Radical resection and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of high risk recurrent retroperitoneal sarcoma-A pilot study in a tertiary Asian centre.

BACKGROUND: Peritoneal sarcomatosis (PS) is a difficult entity to treat with limited options and guarded prognosis. We aimed to determine if the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) could offer superior local recurrence-free survival in patients with retroperitoneal sarcoma at high risk of developing PS as opposed to extended resection alone. METHODS: This is a single arm, phase II intervention study where all patients with recurrent localized retroperitoneal sarcoma considered at high risk of developing PS were considered for enrolment (ClinicalTrials.gov identifier: NCT03792867). Upon enrolment, patients underwent vigorous preoperative testing to ensure fitness for the procedure. During surgery, patients underwent extended resection and HIPEC with doxorubicin. Patients were followed-up every 2 weeks (± 10 days) for the first month and subsequently every three months (± 1 month) up to a year post-surgery, and were assessed for potential chemotherapy toxicity and post-treatment complications. After a year from resection and HIPEC, patients were followed-up either during routine clinic review or contacted via telephone every year (± 1 month) for 3 years. RESULTS: Six patients were recruited but one patient dropped out due to adverse and unexpected intraoperative events. The remaining patients completed the procedure uneventfully. Post-HIPEC, all patients recurred with a disease-free interval ranging from six to 24 months. Three patients died due to complications from recurrent disease whereas the remaining three patients are alive as of their last visit. The overall survival at time at reporting ranged between 22 to 56 months. CONCLUSION: The procedure is feasible with no major morbidity to patients. However, we are unable to recommend for it to be implemented as a routine procedure at this current stage due to lack of improved survival outcomes. Further multi-institutional studies may be conducted to yield better results.

Medical grade honey for the treatment of paediatric abdominal wounds: a case series.

OBJECTIVE: Children are at high risk of injuries and wounds. The application of medical grade honey is a promising approach to improving the healing of wounds of various origin and severity. However, the use of medical grade honey in young paediatric patients remains limited. The aim of this study is to show the safety, efficacy and usefulness of medical grade honey in abdominal wounds, of different causes, in paediatric patients. METHOD: This was a prospective, observational case series evaluating five young infants with abdominal wounds at the General Hospital in Thessaloniki. All wounds were treated in the same manner with daily medical grade honey applied to the wound area and closely monitored. RESULTS: All treated wounds rapidly presented granulation tissue formation and underwent re-epithelialisation. Peripheral oedema and inflammation decreased upon initial application. Necrotic tissue was effectively debrided when present. Slough was removed and no signs of infection were detected, irrespective of initial wound presentations. Scar formation was minimal and the full range of motion was preserved in all cases. CONCLUSION: Based on this case study, medical grade honey is safe and effective in treating different abdominal wounds, including infected or dehisced wounds as well as burns. The easy application and broad applicability make medical grade honey recommendable as a first-line treatment in paediatric patients.

Malnutrition and Perioperative Nutritional Support in Retroperitoneal Sarcoma Patients: Results from a Prospective Study.

INTRODUCTION: Retroperitoneal soft tissue sarcomas (RPSs) are mesenchymal neoplasms. The prevalence of protein energetic malnutrition (PEM) and its impact in RPS patients who were candidates for surgery is unknown. MATERIALS AND METHODS: A prospective feasibility study enrolled 35 patients with primary RPS who were candidates for extended multivisceral resection. PEM was screened at enrollment. Preoperative high protein ß-hydroxy-ß-methyl butyrate oral nutritional support (ONS) was provided according to the degree of PEM. After surgery, nutritional support followed standard practice, targeting at least 1 g/kg/day protein and 20 kcal/kg/day caloric intake within the third postoperative day (POD). PEM was re-evaluated before surgery on POD 10, and at 4 and 12 months after surgery. Primary outcomes were the patient's compliance to preoperative ONS and the physician's compliance to postoperative nutritional targets. RESULTS: PEM was documented in 46% of patients at baseline; ONS met a 91% adherence (overall well tolerated). After ONS, PEM reduced to 38% (p = 0.45). The postoperative caloric target was reached on day 4.1 (standard error ± 2.7), with a protocol adherence rate of 52%. On POD 10, 91% of patients experienced PEM, the worsening of which was greater after resection of four or more organs (p = 0.06). At 4 and 12 months after surgery, almost all patients had fully recovered. A significant correlation between PEM at surgery and postoperative complications was found (p = 0.04). CONCLUSIONS: Relevant PEM prevalence in RPS is documented for the first time. PEM correlates with greater morbidity. In this setting, preoperative ONS was feasible and well-tolerated. Disease-related factors for PEM and the ideal perioperative caloric target in the context of extended multivisceral resection need to be further investigated. Nutritional support should be included in enhanced recovery after surgery programs for RPS. TRIAL REGISTRY: ClinicalTrials.gov identifier: NCT03877588.

Hospital Volume Threshold for the Treatment of Retroperitoneal Sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare, histologically heterogeneous, and anatomically complex tumors. National Comprehensive Cancer Network guidelines recommend evaluation and management by multidisciplinary teams with experience in sarcoma. Our aim was to determine an appropriate hospital volume threshold for the treatment of RPS. PATIENTS AND METHODS: Patients undergoing resection of RPS were identified from the National Cancer Data Base (1998-2012). Multivariable modeling with restricted cubic splines was employed to examine the association between hospital volume and survival and identify possible hospital volume threshold. RESULTS: The study included 5,340 patients who underwent surgery at 909 different hospitals. Median annual volume was two cases per year. After adjustment, hospital volume was associated with improved survival (p=0.01), without cutoff. The cohort was then grouped into: Low-volume (≤5 cases/year), intermediate-volume (6-10 cases/year), and high-volume (>10 cases/year). The majority of patients were treated in low-volume hospitals (86%), compared to 9% in intermediate- and 5% in high-volume centers; 44% of patients were treated in hospitals that performed one case per year. Compared to low-volume, high-volume hospitals more often had patients with high-grade and larger tumors. Adjusted 90-day mortality was significantly lower in high- vs. low-volume hospitals (odds ratio(OR)=0.25, p=0.02). With adjustment, treatment in high- vs. low-volume hospitals was associated with lower odds of margin positivity (OR=0.58, p=0.001), and improved overall survival (hazard ratio(HR)=0.61, p=0.002). CONCLUSION: Treatment of RPS in high-volume centers is associated with significant reduction in short-term mortality and improved long-term survival. Hospital volume may be a surrogate for the infrastructure and support necessary for the optimal management of these complex malignancies.

[Non-secreting paraganglioma retroperitoneal]. / Paragangliome non sécrétant rétropéritonéal: à propos d'une observation.

Non-functional retroperitoneal paragangliomas are rare tumors. They are often asymptomatic and can reach very large sizes. We report the case of a 49-year old woman with retroperitoneal tumor detected during CT scan examination performed to find the cause of non-specific abdominal pain. Malignant forms, more frequent than benign forms, show locoregional invasion and are characterized by delayed-onset metastases. The treatment of these tumors is based on the most complete degree of surgical resection, since prognosis depends on it. There is no consensus on the usefulness of complementary therapies which may nevertheless constitute a supportive treatment.

Effect of intraoperative radiotherapy in the treatment of retroperitoneal sarcoma.

BACKGROUND: Current National Comprehensive Cancer Network guidelines for the treatment of retroperitoneal sarcomas (RPS) endorse surgical resection, but the role of radiotherapy (RT) is less clear. We investigate the utilization and benefits of intraoperative RT (IORT) in the treatment of RPS. METHODS: We queried the Surveillance, Epidemiology and End Results (SEER) database (1988-2013) for the utilization of IORT and perioperative external beam RT (EBRT) in patients who underwent surgical resection of RPS. Groups were defined as any IORT (aIORT), IORT alone (IORT-), IORT with EBRT (IORT+) and preoperative and/or postoperative EBRT without IORT (EBRT). Demographics, tumor characteristics, extent of disease, and survival were compared between groups. RESULTS: We identified 908 patients with RPS who underwent surgical resection with perioperative RT. Demographics of age, sex, and race were similar between groups. There was no difference in baseline tumor characteristics of mean size, tumor grade, or histological subtype between groups. A higher percentage of patients receiving aIORT had tumors >20 cm in size, and extension beyond local tissues. Liposarcoma and leiomyosarcoma were the most common subtypes overall and in each subgroup. Patients with liposarcoma undergoing IORT and EBRT (IORT+) demonstrated a survival benefit over both IORT alone (IORT-) and EBRT alone. CONCLUSION: IORT was used infrequently for RPS but generated equivalent outcomes compared to EBRT, despite being utilized more often for larger tumors and those with peri-tumoral soft-tissue invasion. Patients with the most common subtype (liposarcoma) may benefit from combination IORT with adjuvant EBRT versus other regimens.

Repeat Cytoreductive Surgery and HIPEC for Peritoneal Surface Malignancy and Peritoneal Carcinomatosis.

BACKGROUND: Peritoneal-based malignancy (PBM), especially peritoneal carcinomatosis from gastrointestinal malignancies traditionally carries a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) have been shown to attain long median survival of 34-92 months and 5 year survival of 29-59% in patients with favorable histopathological subtypes. Recurrence after CRS and HIPEC poses a management dilemma. This paper evaluates our institution's experience with repeat CRS and HIPEC, its associated morbidity and outcomes. METHODS: One-hundred and thirty underwent CRS and HIPEC for PBM from April 2001 to June 2013. 49 had peritoneal recurrences, of which 24 had peritoneal only recurrence. 7 out of the 24 underwent a second CRS and HIPEC. RESULTS: Five females and two males with median age of 51 (37-63), underwent a second CRS and HIPEC. The primary malignancies were: 1 peritoneal mesothelioma, 3 appendiceal, 2 ovarian, and 1 colorectal cancers. Median peritoneal cancer indices for the initial and second CRS were 19 and 12, respectively. Completeness of cytoreduction score of 0 was achieved for all patients. Median hospitalization after second CRS and HIPEC was 12 days (7-60). 1 out of 7 (14%) experienced grade 3 or 4 post-operative complications. There was no 30-day or inpatient mortality. Median follow-up was 13 months (1-97). Median disease-free interval between the first CRS and HIPEC to peritoneal recurrence was 20 months (14-87). Median disease-free survival of 6 months (1-97) was achieved after the second CRS and HIPEC. Six patients remained alive without disease and one passed away with disease. Two had recurrences at 12 and 71 months after second CRS and HIPEC, 1 died and the other, still alive, went on to have a third CRS. CONCLUSION: Repeat CRS and HIPEC can achieve prolonged survival in selected patients with peritoneal-based malignancies, and can be performed with acceptable morbidity and mortality.

[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.

Percutaneous embolization of a chylous leak from thoracic duct injury in a child.

Postoperative chylous leak may result from thoracic duct injury during surgical procedures in the chest or neck and can be successfully treated with percutaneous embolization. We report the case of a child with persistent chylothorax and chyloperitoneum following multivisceral transplantation, which was performed due to unresectable inflammatory myofibroblastic tumor of the retroperitoneum. Intranodal lymphangiography was used to demonstrate the site of chylous leak from the lower segment of the thoracic duct and the leak resolved within days following percutaneous embolization of the thoracic duct.

Solitary ganglioneuromatosis of the descending colon, presenting as giant retroperitoneal tumour.

Ganglioneuroma (GN) is a benign neoplasia of the autonomous nervous system, colonic GN is uncommon in adults. There are three subgroups: polypoid GN, ganglioneuromatous polyposis and diffuse ganglioneuromatosis. Ganglioneuromatosis is highly-associated to neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2b (MEN2B). A 68-year-old female, with a discrete retarded emission of stools, was admitted for a large tumor in the left flank; CT scan, urography and barium enema demonstrated a large retroperitoneal mass, presumed as sarcoma. Open surgery discovered a 16 10 11 cm solid and encapsulated tumor, attached to the retroperitoneal descending colon, with no macroscopic mucosal involvement; the pathologic diagnosis of the resected specimen (en-bloc tumorectomy with limited colectomy) was intramural colonic ganglio-neuromatosis. Anamnesis, physical examination and complete endoscopic explorations showed no evidence of personal bearing or familial aggregation of genetic syndromes. In adults, association of transmural ganglioneuromatosis to NF1 or MEN2B is not mandatory; presentation often mimics obstructive carcinoma and positive diagnosis is provided by pathological examination of the resected specimen. In this peculiar case, the loose tissue of the retroperitoneal space favoured a slow development of intramural ganglioneuromatosis, presenting as a gigantic retroperitoneal mass with no radiological evidence of its colonic origin.

[Bloodless medical and surgical procedures for retroperitoneal neoplasm resection].

OBJECTIVE: To investigate the Bloodless Medical and Surgical Procedures for retroperitoneal neoplasm resection. METHODS: Retrospectively analyse the Bloodless Medical and Surgical Procedures during 36 retroperitoneal neoplasm resections from Beijing Shijitan Hospital Affiliated to Capital Medical University from September 2009 to December 2010, to discuss the preoperative preparation, anesthetic induction and maintainance, intraoperative monitoring and use of vasoactive drugs related experience. RESULTS: All the patients were safe during the perioperative period, without any operative and anesthetic complication. By applying the Bloodless Medical and Surgical Procedures, the intraoperative haemodynamics maintained steady, the mean hematocrit decreased from 0.368 ± 0.095 before autologous blood collection to 0.252 ± 0.032 before the ends of operation. Majority of the patients (91.7%) stop using vasoactive drugs and extubated within 1 h after operation, and return wards. CONCLUSION: Erythrocyte-raising medicine therapy and modified preservation autologous blood transfusion are important process of Bloodless Medical and Surgical Procedures.

Primitive retroperitoneal tumors. Vascular involvement--a major prognostic factor.

Primitive retroperitoneal tumors, although very rare, arouse an increased interest, because of the poor prognosis, unsatisfactory surgical and complementary therapy results. Up to now, the very low number of cases has impeded the acquisition of a unitary view of these tumors, a unanimously accepted algorithm of diagnostic and treatment being absent. Randomized trials regarding the effects of different therapies have not been possible. The main factor that can fundamentally increase the survival of these patients is radical resection, some authors even recommending compartmental surgery. We found no significant statistical difference between the survival rates of the patients with different types of non-radical interventions, that shoud be therefore, as much as possible, avoided. Our study evidences that vascular involvement is the main limiting factor in achieving radicality. The involvement of large retroperitoneal vessels makes often impossible a radical intervention, usually because of the lack of an adequate material and human endowment for ample vascular resections followed by laborious reconstructions. That is why, in our study, vascular involvement was associated with a decreased survival rate for operated patients. Therefore, we underline the necessity both of a solid material base and of establishing multidisciplinary surgical teams for adequate vascular interventions in oncologic general surgery.

Clinical considerations on the retroperitoneal liposarcomas.

AIM: It presents a clinical case of undifferentiated retroperitoneal liposarcoma with 5 years' recurrence from the first operation for the rarity of the occurrence, the problems related to surgery and complementary therapeutic approach. MATERIAL OF STUDY: Male patient aged 73 was operated for removal of retroperitoneal mass with involvement of the right kidney at the Second University of Naples in the 2003. In accordance with the interdisciplinary board, complementary therapy is not indicated and follow-up program. The successive controls were negative until at least 2007. Reoperation for recurrence in 2008 for the presence of massive bone formation occupying a large part in the right half of the abdomen at the sub-hepatic level. In both cases histological examination showed undifferentiated liposarcoma. DISCUSSION: It is of unknown etiology and only 25% occurs in well-differentiated cells are also more than 100 histological subtypes, 85% are malignant. The most affected is the male sex and from the beginning looks like malignancy. The trend of growth in general is slow, and in most cases tends to recur over time. The role of chemotherapy and radiation therapy is controversial. CONCLUSIONS: The peculiarity of our case is higher than the average survival despite advanced age and presence of recurrence. This confirms the importance of surgical treatment, thus offering the patient a chance of better long-term survival.

[Current state of neoadjuvant therapy of soft tissue sarcoma]. / Aktueller Stand der neoadjuvanten Therapie bei Weichteilsarkomen.

The treatment of soft tissue sarcoma is clinically challenging. Referral to an experienced center with an interdisciplinary team is strongly recommended. Neoadjuvant therapy, including irradiation and chemotherapy, has been applied to improve local control rates, eradicate micrometastases and assess chemosensitivity. However, the role of neoadjuvant therapy remains controversial, especially for systemic therapy, as the only available randomized trial failed to prove a benefit for survival. Nevertheless, on the basis of the current body of literature, neoadjuvant therapy can be considered on an individual basis for patients with high-risk tumors. Whenever possible, patients should be included in a clinical trial.

Changes induced by surgical and clinical factors in the pharmacology of intraperitoneal mitomycin C in 145 patients with peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated. MATERIALS AND METHODS: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined. RESULTS: The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space (p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced (p = 0.0001) drug concentrations in the plasma. CONCLUSIONS: Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics.

Multifocality in retroperitoneal sarcoma: a prognostic factor critical to surgical decision-making.

OBJECTIVE: To evaluate the significance of multifocality on overall survival (OS) in patients with retroperitoneal sarcoma (RPS) and establish a data-derived, prognostically and therapeutically useful definition of sarcomatosis. SUMMARY BACKGROUND DATA: The incidence, clinical features, and prognostic significance of multifocality in RPS is unknown. No current standardized definition for sarcomatosis is available. METHODS: We conducted a retrospective analysis of 393 patients with primary or recurrent nonmetastatic RPS treated at a comprehensive cancer center between 1996 and 2006. Baseline and treatment variables were compared in patients with unifocal and multifocal disease. A multivariate model was used to evaluate the association of multifocality and OS and identify additional prognostic factors in patients with multifocal disease. RESULTS: The median follow-up time for all patients was 69 months; 79 patients (20%) presented with multifocal disease. The 5-year OS rate was less in the multifocal group compared with the unifocal group (31% vs. 60%, respectively; P < 0.0001). After multivariate analysis, multifocality remained an independent predictor of worse OS {hazard ratio (HR) 1.7 (95% confidence interval (CI), 1.2-2.5); P = 0.004}. Additionally, patients with more tumors had significantly worse prognosis (>7 tumors, HR 2.1 (95% CI, 1.1-3.9); P = 0.03), with a 5-year OS rate of 7%. CONCLUSIONS: Multifocal RPS is associated with worse OS in patients with either primary or recurrent RPS; Patients with >7 tumors had the worst prognosis. This criterion can be used to define sarcomatosis, thereby identifying patients whose survival will ultimately depend on effective systemic therapy.

Giant retroperitoneal sarcomas.

Retroperitoneal sarcomas are rare malignant tumors, which are developing from mesenchymal stem cells residing in muscle, fat, and connective tissues. Underlying the rarity of this kind of tumors in general population, the aim of this paper is to present three cases of retroperitoneal sarcomas operated in Surgical Department of Military Hospital of Craiova (a retroperitoneal liposarcoma, a dedifferentiated liposarcoma and a malignant fibrous histiocytoma). From clinical point of view, we note the poverty of symptoms and non-specificity of these and a great tolerability of retroperitoneal space that offers the possibility for a great development of the tumor. CT-scan and MRI are the best investigations for diagnosis but surgical exploration is the best way for a good evaluation of these tumors. From histological point of view, we try to present new features about these kinds of tumors in order to classify them. Results of surgery correlated with complementary therapies were good without per-operative mortality or postoperative morbidity but we noted a recidive of one tumor (with different histological pattern) 21 months after the surgical intervention. The rarity of retroperitoneal sarcomas, combined with the vast array of histologic subtypes, has complicated our understanding of these tumors and impeded the development of effective therapies.

[Clinical practice guidelines: 2006 update of recommendations for the radiotherapeutic management of patients with soft tissue sarcoma (sarcoma of the extremity, uterine sarcoma and retroperitoneal sarcoma]. / Recommandations pour la pratique clinique: mise à jour 2006 des standards, options et recommandations pour l'irradiaton des patients adultes atteints de sarcome de tissus mous (sarcomes des membres, sarcomes rétropéritonéaux et sarcomes utérins.

CONTEXT: The National French Federation of Comprehensive Cancer Centres (FNCLCC) initiated the update of clinical practice guideline for the management of patients with soft tissue sarcoma in collaboration with the French Sarcoma Group (GSF-GETO), specialists from French public universities, general hospitals and private clinics and with the French National Cancer Institute. This work is based on the methodology developed in the "Standards, Options and Recommendations" (SOR) project. OBJECTIVES: To update SOR guidelines for the management of patients with soft tissue sarcoma previously validated in 1995. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGsaccording to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been developed, they are reviewed by independent reviewers. RESULTS: This article presents the updated recommendations for radiotherapeutic management. The main recommendations are: 1) irradiation before or after surgical treatment is the standard for soft tissue sarcoma of the extremity and uterine sarcoma; 2) no systematic irradiation should be done in case of retroperitoneal sarcoma.