Cisplatin Neoadjuvant Chemotherapy in an Aging Population With Muscle-Invasive Bladder Cancer.

Jun Gong, MD, gives his perspective on neoadjuvant chemotherapy in elderly patients with muscle-invasive bladder cancer.

Use of Neoadjuvant Chemotherapy in Elderly Patients With Muscle-Invasive Bladder Cancer: A Population-Based Study, 2006-2017.

Objectives/Introduction Neoadjuvant chemotherapy (NAC) prior to radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is associated with survival benefit across patients of all ages, yet it is not offered to many elderly patients. We aimed to evaluate age-based disparity in treatment and outcomes of MIBC. Methods Using the National Cancer Database, we identified patients with MIBC from 2006 to 2017. Use of treatment modalities was compared between age groups. A second analysis compared perioperative outcomes and overall survival (OS) in elderly patients (70 years or older) undergoing RC with NAC vs no NAC. Propensity score weighting (PSW) was used for each analysis. Results In 70,911 patients, use of NAC with RC was lower in patients 70 years or older (7.2% vs 20.9%; P < .001). In patients 70 years or older undergoing RC, NAC was associated with shorter inpatient stay (8.5 vs 9.6 days; P < .001), decreased 30-day readmission (8.6% vs 10.6%; P <.001), and lower 30- and 90-day mortality (1.5% vs 3.1%; P = .01; and 4.9% vs 7.7%; P = .003, respectively). On weighted multivariate regressions, NAC predicted shorter length of stay and lower 30-and 90-day mortality. Elderly patients receiving NAC had improved OS compared with RC alone (P = .0011, 2010-2013; P < .001, 2014-2016). Conclusions Despite increased omission of NAC in patients 70 years or older, elderly patients receiving NAC and RC had improved perioperative outcomes and OS compared with those undergoing RC alone. There may be selection bias unaccounted for with our PSW; however, our results provide compelling evidence that NAC does not compromise surgical outcomes in appropriately selected elderly patients. Patients of advanced age who are candidates for RC should be offered NAC.

Practice Patterns and Pain Outcomes for Targeted Muscle Reinnervation: An Informed Approach to Targeted Muscle Reinnervation Use in the Acute Amputation Setting.

BACKGROUND: Targeted muscle reinnervation (TMR) and regenerative peripheral nerve interface (RPNI) procedures have been shown to improve patient-reported outcomes for the treatment of symptomatic neuromas after amputation; however, the specific indications and comparative outcomes of each are unclear. The primary research questions were what complement of nerves most frequently requires secondary pain intervention after conventional amputation, whether this information can guide the focused application of TMR and RPNI to the primary amputation setting, and how the outcomes compare in both settings. METHODS: We performed a retrospective review of records for patients who had undergone lower-extremity TMR and/or RPNI at our institution. Eighty-seven procedures were performed: 59 for the secondary treatment of symptomatic neuroma pain after amputation and 28 for primary prophylaxis during amputation. We reviewed records for the amputation level, TMR and/or RPNI timing, pain scores, patient-reported resolution of nerve-related symptoms, and complications or revisions. We evaluated the relationship between the amputation level and the frequency with which each transected nerve required neurologic intervention for pain symptoms. RESULTS: The mean pain score decreased after delayed TMR or RPNI procedures from 4.3 points to 1.7 points (p < 0.001), and the mean final pain score (and standard deviation) was 1.0 ± 1.9 points at the time of follow-up for acute procedures. Symptom resolution was achieved in 92% of patients. The sciatic nerve most commonly required intervention for symptomatic neuroma above the knee, and the tibial nerve and common or superficial peroneal nerve were most problematic following transtibial amputation. None of our patients required a revision pain treatment procedure after primary TMR targeting these commonly symptomatic nerves. Failure to address the tibial nerve during a delayed procedure was associated with an increased risk of unsuccessful TMR, resulting in a revision surgical procedure (odds ratio, 26 [95% confidence interval, 1.8 to 368]; p = 0.02). CONCLUSIONS: There is a consistent pattern of symptomatic nerves that require secondary surgical intervention for the management of pain after amputation. TMR and RPNI were translated to the primary amputation setting by using this predictable pattern to devise a surgical strategy that prevents symptomatic neuroma pain. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Extranasal extranodal NK/T-cell lymphoma associated with systemic lupus erythematosus.

Increased incidence of lymphoproliferative disorders is reported in patients with autoimmune diseases, majority of which have a B-cell phenotype and are pathogenetically associated with the reactivation of Epstein-Barr virus (EBV). However, EBV-associated T/NK-cell lymphoma has hardly been reported. We present the case of a 68-year-old-woman, who had been diagnosed with systemic lupus erythematosus (SLE) 28 years back and was treated with various immunosuppressive agents including steroids, cyclophosphamide, and tacrolimus. She presented with a progressively worsening swelling of the right thigh for the last few months. Radiological examination revealed an intramuscular bulky tumor without any other lesions and the biopsy results led to a diagnosis of extranodal NK/T-cell lymphoma, nasal type (ENKL). Concurrent chemoradiotherapy resulted in a complete response, which has been sustained for more than 2 years without requiring additional therapy. After the initiation of chemotherapy, SLE did not worsen with the administration of low-dose corticosteroids. To the best of our knowledge, this is the first case report of a localized extranasal ENKL developing in a patient with SLE.

An atypical presentation of leiomyosarcoma causing extremity compartment syndrome of the crural region in a Dutch Warmblood mare: a case report.

A 12-year-old Warmblood mare was presented with an acute onset left hindlimb lameness associated with generalised soft tissue swelling of the entire limb and medial saphenous vein (MSV) thrombophlebitis. A presumptive diagnosis of extremity compartment syndrome (ECS) was made. Due to the clinical deterioration, emergency fasciotomy of the crural fascia and biopsy was performed. Histological and immunohistochemical examination of the samples confirmed a diagnosis of leiomyosarcoma likely originating from the tunica media of the MSV. This report is the first to describe an unique combination of ECS and thrombophlebitis associated with a leiomyosarcoma in a horse.

Post-Traumatic Sarcomas: Do They Exist?

Patients often cite a history of trauma prior to the diagnosis of a sarcoma. Sparse literature suggests that there may be a link between sarcoma development and trauma. A 10-year review of academic tertiary-referral sarcoma center database was examined to identify patients who developed a sarcoma after having a history of a significant musculoskeletal trauma. A total of 501 patients were treated for a sarcoma during this time period. Six patients were identified as previously having a significant musculoskeletal trauma at the site of sarcoma development. Half of the sarcomas arose in bone and the other half in soft tissue. Five (83%) patients had multiple operations for the injury with 3 (50%) patients having a postoperative wound infection. The average time from injury to development of the sarcoma was 19.8 years. Survival after diagnosis was poor, and 4 (67%) of the patients died due to their metastatic disease within 3 years of diagnosis. Our findings suggest the possibility of post-traumatic sarcomas.

Combined Sclerosing and Spindle Cell Rhabdomyosarcoma in Previous Craniotomy Site: A Case Report and a Review of the Literature.

Sclerosing rhabdomyosarcoma (RMS) is a rare subtype of RMS with unique prominent stromal hyalinization and a pseudovascular architecture. It overlaps morphologically with spindle cell RMS and poses both diagnostic and therapeutic challenges because of its rarity and aggressive clinical course. In this article, we report a case of sclerosing RMS arising from a prior craniotomy site, which demonstrated both sclerosing and spindle cell components. A literature review of RMS with sclerosing morphology identified 122 cases. Our review documents the following: sclerosing RMS occurs in both childhood and adult populations, has a predilection for the head and neck areas, and has a worse prognosis in adults. Sclerosing RMS harbors a high frequency of MYOD1 mutations, conferring a poor clinical outcome. Sclerosing RMS and spindle RMS likely represent a morphologic spectrum of one entity.

Injury promotes sarcoma development in a genetically and temporally restricted manner.

Cancer results from the accumulation of genetic mutations in a susceptible cell of origin. We and others have also shown that injury promotes sarcoma development, but how injury cooperates with genetic mutations at the earliest stages of tumor formation is not known. Here, we utilized dual recombinase technology to dissect the complex interplay of the timing of KrasG12D activation, p53 deletion, and muscle injury in sarcomagenesis using a primary mouse model of soft tissue sarcoma. When mutations in oncogenic Kras and p53 are separated by 3 weeks, few sarcomas develop without injury. However, the transformation potential of these tumor-initiating cells can be unmasked by muscle injury. In the absence of Kras mutations, injury of the muscle with global deletion of p53 results in sarcomas with amplification of chromosomal regions encompassing the Met or Yap1 gene. These findings demonstrate a complex interplay between the timing of genetic mutations and perturbations in the tumor microenvironment, which provides insight into the earliest stages of sarcoma development.

Breast Cancer in a Pectoralis Major Myocutaneous Flap Used for the Reconstruction of Tongue Cancer: A Case Report.

Breast cancers are the most common cancers in women. However, breast cancer occurring in a pectoralis major myocutaneous flap is extremely rare. This article describes a case of breast cancer occurring in such a flap used for reconstruction of the tongue in a 72-year-old woman. Follow-up computed tomogram depicted a slowly growing mass in the flap. Thirty-nine months postoperatively, a fine-needle aspiration biopsy specimen taken from the lesion suggested glandular carcinoma. The patient was diagnosed with breast cancer in the neck area of the flap and tumor excision was performed. Histologic examination of the excised tumor showed tumor cells arranged in cords, with tubular and cribriform carcinomas near the pectoral muscle with adipose tissue. The cytoplasm was abundant and eosinophilic. Thus, the patient was diagnosed with invasive ductal carcinoma in the pectoralis major flap. Sequential radiotherapy was performed to the neck with a total radiation dose of 50 Gy. Furthermore, the patient received oral anastrozole 1 mg daily as systemic adjuvant therapy for the receptor-positive breast malignancy. One year after surgery, the patient was alive with no evidence of disease. Including this case, only 2 cases of breast cancer in a pectoralis major myocutaneous flap used for reconstruction in the head and neck region have been reported.

Primary synovial sarcoma of the abdominal wall: a case report and literature review.

Synovial sarcoma (SS) is the fourth most common type of soft tissue sarcoma, following malignant fibrous histiocytoma, liposarcoma, and rhabdomyosarcoma. It usually occurs in the extremities near the large joints of middle-aged patients. We describe a case of synovial sarcoma of the anterior abdominal wall (SSAW) in an adolescent girl and undertake a review of the literature.

Epstein-Barr virus-associated smooth muscle tumors in children following solid organ transplantation: a review.

EBV-SMT are a rare entity following organ transplantation. Given the rarity of the tumor, there is no standard approach to diagnosis and treatment. A literature search identified 28 reported cases of EBV-SMT in addition to our own experience with one case. The aim of this review is to summarize the existing data regarding pathogenesis, diagnosis, and treatment.

Desmoid tumor arising from omohyoid muscle: The first report for unusual complication after transaxillary robotic thyroidectomy.

BACKGROUND: Transaxillary robotic (TAR) thyroidectomy has been performed for better aesthetic results by many surgeons. In this report, we describe a rare case of a desmoid tumor developed after TAR thyroidectomy, which is speculated to be a late-term complication. METHODS AND RESULTS: A 61-year-old woman with a history of papillary microcarcinoma had experienced a large left neck mass that had grown over 2 years. The patient underwent TAR thyroidectomy (right lobectomy and isthmectomy) via the right axilla almost 2.5 years previously. Physical examination revealed a 6-cm, firm mass fixed to the left anterior neck. The mass was fixed to the omohyoid muscle. The 5.9- × 4.7- × 4.5-cm tumor with the surrounding muscles was excised in an en bloc fashion. Pathologic examination confirmed the diagnosis of a desmoid tumor. CONCLUSION: This case suggests that desmoid tumors could develop late after TAR thyroidectomy. Thus, careful observation of the surgical wound may be necessary after TAR thyroidectomy.

Intravesical bacillus Calmette-Guérin instillation therapy for non-muscle-invasive bladder cancer following solid organ transplantation.

BACKGROUND: Solid organ recipients have a substantial risk of developing bladder cancer, with high-risk non-muscle-invasive bladder cancer (NMIBC) being the most frequent diagnosis. Theoretically, adjuvant bacillus Calmette-Guérin (BCG) therapy is contraindicated, but limited data indicate its feasibility. The objective of this study was to evaluate the safety and efficacy of BCG following solid organ transplantation. MATERIALS AND METHODS: We reviewed the data of four solid organ recipients who received adjuvant BCG for high-risk NMIBC at our institution. Additionally, individual data of 12 patients were extracted from case series and case reports, which were identified through a systematic review of the literature. A meta-analysis was performed. RESULTS: Fourteen patients (88 %) had received a kidney, one a heart, and one a liver transplant. The median time from transplantation to bladder cancer was 60.5 months. The regimen of immunosuppression was not modified in 12 patients (75 %). Forty-two percent of patients did not receive prophylactic antibiotics, and 70 % had no side effects. Ten patients (63 %) experienced recurrence after a median of 14 months. Progression to muscle-invasive or metastatic disease was observed in two patients (13 %). Four patients (25 %) underwent radical cystectomy, and two patients died of the disease. CONCLUSIONS: BCG therapy is a safe option for patients with high-risk NMIBC following solid organ transplantation. However, there is a substantial risk of recurrence and progression. Urologists and patients considering BCG therapy should be aware of this and may consider early cystectomy. There is no evidence to support the need for prophylactic antibiotics.

[Recurrent hematomas of the iliopsoas muscle after total hip replacement as a differential diagnosis for chronic groin pain: case series report]. / Rezidivierende Iliopsoaseinblutungen als Differenzialdiagnose bei Chronischen Leistenschmerzen nach Hüfttotalendoprothesenimplantation: Eine Fallserie.

BACKGROUND: Chronic and atraumatic groin pain may be due to a variety of pathologies local to and distal from the hip joint. Aside from frequent entities, such as inguinal hernia, impingement of the iliopsoas muscle by the anterior rim of the acetabular component leading to a hematoma can be a potential cause after total hip replacement (THR). MATERIAL AND METHODS: This article presents three cases of delayed groin pain after THR received due to osteoarthrosis of the hip joint several years prior to the onset of symptoms. In all three cases the patient suffered from chronic groin pain aggravated by active flexion without direct trauma. After thorough clinical, laboratory and radiological (ultrasound, x-ray, computed tomography) examination a hematoma of the iliopsoas muscle was detected. Furthermore, in all three cases the acetabular component appeared to be slightly malpositioned. Considering the least invasive procedure all cases were treated with an excavation of the hematoma. After recurrence the indications for revision of the malpositioned acetabular component were present. RESULTS: All patients clearly showed a reduction of pain after operative revision. There have been no further hematomas and the patients could be easily and rapidly remobilized. CONCLUSIONS: Persistent atraumatic groin pain connected to a deficit in hip flexion after THR needs thorough investigation by the treating physician. The differential diagnosis of a delayed hematoma due to impingement of the iliopsoas muscle is a rare but more complex entity. After careful consideration of the perioperative risks an early indication for revision of a malpositioned acetabular component is promising.

Malignant tumor formation after transplantation of short-term cultured bone marrow mesenchymal stem cells in experimental myocardial infarction and diabetic neuropathy.

RATIONALE: Bone marrow (BM)-derived mesenchymal stem cells (MSCs) hold great promise for cardiovascular cell therapy owing to their multipotency and culture expandability. OBJECTIVE: The aim of the study was to investigate whether MSCs can treat experimental acute myocardial infarction (MI) and diabetic neuropathy. METHODS AND RESULTS: We isolated mononuclear cells from mouse BM and cultured MSCs in a conventional manner. Flow cytometry analyses of these cultured cells at passage 4 showed expression of typical MSC markers such as CD44 and CD29, but not hematopoietic markers such as c-kit, flk1, and CD34. To determine the therapeutic effects of MSCs, we injected MSCs into the peri-infarct area after ligation of the left anterior descending coronary arteries of mice and, as separate experiments, injected the same batch of MSCs into hindlimb muscles of mice with diabetic neuropathy. During the follow-up at 4 to 8 weeks after cell transplantation, growing tumors were observed in 30% of hearts in the MI model, and in 46% of hindlimbs in the diabetic neuropathy model. Histological examination of the tumors revealed hypercelluarity, pleomorphic nucleoli, cytological atypia and necrosis, and positive staining for α-smooth muscle actin, indicative of malignant sarcoma with myogenic differentiation. Chromosomal analysis of these MSCs showed multiple chromosomal aberrations including fusion, fragmentation, and ring formation. CONCLUSIONS: Genetically unmodified MSCs can undergo chromosomal abnormalities even at early passages and form malignant tumors when transplanted in vivo. These results suggest that careful monitoring of chromosomal status is warranted when in vitro expanded MSCs are used for cell therapy such as for MI.