lntramedullary nailing for pathological fractures of the proximal humerus caused

lNTRODUCTlON

Multiple myeloma (MM) is a type of plasma cell dyscrasia that is characterized by immortalized monoclonal plasma cell proliferation within the bone marrow. Different to bone metastasis, no new bone is formed in the osteolytic bone disease of MM[1]. Complications of osteolysis include fractures of the long bones, which often occur in the proximal humerus and femur, usually after minor trauma or can be atraumatic, and vertebral body fractures[2]. The clinical presentation and radiological features are non-specific, making it more difficult to diagnose. Therefore, some scholars have indicated that MM is an important disease that should not be ignored in the differential diagnosis of skeletal pain, even if no typical symptoms are identified initially, particularly in the elderly[3]. Intramedullary (IM) nailing is a technique used to treat humeral diaphysis fractures with minimal invasion, and it is advantageous in small lesions, reduces operation time, there is little soft tissue dissection, and results in early recovery[4]. However, there is controversy as to whether IM nailing should be used to treat proximal humeral fractures as it may lead to fixation loss[5]. As a result, IM nailing is currently restricted to the treatment of diaphyseal fractures[4,6-10]. To date, few studies have described the techniques applied in proximal humeral fractures, particularly if the skeletal defect is not augmented by the application of bone cement.We here describe a 64-year-old male patient suffering from MM bone disease (MMBD) in the proximal humerus. He received combined therapy with IM nailing and chemotherapy. Related reports of MMBD are also reviewed.

CASE PRESENTATlON

Chief complaints

A 64-year-old man who came to our emergency department complaining of left shoulder pain.

History of present illness

He had mild left shoulder trauma due to accidental falling from the standing position while walking 3 h ago.

Blockhead! said they, that is an old wooden shoe without the top! Are you going to send that, too, to the Princess? Of course I shall! returned Blockhead-Hans; and the brothers laughed and rode on a good way

History of past illness

His past medical history included atrial fibrillation treated with aspirin enteric-coated tablets (Bayer SPA), metoprolol succinate sustained-release tablets (AstraZeneca AB), and chronic atrophic gastritis.

After surgery, the patient achieved continuous pain relief and improved activity of the left upper limb,and no complications were reported. At 24 h postoperatively, the visual analog score declined by 7 points to 2. Histopathological examination of the sample revealed MM (IgAλ, IIIA/II). One week postoperatively, the patient received regular dexamethasone and bortezomib chemotherapy at the Department of Hematology. At the 40-mo follow-up, the humeral fracture showed favorable complete lesion healing (Figure 4), and the patient reported no pain. The Musculoskeletal Tumor Society score was 29[11]. In comparison with the contralateral shoulder, forward flexion, and abduction were limited at the terminal 10°, while complete external and internal adduction and rotation were achieved. No adverse events occurred.

Initial X-ray films of the left shoulder were obtained, which showed only a comminuted fracture and degenerative changes in the upper left humerus (Figure 2). Magnetic resonance imaging (MRI) was then performed and showed an abnormal signal intensity of the proximal humerus associated with a comminuted fracture, and multiple soft tissue masses around the fracture, ranging from 4.8 cm to 3.9 cm, which presented as hypointensity and isointensity, as well as hybrid hyperintensity on T1-weighted(T1-W) and T2-W images, respectively. The left humerus, glenoid, and clavicle had multiple sheet-like hyperintensity on T2-W images (Figure 2). A neoplastic lesion with radiological characteristics was highly suspected.

Personal and family history

Heaven help us! cried the boy at the helm, as the boat heeledover and lay on its beam ends. It had struck on a rock, which rosefrom the depths of the sea, and sank at once, like an old shoe in apuddle. It sank at once with mouse and man, as the saying is.There might have been mice on board, but only one man and a half,the skipper and the laborer s boy. No one saw it but the skimmingsea-gulls and the fishes beneath the water; and even they did notsee it properly, for they darted back with terror as the boat filledwith water and sank. There it lay, scarcely a fathom below thesurface, and those two were provided for, buried, and forgotten. Theglass with the foot of blue wood was the only thing that did not sink,for the wood floated and the glass drifted away to be cast upon theshore and broken; where and when, is indeed of no consequence. Ithad served its purpose, and it had been loved, which Anne Lisbeth sboy had not been. But in heaven no soul will be able to say, Neverloved.

Physical examination

Physical examination demonstrated swelling of the left shoulder, localized tenderness, percussion pain on the proximal humerus, and limited shoulder motion. The muscular tone of the upper limb was normal with no hypoesthesia. Physiological reflexes were present without pathological reflexes.

As a girl, all the fresh things can attract their eyes. Yeah. This time curiosity17 can t kill a cat. When coming back, the first thing we want to do is chatting. Talking about all the things in high school. From the talk, I know all the dorm mates are ambitious and they are eager to achieve their own goals. In fact, all the days are almost the same, we didn t know if there were any fresh things in college life except making boyfriend (Just joking here, of course, we have never been so simply). Everyday, except chatting just chatting, maybe some study for the scholarship. And the term passed quickly. You must be strange isn t there any contradiction18 among you and your dorm mates? It s true that we do have. But it won t last several days. (Very happy, isn t it?)

Laboratory examinations

In contrast, routine laboratory evaluation on admission, with the exception of anemia, was unremarkable. Hematopoiesis accounted for 40%, the ratio of granulocytes to erythrocytes was approximately 2:1, and megakaryocytes were 2-7/high power field. Multifocal plasmacytoid cell aggregation was also observed. Immunochemistry showed CD38 (+), kappa (+), lambda (+); MPO (+), CD61 (+) and CK (-) (Figure 1).

Imaging examinations

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Further laboratory tests and imaging examinations were performed. Computed tomography (CT)scans and X-ray examinations revealed multiple areas of reduced bone density throughout the body. In addition, high 18-F-fluorodeoxyglucose metabolism was observed in several ribs on bone scans, and in the fifth lumbar vertebra (L5), and left proximal humerus (Figure 3).

FlNAL DlAGNOSlS

Plasma cell myeloma was diagnosed following bone marrow aspirate and trephine.

TREATMENT

Following consultation with anesthesiologists and medical oncologists regarding the perioperative risks as well as the life expectancy of the patient, locked IM nailing (Sanatmetal Orthopaedic &Traumatologic Equipment Manufacturer Ltd.) was chosen for strong fixation of the humeral fracturethe trans-deltoid muscle approach. With the greater trochanter as the entry point, an IM nail was directly inserted into the humeral medullary cavity without the removal of tumors. The bone defect was not augmented with bone cement. No local adjuvant therapy was administered. We inserted the nail with great caution to avoid impingement of the acromion or rotator cuff tendons by the proximal end of the nail. We also inserted 3 proximal screws as well as 2 distal interlocking screws. On the day after surgery, the patient was encouraged to move his shoulder gently. One week after surgery, the patient was encouraged to perform passive stretching as well as gravity-resistance exercises.

OUTCOME AND FOLLOW-UP

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The patient denied a history of smoking, alcohol consumption, drug intake, and a family history of pathological fracture or osteoporosis.

DlSCUSSlON

MM accounts for 1% of cancer cases, and approximately 10% of hematologic cancer cases[12]. MM has a relatively higher morbidity in males than in females, and morbidity is two-fold higher in blacks than in Caucasians[13,14]. MM affects the older population, and 70% of cases are diagnosed when they are 60 years and older[15]. MM is a type of plasma cell dyscrasia that is characterized by immortalized monoclonal plasma cell growth within the bone marrow. Nearly all MM cases progress from the asymptomatic monoclonal gammopathy of undetermined significance (MGUS) at the pre-malignant stage[16,17]. Moreover, MGUS will further develop into MM or associated cancers at an annual growth rate of 1%[18,19].

Xu GQ wrote and edited the article; Wang G reviewed the literature; Bai XD collected information on the current case; Wang XJ revised the manuscript for important intellectual content; and All authors gave final approval of the version to be submitted.

Bone lesions induced by MM are indicative of MM, and they reduce patient life quality. About 80% of cases have osteolytic bone disorders when diagnosed, which are linked to a higher risk of skeletalrelated events (SREs) that increase morbidity and mortality[20]. Approximately 60% of MM cases develop fractures during the course of the disease[21]. The uncoupled bone-remodeling process lays the pathogenic foundation for bone disorders associated with myeloma. The myeloma cell-bone microenvironment interaction will eventually activate osteoclasts while suppressing osteoblasts, giving rise to bone loss. Multiple intercellular, as well as intracellular signal transduction pathways, participate in the complicated course of MM. The crosstalk mediated by myeloma across diverse molecular pathways forms a forward feedback to maintain the survival of myeloma cells and the decomposition of bone,even after reaching the disease plateau[22].

MM is diagnosed when at least one myeloma defining event (MDE) and at least 10% clonal plasma cells are detected during bone marrow examinations or when plasmacytoma is detected in biopsy samples. MDEs are constituted by the recognized CRAB (hyperCalcaemia, Renal failure, Anaemia, Bony lesions) characteristics and 3 representative biomarkers, including more than one focal lesion detected by MRI, ≥ 60% plasma cells in clonal bone marrow, as well as ≥100 free light chains (FLC) in serum[23].In the case of suspected MM in the clinic, M protein testing is recommended by combining serum immunofixation, serum protein electrophoresis, as well as serum FLC assay[24]. About 2% of MM cases develop the non-secretory disorder with no M protein detected in the above-mentioned tests[25].Positron emission tomography/computed tomography and low-dose whole-body CT scans are the best techniques for assessing bone disorder severity[24,26], which can show the changes in bones and soft tissues more clearly, and display the boundaries of the lesion. Plain radiographs are usually non-specific and can even underestimate the extent of the lesion, and are performed only when no other advanced imaging can be accessed. MRI is a particularly useful imaging technique of choice due to its noninvasive nature and greater anatomic detail, particularly when smoldering MM is suspected, to eliminate the risk of the focal lesion in the bone marrow observed before the occurrence of the actual osteolytic disorder.MRI also greatly contributes to the assessment of suspected cord compression and extramedullary disorder, and when it is necessary to visualize a certain symptomatic region. Although the diagnosis of MM is easy, based on blood and kidney tests and X-rays, in some cases an accurate diagnosis can only be made by pathology[27].

MM can result in progressive relapse. MM may recur with clinical symptoms or with biochemical disorders. Holistic and multidisciplinary treatment is needed for each MM patient[15]. Treatment involves multiple factors, which requires collaboration between radiotherapists, orthopedic surgeons,radiologists, hematologists, and anesthesiologists. In this regard, it is necessary to construct a prognostic model to predict disease stage, evaluate the patient’s general condition, and determine underlying chronic disorders or possible adjuvant treatments[2]. To optimize the outcomes for individuals,elucidating the most suitable maintenance treatment or continuous therapy for the specific patient group is important. It is also important to consider the clinical safety, effectiveness, tolerability, life quality, convenience, feasibility, and long-time treatment burden in patients[23].

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In addition to oncological and antineoplastic systemic therapy, surgical therapy in patients with MM is an essential treatment within the framework of supportive therapy measures and involves orthopedic tumor surgery. For SREs related to myeloma, surgery is mainly performed to maintain and restore skeletal function and recovery, reduce patient suffering such as pain, and improve patient mobility as well as life quality[28,29]. There is a need for surgical intervention not only for the care and treatment of stability-threatening bone lesions and pathological fractures but also for the treatment of tumor-related complications, such as neurological deficits, possible paraplegia, or in the case of conservative therapy,refractory bone pain. The surgical methods and timing of treatment should be decided individually depending on the risk and prognostic outcomes of myeloma cases[28]. Osteolysis of non-supporting skeletal sections such as the ribs, skull, or scapula does not usually require surgical treatment. The physical status grade established by the American Society of Anesthesiologists (ASA) has been extensively used to evaluate the patient's general condition or anesthesia tolerance. Ultrasound-guided intercostal brachial plexus block provides an alternative to general anesthesia for patients with pathologic humeral fractures caused by MM with systemic presentation and chest infections[30].However, patients with ＜ 2 mo survival or ASA = 4 will be treated using conservative methods instead of surgery[31].

Shoulder pain and bone damage due to pathological fractures of the proximal humerus caused by MM can be treated using either the simple bone cement technique or percutaneous microwave ablation and cementoplasty[33].

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Endoprosthetic reconstruction has been extensively used to treat proximal humeral fractures, but it does not achieve a satisfactory effect on impaired function. The prosthesis can be a good way of relieving pain and fixing the fracture, but it has poor functional recovery compared with other treatments[7,34-36]. In addition, more tendons and muscles are sacrificed during resection, which inevitably impairs function[35]. Also, plate fixation is associated with numerous drawbacks, such as short protection length, massive soft tissue stripping, and risk of nerve injury[9,37,38]. Local relapse may give rise to fixation loss or the need for a second operation[34,39]. As a result, plates are restricted in the treatment of metastasis.

IM nailing is thought to be unsuitable for treating proximal humeral fractures due to the bone defect and thin cortex following curettage[34]. Therefore, at present, IM nailing is restricted to the treatment of diaphyseal fractures[6]. Our results revealed that IM nailing is an efficient and robust method for treating proximal humeral fractures. IM nailing to fix proximal humeral fractures is advantageous due to its decreased operation time, can be used to treat small lesions, decreased soft tissue dissection, and early recovery.

In this case, we performed IM nailing to treat a proximal humeral fracture, without bone cement to augment the lesion. At follow-up visits, our patient had marked pain relief and improved shoulder function. At the 40-mo follow-up, the patient had a favorably healed humeral fracture, complete lesion healing was observed, and no pain was reported by the patient. In comparison with the contralateral shoulder, the forward flexion and abduction were limited at the terminal 10°, and complete external and internal adduction and rotation were achieved.

Despite it being generally incurable, the long-time survival of MM patients is greatly improved as more treatments have recently been developed.In addition,improved survival is also associated with early treatment[40]. As suggested by randomized controlled trials which used modern treatments, MM has a median survival of about 6 years. An appropriate treatment for metastases is needed to prolong patient survival[41].

Although this technique achieved a satisfactory effect, few reports describe this method for the treatment of pathological fractures of the proximal humerus caused by MM. Therefore, it is necessary to conduct studies with a large sample size to further validate its efficacy and to identify the surgical indications and related complications.

Our patient was satisfied with his current functional recovery and treatment of the primary disease and agreed to publication of this report, in the hope that more patients suffering from the same disease may benefit.

CONCLUSlON

When a pathological fracture of the proximal humerus caused by multiple myeloma occurs, early surgical treatment is indicated, which can effectively relieve pain and allow early movement. IM nailing can be performed for this type of fracture, without removal of tumors, bone cement augmentation for the bone defect, or local adjuvant therapy. Moreover, patients can receive combined therapy and have a good prognosis.

Surgery is usually conducted to treat MM-induced proximal humeral fractures, to relieve patient suffering and recover bone function and mobility, as well as patient life quality. However, surgical strategies are complicated and demanding[32].

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This had happened so often that her subjects lived in terror of losing her altogether, and tried everything they could think of to keep her to the ground

The patient consented to the publication of this report. Written consent for publication was obtained for all potentially identifying data and accompanying images and these are available for review from the editor of this journal.

The authors declare that they have no competing interests.

The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).

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China

Guo-Qiang Xu 0000-0002-0452-806X; Gang Wang 0000-0002-7314-8693; Xiao-Dong Bai 0000-0002-6363-2764; Xin-Jia Wang 0000-0003-2190-3199.

Ma YJ

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Ma YJ