARU GOTO, YUKA ASANO, YUKIE TAUCHI, KANA OGISAWA, TAMAMI MORISAKI, MASATSUNE SHIBUTANI, HIROAKI TANAKA and KIYOSHI MAEDA
Anticancer Research January 2023, 43 (1) 191-200; DOI: https://doi.org/10.21873/anticanres.16149

Abstract

Background/Aim: Intraoperative blood loss (IBL) during the surgical treatment of various cancers affects complication rates and prognosis. However, few studies have examined the importance of minimal IBL in breast cancer surgery. We used factor analysis to examine the prognostic importance of IBL in breast cancer. Patients and Methods: One hundred ninety-seven patients who underwent mastectomy plus axillary lymph node dissection (level II) after preoperative chemotherapy between June 2007 and June 2021 were included. Pearson’s Chi-square test was used to confirm the relationships between different factors. Kaplan–Meier survival curves and the log-rank test were used to examine prognosis. Logistic regression was performed using a Cox proportional hazards model. Results: The median IBL was 55.0 g (range=5.0-420.0 g). IBL was <100 g in 143 patients (72.5%), 100-200 g in 39 patients (19.8%), and >200 g in 15 patients (7.6%). Logistic regression analysis showed that patients with IBL ≥200 g had a significantly worse prognosis (disease-free survival: p=0.003, log-rank test; overall survival: p<0.001, log-rank test). Factor analysis revealed that HER2-negative status (p=0.015), non-pathological complete response (p=0.031), obesity (p=0.001), heavy smoking (p=0.047), and diabetes mellitus (p=0.004) were significantly associated with increased IBL. Conclusion: IBL in breast cancer was correlated with various clinicopathological factors associated with a poor prognosis, suggesting that increased IBL may be associated with poor prognosis in breast cancer as well.

Key Words:

Surgery is a treatment strategy aimed at radically curing most carcinomas. Surgical intervention is also essential for resectable breast cancer. The amount of intraoperative blood loss (IBL) is an indicator of invasion to the patient, and surgeons are making efforts to reduce the amount of IBL.

Some studies have reported that the amount of IBL affects the prognosis of gastric cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma, and prostate cancer (1-13). However, to the best of our knowledge, no studies have investigated IBL and prognosis in breast cancer. Previous studies have reported that differences in the surgical method cause a difference in the amount of IBL (2-5, 7, 14). Therefore, we examined the correlation between IBL and clinicopathological factors and the effect of IBL on the prognosis of patients with breast cancer who underwent mastectomy and axillary lymph node dissection (ALND) (level II) after preoperative chemotherapy (POC) of the same regimen. We hypothesized that IBL would be associated with prognosis, similar to other forms of cancer (1-13).

Patients and Methods

Patient background. From June 2007 to June 2021, 214 patients with breast cancer underwent mastectomy and ALND (level II) after POC at Osaka City University Hospital. However, since ten patients with large primary tumors underwent additional flap plasty or skin grafting, and seven patients whose amount of IBL was unknown were excluded, 197 patients were included in this study. In these eligible cases, none of the patients required blood transfusions during or after surgery. All breast cancers were pathologically diagnosed by core needle biopsy or vacuum-assisted biopsy, and the expression of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki67 was also evaluated by immunostaining. Based on the results, we classified them into three subtypes according to previous reports (15). Breast cancer with negative ER, PgR, and HER2 expression was defined as triple-negative breast cancer (TNBC), and breast cancer with negative ER and PgR expression negative but HER2 expression positive was defined as HER2-enriched breast cancer (HER2BC). Other breast cancers, that is, breast cancers positive for ER and/or PgR, were defined as hormone receptor-positive breast cancer (HRBC). Breast cancer progression was assessed prior to POC using computed tomography (CT), ultrasonography (US), and bone scintigraphy. Before POC, the smoking status of all patients was confirmed through interviews and each pack-year was calculated. In addition, all patients were confirmed to have hypertension or diabetes as a comorbidity. Height and weight were measured before POC, and the body mass index (BMI) was calculated as weight (kg) divided by the squared height (m) (kg/m2). The BMI cut-off value for this study was 25, which was divided into normal weight and overweight according to the World Health Organization (WHO) category.

Regarding POC, FEC100 (500 mg/m2 fluorouracil, 100 mg/m2 epirubicin, and 500 mg/m2 cyclophosphamide) was administered in four courses every 3 weeks in the first half, and 80 mg/m2 paclitaxel was administered in 12 courses weekly in the second half (16-18). For patients with HER2-positive breast cancer, additional weekly (2 mg/kg) or tri-weekly (6 mg/kg) trastuzumab was administered during the paclitaxel treatment period. After POC, imaging tests were performed again to evaluate the therapeutic effect according to the Response Evaluation Criteria in Solid Tumors (19). The therapeutic effects evaluated as clinical partial response (cPR) and complete response (cCR) were defined as “Responder” in objective response rate (ORR), and those evaluated as clinical stable disease (cSD) and clinical progressive disease (cPD) were defined as “non-responders”. Subsequently, a mastectomy and ALND (level II) were performed. Patients diagnosed with axillary lymph node metastases before POC underwent ALND, even if the lymph node metastases disappeared with POC. ALND was not performed in patients without axillary lymph node metastasis before and/or after POC. Patients who underwent breast-conserving surgery or non-Level II ALND were excluded from the study. The definition of a pathological complete response (pCR) follows the National Surgical Adjuvant Breast and Bowel Project B-18 protocol, that is, “the complete disappearance of the invasive components of the lesion with or without intraductal components, including those in the lymph nodes” (20). After surgery, standard adjuvant therapy was administered according to each subtype and the surgical procedure. The median follow-up time was 1,620 days (range=62-4,817 days) after surgery.

Statistical analysis. All statistical analyses were performed using SPSS version 28.0 (IBM, Armonk, NY, USA). The relationship between each clinicopathological feature was evaluated using Pearson’s chi-square test. Prognostic analyses, such as disease-free survival (DFS) and overall survival (OS), were performed using the Kaplan–Meier method and log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards model, and significant factors were entered into a Cox regression model. The odds ratios (OR) and 95% CIs) were calculated using the logistic analysis. Multivariate analysis was performed using a multivariable logistic regression model. A p-value <0.05 was considered statistically significant.

Results

Clinicopathological features. Table I shows the clinicopathological factors of the 197 patients who underwent mastectomy and ALND (level II) after POC. The median age was 59 years (range=30-75 years), and the median tumor diameter was 37.3 mm (range=9.2-119.8 mm). Breast cancer invaded the skin in 75 patients (38.1%). All patients were diagnosed with axillary lymph node metastasis prior to POC. The results of immunohistochemical staining were ER positive in 92 patients (46.7%), PgR positive in 38 patients (19.3%), HER2 positive in 70 patients (35.5%), and high Ki67 in 130 patients (66.0%). As a result, 95 patients (48.2%) were classified as HRBC, 47 patients (23.9%) were classified as HER2BC, and 55 patients (27.9%) were classified as TNBC. After POC, 161 patients (81.7%) were evaluated as responders in ORR. The median operative time was September 2014. Pathological examination of resected specimens revealed pCR in 44 patients (22.3%). The median BMI before POC was 21.8 kg/m2 (14.3-37.6 kg/m2). There were 141 never-smokers (71.6%), while 22 smokers (11.2%) had more than 20 pack years. Before POC, 15 patients (7.6%) were being treated for diabetes mellitus, and 53 patients (26.9%) were being treated for hypertension.

View this table:
Table I.

Clinicopathological features of 197 patients who underwent a mastectomy and axillary lymph node dissection after preoperative chemotherapy.

The median IBL amount was 55.0 g (range=5.0-420.0 g). In 143 patients (72.5%), the IBL amount was <100 g, named the low-IBL group, whereas in 15 patients (7.6%), the IBL amount was >200 g, named the high-IBL group. Thirty-nine patients (19.8%) that did not belong to either category were named the medium-IBL group.

Impact of intraoperative blood loss on prognosis. The log-rank test was used to compare prognosis between participants grouped according to IBL. The high-IBL group had significantly worse DFS (p=0.003), and OS (p<0.001) compared to the other groups (Figure 1). In a univariate analysis, HER2 (p=0.021, HR=0.511), HER2BC (p=0.010, HR=0.380), TNBC (p=0.011, HR=1.842), ORR (p=0.010, HR=0.499), pCR (p=0.005, HR=0.348), and IBL (p=0.001, HR=2.776) were significantly associated with IBL (Table II and Figure 2). Multivariate analysis revealed that TNBC (p=0.008, HR=2.100), ORR (p=0.049, HR=0.575), and pCR (p=0.022, HR=0.396) were independent predictors of prognosis. However, IBL was not an independent risk factor (p=0.062, HR=1.851). Univariate analysis for OS showed significant differences in ORR (p=0.011, HR=0.390), diabetes mellitus (p=0.003, HR=3.810), and IBL (p<0.001, HR=3.851); however, multivariate analysis revealed no independent risk factors for prognosis, including IBL (p=0.150, HR=1.922) (Table III) (Figure 3).

Figure 1.
Figure 1.

Log-rank tests were performed for prognosis after dividing into three groups by intraoperative blood loss (IBL). The High-IBL group had a significantly worse prognosis for both disease-free survival (DFS) (A) and overall survival (OS) (B) (DFS: p=0.003, log-rank; OS: p<0.001, log-rank).

View this table:
Table II.

Univariate and multivariate analyses concerning disease-free survival.

Figure 2.
Figure 2.

Forest plot. Univariate analysis for disease-free survival (DFS), HER2 (p=0.021, HR=0.511), HER2-enriched breast cancer (HER2BC) (p=0.010, HR=0.380), triple negative breast cancer (TNBC) (p=0.011, HR=1.842), objective response rate (ORR) (p=0.010, HR=0.499), pathological complete response (pCR) (p=0.005, HR=0.348), and intraoperative blood loss (IBL) (p=0.001, HR=2.776) showed significant differences.

View this table:
Table III.

Univariate and multivariate analyses concerning overall survival.

Figure 3.
Figure 3.

Forest plot. Univariate analysis for overall survival (OS) showed significant differences in objective response rate (ORR) (p=0.011, HR=0.390), diabetes (p=0.003, HR=3.810), and intraoperative blood loss (IBL) (p<0.001, HR=3.851), but multivariate analysis revealed no independent factors, including IBL (p=0.150, HR=1.922).

Correlation between intraoperative blood loss and clinicopathological factors. The correlations between IBL and clinicopathological factors are summarized in Table IV. Increased IBL was significantly associated with HER2 negativity (p=0.015), a non-PCR (p=0.031), higher BMI (p=0.001), heavy smoking (p=0.047), and comorbid diabetes mellitus (p=0.004). Trend-level associations between increased IBL and higher Ki67 (p=0.079), TNBC status (p=0.092) and a longer surgical history (p=0.063) were found, but these were not statistically significant (p<0.05). When entered in a multivariable logistic regression model, the OR could not be calculated, because none of the patients with HER2BC or those who achieved pCR had excessive IBL (Table V). However, obesity was a significant risk factor for IBL (p=0.010, OR=5.756).

View this table:
Table IV.

Comparison of clinicopathological features by intraoperative blood loss.

View this table:
Table V.

Univariate and multivariate analyses concerning higher intraoperative blood loss.

Discussion

To date, it has been reported that the amount of IBL adversely affects the prognosis of gastric cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma, and prostate cancer; however, this study is the first of its kind to examine the relationship between IBL and prognosis in breast cancer (1-13). Previous reports have investigated the factors that affect IBL and the causes of increased IBL that adversely affect prognosis. The amount of IBL differs depending on the year of surgery (9), and this tendency was also observed in our study. The reasons for this are that the devices used in surgery have changed, and the surgeon’s technical skills have improved, and we believe that this is the same in this study. The reason for the higher IBL in non-PCR cases may be that the residual tumor made it easier to bleed during resection, but this is just our hypothesis. Previous studies have reported that IBL is significantly correlated with cancer progression (1, 4, 14). One study concluded that this is the main reason why IBL affects prognosis (14). However, these reports did not unify the surgical procedures. In this study, there was no significant difference in the degree of cancer progression by unifying the surgical methods. Furthermore, it has been reported that the amount of IBL affects prognosis even after adjusting for the degree of progression in patients with gastric cancer (5). A previous study reported that IBL was correlated with BMI and surgical procedures (5). There is also a report on colorectal cancer in which IBL correlated with BMI and surgical procedures (2). In this study, a strong correlation was found between IBL and BMI. Obesity has been reported to be a poor prognosis factor for breast cancer in many reports (21-24). Smoking and diabetes mellitus, which are both correlated with IBL, have also been identified as poor prognostic factors in patients with breast cancer (25-30). It is speculated that IBL is correlated with many of these poor prognostic factors described for breast cancer, which is one of the causes of an unfavorable prognosis.

A limitation of this study is the lack of consideration of factors that may affect the amount of IBL, such as the surgeon’s skill or patient’s ability to coagulate. However, we found that IBL was correlated with various poor prognostic factors described for breast cancer, indicating that an increase in IBL is associated with a poor prognosis. Furthermore, in previous studies which examined other carcinomas, there are various reasons why an increase in IBL may have contributed towards a poor prognosis. Some studies have suggested that increased IBL may promote tumor spillage and hematogenous spread during surgery (31-34). It is also possible that increased IBL causes a decrease in host immunity (11). Animal experiments have shown that, as the amount of IBL increases, the activity and cytotoxicity of natural killer cells decrease, and the growth rate of tumors increases (35, 36). In addition, a previous study reported that IBL in upper gastrointestinal tract cancer reduces postoperative natural killer cell activity and adversely affects patient survival (37). A study of IBL in colorectal cancer also suggested that excessive bleeding, rather than transfusion, may lead to immunosuppression, and thus adversely affect long-term survival (1). In breast cancer surgery, immunosuppression due to IBL may lead to an increased risk of postoperative recurrence, and it is necessary to make efforts to reduce the amount of IBL as much as possible.

In conclusion, IBL in breast cancer was correlated with various clinicopathological factors associated with poor prognosis, suggesting that increased IBL is associated with a poor prognosis in breast cancer as well.

Acknowledgements

The Authors thank Tomomi Okawa (Department of Breast Surgical Oncology, Osaka Metropolitan University Graduate School of Medicine) for the helpful advice regarding data management. This study was funded by grants from the Japan Society for the Promotion of Science (KAKENHI, Nos. 20K08938, 26461957, and 17K10559) to Shinichiro Kashiwagi.

Footnotes

  • Authors’ Contributions

    All Authors were involved in the preparation of this manuscript. KT collected the data and wrote the manuscript. SK, NI, RK, AY, WG, YA, YT, KO, and TM performed the operation and designed the study. SK, MS, and HT summarized the data and revised the manuscript. KM provided a substantial contribution to the study design, performed the operation, and revised the manuscript. All Authors read and approved the final manuscript.

  • Conflicts of Interest

    All of the Authors have no conflicts of interest to disclose regarding this study.

  • Received November 3, 2022.
  • Revision received November 14, 2022.
  • Accepted November 15, 2022.

References

  1. ↵
    1. Shibutani M,
    2. Maeda K,
    3. Kashiwagi S,
    4. Hirakawa K and
    5. Ohira M
    : The impact of intraoperative blood loss on the survival after laparoscopic surgery for colorectal cancer. Anticancer Res 41(9): 4529-4534, 2021. PMID: 34475079. DOI: 10.21873/anticanres.15264
    OpenUrlAbstract/FREE Full Text
  2. ↵
    1. Tamagawa H,
    2. Numata M,
    3. Aoyama T,
    4. Kazama K,
    5. Atsumi Y,
    6. Iguchi K,
    7. Sawazaki S,
    8. Sato S,
    9. Kano K,
    10. Ohshima T,
    11. Yamada T,
    12. Godai T,
    13. Higuchi A,
    14. Saeki H,
    15. Yukawa N and
    16. Rino Y
    : Impact of intraoperative blood loss on the survival of patients with stage II/III colorectal cancer: a multicenter retrospective study. In Vivo 35(6): 3483-3488, 2021. PMID: 34697185. DOI: 10.21873/invivo.12649
    OpenUrlAbstract/FREE Full Text
    1. Katz SC,
    2. Shia J,
    3. Liau KH,
    4. Gonen M,
    5. Ruo L,
    6. Jarnagin WR,
    7. Fong Y,
    8. D’Angelica MI,
    9. Blumgart LH and
    10. Dematteo RP
    : Operative blood loss independently predicts recurrence and survival after resection of hepatocellular carcinoma. Ann Surg 249(4): 617-623, 2009. PMID: 19300227. DOI: 10.1097/SLA.0b013e31819ed22f
    OpenUrlCrossRefPubMed
  4. ↵
    1. Liang YX,
    2. Guo HH,
    3. Deng JY,
    4. Wang BG,
    5. Ding XW,
    6. Wang XN,
    7. Zhang L and
    8. Liang H
    : Impact of intraoperative blood loss on survival after curative resection for gastric cancer. World J Gastroenterol 19(33): 5542-5550, 2013. PMID: 24023499. DOI: 10.3748/wjg.v19.i33.5542
    OpenUrlCrossRefPubMed
  5. ↵
    1. Ito Y,
    2. Kanda M,
    3. Ito S,
    4. Mochizuki Y,
    5. Teramoto H,
    6. Ishigure K,
    7. Murai T,
    8. Asada T,
    9. Ishiyama A,
    10. Matsushita H,
    11. Tanaka C,
    12. Kobayashi D,
    13. Fujiwara M,
    14. Murotani K and
    15. Kodera Y
    : Intraoperative blood loss is associated with shortened postoperative survival of patients with stage II/III gastric cancer: analysis of a multi-institutional dataset. World J Surg 43(3): 870-877, 2019. PMID: 30377722. DOI: 10.1007/s00268-018-4834-0
    OpenUrlCrossRefPubMed
    1. Mörner ME,
    2. Gunnarsson U,
    3. Jestin P and
    4. Svanfeldt M
    : The importance of blood loss during colon cancer surgery for long-term survival: an epidemiological study based on a population based register. Ann Surg 255(6): 1126-1128, 2012. PMID: 22498893. DOI: 10.1097/SLA.0b013e3182512df0
    OpenUrlCrossRefPubMed
  7. ↵
    1. Tamagawa H,
    2. Aoyama T,
    3. Yamamoto N,
    4. Kamiya M,
    5. Murakawa M,
    6. Atsumi Y,
    7. Numata M,
    8. Kazama K,
    9. Hara K,
    10. Yukawa N,
    11. Rino Y,
    12. Masuda M and
    13. Morinaga S
    : The impact of intraoperative blood loss on the survival of patients with stage II/III pancreatic cancer. In Vivo 34(3): 1469-1474, 2020. PMID: 32354948. DOI: 10.21873/invivo.11931
    OpenUrlAbstract/FREE Full Text
    1. Bekki T,
    2. Abe T,
    3. Amano H,
    4. Hattori M,
    5. Kobayashi T,
    6. Nakahara M,
    7. Ohdan H and
    8. Noriyuki T
    : Impact of low skeletal muscle mass index and perioperative blood transfusion on the prognosis for HCC following curative resection. BMC Gastroenterol 20(1): 328, 2020. PMID: 33028209. DOI: 10.1186/s12876-020-01472-z
    OpenUrlCrossRefPubMed
  9. ↵
    1. Nagai S,
    2. Fujii T,
    3. Kodera Y,
    4. Kanda M,
    5. Sahin TT,
    6. Kanzaki A,
    7. Yamada S,
    8. Sugimoto H,
    9. Nomoto S,
    10. Takeda S,
    11. Morita S and
    12. Nakao A
    : Impact of operative blood loss on survival in invasive ductal adenocarcinoma of the pancreas. Pancreas 40(1): 3-9, 2011. PMID: 20881897. DOI: 10.1097/MPA.0b013e3181f7147a
    OpenUrlCrossRefPubMed
    1. Chen JS,
    2. Huang JQ,
    3. Chen XL,
    4. Zhan GF and
    5. Feng JT
    : Risk factors associated with intraoperative major blood loss during resection of hepatocellular carcinoma. Hepatogastroenterology 62(140): 790-793, 2015. PMID: 26902002.
    OpenUrlPubMed
  11. ↵
    1. Dhar DK,
    2. Kubota H,
    3. Tachibana M,
    4. Kotoh T,
    5. Tabara H,
    6. Watanabe R,
    7. Kohno H and
    8. Nagasue N
    : Long-term survival of transmural advanced gastric carcinoma following curative resection: multivariate analysis of prognostic factors. World J Surg 24(5): 588-93; discussion 593-4, 2000. PMID: 10787082. DOI: 10.1007/s002689910099
    OpenUrlCrossRefPubMed
    1. Kamei T,
    2. Kitayama J,
    3. Yamashita H and
    4. Nagawa H
    : Intraoperative blood loss is a critical risk factor for peritoneal recurrence after curative resection of advanced gastric cancer. World J Surg 33(6): 1240-1246, 2009. PMID: 19308640. DOI: 10.1007/s00268-009-9979-4
    OpenUrlCrossRefPubMed
  13. ↵
    1. Oefelein MG,
    2. Colangelo LA,
    3. Rademaker AW and
    4. McVary KT
    : Intraoperative blood loss and prognosis in prostate cancer patients undergoing radical retropubic prostatectomy. J Urol 154(2 Pt 1): 442-447, 1995. PMID: 7609106. DOI: 10.1097/00005392-199508000-00029
    OpenUrlCrossRefPubMed
  14. ↵
    1. Arima K,
    2. Hashimoto D,
    3. Okabe H,
    4. Inoue R,
    5. Kaida T,
    6. Higashi T,
    7. Taki K,
    8. Nitta H,
    9. Hayashi H,
    10. Chikamoto A,
    11. Beppu T and
    12. Baba H
    : Intraoperative blood loss is not a predictor of prognosis for pancreatic cancer. Surg Today 46(7): 792-797, 2016. PMID: 26302976. DOI: 10.1007/s00595-015-1238-8
    OpenUrlCrossRefPubMed
  15. ↵
    1. Goldhirsch A,
    2. Wood WC,
    3. Coates AS,
    4. Gelber RD,
    5. Thürlimann B,
    6. Senn HJ and Panel members
    : Strategies for subtypes – dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8): 1736-1747, 2011. PMID: 21709140. DOI: 10.1093/annonc/mdr304
    OpenUrlCrossRefPubMed
  16. ↵
    1. Mauri D,
    2. Pavlidis N and
    3. Ioannidis JP
    : Neoadjuvant versus adjuvant systemic treatment in breast cancer: a meta-analysis. J Natl Cancer Inst 97(3): 188-194, 2005. PMID: 15687361. DOI: 10.1093/jnci/dji021
    OpenUrlCrossRefPubMed
    1. Mieog JS,
    2. van der Hage JA and
    3. van de Velde CJ
    : Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev (2): CD005002, 2007. PMID: 17443564. DOI: 10.1002/14651858.CD005002.pub2
    OpenUrlCrossRefPubMed
  18. ↵
    1. Kawajiri H,
    2. Takashima T,
    3. Onoda N,
    4. Kashiwagi S,
    5. Noda S,
    6. Ishikawa T,
    7. Wakasa K and
    8. Hirakawa K
    : Efficacy and feasibility of neoadjuvant chemotherapy with FEC 100 followed by weekly paclitaxel for operable breast cancer. Oncol Lett 4(4): 612-616, 2012. PMID: 23205071. DOI: 10.3892/ol.2012.801
    OpenUrlCrossRefPubMed
  19. ↵
    1. Eisenhauer EA,
    2. Therasse P,
    3. Bogaerts J,
    4. Schwartz LH,
    5. Sargent D,
    6. Ford R,
    7. Dancey J,
    8. Arbuck S,
    9. Gwyther S,
    10. Mooney M,
    11. Rubinstein L,
    12. Shankar L,
    13. Dodd L,
    14. Kaplan R,
    15. Lacombe D and
    16. Verweij J
    : New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2): 228-247, 2009. PMID: 19097774. DOI: 10.1016/j.ejca.2008.10.026
    OpenUrlCrossRefPubMed
  20. ↵
    1. Wolmark N,
    2. Wang J,
    3. Mamounas E,
    4. Bryant J and
    5. Fisher B
    : Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr (30): 96-102, 2001. PMID: 11773300. DOI: 10.1093/oxfordjournals.jncimonographs.a003469
    OpenUrlCrossRefPubMed
  21. ↵
    1. Kroenke CH,
    2. Chen WY,
    3. Rosner B and
    4. Holmes MD
    : Weight, weight gain, and survival after breast cancer diagnosis. J Clin Oncol 23(7): 1370-1378, 2005. PMID: 15684320. DOI: 10.1200/JCO.2005.01.079
    OpenUrlAbstract/FREE Full Text
    1. Tartter PI,
    2. Papatestas AE,
    3. Ioannovich J,
    4. Mulvihill MN,
    5. Lesnick G and
    6. Aufses AH Jr.
    : Cholesterol and obesity as prognostic factors in breast cancer. Cancer 47(9): 2222-2227, 1981. PMID: 7226116. DOI: 10.1002/1097-0142(19810501)47:9<2222::aid-cncr2820470919>3.0.co;2-5
    OpenUrlCrossRefPubMed
    1. Caan BJ,
    2. Kwan ML,
    3. Hartzell G,
    4. Castillo A,
    5. Slattery ML,
    6. Sternfeld B and
    7. Weltzien E
    : Pre-diagnosis body mass index, post-diagnosis weight change, and prognosis among women with early stage breast cancer. Cancer Causes Control 19(10): 1319-1328, 2008. PMID: 18752034. DOI: 10.1007/s10552-008-9203-0
    OpenUrlCrossRefPubMed
  24. ↵
    1. Dawood S,
    2. Broglio K,
    3. Gonzalez-Angulo AM,
    4. Kau SW,
    5. Islam R,
    6. Hortobagyi GN and
    7. Cristofanilli M
    : Prognostic value of body mass index in locally advanced breast cancer. Clin Cancer Res 14(6): 1718-1725, 2008. PMID: 18347172. DOI: 10.1158/1078-0432.CCR-07-1479
    OpenUrlAbstract/FREE Full Text
  25. ↵
    1. Pierce JP,
    2. Patterson RE,
    3. Senger CM,
    4. Flatt SW,
    5. Caan BJ,
    6. Natarajan L,
    7. Nechuta SJ,
    8. Poole EM,
    9. Shu XO and
    10. Chen WY
    : Lifetime cigarette smoking and breast cancer prognosis in the After Breast Cancer Pooling Project. J Natl Cancer Inst 106(1): djt359, 2014. PMID: 24317179. DOI: 10.1093/jnci/djt359
    OpenUrlCrossRefPubMed
    1. Boone SD,
    2. Baumgartner KB,
    3. Baumgartner RN,
    4. Connor AE,
    5. John EM,
    6. Giuliano AR,
    7. Hines LM,
    8. Rai SN,
    9. Riley EC,
    10. Pinkston CM,
    11. Wolff RK and
    12. Slattery ML
    : Active and passive cigarette smoking and mortality among Hispanic and non-Hispanic white women diagnosed with invasive breast cancer. Ann Epidemiol 25(11): 824-831, 2015. PMID: 26387598. DOI: 10.1016/j.annepidem.2015.08.007
    OpenUrlCrossRefPubMed
    1. Passarelli MN,
    2. Newcomb PA,
    3. Hampton JM,
    4. Trentham-Dietz A,
    5. Titus LJ,
    6. Egan KM,
    7. Baron JA and
    8. Willett WC
    : Cigarette smoking before and after breast cancer diagnosis: mortality from breast cancer and smoking-related diseases. J Clin Oncol 34(12): 1315-1322, 2016. PMID: 26811527. DOI: 10.1200/JCO.2015.63.9328
    OpenUrlAbstract/FREE Full Text
    1. De Bruijn KM,
    2. Arends LR,
    3. Hansen BE,
    4. Leeflang S,
    5. Ruiter R and
    6. van Eijck CH
    : Systematic review and meta-analysis of the association between diabetes mellitus and incidence and mortality in breast and colorectal cancer. Br J Surg 100(11): 1421-1429, 2013. PMID: 24037561. DOI: 10.1002/bjs.9229
    OpenUrlCrossRefPubMed
    1. Gold HT,
    2. Makarem N,
    3. Nicholson JM and
    4. Parekh N
    : Treatment and outcomes in diabetic breast cancer patients. Breast Cancer Res Treat 143(3): 551-570, 2014. PMID: 24442643. DOI: 10.1007/s10549-014-2833-x
    OpenUrlCrossRefPubMed
  30. ↵
    1. Peairs KS,
    2. Barone BB,
    3. Snyder CF,
    4. Yeh HC,
    5. Stein KB,
    6. Derr RL,
    7. Brancati FL and
    8. Wolff AC
    : Diabetes mellitus and breast cancer outcomes: a systematic review and meta-analysis. J Clin Oncol 29(1): 40-46, 2011. PMID: 21115865. DOI: 10.1200/JCO.2009.27.3011
    OpenUrlAbstract/FREE Full Text
  31. ↵
    1. Fisher ER and
    2. Turnbull RB Jr.
    : The cytologic demonstration and significance of tumor cells in the mesenteric venous blood in patients with colorectal carcinoma. Surg Gynecol Obstet 100(1): 102-108, 1955. PMID: 13238159.
    OpenUrlPubMed
    1. Roberts S,
    2. Watne A,
    3. McGrath R,
    4. McGrew E and
    5. COLE WH
    : Technique and results of isolation of cancer cells from the circulating blood. AMA Arch Surg 76(3): 334-346, 1958. PMID: 13507823. DOI: 10.1001/archsurg.1958.01280210004002
    OpenUrlCrossRefPubMed
    1. Nakao A and
    2. Takagi H
    : Isolated pancreatectomy for pancreatic head carcinoma using catheter bypass of the portal vein. Hepatogastroenterology 40(5): 426-429, 1993. PMID: 8270230.
    OpenUrlPubMed
  34. ↵
    1. Kobayashi S,
    2. Asano T and
    3. Ochiai T
    : A proposal of no-touch isolation technique in pancreatoduodenectomy for periampullary carcinomas. Hepatogastroenterology 48(38): 372-374, 2001. PMID: 11379311.
    OpenUrlPubMed
  35. ↵
    1. Angele MK and
    2. Faist E
    : Clinical review: immunodepression in the surgical patient and increased susceptibility to infection. Crit Care 6(4): 298-305, 2002. PMID: 12225603. DOI: 10.1186/cc1514
    OpenUrlCrossRefPubMed
  36. ↵
    1. Hoynck van Papendrecht MA,
    2. Busch OR,
    3. Jeekel J and
    4. Marquet RL
    : The influence of blood loss on tumour growth: effect and mechanism in an experimental model. Neth J Surg 43(4): 85-88, 1991. PMID: 1944994.
    OpenUrlPubMed
  37. ↵
    1. Bruns CJ,
    2. Schäfer H,
    3. Wolfgarten B and
    4. Engert A
    : Effect of intraoperative blood loss on the function of natural killer cells in tumors of the upper gastrointestinal tract. Langenbecks Arch Chir Suppl Kongressbd 113: 146-149, 1996. PMID: 9101816.
    OpenUrlPubMed
Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Reprints and Permissions
Factor Analysis of Intraoperative Bleeding Loss and its Impact on Prognosis in Breast Cancer
KOJI TAKADA, SHINICHIRO KASHIWAGI, NOZOMI IIMORI, RIKA KOUHASHI, AKIMICHI YABUMOTO, WATARU GOTO, YUKA ASANO, YUKIE TAUCHI, KANA OGISAWA, TAMAMI MORISAKI, MASATSUNE SHIBUTANI, HIROAKI TANAKA, KIYOSHI MAEDA
Anticancer Research Jan 2023, 43 (1) 191-200; DOI: 10.21873/anticanres.16149
Twitter logo Facebook logo Mendeley logo

Jump to section

Keywords