Improved guideline compliance and textbook oncologic outcomes among patients undergoing multimodal treatment and minimally invasive surgery for locally advanced gastric cancer.

BACKGROUND: Although receipt of neoadjuvant chemotherapy has been identified to improve unfavorable survival outcomes among patients with locally advanced gastric cancer (LAGC), several randomized controlled trials have not demonstrated a difference in oncological outcomes/overall survival (OS) among patients undergoing minimally invasive surgery (MIS) versus open gastrectomy. This study aimed to investigate National Comprehensive Cancer Network (NCCN) guideline adherence and textbook oncological outcome (TOO) among patients undergoing MIS versus open surgery for LAGC. METHODS: In this cross-sectional study, patients with stage II/III LAGC (cT2-T4N0-3M0) who underwent curative-intent treatment between 2013 and 2019 were evaluated using the National Cancer Database. Multivariable analysis was performed to assess the association between surgical approach, NCCN guideline adherence, TOO, and OS. The study was registered on the International Standard Randomised Controlled Trial Number registry (registration number: ISRCTN53410429) and conducted according to the Strengthening The Reporting Of Cohort Studies in Surgery and Strengthening the Reporting of Observational Studies in Epidemiology guidelines. RESULTS: Among 13,885 patients, median age at diagnosis was 68 years (IQR, 59-76); most patients were male (n = 9887, 71.2%) and identified as White (n = 10,295, 74.1%). Patients who underwent MIS (n = 4692, 33.8%) had improved NCCN guideline adherence and TOO compared with patients who underwent open surgery (51.3% vs 43.5% and 36.7% vs 27.3%, respectively; both P < .001). Adherence to NCCN guidelines and likelihood to achieve TOO increased from 2013 to 2019 (35.6% vs 50.9% and 31.4% vs 46.4%, respectively; both P < .001). Moreover, improved median OS was observed among patients with NCCN guideline adherence and TOO undergoing MIS versus open surgery (57.3 vs 49.8 months [P = .041] and 68.4 vs 60.6 months [P = .025], respectively). CONCLUSIONS: An overall increase in guideline-adherent treatment and achievement of TOO among patients with LAGC undergoing multimodal and curative-intent treatment in the United States was observed. Adoption of minimally invasive gastrectomy may result in improved short- and long-term outcomes.

Guideline discordant care in patients with metastatic germ cell tumors.

INTRODUCTION: Despite high curability, patients with metastatic germ cell tumors (GCT) in the United States general population persistently face inferior outcomes compared with those treated in specialty referral centers. We characterized guideline discordant management in patients with metastatic GCT who experienced relapse after first-line chemotherapy and compared those who were initially treated in community practices vs. academic referral centers. PATIENTS/METHODS: Retrospective analysis of 53 patients with relapsed GCT between 2005 and 2018. First-line GCT management was assessed against the National Comprehensive Cancer Network guidelines. Guideline discordant management, predictors of discordance, and associations with outcomes were assessed. RESULTS: Of 53 patients with relapsed GCT, 34% received guideline discordant care in the first-line setting. Guideline discordant care was more prevalent in patients initially treated in community practices (12/30, 40%) vs. those initially treated in academic centers (3/22, 14%), though in multivariate logistic regression, this difference was not statistically significant (odds ratio: 4.07, P = 0.08). Most patients in community settings who received guideline discordant care were undertreated (10/12, 83%). There were 3 major reasons for guideline discordant care: (1) failure to resect residual masses after chemotherapy (27%, 4/15), (2) mismanagement of chemotherapy-related adverse events (27%, 4/15), and (3) under staging at diagnosis, resulting either insufficient chemotherapy regimen intensity (13%, 2/15) and/or inappropriately receiving primary surgical resection for metastatic disease (20%, 3/15). CONCLUSION: Under treatment was identified in nearly half of patients initially treated in a community setting who later developed relapsed GCT. Referral to specialized centers for a second opinion should be considered for all metastatic GCT patients in the first-line setting and all patients with post-chemotherapy residual disease. More effective methods should be developed to facilitate second opinions from expert centers in the United States.

Multiple Primary Tumors Originating From the Prostate and Colorectum A Clinical-Pathological and Therapeutic Challenge.

Considering that the incidence of colorectal (CRC) and prostatic cancer (PC) increases with age, metachronous and synchronous tumors can often affect the same patient. Despite the importance of this subject for the diagnosis and management of oncologic patients, in medical literature the data are scarce. The aim of the study was to evaluate the incidence and the characteristics of double/multiple primary malignant tumors (D/MPMTs) with colorectal and prostatic origin, in patients admitted to a reference hospital in West Romania. A 4-year retrospective observational study (2016-2019) was conducted by analyzing the medical records of all patients admitted in the hospital. Demographic and clinical data, as well as tumor-related parameters, were extracted. We identified 413 consecutive hospitalized patients with PC, and 21 (5%) of them also had a primary CRC. At the time of diagnosis, the mean age of the patients with PC was 71.2 ± 6 years, and 71.8 ± 10 years for patients with CRC. Synchronous PC and CRC tumors were identified in 3/21 cases and metachronous tumors in 18/21 cases. Prostate cancer was the first tumor to be diagnosed in 13/18 cases and CRC in 5/18 cases. The most frequent subtype of PC was acinar adenocarcinoma (90%) and for CRC cases, conventional adenocarcinoma (90%). Prostate and colorectal cancers tend to co-occur in a single patient. The diagnosis of one of these two types of tumors should imply the screening for the other one, because these patients require a multidisciplinary and personalized approach.

Pathology of BRCA1- and BRCA2-associated Breast Cancers: Known and Less Known Connections.

INTRODUCTION: BRCA1/BRCA2 mutation carriers indefinitely comprise a distinct group of patients with breast cancer (BC), with their tumors displaying specific pathologic characteristics. Although these connections are known, they are not fully elucidated. We therefore sought to investigate the clinicopathologic characteristics and overall survival of Greek patients with BC carrying BRCA1/BRCA2 mutations. PATIENTS AND METHODS: Greek patients with BC diagnosed between 1999 and 2016, fulfilling the National Comprehensive Cancer Network criteria for genetic testing, were analyzed for BRCA1/BRCA2 mutations by Sanger sequencing or by a 94-gene panel. Medical records and pathology reports were retrospectively reviewed to retrieve patient and tumor baseline characteristics. Potential associations with mutation status were assessed using the Fisher exact, Pearson χ2, and Mann-Whitney tests. RESULTS: Of 2096 selected patients with BC, we identified 297 (14.2%) BRCA1 and 88 (4.2%) BRCA2 carriers. The mean age at BC diagnosis was 40 and 42.6 years, respectively (P = .02). Tumor histologic subtypes in BRCA1 and BRCA2 carriers were predominantly ductal (79%) followed by medullary (10%), and ductal (72%) followed by lobular (15%), respectively. A significantly higher percentage of BRCA2 tumors were human epidermal growth factor receptor 2-positive, compared with BRCA1 tumors (21.7% vs. 5.8%; P < .001). Second primary cancer diagnosis was more frequent in BRCA1 compared with BRCA2 mutation carriers (36.2% vs. 10.7%; P < .001), whereas there was no difference in 15-year overall survival (hazard ratio, 0.92; 95% confidence interval, 0.48-1.83; P = .804) between the 2 groups. CONCLUSIONS: These data confirm established observations in the pathology of BRCA-related tumors and provide further insight on the association of rare histologic entities with mutations in these genes, which can be clinically beneficial.

Identifying Clonal Origin of Multifocal Hepatocellular Carcinoma and Its Clinical Implications.

Hepatocellular carcinoma (HCC) is characterized by high prevalence of multifocality. Multifocal HCC can arise synchronously or metachronously either from intrahepatic metastasis (IM) or multicentric occurrence (MO). To date, there have been no established criteria to accurately distinguish whether multifocal HCC originates from IM or MO. Histopathological features remain the most convenient strategy but with subjectivity and limited accuracy. Various molecular biological techniques involving assessment of TP53 mutation status, hepatitis B virus integration sites, and chromosomal alterations have been applied to determine the clonal origin. The introduction of next-generation sequencing facilitates a more comprehensive annotation of intertumor heterogeneity, resulting in more sensitive and accurate clonal discrimination. Generally, MO-HCC has better overall survival than IM-HCC after curative resection. Adjuvant antiviral treatment has been proved to decrease post-treatment recurrence probably by reducing MO-HCC recurrence, whereas adjuvant sorafenib treatment targeting prior micrometastasis failed to reduce IM-HCC recurrence. Recent studies recommended transcatheter arterial chemoembolization (TACE) and traditional Chinese medicine Huaier granule as effective adjuvant treatments probably by preventing IM and both types of recurrences respectively. Immunotherapy that inhibits immune checkpoint interaction may be an optimal choice for both MO- and IM-HCC. In the future, effective personalized therapy against multifocal HCC may be achieved.

Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study.

BACKGROUND: Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. METHODS: Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien-Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan-Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. RESULTS: The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18-2.26). CONCLUSIONS: Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.

Metachronous Peritoneal Metastases After Adjuvant Chemotherapy are Associated with Poor Outcome After Cytoreduction and HIPEC.

INTRODUCTION: Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of colorectal cancer (CRC) patients with peritoneal metastases. Patient selection is key since this treatment is associated with high morbidity. Patients with peritoneal recurrence within 1 year after previous adjuvant chemotherapy are thought to benefit less from HIPEC treatment; however, no published data are available to assist in clinical decision making. This study assessed whether peritoneal recurrence within 1 year after adjuvant chemotherapy was associated with survival after HIPEC treatment. METHODS: Peritoneal recurrence within 1 year after adjuvant chemotherapy, as well as other potentially prognostic clinical and pathological variables, were tested in univariate and multivariate analysis for correlation with primary outcomes, i.e. overall survival (OS) and disease-free survival (DFS). Two prospectively collected databases from the VU University Medical Center Amsterdam and Catherina Hospital Eindhoven containing 345 CRC patients treated with the intent of HIPEC were utilized. RESULTS: High Peritoneal Cancer Index (PCI) scores were associated with worse DFS [hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00-1.08, p = 0.040] and OS (HR 1.11, 95% CI 1.07-1.15, p < 0.001) in multivariate analysis. Furthermore, patients with peritoneal recurrence within 1 year following adjuvant chemotherapy had worse DFS (HR 2.13, 95% CI 1.26-3.61, p = 0.005) and OS (HR 2.76, 95% CI 1.45-5.27, p = 0.002) than patients who did not receive adjuvant chemotherapy or patients with peritoneal recurrence after 1 year. CONCLUSION: Peritoneal recurrence within 1 year after previous adjuvant chemotherapy, as well as high PCI scores, are associated with poor survival after cytoreduction and HIPEC. These factors should be considered in order to avoid high-morbidity treatment in patients who might not benefit from such treatment.

Identification of novel MECOM gene fusion and personalized therapeutic targets through integrative clinical sequencing in secondary acute myeloid leukemia in a patient with severe congenital neutropenia: a case report and literature review.

Severe congenital neutropenia (SCN) is a rare hematologic disorder characterized by defective myelopoiesis and a high incidence of malignant transformation to myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). SCN patients who develop MDS/AML have excessive toxicities to traditional chemotherapy, and safer therapies are needed to improve overall survival in this population. In this report, we outline the use of a prospective integrative clinical sequencing trial (PEDS-MIONCOSEQ) in a patient with SCN and AML to help identify oncogenic targets for less toxic agents. Integrative sequencing identified two somatic cis-mutations in the colony stimulating factor 3 receptor (CSF3R) gene, a p.T640N mutation in the transmembrane region and a p.Q768* truncation mutation in the cytoplasmic domain. A somatic mutation p.H105Y, in the runt homology domain (RHD) of runt-related transcription factor 1 (RUNX1), was also identified. In addition, sequencing discovered a unique in-frame EIF4A2-MECOM (MDS1 and ectopic viral integration site 1 complex) chromosomal translocation with high MECOM expression. His mutations in CSF3R served as potential targets for tyrosine kinase inhibition and therefore provided an avenue to avoid more harmful therapy. This study highlights the utility of integrative clinical sequencing in SCN patients who develop leukemia and outlines a strategy on how to approach these patients in a future clinical sequencing trial to improve historically poor outcomes. A thorough review of leukemia in SCN and the role of CSF3R mutations in oncologic therapy are provided to support a new strategy on how to approach MDS/AML in SCN.

Systematic Second-look Surgery Plus HIPEC in Patients Without Evidence of Recurrence, at High Risk of Carcinomatosis After Colorectal Cancer Resection. / Cirugía de second look más HIPEC en pacientes sin evidencia de recidiva con alto riesgo de desarrollar carcinomatosis tras resección de cáncer colorrectal.

INTRODUCTION: To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor, in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). METHODS: Between 2012-2016, 33 patients without any sign of peritoneal recurrence on imaging studies were prospectively included in the study and underwent second-look surgery aimed at treating limited PC earlier and were prospectively recorded. They were selected based on 5 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 10), synchronous ovarian metastases (n = 2), positive peritoneal cytology (n = 2), pT4 primary tumors (n = 15) and perforation (n = 4). RESULTS: PC was found and treated by cytoreduction plus HIPEC in 10 of the 33 (30.3%) patients, although it was detected in only 2/15 patients of the pT4 subgroup (13.3%). The patients without PC underwent complete abdominal exploration plus HIPEC. Median follow-up was 14.5 months. One patient died postoperatively at day 55. Severe morbidity rate (Clavien-Dindo III-V) was low (15.2%). The 3-year overall survival rate was 93% and the 3-year disease-free survival rate was 33%. Peritoneal recurrences occurred in 4 patients (12.1%), 2 of whom had macroscopic PC discovered at the second-look (20%), while the other 2 patients had no macroscopic PC (8.7%) (P = .04). CONCLUSIONS: The second look + HIPEC strategy in our series of patients at high risk of developing PC, allows its early detection and its treatment in 30.3% of cases, with a very low rate of peritoneal recurrence. It is important to continue evaluating the results to increase the accuracy of the inclusion criteria, especially the pT4 criterion that in this series has a low predictive power for the occurrence of PC.

Laparoscopic Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosisfrom Gastric Cancer: Its Beneficial Effects on Reduction and Exact Evaluation of the Peritoneal Cancer Index.

We assessed whether the laparoscopic hyperthermic intraperitoneal chemotherapy (L-HIPEC) + neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) could reduce the peritoneal cancer index (PCI; which is defined by Sugerbaker) and improve the possibility to obtain a complete cytoreductive surgery (CRS with peritonectomy; basically according to the Sugerbaker's procedure). After L-HIPEC + NIPS, the PCI score was decreased in 89.5 per cent of patients, and the average score was significantly reduced. The average PCI reduction of improved PCI cases was 10.2 ± 8.4. The hypothetical cut-off was at a PCI score of six with significant higher possibility of CRS completeness. Twelve patients had high-PCI (PCI > 6), and six of them (50.0%) were converted to low-PCI (PCI ≦ 6) and got a complete CRS. There was a significant relationship between post-PCI (PCI after L-HIPEC + NIPS) and CRS completeness; however, pre-PCI (PCI before L-HIPEC + NIPS) value was not a relevant factor. The high-PCI and increased PCI even after L-HIPEC + NIPS (deteriorated-PCI) were suggested as important risk factors for surgical completeness. Neither pre- nor postcytological results had a significant relationship between CRS completeness. However, the deteriorated cytological class was considered as a risk factor for CRS completeness. The second-look laparoscopy would be recommended for the better selection of the patients who can receive benefits by this extensive surgery.

Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy.

We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.

[Percutaneous ablation of hepatocellular carcinoma in older patients in clinical practice]. / Tratamiento percutáneo del carcinoma hepatocelular en pacientes con edad avanzada en la práctica clínica.

INTRODUCTION: A high percentage of older patients with early-stage hepatocellular carcinoma (HCC) are potential candidates for percutaneous ablation. MATERIAL AND METHODS: We prospectively assessed data from patients older than 70 years with HCC. We determined their demographic and clinical characteristics, the treatment provided and the response, complications and survival among those treated with radiofrequency ablation (RFA) and/or percutaneous ethanol injection (PEI). RESULTS: Of 194 patients with HCC, 84 were older than 70 years (43.3%). The mean age was 76.8 ± 4.5 years. Seventy-five percent were male and 91.7% had cirrhosis. Cancer was initially identified by a surveillance program in 61.9%. According to the Barcelona Clinic Liver Cancer staging system, 60.7% were classified as having early stage cancer (0-A), 19% as stage B, 12% as stage C, and 8.3% as stage D. Potentially curative initial treatment was provided in 38.2% (surgical resection in 4.8%, PEI in 22.6%, RFA in 4.8%, PEI+RFA in 6%), transarterial chemoembolization in 20.2%, and sorafenib in 3.6%. Twenty-five percent of patients were not treatment candidates and 13% refused the recommended treatment. The median follow-up after percutaneous ablation was 23 months (IQR 14.2-40.6). The mean number of sessions was 3.5 ± 2.2 for PEI and 1.8 ± 1.6 for RFA. The complications rate per session was 4%. Remission was achieved in 35.7%. The overall median survival was 45.7 months (95% CI 20.8-70.6). CONCLUSIONS: Almost half of the patients with HCC in our sample were elderly and more than half were diagnosed at an early stage. Percutaneous ablation was performed in one-third of the sample, achieving remission in 37.5%. There were few complications. Therefore, these patients should be assessed for percutaneous ablation.

Long-term survival of a patient with metachronous rectal metastasis from primary cecal cancer who underwent repetitive resection and chemotherapy: a case report.

There are few reported cases of colorectal metastasis from cancers of other organs, particularly other segments of the colon. Here we describe the long-term survival of a 68-year-old male patient with metachronous rectal metastasis from cecal cancer who underwent repetitive resection and chemotherapy. The patient underwent ileocecal resection and hepatectomy for cecal cancer with liver metastasis (T3, N1a, M1a, Stage IVA) in 2006. The patient subsequently underwent splenectomy for splenic metastasis in 2007. In August 2008, barium enema revealed compression of the rectal wall, and abdominal computed tomography (CT) detected a mass along the rectum extending into the pelvis. Rectal metastasis from cecal cancer was suspected and Hartmann's operation with bilateral seminal vesicle dissection was performed. Histological examination of the excised tumor revealed moderately differentiated adenocarcinoma formed in the muscularis propria of the rectum and infiltrating the connective tissue between the seminal vesicle and rectum. However, no tumor was detected in the rectal mucosa or submucosa. These histological findings supported the diagnosis of rectal metastasis from cecal cancer. The patient has been monitored at our clinic for 60 months after surgical removal of the rectal metastasis. The findings from this case should alert oncologists to the potential danger of rectal metastasis from primary colon cancer and the benefits of timely complete resection in terms of improved patient outcomes.

[Peritoneal carcinomatosis of colorectal origin: results of cytoreductive surgery with peritonectomy and hyperthermic intraoperative chemotherapy]. / Peritonealkarzinose kolorektalen Ursprungs : Ergebnisse der zytoreduktiven Chirurgie mit Peritonektomie und hyperthermer intraoperativer Chemotherapie.

Until recently peritoneal carcinomatosis (PC) arising from colorectal cancer (CRC) was considered to be a terminal disease manifestation. Despite palliative systemic chemotherapy (CHT) the majority of patients died within a few months. Nowadays cytoreductive surgery (CRS) of the peritoneal cavity in combination with hyperthermic intraperitoneal CHT and perioperative systemic CHT may offer a chance for long-term survival in selected groups of patients. In this study we report the results obtained with this treatment strategy in 30 consecutive patients. Data were assessed prospectively. After a median follow-up of 16.9 months the median survival time in all 30 patients reached 24.3 months. Favorable prognostic factors are a low extent of intraperitoneal metastases as characterized by a low peritoneal cancer index (median survival PCI ≤ 10: 33.2 months vs. PCI 11-19: 12.1 months) and a complete or nearly complete CRS (median survival CCR 0/1: 33.1 months vs. CCR2/3: 12.1 months). The 2-year overall survival was 89% for patients with a PCI ≤ 10 and 65% for those with surgical CCR 0/1 cytoreduction. As not every patient with CRC and PC may profit from this relatively aggressive therapy an interdisciplinary patient selection (tumor board) and treatment in experienced surgical oncology centers is recommended.

Long-term treatment of localized gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma including incidence of metachronous gastric cancer.

BACKGROUND AND AIM: According to a few recent reports on the long-term clinical outcome of gastric marginal zone B-cell mucosa associated lymphoid tissue lymphoma (MALT lymphoma); localized gastric MALT lymphoma generally has a favorable prognosis. However, the risk of metachronous gastric cancer has not been evaluated. In this study, we analyzed long-term outcomes of localized gastric MALT lymphoma including the incidence of metachronous gastric cancer. METHODS: Between April 1996 and May 2008, 60 patients (31 men and 29 women; mean age 58.1 years) with localized gastric MALT lymphoma (stage I and II(1) according to Lugano classification) were analyzed retrospectively. RESULTS: Forty-eight patients (82.6%) achieved complete remission by eradication therapy. Radiation therapy was conducted on eight patients as second-line treatment, and all of them achieved remission. The median follow-up period was 76 months (range, 12-157 months). One patient had local relapse after remission for 5 years and three patients developed early gastric cancer without recurrence of lymphoma (5%). All of the three gastric cancers appeared in the same areas where MALT lymphoma had been eradicated. CONCLUSION: Eradication therapy and radiation therapy for localized gastric MALT lymphoma have a favorable long-term outcome, though regular follow-up endoscopy should be performed for detecting metachronous early gastric cancer.

[High risk of cardiac dysfunction after treatment of secondary acute myeloid leukemia following chemotherapy and radiotherapy for breast cancer]. / Risque élevé de dysfonction cardiaque des leucémies aiguës myéloïdes secondaires à un cancer du sein.

Secondary acute myeloid leukaemia (AML) occurring after breast cancer is a rare long-term complication of the chemo- and/or radiation therapy required to treat breast cancer. The usually recognized curative option of these secondary AML includes courses of anthracycline-based chemotherapy followed by haematopoietic stem cell transplantation (HSCT). Cardiac dysfunction during AML treatment of these patients previously treated with anthracyclines for breast cancer has not been reported to date. We evaluated the evolution of cardiac function in seven patients treated with anthracyclines and/or autologous or allogeneic bone marrow transplantation for secondary AML occurring after breast cancer. All of the patients who received a cumulative anthracycline dose above the cardiac toxicity threshold developed cardiac symptoms during AML chemotherapy courses. Moreover, four of the five transplanted patients developed severe heart failure among which two were fatal. Thus, the risk of severe cardiac dysfunction after treatment of secondary AML following breast cancer must be taken in account as part of the therapeutic strategy of those patients. As discussed here, an accurate evaluation of risk factors, the use of sensitive detection tests and of cardioprotective drugs as well as that of non-cardiotoxic chemotherapy might decrease the occurrence and severity of this life-threatening complication.

Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation.

We report on a retrospective analysis examining the influence of pre-transplant serum ferritin on transplant outcomes of 99 MDS patients receiving reduced intensity conditioning (RIC) HSCT. The median pre-transplant ferritin value was 1992 ng/ml (range: 6-9580 ng/ml). No patients received iron chelation therapy preceding transplantation. On univariate analysis, there was a strong correlation between a higher pre-transplant serum ferritin (>1500 ng/ml) and a significantly inferior 3-year OS (64.6+/-7.5% vs 39.6+/-7.3%, p=0.01). However, pre-transplant serum ferritin did not influence 3-year TRM (20.2+/-7% vs 27.4+/-7%, p=0.24). There was no difference in infection-related mortality, and incidence of acute or chronic GvHD between cohorts. On multivariate analysis, a raised serum ferritin (HR: 2.00, 95% CI: 0.97-3.57, p=0.03), and the presence of >5% bone marrow blasts at time of transplantation (HR: 2.14, 95% CI: 0.84-4.58, p=0.06) were independent predictors of an inferior overall survival. However, pre-transplant serum ferritin was not a significant predictor of disease-free survival, relapse or TRM. When compared with myeloablative regimens, RIC regimens may attenuate the impact of iron overload related end-organ toxicity. Prospective studies incorporating alternative biomarkers of iron metabolism alongside serum ferritin levels are needed to improve our understanding of the significance of iron overload in MDS patients undergoing allogeneic transplantation.

Pediatric thyroid cancer arising after treatment for pleuropulmonary blastoma.

A 3-year-old female presented with a large tumor occupying the right thoracic space. Open biopsy revealed the pathological diagnosis of pleuropulmonary blastoma. After the first-line chemotherapy, the patient underwent surgical resection, then two courses of high-dose chemotherapy. Three years later, follicular carcinoma of the right thyroid lobe was found, so a right hemithyroidectomy was performed. Five months later, the thyroid tumor recurred. The remaining thyroid lobe was completely excised and radioiodine therapy was administered. The patient has remained tumor-free for 3 years. The etiology and treatment of the uncommon combination of pleuropulmonary blastoma and thyroid carcinoma is discussed.

Ewing's sarcoma as second malignant neoplasm after retinoblastoma: a case report.

OBJECTIVES: To report a case of a child with the hereditary form of unilateral retinoblastoma (RB), who developed Ewing's sarcoma of the right fibula 3 years after the enucleation of the right eye. CASE PRESENTATION AND INTERVENTION: The child was diagnosed as a case of RB of the right eye at the age of 9 months. He was fully investigated and found to have locally advanced RB with bone marrow involvement (Reese-Ellsworth stage IVA). Enucleation was recommended to the family, but they refused. The patient received chemotherapy and diode laser thermotherapy in Kuwait and the UK. He had a local relapse after 11 months and subsequently underwent enucleation of the right eye. After 3 years, he was investigated for a small swelling in his right lower leg. After extensive investigations, it was reported as Ewing's sarcoma. He was treated with chemotherapy, surgery (complete excision of the fibula) and high-dose chemotherapy followed by autologous stem cell transplantation. The child is now nearly 2 years after completing the treatment and is disease free. CONCLUSIONS: This case confirms the increased risk of a second malignant neoplasm (SMN) in children with hereditary RB. These children need a very close follow-up for the early diagnosis of SMNs or even subsequent malignancies.