Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma

BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports

A core microbiome associated with the peritoneal tumors of pseudomyxoma peritonei

Pseudomyxoma peritonei (PMP) is a malignancy characterized by dissemination of mucus-secreting cells throughout the peritoneum. This disease is associated with significant morbidity and mortality and despite effective treatment options for early-stage disease, patients with PMP often relapse. Thus, there is a need for additional treatment options to reduce relapse rate and increase long-term survival. A previous study identified the presence of both typed and non-culturable bacteria associated with PMP tissue and determined that increased bacterial density was associated with more severe disease. These findings highlighted the possible role for bacteria in PMP disease. To more clearly define the bacterial communities associated with PMP disease, we employed a sequenced-based analysis to profile the bacterial populations found in PMP tumor and mucin tissue in 11 patients. Sequencing data were confirmed by in situ hybridization at multiple taxonomic depths and by culturing. A pilot clinical study was initiated to determine whether the addition of antibiotic therapy affected PMP patient outcome. We determined that the types of bacteria present are highly conserved in all PMP patients; the dominant phyla are the Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. A core set of taxon-specific sequences were found in all 11 patients; many of these sequences were classified into taxonomic groups that also contain known human pathogens. In situ hybridization directly confirmed the presence of bacteria in PMP at multiple taxonomic depths and supported our sequence-based analysis. Furthermore, culturing of PMP tissue samples allowed us to isolate 11 different bacterial strains from eight independent patients, and in vitro analysis of subset of these isolates suggests that at least some of these strains may interact with the PMP-associated mucin MUC2. Finally, we provide evidence suggesting that targeting these bacteria with antibiotic treatment may increase the survival of PMP patients. Using 16S amplicon-based sequencing, direct in situ hybridization analysis and culturing methods, we have identified numerous bacterial taxa that are consistently present in all PMP patients tested. Combined with data from a pilot clinical study, these data support the hypothesis that adding antimicrobials to the standard PMP treatment could improve PMP patient survival.https://doi.org/10.1186/1750-1172-8-10

Progresión de adenomucinosis peritoneal en el escroto de dos pacientes y tratamiento con cirugía citorreductora y quimioperfusión hipertérmica

Introduction: Disseminated Peritoneal Adenomucinosis (DPAM) is an infrequent presentation of appendiceal cancer. Infrequently, umbilical or inguinal hernias could be the first clinical manifestation of this condition; DPAM extension to the scrotum may be anatomically viable. Treatment with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the standard of treatment for DPAM. We hypothesize that these same treatment principles, consisting of CRS with hyperthermic chemoperfusion of the scrotum (HCS), could be applied to the scrotal dissemination of DPAM. Methods: We reviewed our Institution’s prospective cancer database and identified two cases of DPAM with extension to the scrotum. Their medical records were examined, and close follow-up was performed. Tumor histopathology and cytoreduction scores were evaluated. Tumor progression was monitored on follow-up by physical examination, tumor markers (CEA, CA 125, CA 19.9) and abdomino-pelvic CT scan. Results: Two patients who previously had CRS/ HIPEC for DPAM were successfully treated with HSC. Both patients are alive and free of disease at 88 and 57 months following initial CRS/HIPEC, and 50 and 32 months following CRS/HCS, respectively. Conclusion: Increased awareness by surgeons to the coexistence of inguinal hernia with peritoneal neoplasm and the need for a surgical repair is raised. CRS/HCS may be employed to treat patients with DPAM extension to the scrotum. Successful outcome is dependent on complete cytoreduction of metastatic tumor. . La CRS/HCS puede ser empleada en el tratamiento a pacientes con DPAM con extensión al escroto. Los resultados clínicos son dependientes de una citoreducción completa del tumor metastásico

Selective management of patients with neutropenic enterocolitis using peritoneal lavage

Neutropenic enterocolitis is a symptom complex of fever, abdominal pain, distention, nausea, vomiting, diarrhea, and bloody stools occurring in a patient with a low neutrophil count and is most often seen in patients with acute leukemia after a course of chemotherapy. In most cases, neutropenic entercolotis is a self-limited condition, but complications of transmural intestinal necrosis and bowel perforation may occur in a small number of patients. Surgical management should be reserved for those patients with bowel wall necrosis of perforation; however, early identification of these patients is difficult. We report our experience with the use of diagnostic peritoneal lavage in three patients with the symptoms and signs of neutropenic enterocolitis. In each case, Gram's stain of lavage fluid revealed no evidence of polymicrobial contamination of the peritoneal cavity. All three patients were managed medically, with resolution of their abdominal symptoms. Peritoneal lavage is helpful in excluding bowel perforation and avoiding unnecessary surgical intervention in patients with neutropenic enterocolitis

Management of Low-Grade Appendiceal Mucinous Neoplasm with Extensive Peritoneal Spread Diagnosed during Pregnancy: Two Case Reports and Literature Review

Background. Clinical decisions in patients with peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMN) diagnosed during pregnancy are challenging. However, their slow progression and favorable prognosis allow deferring definitive treatment until after spontaneous delivery, a reasonable period of breastfeeding, and fertility preservation. Case Presentation. Two pregnant patients were incidentally diagnosed with LAMN and extensive peritoneal spread at 20 weeks gestation and at cesarean section. Treatment with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in both cases was delayed until spontaneous delivery at term and breastfeeding in the first patient and breastfeeding and fertility preservation in the second patient. Both patients remain disease-free for over 5 years, and their children are healthy. The literature review highlights the challenges that physicians face in treating pregnant patients with stage IV appendiceal tumors. Conclusion. Pregnancy management decisions in patients with peritoneal spread from mucinous appendiceal tumor should be based on understanding the tumor biology and prognosis. Definitive treatment in pregnant patients with favorable tumors, such as LAMN, may be delayed until spontaneous delivery without compromising maternal survival

Total pelvic exenteration with or without sacral resection in patients with recurrent colorectal cancer

Pelvic recurrence from colorectal cancer produces significant morbidity. Radiation can help palliate the pain produced by this recurrence. Frequently patients with recurrent colorectal cancer will progress to a constant unrelenting pain and obstructive uropathy with sacral and bladder involvement. These patients can be candidates for an aggressive surgical resection with the hope of significant palliation and prolonged survival. From October 1988 to December 1991, six patients had total pelvic exenteration at our institution. Of these six patients, two had en bloc sacral resection at levels S1-S2 and one at S2-S3. Two patients had residual disease at the time of primary surgery, and in the other four patients, recurrence occurred 7 to 48 months after primary resection. One patient died with disease at 7 months, and five patients are alive at 9, 25, 25, 37, and 37 months since the pelvic resection; four have no evidence of disease. The present Karnofsky performance status is 80% or greater in all patients. There were no operative deaths. Of the five living patients, the survival from diagnosis of the primary lesion is 25 to 97 months. Total pelvic exenteration and abdomino-sacral exenteration can produce significant palliation and prolong survival in a selected group of patients with pelvic recurrence from colorectal cancer

Comparison of Survival in Patients with Isolated Peritoneal Carcinomatosis from Colorectal Cancer Treated with Cytoreduction and Melphalan or Mitomycin-C as Hyperthermic Intraperitoneal Chemotherapy Agent

Background. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is debated. Melphalan as a perfusion agent has also demonstrated survival benefit in other recurrent and chemoresistant malignancies. Thus, we hypothesize that melphalan as a HIPEC agent may improve overall survival (OS) and progression-free survival (PFS) in patients with PC from CRC. Methods. A retrospective review of a prospective database of 48 patients who underwent optimal CRS (CC-0/1) and HIPEC from 2001-2016 was performed. Nineteen had CRS/HIPEC with melphalan (group I) and 29 with mitomycin-C (group II). Survival was estimated using the Kaplan-Meier method. Cox regression was used for multivariate analysis. Perioperative variables were compared. Results. Mean age at CRS/HIPEC was 53±10 years. Median peritoneal cancer index (PCI) was 17 vs 13 in groups I and II, respectively (p=0.86). PCI≥20 occurred in 9 (47%) and 13 (45%) patients in groups I and II, respectively. Positive lymph nodes were identified in 8/19 (42%) vs 12/29 (41%) in groups I and II, respectively (p=0.73). Multivariate analysis identified PCI≥20 as a predictive factor of survival (HR: 7.5). Median OS in groups I and II was 36 and 28 months, respectively (p=0.54). Median PFS in groups I and II was 10 and 20 months, respectively (p=0.05). Conclusions. CRS/HIPEC with MMC had longer median PFS in PC from CRC. PCI≥20 was the only independent predictive factor for survival. Until longer follow-up is available, we recommend using MMC in CRS/HIPEC for PC from CRC. Further prospective randomized studies are necessary

Prognostic value of DNA flow cytometry in thymomas and thymic carcinomas

Thymomas are the most common anterior mediastinal masses. Malignant potential and prognosis are unrelated to histologic appearance. Deoxyribonucleic acid (DNA) flow cytometry is of prognostic significance in a variety of tumors. We reviewed the records of 35 patients who on pathologic examination had a thymoma or thymic carcinoma. Flow cytometric studies, including DNA indices (ploidy) and S phase fraction, were done on paraffin block specimens from 31 patients. We believe this is the first report of DNA flow cytometric studies in thymic pathology. Mean survival was 63.5 ± 13.3 months for patients with benign thymomas, 10.5 ± 4.6 months for patients with malignant thymomas, and 19.3 ± 4.1 months for patients with thymic carcinomas. Patients with benign thymomas lived significantly longer than those with malignant thymomas (P = .001) and thymic carcinomas (P = .03). DNA flow cytometry demonstrated four aneuploid tumors (two benign thymomas and two malignant thymomas). All thymic carcinomas were diploid. There was no statistically significant difference among the groups. The mean S phase fraction was 15.22% for benign thymomas, 11.15% for malignant thymomas, and 14.31% for thymic carcinomas. No statistically significant difference was found among the groups. We conclude that flow cytometry is not a useful guide to malignant potential or prognosis in thymomas and thymic carcinomas