Novel Therapy for Pediatric Angiosarcoma With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

The management of pediatric abdominopelvic angiosarcoma remains unclear due to limited clinical experience. Herein, we presented the first 2 pediatric patients with abdominal angiosarcoma who were treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant therapy. The first patient is alive with recurrent disease at 1-year follow-up and the second patient remains disease free after 1 year. CRS and HIPEC should be considered as a therapeutic option in the management of pediatric abdominal angiosarcomas. A multi-institutional international shared registry is needed to further evaluate the role of CRS and HIPEC in inducing remission of abdominopelvic angiosarcomas in the pediatric population.

Best practice for perioperative management of patients with cytoreductive surgery and HIPEC.

Due to the significantly improved outcome and quality of life of patients with different tumor entities after cytoreductive surgery (CRS) and HIPEC, there is an increasing number of centers performing CRS and HIPEC procedures. As this procedure is technically challenging with potential high morbidity and mortality, respectively, institutional experience also in the anesthetic and intensive care departments is essential for optimal treatment and prevention of adverse events. Clinical pathways have to be developed to achieve also good results in more comorbid patients with border line indications and extensive surgical procedures. The anesthesiologist has deal with relevant fluid, blood and protein losses, increased intraabdominal pressure, systemic hypo-/hyperthermia, and increased metabolic rate in patients undergoing cytoreductive surgery with HIPEC. It is of utmost importance to maintain or restore an adequate volume by aggressive substitution of intravenous fluids, which counteracts the increased fluid loss and venous capacitance during this procedure. Supplementary thoracic epidural analgesia, non-invasive ventilation, and physiotherapy are recommended to guarantee adequate pain therapy and postoperative extubation as well as fast-track concepts. Advanced hemodynamic monitoring is essential to help the anesthesiologist picking up information about the real-time fluid status of the patient. Preoperative preconditioning is mandatory in patients scheduled for HIPEC surgery and will result in improved outcome. Postoperatively, volume status optimization, early nutritional support, sufficient anticoagulation, and point of care coagulation management are essential. This is an extensive update on all relevant topics for anesthetists and intensivists dealing with CRS and HIPEC.

[Desmoid tumors in an adolescent girl with familial adenomatous polyposis]. / Tumeurs desmoïdes dans le cadre d'une polypose adénomateuse familiale chez une adolescente.

Desmoid tumors (DT) are rare and nonmetastasizing fibroblastic neoplasms, characterized by local invasiveness. They occur sporadically or arise in the context of familial adenomatous polyposis (FAP; 5-10% of cases). Most cases develop sporadically in young adults, but some cases also occur in children. We report the case of an adolescent girl with FAP and DT, and we discuss the therapeutic strategies. An adolescent girl with FAP underwent surgery at the age of 14 years with total proctocolectomy. She had a neo-mutation in the APC gene at codon 1068, which is not usually associated with DT. Three years later, she had painful defecations. Imaging showed two abdominal DT. After a multidisciplinary team meeting, the patient was refused for surgery, and medical treatment with antihormonal agents and nonsteroidal anti-inflammatory drugs was started. Imaging 18 months later showed DT stabilization, but the patient had difficulties to control chronic pains, which required morphine treatment, hypnotic sessions, and transcutaneous electric nerve stimulation. This case highlights the importance of DT screening in patients with FAP, mainly after surgery, regardless of their age and genetic mutation. Progress remains to be made in determining DT risk factors and in developing treatment. DT are still difficult to cure because of their potential for local invasion and local recurrence, and need to be managed by a multidisciplinary team.

Outcomes with cytoreductive surgery and HIPEC for peritoneal metastasis.

Peritoneal metastasis (PM) has traditionally been approached with therapeutic nihilism. The evolution of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) over the last two decades, however, has caused a paradigm shift in treatment for PM. This modality is rapidly gaining acceptance as standard of care for PM from various cancers. This article reviews the current literature regarding the use of CRS/HIPEC for PM from the most common intra-abdominal malignancies.

[Operative therapy of abdominal and retroperitoneal sarcoma]. / Operative Therapie der abdominellen und retroperitonealen Sarkome.

Retroperitoneal soft tissue sarcomas are characterized by a high rate of local recurrence. Complete tumor resection is the only potentially curative therapeutic option. The concept of a systematic compartmental resection is to remove the tumor en bloc with a margin of uninvolved tissue and organs. This is frequently only achieved by multivisceral resection which often includes kidney, colon, pancreas and parts of the diaphragm or the psoas muscle. The adoption of such a policy of multivisceral organ resection improves the proportion of curative resections and, ultimately, results in lower local recurrence rates. The present article comprehensively describes the operative procedures, perioperative treatment and the oncological results of surgery for retroperitoneal sarcomas. The role of surgery in oncological treatment plans and the importance of specialized centres are outlined in detail.

[Multimodal management in soft tissue sarcoma of the trunk and extremities]. / Multimodales Management bei Weichteilsarkomen des Stammes und der Extremitäten.

Soft tissue sarcoma (STS) is a rare, extremely heterogeneous group of malignant tumors of mesodermal origin. With an incidence of 1-5 per 100,000/year they account for only 1 % of all human malignancies. The STSs occur predominantly in the lower extremities and the trunk. To date 100 different histopathological subentities can be defined. The prognosis varies substantially depending on the localization and histology. Whereas local recurrence rates and overall survival of sarcomas of the extremities have benefited from the introduction of multimodal therapies, only marginal progress has been made in the management of trunk STSs. This manuscript gives an overview of preoperative diagnostics, pathology and neoadjuvant as well as adjuvant therapeutic options for soft tissue sarcoma.

Intraperitoneal chemotherapy for peritoneal surface malignancy: experience with 1,000 patients.

BACKGROUND: Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we use cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A prospective database of patients has been maintained since 1992. Patients with biopsy-proven peritoneal surface disease were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (Eastern Cooperative Oncology Group), resection status, and peritoneal surface disease were classified according to primary site. Univariate and multivariate analyses were performed. The experience was divided into quintiles and outcomes compared. RESULTS: Between 1991 and 2013, a total of 1,000 patients underwent 1,097 HIPEC procedures. Mean age was 52.9 years and 53.1% were female. Primary tumor site was appendix in 472 (47.2%), colorectal in 248 (24.8%), mesothelioma in 72 (7.2%), ovary in 69 (6.9%), gastric in 46 (4.6%), and other in 97 (9.7%). Thirty-day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival was 29.4 months, with a 5-year survival rate of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p ≤ 0.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p = 0.04). For the 5 quintiles, the 1- and 5-year survival rates, as well as the complete cytoreduction score (R0, R1, R2a) have increased, and transfusions, stoma creations, and complications have all decreased significantly (p < .001 for all). CONCLUSIONS: This largest reported single-center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data show that outcomes have improved over time, with more complete cytoreduction and fewer serious complications, transfusions, and stomas. This was due to better patient selection and increased operative experience. Cytoreductive surgery with HIPEC represents a substantial improvement in outcomes compared with historical series, and shows that meaningful long-term survival is possible for selected carcinomatosis patients. Multi-institutional cooperative trials are needed to refine the use of CS and HIPEC.

Updates on the multimodality management of desmoplastic small round cell tumor.

Desmoplastic Small Round Cell Tumor (DSRCT) is a rare and an aggressive malignancy with poor outcome. This tumor can co-express epithelial, neural, and mesenchymal markers. The molecular hallmark of DSRCT is the EWS-WT1 fusion protein. Despite the diversities in treatment modality, the best results have been seen with radical surgery and adjuvant or neoadjuvant chemotherapy.

Successful treatment of a patient with HER2-positive metastatic gastric cancer with third-line combination therapy with irinotecan, 5-fluorouracil, leucovorin and trastuzumab (FOLFIRI-T).

BACKGROUND: For patients with HER2-overexpressing gastric cancer, there is an improved prognosis with additional trastuzumab to chemotherapy with a platinum compound and a fluoropyrimidin in first-line therapy. Second-line combinations are currently evaluated in various studies. CASE REPORT: We report the case of a 43-year-old male patient who came to our hospital with recurrent metastatic gastric cancer after curative surgery 18 months before. His disease responded well to several therapeutic regimens. Firstline chemotherapy with a combination of epirubicin, oxaliplatin and capecitabine (EOX) and the following therapies -- peritonectomy, multivisceral resection, hyperthermic intraperitoneal chemotherapy (HIPEC), and secondline chemotherapy with oxaliplatin, 5-fluorouracil and leucovorin (FLO) - induced a complete remission. At the time of the subsequent progression, HER2 overexpression was detected. We administered the combination of irinotecan, 5-fluorouracil, leucovorin (FOLFIRI) and trastuzumab, which to our knowledge was used for the first time in a patient with metastatic gastric cancer in third-line therapy. This regimen again induced a complete remission of the disease, which has been sustained now for at least 8 months. CONCLUSION: This is the first time in the literature that a combination of FOLFIRI and trastuzumab (FOLFIRIT) was used successfully in a patient with recurrent metastatic gastric cancer.

The diagnosis and management of desmoplastic small round cell tumor: a review.

PURPOSE OF REVIEW: Desmoplastic small round cell tumor (DSRCT) is a rare disease of children, adolescents and young adults, which begins in the abdominal cavity. Less than 200 cases are reported in the world literature. Because of the rarity of this disease, little is known about optimal treatment. Patients may present with dozens to hundreds of tumors studding the peritoneal cavity. Despite this presentation, it is not primarily considered metastatic but multifocal. It can metastasize to the liver or lung. Chemotherapy, radiotherapy, and surgical approaches have not been standardized. Neoadjuvant chemotherapy often yields a partial response; however, tumors may remain surgically un-resectable. An aggressive approach to treatment is required to maximize long-term remission. This review is designed to outline the evidence-based multidisciplinary approach to DSRCT. RECENT FINDINGS: Complete surgical resection, including 1-2 mm implants, is necessary to achieve long-term disease control. Hyperthermic intraperitoneal chemotherapy using cisplatin has recently been found to be a low morbidity treatment option for DSRCT patients. Yttrium microspheres have been used successfully to treat liver metastasis from DSRCT. SUMMARY: DSRCT is a rare tumor that requires a multidisciplinary approach which includes aggressive surgical extirpation to provide long-term disease control.

Treatment recommendations for primary extradural meningiomas.

Primary extradural meningiomas (PEMs) represent about 2% of all meningiomas and are often encountered by non-neurosurgeons. These lesions typically present as enlarging, painless, benign masses that can be surgically cured. Imaging is critical for defining involvement of adjacent structures; however, diagnosis depends on classic histologic patterns. Treatment for benign PEMs (WHO I) consists of resection with wide margins, whereas adjuvant therapy after resection of atypical (WHO II) or malignant (WHO III) PEMs should be considered. By using the collective experience from our comprehensive cancer center, including neuro-oncologists, neuroradiologists, and neurosurgeons, in addition to a complete literature review, the authors have established treatment guidelines not previously reported. This manuscript describes key features of these challenging tumors to aid in diagnosis, presents the largest published review of all reported PEMs (n = 163), and provides salient treatment guidelines to surgeons unfamiliar with these challenging tumors.

Desmoplastic small round-cell tumor: an adult with previous exposure to agent orange.

Desmoplastic small round-cell tumor is an uncommon, highly aggressive tumor with a predilection for pediatric age groups and young adults. It is very unusual in the elderly population. Although Agent Orange has been associated with soft-tissue sarcoma, an association with desmoplastic small round-cell tumor has not been reported. A 52-year-old male presented with abdominal distention, dyspnea, and a 9 kg weight loss. Prior history was significant for hepatitis C and diabetes. He was a Vietnam veteran and he admitted being exposed to Agent Orange. On physical examination, the abdomen was distended and tense. Computed tomography scan of the chest, abdomen and pelvis demonstrated extensive mediastinal and retroperitoneal adenopathy, diffuse omental masses and extensive pleural, intra-abdominal and pelvic ascites. Omental core needle biopsy was consistent with desmoplastic small round-cell tumor based on morphology and immunohistochemistry. He responded poorly to chemotherapy with high-dose cyclophosphamide, doxorubicin and vincristine and died 5 months after presentation secondary to neutropenic sepsis despite G-CSF support and antibiotics.

Effects of supportive-expressive group therapy on pain in women with metastatic breast cancer.

OBJECTIVE: To examine whether a group intervention including hypnosis can reduce cancer pain and trait hypnotizability would moderate these effects. DESIGN: This randomized clinical trial examined the effects of group therapy with hypnosis (supportive-expressive group therapy) plus education compared to an education-only control condition on pain over 12 months among 124 women with metastatic breast cancer. MAIN OUTCOME MEASURES: Pain and suffering, frequency of pain, and degree of constant pain were assessed at baseline and 4-month intervals. Those in the treatment group also reported on their experiences using the hypnosis exercises. RESULTS: Intention-to-treat analyses indicated that the intervention resulted in significantly less increase in the intensity of pain and suffering over time, compared to the education-only group, but had no significant effects on the frequency of pain episodes or amount of constant pain, and there was no interaction of the intervention with hypnotizability. Within the intervention group, highly hypnotizable participants, compared to those less hypnotizable, reported greater benefits from hypnosis, employed self-hypnosis more often outside of group, and used it to manage other symptoms in addition to pain. CONCLUSION: These results augment the growing literature supporting the use of hypnosis as an adjunctive treatment for medical patients experiencing pain.

The consensus statement on the locoregional treatment of abdominal sarcomatosis.

Abdominal sarcomatosis (AS) is a rare condition characterized by soft tissue sarcoma spreading throughout the abdomen, in the absence of extra-abdominal dissemination. Retroperitoneal sarcomas, pelvic sarcomas, particularly uterine leiomyosarcoma, and gastrointestinal stromal tumors (GISTs) most frequently give rise to AS. Systemic chemotherapy is the standard of care for AS from non-GIST sarcomas, but with an essentially palliative aim and major limitations. Innovative targeted therapies has deeply affected the natural history of GIST, at least in prolonging significantly survival in responsive patients. In this context, the notion that abdominal spread in the lack of extra-peritoneal lesions may typically occur in a number of patients, along with the dismal prognosis generally carried by AS, has prompted a few centers to perform cytoreductive surgery and perioperative intraperitoneal chemotherapy. To date, the rarity of these presentations makes it difficult to evaluate the clinical results and the role of combined local-regional treatment is still a matter of debate. This article presents the results of a group of experts from around the World trying to achieve a consensus statement in AS comprehensive management. A questionnaire was placed on the website of the 5th International Workshop on Peritoneal Surface Malignancy and the experts voted via internet.

Continuous hyperthermic peritoneal perfusion for desmoplastic small round cell tumor.

Desmoplastic small round cell tumor (DSRCT) is a rare disease of children, adolescents, and young adults that begins and spreads on the peritoneal surfaces. Desmoplastic small round cell tumor usually presents with diffuse abdominal metastatic disease similar in gross appearance to carcinomatosis. To date, very aggressive treatment programs have yielded dismal outcomes. Here we present 2 cases of DSRCT that were treated with aggressive surgical excision followed by intraoperative continuous hyperthermic peritoneal perfusion using cisplatin. These are the first pediatric case reports of DSRCT being treated with continuous hyperthermic peritoneal perfusion, a procedure usually used in treatment of adult carcinomatosis.

Instillation of taurolidine/heparin after laparotomy reduces intraperitoneal tumour growth in a colon cancer rat model.

OBJECTIVE: To investigate whether irrigation of the abdominal cavity after laparotomy for caecum resection with taurolidine/heparin or adhesion prophylactic substances reduces intraperitoneal tumour growth or the local recurrence rate in a colon carcinoma rat model. METHODS: 60 BDIX rats underwent caecum resection after intraperitoneal inoculation of 1 x 10(4) colon carcinoma cells (DHD/K12/TRb). Intergel, Interceed, taurolidine/heparin or NaCl 0.9% were intraperitoneally applied after randomisation. Finally, the total number and total weight of intraperitoneal metastases were determined as well as the adhesion score according to Moreno. Metastatic tissue was examined histologically and immunohistochemically (E-cadherin, CD44, beta(1)-integrin). RESULTS: Taurolidine/heparin significantly reduced not only the total number (3 vs. 11 in the control group) but also the total weight (65 vs. 330 mg) of intraperitoneal metastases in comparison to the control group (p = 0.003 and p = 0.005). E-Cadherin expression in the metastatic tissue of animals treated with taurolidine/heparin was significantly decreased (p = 0.016). CONCLUSION: Taurolidine/heparin effectively reduces intraperitoneal tumour growth when used as an intraoperative lavage. These results represent a good rationale for intraoperative adjuvant irrigation with taurolidine/heparin during resection of colon cancer.

[Intraoperative therapeutic intensification techniques in locally advanced abdominal sarcomas]. / Intensificación terapéutica intraoperatoria en el tratamiento de los sarcomas abdominales localmente avanzados.

INTRODUCTION: Sarcomas are rare tumors that develop from mesenchymal cells. Their management is difficult due to their changing histology, location, and behavior. In this article, we discuss the use of two intraoperative therapeutic intensification techniques, intraoperative radiotherapy (IORT) and hyperthermic intraoperative intraperitoneal chemotherapy (HIIC), in the treatment of locally advanced abdominal sarcomas and peritoneal sarcomatosis. MATERIAL AND METHODS: We analyzed a series of 20 consecutive patients diagnosed with advanced abdominal sarcoma and 5 patients with a diagnosis of peritoneal sarcomatosis who were evaluated and treated in our department from December 1996 to October 2005. In advanced abdominal sarcoma, we performed complete or maximal resection followed by IORT. In peritoneal sarcomatosis we performed massive cytoreduction followed by HIIC. RESULTS: The survival rate in advanced abdominal sarcomas without sarcomatosis was 65% at 26 months. Among the 5 patients diagnosed with peritoneal sarcomatosis, 3 were alive, and 2 were without recurrence at 20 months of follow-up. CONCLUSIONS: IORT associated with radical surgery seems to improve local control and survival in advanced abdominal sarcomas. Maximal cytoreduction plus HIIC used as treatment of peritoneal sarcomatosis is a feasible technique that offers a therapeutic option with curative intent.

Combined resection and multi-agent adjuvant chemotherapy for desmoplastic small round cell tumor arising in the abdominal cavity: report of a case.

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.

Hyperthermic intraperitoneal intraoperative chemotherapy after cytoreductive surgery for the treatment of abdominal sarcomatosis: clinical outcome and prognostic factors in 60 consecutive patients.

BACKGROUND: Abdominal sarcomatosis is a rare nosologic entity with a poor prognosis. After a Phase I study on cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy (HIIC), the authors reported the results of the treatment of 60 patients using this novel multimodal approach. METHODS: Twenty-nine patients had multifocal primary disease and 31 patients had recurrent abdominal sarcoma. Tumor histology was represented by visceral (n = 26 [43%]) and retroperitoneal (n = 34 [57%]) sarcoma. All patients underwent cytoreductive surgery (with no or minimal residual disease) and 90-minute HIIC with doxorubicin (15.25 mg/L of perfusate) and cisplatin (43 mg/L). The clinical outcome and the prognostic value of 11 clinicopathologic variables were analyzed. RESULTS: No postoperative deaths occurred. The morbidity rate was 33% and the moderate to severe locoregional toxicity rate was 15%. The median time to local disease progression and the median overall survival were 22 months and 34 months, respectively. Using multivariate analysis, histologic grading and completeness of surgical cytoreduction predicted patient prognosis, indicating that both local progression-free and overall survival were affected significantly by tumor aggressiveness and local disease control. CONCLUSIONS: Although these results were encouraging, there was no definitive conclusion reached regarding the therapeutic activity of this locoregional treatment. In addition, the toxicity rate was substantial. In the absence of effective systemic agents, the therapeutic potential of cytoreductive surgery plus HIIC should be explored further in comparative trials.