Delayed Chest Wall Osteoradionecrosis with Pseudomonal Empyema Neccesitans: A Cataclysmic Adverse Effect of Radiation Therapy Post Modified Radical Mastectomy

Delayed Chest Wall Osteoradionecrosis with Pseudomonal Empyema Neccesitans: A Cataclysmic Adverse Effect of Radiation Therapy Post Modified Radical Mastectomy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Delayed Chest Wall Osteoradionecrosis with Pseudomonal Empyema Neccesitans: A Cataclysmic Adverse Effect of Radiation Therapy Post Modified Radical Mastectomy Snehasis Das, Karthik Kanna Venkatesh This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6419357/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract The inclusion of adjuvant chemoradiation, especially in the form of whole breast radiation therapy, has been seen to reduce chances for future recurrences and provide long-term survival benefits [1]. Several early and late toxicities of radiation treatment are known, which include lymphoedema, skin changes, breast fibrosis, pneumonitis, pericarditis, and secondary malignancies [2]. The risk of an RT-induced rib cage fracture is low, with reports ranging from 0.3 to 1.8% [2], and it seldom transforms into osteoradionecrosis (ORN). The diagnosis lies mostly with imaging studies and the biopsy of the soft tissues and the bony component, which will demonstrate extensive inflammatory necrosis. Less than five cases of pseudomonal empyema have been reported in the literature and are usually seen in the immunocompromised. Treatment modalities available comprise source control of infection, extensive debridement, targeted antibiotics, hyperbaric oxygen, and finally reconstruction in cases of loss of framework [3]. Herein, we present the case of a 63 years old female who had the didactic recherche combination of both rare syndromes in one setting and her effective sequential management. Surgery Modified Radical Mastectomy Osteoradionecrosis Lymphedema Empyema necessitans Adjuvant Radiotherapy Figures Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 CASE PRESENTATION A 63-year-old female, a known case of diabetes mellitus for 12 years with poor control and irregular medications was diagnosed as a case of carcinoma of the right breast (cT4aN1M0) 10 years ago. She received 3 cycles of neoadjuvant chemotherapy with CAF, following which she underwent a right modified radical mastectomy (MRM) and subsequent 3 cycles of adjuvant chemotherapy with the same regimen. In addition, she underwent adjuvant radiotherapy of 150 Gy in 25#, following which she had a complete response to the therapy. She developed lymphedema of the right arm after radiation therapy and has been asymptomatic for over a decade. Now she presented with complaints of pain and swelling in the right upper limb for 10 days with ulcerative, purulent discharge from the right hemithorax adjacent to the old MRM site. The swelling initially started over the right shoulder, extending up to the hands and fingers, and was associated with a continuous, non-radiating and aching pain in the right upper limb, which aggravated on moving. The patient also had 1 episode of fever 10 days ago, which was not associated with chills and was low-grade, relieved with medications. The patient was conscious and oriented at the time of presentation with stable vitals. Right upper limb edema was present, with cellulitic changes. All the pulses in the right upper limb were intact, and the systemic examinations were normal. The healed MRM scar was associated with induration and ulcerative lesion of size 2*3 cm with slough present over it and active pus discharge from it. INVESTIGATION Blood investigations: The patient had mild anemia (11.0 g/dL) and leukocytosis (13960 cells/microlitre). The liver function test (LFT) and renal function test (RFT) were normal. Blood and exudate cultures grew Pseudomonas aeruginosa pan-resistant with intermediate sensitivity to colistin (Fig. 1). The tuberculosis workup was negative. Contrast-enhanced computed tomography (CECT) abdomen and thorax and radiography, showed an ill-defined heterogeneous collection with multiple air foci and gross fat stranded in the surrounding region was seen in the right lateral chest wall, measuring 3.9*4.9*6.7cm (ML*AP*CC) (Fig. 2). Medially, the lesion is extending into the thoracic cavity through the intercostal spaces and was communicating with the pleural space. Right loculated pleural effusion was seen with a mild amount of air. Inferiorly, the collection extended behind the pectoralis muscle while superiorly, the collection extended till the apex of the axilla. Right subclavian vessels were seen superior and lateral to the collection. Laterally, there was no extension of the lesion into the right arm and inferiorly, there was a defect in the skin of the chest wall. Discontinuity and irregular erosions were seen in the right 2nd to 8th ribs with osteopenia. Multiple bone fragments are seen in the adjacent soft tissue (Fig. 3, Fig. 4 and Fig. 5) but obvious sequestrum or involucrum wasn’t appreciated, this finding pointed towards osteoradionecrosis. In addition to that, there was collapse and consolidation in the adjacent lung with small cavitary changes. There may have been a possible communication between the bronchioles and the pleural cavity. A few prominent mediastinal nodes are seen in the right upper and lower paratracheal regions, with the largest SAD measuring 1 cm—reactive nodes. Few enlarged left axillary lymph nodes—largest SAD 1.2cm with maintained fatty hilum. Otherwise, there was no obvious suspicious focal lesion in the left breast. The right axillary lymph nodes were not visible. Fat stranding was seen in the subcutaneous plane of the left arm which was likely to be edematous. There was no evidence of recurrence, or distant occult metastasis. TREATMENT The patient was diagnosed with a case of delayed chest wall post-radiation osteoradionecrosis with right upper limb cellulitis. The patient underwent minimal debridement, and daily dressings were applied. A CECT was done, which suggested a collection in the surgical site cavitation with intrathoracic extension and ruled out evidence of any recurrence or metastatic disease. Due to persistent pus discharge from the ulcer, pigtail was placed into pleural space collection with daily pigtail charting and culture-based antibiotics being administered based on exudate and blood culture, which grew Pseudomonas aeruginosa with intermediate sensitivity to colistin. Gradually, the pigtail drain came down, and the ulcerative lesion was sealed off with granulation tissue after the removal of the pigtail. The patient was followed up for the next 3 months without any complications. OUTCOMES AND FOLLOWUP The patient's ulcerative lesion was well granulated with daily dressings and had no purulent discharge. There was no evidence of recurrence or residual disease. The patient was followed up for the next 3 months with no further complications. DISCUSSION Local radiation therapy, especially to the chest wall, is an effective multidisciplinary adjunct to treatment in cases of carcinoma of the breast and the lungs. It has been postulated to reduce tumor recurrences and increase the chances of survival by reducing microscopic malignant disease [1, 4]. A considerable number of diverse complications have been documented with radiation treatment. Early complications (during the weeks to months after completion of RT) include skin changes, breast edema, fat necrosis, radiation-induced pneumonia, and pleural effusion [5]. On the other hand, late complications taking more than 10 years to present would include cardiomyopathy and secondary malignancies [2, 5]. The most lethal among all of them would include osteoradionecrosis (ORN), radiation-induced rib cage fractures, and radiation-induced sarcoma. Predisposing factors for ORN include trauma, infection, overdose RT application, involvement of the tumor with bone tissue or its occurrence around the bone tissue, and individual sensitivity and endurance characteristics of the patient [6]. Theoretically, as the doses of field radiation increase, the changes in the corresponding tissues become more irreversible and malefic. It has been seen that in doses greater than 4000 cGv, permanent changes take place in the bones, but ORN requires doses of over 6000 cGv, which even confers resistance to the lesion in terms of conservative treatment. A further radiation-induced rib fracture is another very late complication of traditional radiotherapy with a reported incidence of 0.1–5% [2, 7] and would seed the development of ORN in some of the cases. On one hand, while ORN of the mandible is relatively common due to higher radiation and poor vascularity [8], ORN of the chest wall is extremely rare, with less than 5 cases documented in the literature [9, 10]. The pathogenesis of ORN is seen to be related primarily to reactive oxygen species-mediated damage to differentiated soft tissues, progenitor cells, and vascular endothelial cells. This leads to fibrosis, chronic, prolonged hypoxemia, and cell death [11]. In addition, the cytokine-chemokine system is seemingly activated after the irradiation procedure, which perpetuates a never-ending chronic inflammatory response with a self-triggering mechanism. The main elements of this inflammatory storm seem to be interleukin-1, interleukin-6, transforming growth factor-β1, and tumor necrosis factor-α, which cause tissue injury [12, 13]. ORN usually presents with pain, infection, and pathological fractures, with rare instances of chest wall ORN compounding into an empyema neccesitans. It is usually diagnosed using radiological and histopathological examination, confounding very closely with skeletal metastasis. In a CECT scan, ORN presents as a focal lucent area in the bone with periostitis, sclerosis, cortical thinning, fatty marrow changes, and insufficiency fractures [2]. A bone scan will demonstrate a reduced uptake of the radioisotopes in the initial stages, and later, increased uptake with fractures will be evident. PET-CT images might be relatively unreliable in diagnosing the condition against skeletal metastasis [14]. In CT images themselves, a permeative pattern of bone loss, 75% loss is envisaged in a case of skeletal metastasis [14]. Moreover, the presence of intraosseous air specks almost always indicates ORN caused by superimposed osteomyelitis [14]. ORN affects both bones and the soft tissues associated with it. Multiple approaches have been researched, of which radical debridement followed by surgical reconstruction has been seen to offer the best prognosis. As in our case of a chest wall ORN with rib framework loss, any deficit greater than 3 contiguous ribs or more than 5 cm between the largest dimension of the defect is to be surgically reconstructed with mesh or implants to prevent herniation and paradoxical breathing [15]. Hyperbaric oxygen chamber treatment has also been proposed to be used as a complementary strategy to augment wound healing [16]. Ongoing research is based on rheological agents like pentoxifylline and vitamin E, which have shown promising reports in the recovery of such cases [17]. Few scientists have been able to establish a genetic connection with this ailment in the form of single nucleotide polymorphisms and the degree of different radiation sensitivity [18], which might pave the way for genetic treatments in the future. In our case, the patient presented with chest wall ORN after 10 years following MRM. The framework loss in our case, compounded with the pre-existing immunocompromised state, led to systemic involvement in the form of empyema which has ruptured and degenerated into an empyema necessitans (EN). In addition to this, EN has been seen to be mostly caused by mycobacterium and actinomyces, accounting for three-fourth of the cases [19]. To our knowledge, there have been only a handful of documented cases of pseudomonal empyema [20, 21] that have been documented in the literature with the cepacia species. This would be the first case report of an EN being precipitated by pseudomonas aeruginosa in a patient with chest wall ORN as the predisposition factor. As far as diagnosis is concerned, blood and exudate cultures would initiate the treatment by isolating the organism and the sensitivity pattern. In our case, Pseudomonas aeruginosa was intermediately sensitive to colistin, based on which the initiation of intravenous antibiotics was done to tackle the septicemia. Secondly, the empyema needs to be drained to remove the primary source of the infection. In our patient, the empyema was drained with the help of an intrapleural pigtail. Associated ORN might warrant extensive surgical en-bloc resection with possible reconstruction surgery, but in our case, conservative management in the form of sequential debridements and regular dressing helped in granulation cover over the defect and full recovery of the patient's ailment. Post-recovery, the patient was followed up for 3 months without any further complaints. LEARNING POINTS Chest wall ORN is the rarest and most serious complication following adjuvant radiation therapy, with dose-dependent severity and possible inflammatory pathogenesis in breast carcinoma patients. Imaging studies, along with histopathological examination, are necessary for confirmation of the diagnosis. The surgical approach in the form of en-bloc resection and reconstruction thereafter is the most approved. The treatment protocol also includes culture-based targeted antibiotics, image-guided drainage, and conservative dressings, which aid in the augmentation of the healing process. Pseudomonal EN is a recherche phenomenon with only a handful of documented cases. In our knowledge, this is the first documented case of EN caused by Pseudomonas aeruginosa, whereas all others were caused by Cepacia species. Declarations Statement on Participant Consent: The patient gave consent to publish their case. Compliance with Ethical Standard Ethics Approval, Informed consent and Patient Consent: The authors of this article have received and archived written patient consent, and the authors adhered to the ethical guidelines Conflict of interest: There is no conflict of interest between the authors of this article Sources of support: There was no source of support Funding or grant support: No financial or funding support was received Data Statement and Disclaimer: Alldetails of the case are available with the authors Author Contribution: All authors contributed to the study conception and design, material preparation, and first draft preparation, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. References Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E et al (2005) Effects of radiotherapy and differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet 366:2087–2106 Meric F, Buchholz TA, Mirza NQ, Vlastos G, Ames FC, Ross MI et al (2002) Long-term complications associated with breast-conservation surgery and radiotherapy. Ann Surg Oncol 9:543–549 Pandey M, Chandramohan KN, Mathew A (2004) An unusual lesion on the chest wall. Int Wound J 1(2):152–154 (PMID: 16722890) Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectom, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233–1241 (PMID: 12393820) Yi A, Kim HH, Shin HJ, Huh MO, Ahn SD, Seo BK (2009) Radiation-induced complications after breast cancer radiation therapy: a pictorial review of multimodality imaging findings. Korean J Radiol 10:496–5072 Peleg M, Lopez EA (2006) The treatment of osteoradionecrosis of the mandibula: the case for hyperbaric oxygen and bone graft reconstruction. J Oral Maxillofac Surg 64:956–960 (PMID: 16713813 Whelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L et al (2002) Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 94:1143–1150 Reuther T, Schuster T, Mende U, Kübler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients–a report of a thirty year retrospective review. Int J Oral Maxillofac Surg. ;32:289–2957. Alhilali L, Reynolds A 2002;94:1143–1150 Makboul M, Salama Ayyad MA (2012) Is myocutaneous flap alone sufficient for reconstruction of chest wall osteoradionecrosis? Interact Cardiovasc Thorac Surg 15:447–451 Nicholls L, Gorayski P, Harvey J Osteoradionecrosis of the ribs following breast radiotherapy. Case RepOncol 2 015;8:332–338 Raz DJ, Clancy SL, Erhunmwunsee LJ (2017) Surgical management of the radiated chest wall and its complications. Thorac Surg Clin 27:171–179 Rivero JA, Shamji O, Kolokythas A (2017) Osteoradionecrosis: a review of pathophysiology, prevention and pharmacologic management using pentoxifylline, α-tocopherol, and clodronate. Oral Surg Oral Med Oral Pathol Oral Radiol 124:464–471 Marx RE (1983) Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg 41:283–288 Alhilali L, Reynolds AR, Fakhran S (2014) Osteoradionecrosis after radiation therapy for head and neck cancer: differentiation from recurrent disease with CT and PET/CT imaging. AJNR Am J Neuroradiol 35:1405–1411 Momeni A, Kovach SJ (2016) Important considerations in chest wall reconstruction. J Surg Oncol 113:913–922 Bennett MH, Feldmeier J, Hampson NB, Smee R, Milross C (2016) Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst Rev 4:CD005005 Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL (2011) Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys 80:832–839 Alsbeih G, El-Sebaie M, Al-Harbi N (2013) SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers. Radiat Oncol 8:125 Freeman AF, Ben-Ami T, Shulman ST (2004) Streptococcus pneumoniae empyema necessitatis. Pediatr Infect Dis J 23(2):177–179. https://doi.org/10.1097/01.inf.00001 10625.41967 . .cc RobinsonDR (1984) Chaudhary BA.Speir WA.Successful treatment of Pseudomonas pneumonia complicated by bacteremia and empyema.JMed. Assoc Ga 73:289–291 Young IN, Samson PC (1980) Pseudomonas aeruginosa septicemia with gangrene of the lung and empyema.AnnThoracSurg. 29:254–257 Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6419357","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":441139331,"identity":"cd5bd9ba-c5c3-4e5f-b601-35cccab2e3e3","order_by":0,"name":"Snehasis 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version\u003c/p\u003e","description":"","filename":"MRMCasereportimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6419357/v1/dbd7f4f265d9e4e15d537f32.png"},{"id":80727067,"identity":"c122e260-400b-48de-a6f0-376b44d2dde0","added_by":"auto","created_at":"2025-04-16 11:55:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3563758,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6419357/v1/b3c00e91-33bb-463e-82a5-b4eacf2314fc.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eDelayed Chest Wall Osteoradionecrosis with Pseudomonal Empyema Neccesitans: A Cataclysmic Adverse Effect of Radiation Therapy Post Modified Radical Mastectomy\u003c/p\u003e","fulltext":[{"header":"CASE PRESENTATION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eA 63-year-old female, a known case of diabetes mellitus for 12 years with poor control and irregular medications was diagnosed as a case of carcinoma of the right breast (cT4aN1M0) 10 years ago. She received 3 cycles of neoadjuvant chemotherapy with CAF, following which she underwent a right modified radical mastectomy (MRM) and subsequent 3 cycles of adjuvant chemotherapy with the same regimen. In addition, she underwent adjuvant radiotherapy of 150 Gy in 25#, following which she had a complete response to the therapy. She developed lymphedema of the right arm after radiation therapy and has been asymptomatic for over a decade. Now she presented with complaints of pain and swelling in the right upper limb for 10 days with ulcerative, purulent discharge from the right hemithorax adjacent to the old MRM site. The swelling initially started over the right shoulder, extending up to the hands and fingers, and was associated with a continuous, non-radiating and aching pain in the right upper limb, which aggravated on moving. The patient also had 1 episode of fever 10 days ago, which was not associated with chills and was low-grade, relieved with medications.\u003c/p\u003e \u003cp\u003eThe patient was conscious and oriented at the time of presentation with stable vitals. Right upper limb edema was present, with cellulitic changes. All the pulses in the right upper limb were intact, and the systemic examinations were normal. The healed MRM scar was associated with induration and ulcerative lesion of size 2*3 cm with slough present over it and active pus discharge from it.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e"},{"header":"INVESTIGATION","content":"\u003cp\u003e \u003cdiv class=\"BlockQuote\"\u003e \u003cp\u003eBlood investigations: The patient had mild anemia (11.0 g/dL) and leukocytosis (13960 cells/microlitre). The liver function test (LFT) and renal function test (RFT) were normal. Blood and exudate cultures grew Pseudomonas aeruginosa pan-resistant with intermediate sensitivity to colistin (Fig.\u0026nbsp;1). The tuberculosis workup was negative.\u003c/p\u003e \u003cp\u003eContrast-enhanced computed tomography (CECT) abdomen and thorax and radiography, showed an ill-defined heterogeneous collection with multiple air foci and gross fat stranded in the surrounding region was seen in the right lateral chest wall, measuring 3.9*4.9*6.7cm (ML*AP*CC) (Fig.\u0026nbsp;2). Medially, the lesion is extending into the thoracic cavity through the intercostal spaces and was communicating with the pleural space. Right loculated pleural effusion was seen with a mild amount of air. Inferiorly, the collection extended behind the pectoralis muscle while superiorly, the collection extended till the apex of the axilla. Right subclavian vessels were seen superior and lateral to the collection. Laterally, there was no extension of the lesion into the right arm and inferiorly, there was a defect in the skin of the chest wall. Discontinuity and irregular erosions were seen in the right 2nd to 8th ribs with osteopenia. Multiple bone fragments are seen in the adjacent soft tissue (Fig.\u0026nbsp;3, Fig.\u0026nbsp;4 and Fig.\u0026nbsp;5) but obvious sequestrum or involucrum wasn\u0026rsquo;t appreciated, this finding pointed towards osteoradionecrosis. In addition to that, there was collapse and consolidation in the adjacent lung with small cavitary changes. There may have been a possible communication between the bronchioles and the pleural cavity. A few prominent mediastinal nodes are seen in the right upper and lower paratracheal regions, with the largest SAD measuring 1 cm\u0026mdash;reactive nodes. Few enlarged left axillary lymph nodes\u0026mdash;largest SAD 1.2cm with maintained fatty hilum. Otherwise, there was no obvious suspicious focal lesion in the left breast. The right axillary lymph nodes were not visible. Fat stranding was seen in the subcutaneous plane of the left arm which was likely to be edematous. There was no evidence of recurrence, or distant occult metastasis.\u003c/p\u003e \u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTREATMENT\u003c/h2\u003e \u003cp\u003eThe patient was diagnosed with a case of delayed chest wall post-radiation osteoradionecrosis with right upper limb cellulitis. The patient underwent minimal debridement, and daily dressings were applied. A CECT was done, which suggested a collection in the surgical site cavitation with intrathoracic extension and ruled out evidence of any recurrence or metastatic disease. Due to persistent pus discharge from the ulcer, pigtail was placed into pleural space collection with daily pigtail charting and culture-based antibiotics being administered based on exudate and blood culture, which grew Pseudomonas aeruginosa with intermediate sensitivity to colistin. Gradually, the pigtail drain came down, and the ulcerative lesion was sealed off with granulation tissue after the removal of the pigtail. The patient was followed up for the next 3 months without any complications.\u003c/p\u003e \u003c/div\u003e"},{"header":"OUTCOMES AND FOLLOWUP","content":"\u003cp\u003eThe patient's ulcerative lesion was well granulated with daily dressings and had no purulent discharge. There was no evidence of recurrence or residual disease. The patient was followed up for the next 3 months with no further complications.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eLocal radiation therapy, especially to the chest wall, is an effective multidisciplinary adjunct to treatment in cases of carcinoma of the breast and the lungs. It has been postulated to reduce tumor recurrences and increase the chances of survival by reducing microscopic malignant disease [1, 4]. A considerable number of diverse complications have been documented with radiation treatment. Early complications (during the weeks to months after completion of RT) include skin changes, breast edema, fat necrosis, radiation-induced pneumonia, and pleural effusion [5]. On the other hand, late complications taking more than 10 years to present would include cardiomyopathy and secondary malignancies [2, 5]. The most lethal among all of them would include osteoradionecrosis (ORN), radiation-induced rib cage fractures, and radiation-induced sarcoma.\u003c/p\u003e \u003cp\u003ePredisposing factors for ORN include trauma, infection, overdose RT application, involvement of the tumor with bone tissue or its occurrence around the bone tissue, and individual sensitivity and endurance characteristics of the patient [6]. Theoretically, as the doses of field radiation increase, the changes in the corresponding tissues become more irreversible and malefic. It has been seen that in doses greater than 4000 cGv, permanent changes take place in the bones, but ORN requires doses of over 6000 cGv, which even confers resistance to the lesion in terms of conservative treatment. A further radiation-induced rib fracture is another very late complication of traditional radiotherapy with a reported incidence of 0.1\u0026ndash;5% [2, 7] and would seed the development of ORN in some of the cases. On one hand, while ORN of the mandible is relatively common due to higher radiation and poor vascularity [8], ORN of the chest wall is extremely rare, with less than 5 cases documented in the literature [9, 10].\u003c/p\u003e \u003cp\u003eThe pathogenesis of ORN is seen to be related primarily to reactive oxygen species-mediated damage to differentiated soft tissues, progenitor cells, and vascular endothelial cells. This leads to fibrosis, chronic, prolonged hypoxemia, and cell death [11]. In addition, the cytokine-chemokine system is seemingly activated after the irradiation procedure, which perpetuates a never-ending chronic inflammatory response with a self-triggering mechanism. The main elements of this inflammatory storm seem to be interleukin-1, interleukin-6, transforming growth factor-β1, and tumor necrosis factor-α, which cause tissue injury [12, 13].\u003c/p\u003e \u003cp\u003eORN usually presents with pain, infection, and pathological fractures, with rare instances of chest wall ORN compounding into an empyema neccesitans. It is usually diagnosed using radiological and histopathological examination, confounding very closely with skeletal metastasis. In a CECT scan, ORN presents as a focal lucent area in the bone with periostitis, sclerosis, cortical thinning, fatty marrow changes, and insufficiency fractures [2]. A bone scan will demonstrate a reduced uptake of the radioisotopes in the initial stages, and later, increased uptake with fractures will be evident. PET-CT images might be relatively unreliable in diagnosing the condition against skeletal metastasis [14]. In CT images themselves, a permeative pattern of bone loss, \u0026lt; 75% loss of the total bone trabeculae, commonly indicates ORN, while a lucent pattern with \u0026gt;\u0026thinsp;75% loss is envisaged in a case of skeletal metastasis [14]. Moreover, the presence of intraosseous air specks almost always indicates ORN caused by superimposed osteomyelitis [14].\u003c/p\u003e \u003cp\u003eORN affects both bones and the soft tissues associated with it. Multiple approaches have been researched, of which radical debridement followed by surgical reconstruction has been seen to offer the best prognosis. As in our case of a chest wall ORN with rib framework loss, any deficit greater than 3 contiguous ribs or more than 5 cm between the largest dimension of the defect is to be surgically reconstructed with mesh or implants to prevent herniation and paradoxical breathing [15]. Hyperbaric oxygen chamber treatment has also been proposed to be used as a complementary strategy to augment wound healing [16]. Ongoing research is based on rheological agents like pentoxifylline and vitamin E, which have shown promising reports in the recovery of such cases [17]. Few scientists have been able to establish a genetic connection with this ailment in the form of single nucleotide polymorphisms and the degree of different radiation sensitivity [18], which might pave the way for genetic treatments in the future.\u003c/p\u003e \u003cp\u003eIn our case, the patient presented with chest wall ORN after 10 years following MRM. The framework loss in our case, compounded with the pre-existing immunocompromised state, led to systemic involvement in the form of empyema which has ruptured and degenerated into an empyema necessitans (EN). In addition to this, EN has been seen to be mostly caused by mycobacterium and actinomyces, accounting for three-fourth of the cases [19]. To our knowledge, there have been only a handful of documented cases of pseudomonal empyema [20, 21] that have been documented in the literature with the cepacia species. This would be the first case report of an EN being precipitated by pseudomonas aeruginosa in a patient with chest wall ORN as the predisposition factor.\u003c/p\u003e \u003cp\u003eAs far as diagnosis is concerned, blood and exudate cultures would initiate the treatment by isolating the organism and the sensitivity pattern. In our case, Pseudomonas aeruginosa was intermediately sensitive to colistin, based on which the initiation of intravenous antibiotics was done to tackle the septicemia. Secondly, the empyema needs to be drained to remove the primary source of the infection. In our patient, the empyema was drained with the help of an intrapleural pigtail. Associated ORN might warrant extensive surgical en-bloc resection with possible reconstruction surgery, but in our case, conservative management in the form of sequential debridements and regular dressing helped in granulation cover over the defect and full recovery of the patient's ailment. Post-recovery, the patient was followed up for 3 months without any further complaints.\u003c/p\u003e"},{"header":"LEARNING POINTS","content":"\u003cp\u003eChest wall ORN is the rarest and most serious complication following adjuvant radiation therapy, with dose-dependent severity and possible inflammatory pathogenesis in breast carcinoma patients.\u003c/p\u003e \u003cp\u003eImaging studies, along with histopathological examination, are necessary for confirmation of the diagnosis.\u003c/p\u003e \u003cp\u003eThe surgical approach in the form of en-bloc resection and reconstruction thereafter is the most approved. The treatment protocol also includes culture-based targeted antibiotics, image-guided drainage, and conservative dressings, which aid in the augmentation of the healing process.\u003c/p\u003e \u003cp\u003ePseudomonal EN is a recherche phenomenon with only a handful of documented cases. In our knowledge, this is the first documented case of EN caused by Pseudomonas aeruginosa, whereas all others were caused by Cepacia species.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eStatement on Participant Consent: \u003c/strong\u003eThe patient gave consent to publish their case.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standard\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval, Informed consent and Patient Consent:\u0026nbsp;\u003c/strong\u003eThe authors of this article have received and archived written patient consent, and the authors adhered to the ethical guidelines\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest:\u0026nbsp;\u003c/strong\u003eThere is no conflict of interest between the authors of this article\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSources of support:\u003c/strong\u003e There was no source of support\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding or grant support:\u0026nbsp;\u003c/strong\u003e No financial or funding support was received\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Statement and Disclaimer:\u0026nbsp;\u003c/strong\u003eAlldetails of the case are available with the authors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design, material preparation, and first draft preparation, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eClarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans E et al (2005) Effects of radiotherapy and differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomized trials. Lancet 366:2087\u0026ndash;2106\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeric F, Buchholz TA, Mirza NQ, Vlastos G, Ames FC, Ross MI et al (2002) Long-term complications associated with breast-conservation surgery and radiotherapy. Ann Surg Oncol 9:543\u0026ndash;549\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePandey M, Chandramohan KN, Mathew A (2004) An unusual lesion on the chest wall. Int Wound J 1(2):152\u0026ndash;154 (PMID: 16722890)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, Jeong JH, Wolmark N (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectom, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347(16):1233\u0026ndash;1241 (PMID: 12393820)\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYi A, Kim HH, Shin HJ, Huh MO, Ahn SD, Seo BK (2009) Radiation-induced complications after breast cancer radiation therapy: a pictorial review of multimodality imaging findings. Korean J Radiol 10:496\u0026ndash;5072\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeleg M, Lopez EA (2006) The treatment of osteoradionecrosis of the mandibula: the case for hyperbaric oxygen and bone graft reconstruction. J Oral Maxillofac Surg 64:956\u0026ndash;960 (PMID: 16713813\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhelan T, MacKenzie R, Julian J, Levine M, Shelley W, Grimard L et al (2002) Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 94:1143\u0026ndash;1150\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReuther T, Schuster T, Mende U, K\u0026uuml;bler A (2003) Osteoradionecrosis of the jaws as a side effect of radiotherapy of head and neck tumour patients\u0026ndash;a report of a thirty year retrospective review. Int J Oral Maxillofac Surg. ;32:289\u0026ndash;2957. Alhilali L, Reynolds A 2002;94:1143\u0026ndash;1150\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMakboul M, Salama Ayyad MA (2012) Is myocutaneous flap alone sufficient for reconstruction of chest wall osteoradionecrosis? Interact Cardiovasc Thorac Surg 15:447\u0026ndash;451\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNicholls L, Gorayski P, Harvey J Osteoradionecrosis of the ribs following breast radiotherapy. Case RepOncol 2 015;8:332\u0026ndash;338\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaz DJ, Clancy SL, Erhunmwunsee LJ (2017) Surgical management of the radiated chest wall and its complications. Thorac Surg Clin 27:171\u0026ndash;179\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRivero JA, Shamji O, Kolokythas A (2017) Osteoradionecrosis: a review of pathophysiology, prevention and pharmacologic management using pentoxifylline, α-tocopherol, and clodronate. Oral Surg Oral Med Oral Pathol Oral Radiol 124:464\u0026ndash;471\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarx RE (1983) Osteoradionecrosis: a new concept of its pathophysiology. 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Pediatr Infect Dis J 23(2):177\u0026ndash;179. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/01.inf.00001 10625.41967\u003c/span\u003e\u003cspan address=\"10.1097/01.inf.00001 10625.41967\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. .cc\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRobinsonDR (1984) Chaudhary BA.Speir WA.Successful treatment of Pseudomonas pneumonia complicated by bacteremia and empyema.JMed. Assoc Ga 73:289\u0026ndash;291\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoung IN, Samson PC (1980) Pseudomonas aeruginosa septicemia with gangrene of the lung and empyema.AnnThoracSurg. 29:254\u0026ndash;257\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Modified Radical Mastectomy, Osteoradionecrosis, Lymphedema, Empyema necessitans, Adjuvant Radiotherapy","lastPublishedDoi":"10.21203/rs.3.rs-6419357/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6419357/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe inclusion of adjuvant chemoradiation, especially in the form of whole breast radiation therapy, has been seen to reduce chances for future recurrences and provide long-term survival benefits [1]. Several early and late toxicities of radiation treatment are known, which include lymphoedema, skin changes, breast fibrosis, pneumonitis, pericarditis, and secondary malignancies [2]. The risk of an RT-induced rib cage fracture is low, with reports ranging from 0.3 to 1.8% [2], and it seldom transforms into osteoradionecrosis (ORN). The diagnosis lies mostly with imaging studies and the biopsy of the soft tissues and the bony component, which will demonstrate extensive inflammatory necrosis. Less than five cases of pseudomonal empyema have been reported in the literature and are usually seen in the immunocompromised. Treatment modalities available comprise source control of infection, extensive debridement, targeted antibiotics, hyperbaric oxygen, and finally reconstruction in cases of loss of framework [3]. Herein, we present the case of a 63 years old female who had the didactic recherche combination of both rare syndromes in one setting and her effective sequential management.\u003c/p\u003e","manuscriptTitle":"Delayed Chest Wall Osteoradionecrosis with Pseudomonal Empyema Neccesitans: A Cataclysmic Adverse Effect of Radiation Therapy Post Modified Radical Mastectomy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-16 11:39:45","doi":"10.21203/rs.3.rs-6419357/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"365ecfa9-53f7-4c2d-b6fc-c6a3a1d05bce","owner":[],"postedDate":"April 16th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":46970226,"name":"Surgery"}],"tags":[],"updatedAt":"2025-04-16T11:39:45+00:00","versionOfRecord":[],"versionCreatedAt":"2025-04-16 11:39:45","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6419357","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6419357","identity":"rs-6419357","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}