Managing Seroma Formation Post Breast Surgery through Somatostatin Analogs

After axillary dissection, the lack of sufficient lymphatic drainage of the breast and the axilla can lead to seroma formation, which is an abnormal collection of serous fluid. The reported incidence rate of seroma can vary from 15% to 90% and is known as one of the most common complications of breast cancer surgery . Seroma can be a source of morbidity and discomfort among patients and, if untreated, could lead to delayed wound healing, skin flap necrosis, and infection. It is usually diminished with drain placements in the axillary space or managed via percutaneous aspiration after drains are removed. Multiple risk factors for seroma are suggested, including age, body weight, hypertension, number of lymph nodes removed, and extent of surgery . A few patients with seroma need significant clinical intervention for their prolonged or severe symptoms. The placement of suction drains, use of fibrin glue, restricting the use of arm, and compression dressings are reported as preventive measures for seroma formation; however, the only clinically meaningful and established method is the placement of drains . Somatostatin is a cyclic polypeptide derived from a precursor protein processed into several peptide hormones such as somatostatin-14, somatostatin-28, and neuronostatin . Octreotide acetate, a somatostatin analog, is the major treatment option for acromegaly and gastroenteropancreatic neuroendocrine tumor, as well as for managing intestinal fistula (Table 1) . The splanchnic blood flow inhibition and triglyceride absorption by somatostatin are believed to reduce lymphatic fluid . Hirono et al. conducted a systematic review and metaanalysis to evaluate the efficacy and safety of somatostatin analog after axillary lymph node dissection in patients with breast cancer . This study included seven randomized control trials and compared the volume of drained fluid, duration of drainage, seroma incidence, as well as adverse events such as hematoma, infection, and the length of hospital stay. They found a slight reduction in the lymphatic drainage volume but not a significant reduction in the duration and incidence of seroma. Based on the limited efficacy and some adverse event reports such as vomiting, diarrhea, and infection site pain, the authors concluded that somatostatin analogs are not much effective or safe for seroma management after breast surgery. Although seroma formation could be a source of more serious complications such as surgical site infection or slow wound healing in addition to the patients’ social/economic burden due to prolonged hospital stay or frequent visits, the conventional care of percutaneous aspiration would remain as a mainstay for its management. The analysis of “who is at high risk of prolonged seroma formation” and “who would benefit from adding somatostatin analog treatment to the current standard management of seroma” is still in question. For example, Prajapati et al. assessed the efficacy of octreotide after modified radical mastectomy and demonstrated the statistically significant seroma volume reduction with octreotide usage . However, the phase 3 randomized trial by Gauthier et al. did not show a significant reduction of lymphatic fluid with the lanreotide injection use in patients who underwent lumpectomy/mastectomy with axillary lymph node dissection . In clinical practice, the extent of surgery seems to be one of the important factors determining the risk of severe or prolonged seroma. Additionally, the conflicting results from multiple trials may be a result of patient/surgical background variability. Moreover, the management of drains after surgery may influence the severity or duration of the seroma. To our knowledge, somatostatin analog treatment is not routinely recommended for patients who undergo axillary lymph node dissection. More reasonably, patients with prolonged seroma or at high risk of significant seroma can be good candidates for more intervention. In the future, well-designed, prospective trials, defining patients at risk for compli-

After axillary dissection, the lack of sufficient lymphatic drainage of the breast and the axilla can lead to seroma formation, which is an abnormal collection of serous fluid. The reported incidence rate of seroma can vary from 15% to 90% and is known as one of the most common complications of breast cancer surgery (1) . Seroma can be a source of morbidity and discomfort among patients and, if untreated, could lead to delayed wound healing, skin flap necrosis, and infection. It is usually diminished with drain placements in the axillary space or managed via percutaneous aspiration after drains are removed. Multiple risk factors for seroma are suggested, including age, body weight, hypertension, number of lymph nodes removed, and extent of surgery (1) . A few patients with seroma need significant clinical intervention for their prolonged or severe symptoms. The placement of suction drains, use of fibrin glue, restricting the use of arm, and compression dressings are reported as preventive measures for seroma formation; however, the only clinically meaningful and established method is the placement of drains (1) .
Somatostatin is a cyclic polypeptide derived from a precursor protein processed into several peptide hormones such as somatostatin-14, somatostatin-28, and neuronostatin (2) . Octreotide acetate, a somatostatin analog, is the major treatment option for acromegaly and gastroenteropancreatic neuroendocrine tumor, as well as for managing intestinal fistula ( Table 1) (2) . The splanchnic blood flow inhibition and triglyceride absorption by somatostatin are believed to reduce lymphatic fluid (3) .
Hirono et al. conducted a systematic review and metaanalysis to evaluate the efficacy and safety of somatostatin analog after axillary lymph node dissection in patients with breast cancer (4) . This study included seven randomized control trials and compared the volume of drained fluid, duration of drainage, seroma incidence, as well as adverse events such as hematoma, infection, and the length of hospital stay. They found a slight reduction in the lymphatic drainage volume but not a significant reduction in the duration and incidence of seroma. Based on the limited efficacy and some adverse event reports such as vomiting, diarrhea, and infection site pain, the authors concluded that somatostatin analogs are not much effective or safe for seroma management after breast surgery. Although seroma formation could be a source of more serious complications such as surgical site infection or slow wound healing in addition to the patients' social/economic burden due to prolonged hospital stay or frequent visits, the conventional care of percutaneous aspiration would remain as a mainstay for its management.
The analysis of "who is at high risk of prolonged seroma formation" and "who would benefit from adding somatostatin analog treatment to the current standard management of seroma" is still in question. For example, Prajapati et al. assessed the efficacy of octreotide after modified radical mastectomy and demonstrated the statistically significant seroma volume reduction with octreotide usage (5) . However, the phase 3 randomized trial by Gauthier et al. did not show a significant reduction of lymphatic fluid with the lanreotide injection use in patients who underwent lumpectomy/mastectomy with axillary lymph node dissection (3) . In clinical practice, the extent of surgery seems to be one of the important factors determining the risk of severe or prolonged seroma. Additionally, the conflicting results from multiple trials may be a result of patient/surgical background variability. Moreover, the management of drains after surgery may influence the severity or duration of the seroma.
To our knowledge, somatostatin analog treatment is not routinely recommended for patients who undergo axillary lymph node dissection. More reasonably, patients with prolonged seroma or at high risk of significant seroma can be good candidates for more intervention. In the future, well-designed, prospective trials, defining patients at risk for compli-cated seroma will be needed.

Conflicts of Interest
Y Kitagawa received lecture fees from ASUKA Pharmaceutical Holdings and scholarship donation from TEIJIN Pharma.

Disclaimer
Yuko Kitagawa is one of the Editors of JMA Journal and on the journal's Editorial Staff. He was not involved in the editorial evaluation or decision to accept this article for publication at all.