Development of Desmoid Tumors After Ileorectal Anastomosis Versus Ileal Pouch-Anal Anastomosis in Familial Adenomatous Polyposis.

BACKGROUND & AIMS: Desmoid tumors (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). METHODS: We performed an international historical cohort study in patients with FAP who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal, or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. RESULTS: We analyzed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up, 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The postoperative risk was significantly higher after IPAA (P < .01) in multivariable analysis, whereas approach did not significantly influence the risk. CONCLUSIONS: The risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.

Desmoid Tumors: Current Perspective and Treatment.

OPINION STATEMENT: Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.

Radiation-induced Desmoid Tumor Development in the Radiotherapy Field in a Child With Pineoblastoma: A Case Report.

Although treatment-related secondary malignancies are rare, they are important problems after the treatment of childhood malignant diseases. Irradiation-induced sarcomas are the development of sarcoma different from the primary tumor after a latent period of ≥3 years or more in the radiotherapy field. Desmoid tumor is extremely rare as irradiation-induced tumor. A 7.5-year-old girl was referred to our hospital after a subtotal mass excision for a solid lesion with a cystic component located in the pineal gland. Pathologic examination revealed pineoblastoma. After surgery, craniospinal radiotherapy, and chemotherapy consisting of vincristine, cisplatin, and etoposide were performed. Painless swelling in the left parieto-occipital region ~75 months after the end of the treatment developed in the patient. A mass was detected in the intracranial but extra-axial region by radiologic imaging methods. Due to the total removal of the mass and the absence of a tumor in the surgical margins, she was followed up without additional treatment. The pathologic diagnosis was a desmoid tumor. She was followed up disease free for ~7 years after the primary tumor and ~7 months after the secondary tumor. Treatment-related desmoid tumor development after treatment for a central nervous system tumor in a child is extremely rare.

The Role of Radiation Therapy for Symptomatic Desmoid Tumors.

OPINION STATEMENT: Desmoid tumors have a variable clinical course that ranges from indolence or spontaneous regression to an aggressive pattern marked by local invasion. Up to half may remain stable or regress; watchful waiting is the preferred approach in the initial management of desmoid tumors. Symptomatic or progressive tumors or those that may affect adjacent critical structures require surgery, radiotherapy, or systemic therapy. Although radiotherapy effectively controls desmoid tumors in most cases, concerns regarding late toxicity exist. Definitive radiotherapy for macroscopic disease is indicated when a non-morbid complete surgical resection cannot be accomplished and provides similar control rates to surgery plus radiotherapy but avoids toxicity from combined-modality treatment (surgery and radiotherapy). Adjuvant radiotherapy can be considered for microscopically involved margins, particularly for recurrent cases or when a future recurrence may be challenging to treat. Large size, extremity site, and younger age are poor prognostic factors after radiotherapy. In the extremity, radiotherapy may have superior outcomes to surgery. Younger patients, especially children, are challenging to manage as they are at particular risk for late toxicity due to the number of potential years at risk. For patients under 20 years old, for whom a non-morbid complete resection is not possible, we recommend systemic therapy as the first line of treatment. Although the long-term efficacy of systemic therapy is unproven, this strategy allows additional time for growth and development prior to radiotherapy. In younger patients and those with axial desmoid tumors adjacent to critical organs, consideration should be given to using proton therapy as the dosimetric advantages may mitigate some of the toxicity associated with conventional radiotherapy.

Does ileoanal pouch surgery increase the risk of desmoid in patients with familial adenomatous polyposis?

PURPOSE: Patients with familial adenomatous polyposis (FAP) may undergo either ileorectal anastomosis (IRA) or ileal pouch anal anastomosis (IPAA) depending on the degree of rectal involvement. Desmoid tumors (DTs) may arise postoperatively. Whether IPAA is associated with a higher risk of DTs as compared with IRA remains controversial. The purpose of this study was to determine whether IPAA increased the risk of DTs by analyzing the published data that compared IRA and IPAA as the primary treatment for FAP. METHODS: A metaanalysis was performed to analyze the published data between 1989 and 2019. IRA and IPAA were compared with respect to the incidence of DTs. RESULTS: Eight retrospective studies with a total of 1072 patients were identified: 491 underwent IPAA and 581 IRA. There was no significant difference in the incidence of DTs between IPAA and IRA (11.81% vs. 9.47%, OR 0.95, P = 0.85). Meanwhile, the overall complication (42.97% vs. 36.76%, OR 1.32, P = 0.11), incidence of cancer (4.88% vs. 8.37%, OR 0.28, P = 0.26), and overall mortality (0.33% vs. 5.20%, OR 0.49, P = 0.53) were comparable too. CONCLUSION: Ileoanal pouch surgery is associated with similar risk of desmoid in patients with FAP after surgery.

Neuromuscular choristoma-associated desmoid-type fibromatosis: Establishing a nerve territory concept.

INTRODUCTION: Desmoid-type fibromatosis (DTF) frequently arises in patients with neuromuscular choristoma (NMC). We hypothesize that NMC-associated DTF occurs in soft tissues innervated by the NMC-affected nerve, and arises from CTNNB1-mutated (myo) fibroblasts within or directly adjacent to the NMC. MATERIALS AND METHODS: A retrospective review of patients treated at our institution was performed for patients with biopsy-confirmed diagnosis of NMC-DTF. Clinical presentation, physical examination, electrodiagnostic findings and radiological features (MR and FDG PET/CT images for each NMC-DTF) and pathologic re-review of available materials were analyzed. A literature review was also performed. RESULTS: Eight patients from our institution met the inclusion criteria. All patients presented with neuropathic symptoms and soft tissue or bone changes in the nerve territory innervated by the NMC. All MR images (N=8 cases) showed the characteristic features of NMC, and also showed direct contact between unifocal (N=5) or multifocal (N=3) DTF(s) and the NMC-affected nerve NMC. FDG PET/CT (N=2 cases) showed diffuse, increased FDG uptake along the entire affected nerve segment, contiguous with the FDG-avid DTF. In all cases, the DTFs arose in the soft tissues of the NMC-affected nerve's territory. No patient developed DTF at any other anatomic site. CONCLUSIONS: These data demonstrate that NMC-DTF arises solely within the NMC-affected nerve territory, and has direct contact with the NMC itself. Based on all these findings and the multifocality of NMC in several cases, we recommend imaging and surveillance of the entire NMC-affected nerve (from spine to distal extremity) to identify clinically-occult DTF in patients with NMC.

[A Case of Intra-Abdominal Desmoid Tumors Occuring Four Years after Open Radical Prostatectomy].

Desmoid tumor is one kind of fibromatosis, and much occurs the abdominal wall and outside the abdominal wall. Intra- abdominal desmoid tumor is rare at about 8%. We experienced a case of intra-abdominal desmoid tumors occurring 4 years after open radical prostatectomy with some literature review. A 72-year-old man had undergone open radical prostatectomy for prostate cancer. Four years after that resection, multiple intra-abdominal tumors measuring 56 mm in maximum diameter was identified on follow-up computed tomography, and he was referred to our department for management. We performed laparotomy and investigation of the biopsy. Immunohistochemistry of the resected specimen indicated the tumor cells were positive for vimentin and ß-catenin, and the diagnosis was desmoid. We performed partial resection of the small intestine and ileocecal resection. His postoperative course was uneventful and he was discharged on the 12th postoperative day. He has shown no sign of recurrence in the 4 months follow-up since surgery. In the past, an operation was the best treatment for intra-abdominal desmoid tumor. But it is reported that watchful waiting is also possible by the case which has no symptom and dysfunction in NCCN guidelines 2019. Further research is needed.

[Complex morphological (cytological, histological) diagnostics of desmoid fibroma associated with a breast implant (case report from practice).]

A rare clinical observation of desmoid fibroma associated with a breast implant is presented. When making a morphological (cytological, histological) diagnosis at the light-optical level before surgery, a differential morphological diagnosis was performed between cicatricial changes, the stromal component of the phyloid tumor and desmoid fibroma. Only immunohistochemistry allowed us to establish a diagnosis of desmoid fibroma, since tumor cells expressed diffusely SMA, focally desmin, and most importantly, ß-catenin expression was observed in some cells.

Yield of Colonoscopy in Identification of Newly Diagnosed Desmoid-Type Fibromatosis with Underlying Familial Adenomatous Polyposis.

BACKGROUND: Desmoid-type fibromatosis can arise in patients with familial adenomatous polyposis (FAP), therefore patients with desmoids often undergo colonoscopy to rule out FAP. Because finding FAP is uncommon, we sought to define subsets of desmoid patients in whom colonoscopy frequently identified FAP. METHODS: Patients with desmoid-type fibromatosis were identified from surgery and pathology databases at a single institution, and information on colonoscopy and FAP diagnosis was collected retrospectively. CTNNB1 mutation status was defined by Sanger sequencing and digital polymerase chain reaction of archived specimens. RESULTS: Among 626 patients with desmoids, 26 were diagnosed with FAP. In 20 patients, FAP diagnosis predated the desmoid diagnosis. Among patients without prior FAP diagnosis, 161 underwent colonoscopy, which identified only six cases of FAP (diagnostic yield 3.7%). Yields were substantially higher among patients with four characteristics: age < 40 years (11% yield), intra-abdominal or retroperitoneal tumors (5.4%), multifocal disease (29%), and family history (8%) (all p < 0.001). All cases of FAP were detected in patients younger than 40 years of age and with at least one of the other three characteristics. CTNNB1 mutation status was available in 82 patients with known FAP status. None of the 61 patients with CTNNB1 mutations were diagnosed with FAP, while 7 of the 21 patients with no CTNNB1 mutation detected (24%) were FAP patients. CONCLUSIONS: Patients with desmoid-type fibromatosis and undiagnosed FAP generally have multiple risk factors, which may be used to selectively recommend colonoscopic screening. Routine CTNNB1 sequencing may also rule out FAP and allow for deferral of colonoscopy.

Abnormal Presentation of Aggressive Fibromatosis After Radiotherapy for Keloids: Case Report and Brief Literature Review.

RATIONALE: Keloids, dermal fibroproliferative lesions, often occur secondary to skin injury and extend beyond the margins of the original lesion. Aggressive fibromatosis (AF) is a rare condition arising from fibroblasts and is characterized clinically as a nonmetastasizing but locally invasive tumor. In this work, we present the case of a patient who developed AF in the chest 3 years after surgery and postoperative radiotherapy for keloids. PATIENT CONCERNS: A 15-year-old female patient who underwent surgery and postoperative radiotherapy for keloids presented with AF in the chest 3 years after intervention. DIAGNOSES AND OUTCOMES: Physical examination revealed a fan-shaped scar on the manubrium sterni with a radius of 7 cm, as well as a 9 (L) × 2-cm (W) longitudinal reddish and irregularly surfaced scar arising from previous incisions. By comparing this case with similar cases reported previously, we infer that a history of exposure to radiation is the main factor that contributes to the development of AF in patients suffering from keloid scars. We also discussed the clinical characteristics of AF and treatment options and suggest factors that should be considered when using radiotherapy in patients with keloids. LESSONS: To our knowledge, this is the first reported case of AF developing in a patient after radiotherapy for keloids. Radiotherapy may be a causal factor of AF.

Desmoid-Type Fibromatosis: Who, When, and How to Treat.

OPINION STATEMENT: Desmoid-type fibromatosis is a sarcoma subtype that gathers some singular characteristics, making it a difficult challenge to face in clinical practice. Despite its excellent survival prognosis, these tumors may be unpredictable, ranging from an asymptomatic indolent course to persistent, local, and extended recurrences that significantly impair quality of life. Although surgery was initially considered the first elective treatment, collected published data during the past few years are now pointing to the "wait and see" approach as a reasonable initial strategy because many patients can live a long life with the disease without having symptoms. When symptoms appear or there is a risk of functional impairment, a wide spectrum of therapies (local and systemic) can be useful in improving symptoms and controlling the disease. Because of the low incidence of desmoid-type fibromatosis, there is scarce scientific evidence supporting any specific treatment. Nonetheless, if volumetric responses are needed, chemotherapy may be a reasonable early option. However, if long-term control of disease is desirable, hormonal therapy, NSAIDs, and TKIs are the likely treatments of choice. Recent new findings in the biologic development of these tumors, such as the role of Wnt/ß-catenin dependent pathway, have shown that the prognostic information provided by specific CTNNB1 gene mutations and other genetic profiles can lead to better methods of selecting patients as candidates for other approaches. Based on recent research, the Notch pathway inhibition in DF is one of the most promising potential targets to explore. As an orphan disease, it is mandatory that as many patients as possible be included in clinical trials.

The treatment of desmoid tumors associated with familial adenomatous polyposis: the results of a Japanese multicenter observational study.

PURPOSE: Familial adenomatous polyposis (FAP)-associated desmoid tumor (DT) is sometimes life threatening. However, the optimal treatment for DTs has not been established. The aim of this study was to analyze the outcomes of surgical and pharmacological treatments for DT in Japanese FAP patients. METHODS: We retrospectively reviewed the data of 303 patients who underwent colectomy for FAP between 2000 and 2012. We analyzed 41 patients with DTs in which the location was apparent. The selection of treatment for intra-abdominal DTs was also evaluated according to Church's classification. RESULTS: Surgery was frequently used to treat extra-abdominal DTs. Multimodal treatments, including surgery, and the administration of non-steroidal anti-inflammatory drugs, hormonal therapy, and chemotherapy were widely used for intra-abdominal DTs. The most effective pharmacological treatment was cytotoxic chemotherapy, which was associated with a response rate of 45.5% and a disease control rate of 72.7%. After a median follow-up period of 53.0 months, the 5-year DT-specific survival rate in patients with stage IV disease was 71.4%; in contrast, the rate in patients with other stages was 100%. Four-stage IV patients died of DT due to uncontrollable rapid progression. No cytotoxic chemotherapy was administered; however, incomplete resection was performed in three cases. CONCLUSION: Our findings will provide clues that may help physicians in selecting the optimal strategy for this rare disease.

[The Characteristics and Treatment Outcomes for Desmoid Tumors Associated with Familial Adenomatous Polyposis].

INTRODUCTION: The characteristics of desmoid tumors(DTs)associated with familial adenomatous polyposis(FAP)and relationships between the development of DTs and the sites of APC germline mutation have not closely been examined Japan. PATIENTS AND METHODS: This retrospective study was performed to address these issues by examining patients with FAP who underwent proctocolectomy between 1981 and 2015. RESULTS: The cumulative 2-year incidence of DT development was 50%. The DTs developed in the abdominal wall only in 2, in the abdominal wall plus intra-abdominally in 4, and intra-abdominally in 2. Clinical stages according to the Church's classification included Stage I in 3, Stage II in 2, Stage III in 1, and Stage IV in 2. Among 31 patients with a confirmed pathogenic germline APC mutation, patients with mutation in 3' site of codon 1400 (n=7)tended to develop DTs more frequently than those with mutation in 5' site of codon 1400(n=24)(p=0.08). The cumulative 5-year survival rate in patients with DT development was 73.3%. Including 2 patients undergoing initial colectomy at other institutions, the therapeutic efficacy in 4 patients with severe intraabdominal DTs(Stage III /Stage IV )who were given chemotherapy comprising doxorubicin plus dacarbazine(DOX plus DTIC)revealed partial response in 3 and complete response in 1. Febrile neutropenia was recorded in 2 of these patients. CONCLUSION: The frequency of DTs development and genotype-phenotype relationship of FAP patients seems to concur with those reported from Western countries. Since the DOX plus DTIC therapy for severe DTs is valid but toxicity is high, the development of less toxic regimens are warranted.

Intestinal perforation during chemotherapeutic treatment of intra-abdominal desmoid tumor in patients with Gardner's syndrome: report of two cases.

BACKGROUND: A minority of intra-abdominal desmoid tumors is associated with Gardner's syndrome in which desmoid tumors become an important cause of morbidity and mortality if they are surgically unresectable. CASE PRESENTATION: Here, we report two cases of intestinal perforation during chemotherapy in patients with Gardner's syndrome-associated intra-abdominal desmoids. One female and one male patients who developed inoperable desmoids were given the chemotherapeutic regimen of doxorubicin plus dacarbazine, followed by meloxicam. Significant tumor regression was observed clinically. However, intestinal perforation happened in both patients. They were subjected to emergency surgery, follow-up management, and survived up to now. CONCLUSIONS: The doxorubicin plus dacarbazine chemotherapy is an effective treatment for intra-abdominal demoid tumors in patients with Gardner's syndrome. On the other hand, given severe adverse events might occur, clinicians should pay more attention that tumor quick regression may cause intestinal perforation in which urgent surgical intervention is necessary.

Targeting the Notch pathway: A potential therapeutic approach for desmoid tumors.

BACKGROUND: Desmoid tumors (DTs) are rare mesenchymal lesions that can recur repeatedly. When it is feasible, DTs are surgically resected; however, this often results in high recurrence rates. Recently, treatment with PF-03084014, a potent γ-secretase inhibitor, has been shown to have antitumor activity in several tumor types by affecting the WNT/ß-catenin pathway. Consequently, Notch pathway inhibition by PF-03084014 might be a promising approach for DT treatment. METHODS: The expression of Notch pathway components was analyzed in DT tissues and cell strains with immunohistochemistry and Western blotting, respectively. A panel of DT cell strains was exposed to PF-03084014 and evaluated for cell proliferation. Antitumor effects were assessed via cell cycle, apoptosis, and migration and invasion analysis. Cells treated with PF-03084014 were characterized with a gene array analysis combined with Ingenuity Pathway Analysis. RESULTS: The results showed that Notch pathway components were expressed at different levels in DTs. Hes1 (Hes Family BHLH Transcription Factor 1) was overexpressed in DT tumors versus dermal scar tissue, and PF-03084014 caused significant decreases in Notch intracellular domain and Hes1 expression in DT cell strains. PF-03084014 decreased DT cell migration and invasion and also caused cell growth inhibition in DT cell strains, most likely through cell cycle arrest. Gene array analysis combined with Ingenuity Pathway Analysis showed that Wnt1-inducible signaling pathway protein 2 possibly regulated Notch and WNT pathways after treatment with PF-03084014 through integrin. CONCLUSION: Our findings suggest that the Notch pathway is an important DT therapeutic target. Furthermore, PF-03084014 has significant antitumor activity against DTs, and it may be an alternative strategy for DT treatment.

[A Case of Abdominal Wall Desmoid Tumor after Radical Nephrectomy for Renal Cancer].

A 71-year-old man with a right renal tumor underwent nephrectomy. The procedure was converted from laparoscopy to open surgery due to profound bleeding from the renal vein. Pathological diagnosis was clear cell carcinoma G2pT3b v1 ly1 INFα. Three years after surgery, a 5 cm tumor in the abdominal wall was found on computed tomography (CT). A mild uptake was shown on positron emission tomography/CT and as the tumor was located near the surgical wound, recurrence of the renal cell carcinoma was suspected. However, desmoid tumor was suggested by the pathological examination of the tumor biopsy. En-bloc resection of the mass was carried out and the pathological examination showed an array of proliferating and tangling atypical spindle-shaped tumor cells. Immunohistochemical staining of the tumor cells was positive for vimentin, but negative for CD34, c-kit, and s100. Pathological diagnosis was desmoid tumor. There has been no recurrence so far. Desmoid tumor, despite its extremely low incidence, should be considered in a postoperative neoplasm.

Risk of desmoid tumours after open and laparoscopic colectomy in patients with familial adenomatous polyposis.

BACKGROUND: Desmoid tumour (DT) is a main cause of death after prophylactic colectomy in patients with familial adenomatous polyposis (FAP). The purpose of this study was to evaluate the impact of prophylactic laparoscopic colectomy on the risk of developing DT in patients with FAP. METHODS: The database of a single institution was reviewed. Patients with classical FAP with defined genotype who underwent either open or laparoscopic colectomy between 1947 and 2011 were included in the study. The impact of various demographic and clinical features on the risk of developing DT was assessed. RESULTS: A total of 672 patients underwent prophylactic colectomy: 602 by an open and 70 by a laparoscopic approach. With a median (range) follow-up of 132 (0-516) months in the open group and 60 (12-108) months in the laparoscopic group, 98 patients (16·3 per cent) developed DT after an open procedure compared with three (4 per cent) following laparoscopic surgery. The estimated cumulative risk of developing DT at 5 years after surgery was 13·0 per cent in the open group and 4 per cent in the laparoscopic group (P = 0·042). In multivariable analysis, female sex (hazard ratio (HR) 2·18, 95 per cent confidence interval 1·40 to 3·39), adenomatous polyposis coli mutation distal to codon 1400 (HR 3·85, 1·90 to 7·80), proctocolectomy (HR 1·67, 1·06 to 2·61), open colectomy (HR 6·84, 1·96 to 23·98) and year of surgery (HR 1·04, 1·01 to 1·07) were independent risk factors for the diagnosis of DT after prophylactic surgery. CONCLUSION: Laparoscopic surgery decreased the risk of DT after prophylactic colectomy in patients with FAP.

The challenge of extraabdominal desmoid tumour management in patients with Gardner's syndrome: radiofrequency ablation, a promising option.

Desmoid tumours are benign, myofibroblastic stromal neoplasms common in Gardner's syndrome, which is a subtype of familial adenomatous polyposis characterized by colonic polyps, osteomas, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The primary treatment is surgery, followed by adjuvant radiotherapy, but the local recurrence rate is high, and wide resection can result in debilitating loss of function. We report the case of a 39-year-old man with Gardner's syndrome who had already undergone a total prophylactic colectomy. He developed desmoid tumours localized in the mesenteric root, abdominal wall and dorsal region, which were treated from 2003 through 2013 with several surgical procedures and percutaneous radiofrequency ablation. In 2008 and 2013, RFA was applied under ultrasonographic guidance to two desmoid tumours localized in the dorsal thoracic wall. The outcomes were low-grade pain and one case of superficial skin necrosis, but so far there has been no recurrence of desmoid tumours in these locations. Surgical resection remains the first-line therapy for patients with desmoid tumours, but wide resection may lead to a poor quality of life. Radiofrequency ablation is less invasive and expensive and is a possible therapeutic option for desmoid tumours in patients with Gardner's syndrome.