Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

Uncommon Presentation of Metastatic Squamous Cell Carcinoma of the Skin and Treatment Challenges.

BACKGROUND Squamous cell carcinoma is one of the most common keratinocytic skin cancers, the other being basal cell carcinoma. It is the second most common skin cancer after melanoma. Cutaneous squamous cell carcinoma is mostly a localized disease. The metastatic presentation is rare even in the presence of invasive disease. The metastatic potential depends on the presence of high-risk features at the time of diagnosis. Lung, liver, and bone are the frequent sites of metastasis. Local and locoregional disease undergoes excision with or without adjuvant radiation. However, we lack proper treatment paradigms for this metastatic disease. CASE REPORT We are reporting a case of an elderly female with a history of high-risk localized cutaneous squamous cell carcinoma treated with complete local excision and radiation presenting 5 years later with extensive disease to the lung and liver, abdominal nodes, and spinal fracture. The patient was not a candidate for chemotherapy due to kidney failure. On the basis of ongoing separate trials on different immunotherapies, she was started on nivolumab. CONCLUSIONS Treating metastatic cutaneous squamous cell carcinoma is a challenge considering the absence of phase III trials due to the rarity of this disease. Historically, platinum with or without 5-FU (fluorouracil), bleomycin, doxorubicin, and retinoic acid were used with variable responses. Data on epidermal growth factor receptor (EGFR) inhibitors on EGFR expressing tumors are available. However, even with the most recent reports on immunotherapy in patients with high programmed death-1 expression or high mutation burden, it is difficult to achieve good response.

Epidemiological Data on the Nutritional Status of Cancer Patients Receiving Treatment with Concomitant Chemoradiotherapy, Radiotherapy or Sequential Chemoradiotherapy to the Abdominopelvic Area.

Cancer patients are particularly susceptible to undernourishment so associated weight loss is frequent. Approximately 15% of patients lose >10% of their usual body weight, 40-80% become undernourished, and about 20% die as a result. Well-nourished patients have a higher survival rate when compared with patients at risk of undernourishment (19.9 vs. 3.7 months); hence, nutritional intervention is pivotal. Undernourishment negatively influences the patient's prognosis, and its prevalence depends on the tumor type and location, disease stage, treatment, and the applied nutritional evaluation tool. During abdominopelvic radiotherapy, up to 90% of patients experience symptoms of varying severity; weight loss during radiotherapy is an early indicator of nutritional deterioration, and he the use of radiation is associated with a higher likelihood of undernourishment. In patients with gynecological malignancies, 12.5-54% are malnourished before receiving oncological treatment, worsening after treatment in 35.8-82% of cases. There is also deterioration of the nutritional status in patients with colorectal cancer once pelvic radiotherapy is initiated, whereby 50% of cases are malnourished at the beginning of treatment, and 66.7% are so when it ends. Although there are notable differences in the impact of radiotherapy on weight according to the radiated region, 88% patients receiving abdominal radiotherapy were found to lose weight compared to 38% of patients whose treatment was limited to the pelvis.

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.

Hospital readmission rates and risk factors for readmission following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies.

BACKGROUND: Cytoreductive surgery and Hyperthermic intra-peritoneal chemotherapy (CRS/HIPEC) for peritoneal surface malignancies is associated with high morbidity. The increased numbers of patients undergoing CRS/HIPEC in recent years mandates risk analysis and quality assurance. However, only scarce data exist regarding causative parameters for readmission. The aim of this study was to assess readmission rates and risk factors associated with readmission. METHODS: A retrospective-cohort study including patients from two high-volume centers who underwent CRS/HIPEC surgery between the years 2007-2016 was performed. Patients' demographics, peri-operative data and readmission rates were recorded. RESULTS: 223 patients were included in the study. The 7 and 30-day readmission rates were 3.5% (n = 8) and 11% (n = 25), respectively. Late readmission rates (up to 90 days) were 11% (n = 25). The most common causes of readmission were surgical related infections (35%), small bowel obstruction (17.5%) and dehydration (14%). Post-operative complications were associated with higher readmission rates (p = 0.0001). PCI score was not associated with higher rates of readmission. CONCLUSION: Readmissions following CRS/HIPEC occur mainly due to infectious complications and dehydrations. Patients following CRS/HIPEC should be discharged after careful investigation to a community based continuing care with access for IV fluid replacement or antibiotics administration when required.

Allogenic Blood Transfusion Is an Independent Predictor of Poorer Peri-operative Outcomes and Reduced Long-Term Survival after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a Review of 936 Cases.

INTRODUCTION: There is a paucity of data on the impact of allogenic blood transfusion (ABT) on morbidity and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 at a high-volume institution in Sydney, Australia. Of these, 337(36%) patients required massive ABT (MABT) (≥5 units). Peri-operative complications were graded according to the Clavien-Dindo classification. The association of concomitant MABT with 21 peri-operative outcomes and overall survival (OS) was assessed using univariate and multivariate analyses. RESULTS: In-hospital mortality was 1.8%. Patients requiring MABT had more extensive disease as reflected by a higher peritoneal cancer index (≥17) (70 vs. 29%, p < 0.001) and longer operative times (≥9 h) (82 vs. 35%, p < 0.001). After accounting for confounding factors, MABT was associated with in-hospital mortality (relative risk (RR), 7.72; 95% confidence interval (CI), 1.35-10.11; p = 0.021) and grade III/IV morbidity (RR, 2.05; 95% CI, 1.42-2.95; p < 0.001). MABT was associated with an increased incidence of prolonged hospital stay (≥28 days) (RR, 1.86; 95% CI, 1.26-2.74; p = 0.002) and intensive care unit stay (≥4 days) (RR, 1.83; 95% CI, 1.24-2.70, p = 0.002). It was also associated with a significant OS in patients with colorectal cancer peritoneal carcinomatosis (RR 4.49; p < 0.001) and pseudomyxoma peritonei (RR, 4.37; p = 0.026), but not appendiceal cancer (p = 0.160). CONCLUSION: MABT is an independent predictor for poorer peri-operative outcomes including in-hospital mortality and grade III/IV morbidity. It may also compromise long-term survival, particularly in patients with colorectal cancer peritoneal carcinomatosis.

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.

Isolated limb perfusion as a treatment option for rare types of tumours.

BACKGROUND: Isolated limb perfusion (ILP) is an established and effective treatment for advanced melanoma and soft tissue sarcomas of the extremities with a high overall response rate. The aim of this study was to describe our experience of ILP for more rare types of tumours. METHODS: Patients with Merkel cell carcinoma (MCC) (n = 4), squamous cell carcinoma (SCC) (n = 2), B-cell lymphoma (n = 1), desmoid tumours (n = 3), pigmented villonodular synovitis (PVNS) (n = 1) and giant cell tumour (n = 1) were treated with ILP and analysed retrospectively. RESULTS: The four patients with in-transit MCC had three complete responses (CR) and one partial response (PR); the two patients with SCC had one CR and one stable disease (SD); the patients with desmoid tumours had two PR and one SD. A CR was also observed for the patient with a giant cell tumour, but the patient with PVNS had a SD. The patient with cutaneous metastases of B-cell lymphoma showed a CR, however with rapid systemic progression. Local toxicity according to Wieberdink was grade II in 10 patients (83%) and grade III in two patients (17%). CONCLUSIONS: These results show that ILP can be used as a treatment option also for more rare disease entities when other treatments have failed.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for gallbladder cancer: a retrospective review.

Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) often prolongs survival in patients with peritoneal surface disease, yet is generally avoided in patients with peritoneal spread from gallbladder cancer as a result of its aggressive biologic behavior. Therefore, we reviewed our experience with CRS/HIPEC for patients with gallbladder cancer. We retrospectively evaluated the outcomes of CRS/HIPEC procedures performed from 1991 to 2013 using a prospectively maintained database of 1069 procedures. Patient and tumor characteristics, morbidity, mortality, and survival were reviewed. CRS/HIPEC was performed six times in five patients with peritoneal spread from gallbladder cancer. Patients were young (age 28 to 54 years) without pre-existing comorbidities. Eighty per cent had an Eastern Cooperative Oncology Group score of 0 or 1. At CRS, organs resected included omentum (n = 4), liver (n = 3), colon (n = 2), ovaries (n = 1), and diaphragm (n = 1). A complete macroscopic cytoreduction of intraperitoneal disease was achieved in every case. Clavien graded major morbidity was 17 per cent. There was no observed mortality. Median and 3-year survival were 22.4 months and 30 per cent, respectively. CRS/HIPEC may be performed safely in patients with peritoneal dissemination from gallbladder cancer. Carefully selected patients with low-volume disease amenable to complete cytoreduction may experience a meaningful survival benefit.

[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.

Hyperthermia in the treatment of recurrent abdominal desmoid tumor.

The most suitable management of recurrent abdominal desmoid tumor is still unclear. A case of recurrent huge abdominal desmoid tumor successfully treated by hyperthermia therapy is described. A 63-year-old man was operated upon for desmoid tumor in the retroperitoneum involving pancreas, posterior wall of the stomach and transverse mesocolon in 2007. In 2008, the tumor recurred and could not be resected because of the patient refused the operation. Several therapies using tamoxifen, anastrozole, imatinib mesylate and radiotherapy were all ineffective. The tumor grew bigger and bigger during a treatment period. Finally, hyperthermia treatment was applied to the tumor. The size of the recurrent desmoid tumor reduced 75% by hyperthermia treatment for 46-month. Base on this experience, we recommend hyperthermia as the treatment for patients with recurrent abdominal desmoid tumor that several therapeutic strategies did not achieve a remarkable response.

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.

[Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy associated toxicity in treatment of peritoneal carcinomatosis]. / Toxicidad asociada a la cirugía citorreductora y quimioterapia intraperitoneal hipertérmica en el tratamiento de la carcinomatosis peritoneal.

INTRODUCTION: Peritoneal carcinomatosis is a form of intra-abdominal dissemination of several tumours, which is associated with a poor prognosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is an alternative treatment. The aim of this study is to describe the toxicity associated with this procedure in patients with peritoneal carcinomatosis. METHOD: We conducted a descriptive, retrospective, single-centre study, including all patients undergoing this procedure between December 2007 and January 2010. The following data were recorded: anthropometric data, personal and surgical events, indication, previous treatments, extent of carcinomatosis, intervention duration, hospital stay, and type of complications and/or adverse events following application of the multidisciplinary treatment. RESULTS: We performed 46 interventions on 45 patients diagnosed with peritoneal carcinomatosis from different causes, mainly ovarian cancer (83%). Paclitaxel was the most-used drug (35 interventions). There was no associated mortality, the average intervention time was 6.4 hours and the average hospital stay 7 days. We recorded adverse effects for 42 procedures, being grade 3-4 in 28.3% of the patients. The severe adverse events were: 10.9% gastrointestinal, 10.9% infectious, 6.5% haemorrhage or bleeding, 6.5% medullary toxicity, 4.4% respiratory, 2.2% coagulation and 2.2% hepatobiliary disorders. One patient developed grade III neutropaenia, probably associated with cisplatin. CONCLUSION: The morbidity and mortality is in line with the average of published studies, and has mainly been attributed to surgical complications. Toxicity data lower than other studies can be due to using more tolerable chemotherapy regimens, not including drug combinations and given that paclitaxel was the main drug.

SAR analysis of the improved resonant cavity applicator with electrical shield and water bolus for deep tumors by a 3-D FEM.

This paper discusses the improvements of the re-entrant resonant cavity applicator, such as an electromagnetic shield and a water bolus for concentrating heating energy on deep tumors in an abdominal region of the human body. From our previous study, it was found that the proposed heating system using the resonant cavity applicator, was effective for heating brain tumors and also for heating other small objects. However, when heating the abdomen with the developed applicator, undesirable areas such as the neck, arm, hip and breast were heated. Therefore, we have improved the resonant cavity applicator to overcome these problems. First, a cylindrical shield made of an aluminum alloy was installed inside the cavity. It was designed to protect non-tumorous areas from concentrated electromagnetic fields. Second, in order to concentrate heating energy on deep tumors inside the human body, a water bolus was installed around the body. Third, the length of the lower inner electrode was changed to control the heating area. In this study, to evaluate the effectiveness of the proposed methods, specific absorption rate (SAR) distributions were calculated by FEM with the 3-D anatomical human body model reconstructed from MRI images. From these results, it was confirmed that the improved heating system was effective to non-invasively heat abdominal deep tumors.

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.

Heating properties of non-invasive hyperthermia treatment for abdominal deep tumors by 3-D FEM.

This paper discusses the heating properties of a new type of hyperthermia system composed of a re-entrant type resonant cavity applicator for deep tumors of the abdominal region. In this method, a human body is placed in the gap of two inner electrodes and is non-invasively heated with electromagnetic fields stimulated in the cavity. Here, we calculated temperature distributions of a simple human abdominal phantom model that we constructed to examine the heating properties of the developed hyperthermia system. First, the proposed heating method and a simple abdominal model to calculate the temperature distribution are presented. Second, the computer simulation results of temperature distribution by 3-D FEM are presented. From these results, it was found that the proposed simple human abdominal phantom model composed of muscle, fat and lung was useful to test the heating properties of our heating method. Our heating method was also effective to non-invasively heat abdominal deep tumors.

[Therapies by focused ultrasound]. / Thérapies par ultrasons focalisés.

Many techniques of thermotherapy have emerged over the last several years in the field of oncology using different types of physical agents, including ultrasound. Only ultrasound can target deep seated lesions non-invasively without need for percutaneous probe insertion. Depending on their utilization, it is possible to select either thermal effects, in a continuous mode, at low temperature (allowing thermo-induced biological effects) or at high temperature (allowing thermoablation), or mechanical effects, in a pulsed mode, at low energy level (allowing biological effects) or at high energy levels (histotripsy). Thermoablation by focused ultrasound is now developing fast for applications in many organs. It gained a well defined role for the treatment of prostatic cancer and uterine leiomyoma but needs to be better evaluated in other organs such as the breast. Treatment of abdominal tumors must still be considered as experimental as long as problems related to acoustic interfaces (produced by ribs and gas) and movement correction are not resolved. Biological applications of focused ultrasound are currently being explored and have a great long term potential.

Combined surgery and chemoradiation as a treatment for the Buschke-Löwenstein tumour.

BACKGROUND: The Buschke-Löwenstein tumour (BLT) or giant condyloma acuminata is a rare disease which affects the anogenital region. Although histologically benign, it behaves in a malignant fashion, infiltrating the surrounding tissues. The morbidity and mortality from this tumour is high, as is the risk of recurrence following treatment. It lies on the continuum between the benign condylomata acuminata and squamous cell carcinoma. The human papillomavirus is implicated in its aetiology. Treatment is controversial, with topical chemotherapy, radiotherapy, immunotherapy and radical surgery all having been employed. Chemoradiation remains the mainstay of treatment for anal cancers but has not been routinely employed in the management of the BLT without squamous cell carcinoma transformation. METHODS: Two cases of extensive perineal BLT treated with chemoradiation and subsequent surgical excision are presented. RESULTS: The first patient had a good symptomatic response to the chemoradiation but unfortunately died of recurrent disease following surgery. The second patient had a macroscopically complete response to chemoradiation and remains well following abdominoperineal excision. CONCLUSION: Pre-operative chemoradiation has proved to be useful in management for histologically proven benign BLT

Long-term survival of a patient with widespread metastases from epithelial ovarian carcinoma receiving mind-body therapies: case report and review of the literature.

Five-year survival of patients with stage IV epithelial ovarian carcinoma not treated after recurrence is almost non-existent in oncological literature. The authors report a patient almost 30 years after surgery of the primary epithelial ovarian carcinoma lesion and 15 years after recurrent disease and incomplete chemotherapy who is alive without evidence of disease. She received no conventional oncological therapy during the past 15 years but rather used many types of alternative medicine, predominantly mind body therapies. The authors review the relevant literature on this subject and describe what they believe to be the first report of long-term survival of such a patient.