Treatment of Peritoneal Metastasis with Pressurized Intraperitoneal Aerosol Chemotherapy: Results from the Prospective PIPAC-OPC2 Study.

BACKGROUND: Pressurized Intraperitoneal Aerosol chemotherapy (PIPAC) is a local treatment for peritoneal metastasis (PM). Prospective data are scarce and evaluation of treatment response remains difficult. This study evaluated the use of the Peritoneal Regression Grading score (PRGS) and its prognostic value. PATIENTS AND METHODS: This was a prospective, controlled phase II trial in patients with PM from gastrointestinal, gynaecological, hepatopancreatobiliary, primary peritoneal, or unknown primary cancer. Patients in performance status 0-1, with a non-obstructed gastrointestinal tract, and a maximum of one extraperitoneal metastasis were eligible. Colorectal or appendiceal PM had PIPAC with oxaliplatin, other primaries had PIPAC with cisplatin and doxorubicin. Biopsies were taken at each PIPAC and evaluated using the PRGS. Quality-of-life questionnaires were reported at baseline and after three PIPACs. RESULTS: One hundred ten patients were treated with 336 PIPACs (median 3, range 1-12). One hundred patients had prior palliative chemotherapy and 45 patients received bidirectional treatment. Complete or major histological response to treatment (PRGS 1-2) was observed in 38 patients (61%) who had three PIPACs, which was the only independent prognostic factor in a multivariate analysis. The median overall survival (mOS) from PIPAC 1 was 10 months, while patients with PM from gastric, colorectal, and pancreatic cancer had a mOS of 7.4, 16.7, and 8.2 months, respectively. Global health scores were significantly reduced, but patients were less fatigued, nauseated, constipated, and had better appetite after three PIPACs. CONCLUSIONS: PIPAC with oxaliplatin or cisplatin and doxorubicin was able to induce a major or complete histological response during three PIPACs, which may provide significant prognostic information, both at baseline and after treatment.

Feasibility and Safety of Laparoscopic D2 Gastrectomy in Combination with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients with Gastric Cancer at High Risk of Recurrence-The PIPAC-OPC4 Study.

BACKGROUND: Patients with gastric adenocarcinoma (GAC) are at high risk of peritoneal recurrence despite perioperative chemotherapy and radical resection. This study evaluated feasibility and safety of laparoscopic D2 gastrectomy in combination with pressurized intraperitoneal aerosol chemotherapy (PIPAC). METHODS: This was a prospective, controlled bi-institutional study in patients with GAC at high risk of recurrence treated with PIPAC with cisplatin and doxorubicin (PIPAC C/D) after laparoscopic D2 gastrectomy. High risk was defined as a poorly cohesive subtype with predominance of signet-ring cells, clinical stage ≥ T3 and/or ≥ N2, or positive peritoneal cytology. Peritoneal lavage fluid was collected before and after resection. Cisplatin (10.5 mg/m2) and doxorubicin (2.1 mg/m2) were aerosolized after anastomosis (flow 0.5-0.8 ml/s, maximum pressure 300 PSI). Treatment was feasible and safe if ≤ 20% had Dindo-Clavien ≥ 3b surgical complications or CTCAE ≥ 4 medical adverse events within 30 days. Secondary outcomes were length of stay (LOS), peritoneal lavage cytology, and completion of postoperative systemic chemotherapy. RESULTS: Twenty-one patients were treated with a D2 gastrectomy and PIPAC C/D. The median age was 61 years (range 24-76), there were eleven female patients, and 20 patients had preoperative chemotherapy. There was no mortality. Two patients had grade 3b complications that were potentially related to PIPAC C/D (one anastomotic leakage, and one late duodenal blow-out). One patient had severe neutropenia, and nine patients had moderate pain. The LOS was 6 days (4-26). One patient had positive peritoneal lavage cytology before resection, and none were positive after. Fifteen patients had postoperative chemotherapy. CONCLUSIONS: Laparoscopic D2 gastrectomy in combination with PIPAC C/D is feasible and safe.

The role of home visits by a nurse to improve palliation in patients treated with self-expandable metallic stents due to incurable esophageal cancer.

Self-expandable metallic stent (SEMS) is a preferred option to relieve dysphagia and to palliate patients with incurable esophageal or gastro-esophageal junction (GEJ) cancer. Health Related Quality of Life (QoL) represents a clinically relevant outcome measure in research focused on palliation of patients with advanced GI cancer. In this context, home visits by a nurse carry the potential to offer important advantages. Eighty patients with incurable esophageal or GEJ cancer were randomized to either standard follow up or to an intervention containing regular home visits by a nurse. The primary outcome variable QoL was assessed by EORTC QLQ-C30 and OES-18 before insertion of SEMS, and at 2, 7 and 12 weeks thereafter. Secondary outcomes were; need for re-interventions, number of patients receiving palliative oncological therapy and overall survival. Sixty-six males and 13 females, with a median age of 71, were included. Self-reported overall QoL was significantly higher in the intervention group (P = 0.03). The organ specific module OES-18 revealed a significant reduction in dysphagia by the intervention (P = 0.03) as well as fewer eating disabilities (P = 0.04). No differences were observed in secondary outcomes except for overall survival, where the median survival was increased from 114 to 183 days by the active intervention (P = 0.02). Home visits by a nurse seem to play an important palliative role after placement of SEMS in patients with incurable esophageal or GEJ cancer by improving QoL and may carry the potential to increase overall survival.

Phase II randomized clinical trial of endosonography and PET/CT versus clinical assessment only for follow-up after surgery for upper gastrointestinal cancer (EUFURO study).

BACKGROUND: Upper gastrointestinal malignancies have a poor prognosis. There is no consensus on how patients should be followed after surgery. The authors hypothesized that a structured follow-up programme including endoscopic ultrasonography (EUS) and [18 F]fluorodeoxyglucose (FDG) PET/CT would detect cancer recurrences, leading to more patients being eligible for therapy. METHODS: After surgery with curative intent for adenocarcinomas in the gastro-oesophageal junction, stomach or pancreas, patients were randomized 1 : 1 to standard clinical assessment in the outpatient clinic at 3, 6, 9, 12, 18 and 24 months after operation, or clinical assessment plus imaging including [18 F]FDG PET/CT and EUS. The primary endpoint was number of patients receiving oncological treatment for recurrence. Secondary endpoints were overall and progression-free survival, survival after recurrence detection of isolated locoregional recurrences and risk factors affecting survival. RESULTS: In total, 183 patients were enrolled, including 93 who underwent standard follow-up and 90 who had follow-up plus imaging. A recurrence was detected in 84 patients within 2 years after surgery (42 in each group), including 33 of 42 patients in the imaging group who were asymptomatic. Some 25 of 42 patients in the imaging group and 14 of 42 in the standard group received chemotherapy (P = 0·028). Although survival after detection of recurrence in asymptomatic patients was significantly longer than that for symptomatic patients (P < 0·001), overall survival from date of surgery in the two treatment groups was comparable. CONCLUSION: Follow-up after surgery for upper gastrointestinal cancer with EUS and PET/CT leads to detection of more asymptomatic cancer recurrences and patients referred for treatment without prolonging overall survival. Registration number: NCT02209415 ( http://www.clinicaltrials.gov).

ANTECEDENTES: Las neoplasias del tracto digestivo superior tienen un mal pronóstico. No existe consenso sobre en qué pacientes debe indicarse un seguimiento tras la cirugía. Se estableció la hipótesis de que un programa de seguimiento estructurado en el que se incluía ecoendoscopia (endosonography, EUS) y 18F-FDG-PET/CT detecta recidivas del cáncer logrando que más pacientes sean elegibles para tratamiento. MÉTODOS: Después de cirugía con intención curativa para adenocarcinomas de la unión gastroesofágica, estómago o páncreas, los pacientes fueron aleatorizados 1:1 a evaluación clínica estándar en consultas externas a los 3, 6, 9, 12, 18, y 24 meses postoperatorios o evaluación clínica más pruebas de diagnóstico por la imagen en las que se incluían 18F-FDG-PET/CT y EUS. La variable principal fue el número de pacientes que recibieron tratamiento oncológico para la recidiva. Las variables secundarias fueron la supervivencia global y libre de progresión, supervivencia tras la recidiva, la detección de recidivas locorregionales aisladas (isolated loco-regional recurrences, ILR) y factores de riesgo que afectan a la supervivencia. RESULTADOS: En total se reclutaron 183 pacientes, incluyendo 93 pacientes sometidos a un seguimiento estándar (controles) y 90 pacientes con seguimiento y pruebas de imagen. Se detectó recidiva en 84 pacientes dentro de los primeros dos años tras la cirugía (42 pacientes en cada grupo), incluyendo 33 de 42 pacientes (78%) en el grupo con pruebas de imagen que estaban asintomáticos. Veinticinco de 42 pacientes (60%) del grupo con pruebas de imagen y 14 de 42 pacientes (33%) del grupo control recibieron quimioterapia (P = 0,03). Aunque la supervivencia tras la detección de la recidiva en pacientes asintomáticos fue significativamente más larga en comparación con los pacientes sintomáticos (P < 0,001), la supervivencia global desde la fecha de la cirugía en las dos ramas del tratamiento fue comparable. CONCLUSIÓN: El seguimiento tras la cirugía del cáncer gastrointestinal del tracto superior con EUS y PET-CT permite detectar más recidivas asintomáticas de la enfermedad y derivar a los pacientes para tratamiento sin que ello prolongue la supervivencia global.

Multicentre study of multidisciplinary team assessment of pancreatic cancer resectability and treatment allocation.

BACKGROUND: Multidisciplinary team (MDT) meetings have been adopted widely to ensure optimal treatment for patients with cancer. Agreements in tumour staging, resectability assessments and treatment allocation between different MDTs were assessed. METHODS: Of all patients referred to one hospital, 19 patients considered to have non-metastatic pancreatic cancer for evaluation were selected randomly for a multicentre study of MDT decisions in seven units across Northern Europe. Anonymized clinical information and radiological images were disseminated to the MDTs. All patients were reviewed by the MDTs for radiological T, N and M category, resectability assessment and treatment allocation. Each MDT was blinded to the decisions of other teams. Agreements were expressed as raw percentages and Krippendorff's α values, both with 95 per cent confidence intervals. RESULTS: A total of 132 evaluations in 19 patients were carried out by the seven MDTs (1 evaluation was excluded owing to technical problems). The level of agreement for T, N and M categories ranged from moderate to near perfect (46·8, 61·1 and 82·8 per cent respectively), but there was substantial variation in assessment of resectability; seven patients were considered to be resectable by one MDT but unresectable by another. The MDTs all agreed on either a curative or palliative strategy in less than half of the patients (9 of 19). Only fair agreement in treatment allocation was observed (Krippendorff's α 0·31, 95 per cent c.i. 0·16 to 0·45). There was a high level of agreement in treatment allocation where resectability assessments were concordant. CONCLUSION: Considerable disparities in MDT evaluations of patients with pancreatic cancer exist, including substantial variation in resectability assessments.

Nurse-Assisted Percutaneous Endoscopic Gastrostomy Tube Placement Is a Safe Procedure in Adult Patients.

The percutaneous endoscopic gastrostomy (PEG) procedure is normally carried out by two doctors. Preliminary experience has suggested that this procedure may be accomplished with the same safety level using one doctor and a specially trained endoscopy nurse. The aim of the study was to assess the immediate outcome and 30 days' procedure-related morbidity following nurse-assisted percutaneous endoscopic gastrostomy (NA-PEG) in an unselected population of adult patients. Retrospective, nonconsecutive analysis of NA-PEG procedures were registered between 2008 and 2014. Demographic data, indications, and early and late procedure complications were registered. During the study period, a total of 222 nonconsecutive adult patients had a NA-PEG placement. Neurologic (56%) and malignant diseases (35%) were the major indications for the PEG placement. The NA-PEGs were performed by six specially trained endoscopy nurses. NA-PEG-related overall morbidity was 24%, and all complications were minor. No procedure-related mortality occurred. When NA-PEG was compared with standard PEG placement literature, there was no increase in the number of complications, and the types of complications were similar. Despite being performed in patients with multiple co-morbid conditions, NA-PEG was a safe procedure with no mortality and minor complications. We suggest that NA-PEG should be used on a larger scale with the intention of saving time and medical costs.

Randomized clinical trial of laparoscopic ultrasonography before laparoscopic colorectal cancer resection.

BACKGROUND: Intraoperative ultrasonography during open surgery for colorectal cancer may be useful for the detection of unrecognized liver metastases. Laparoscopic ultrasonography (LUS) for the detection of unrecognized liver metastasis has not been studied in a randomized trial. This RCT tested the hypothesis that LUS would change the TNM stage and treatment strategy. METHODS: Patients with colorectal cancer and no known metastases were randomized (1 : 1) to laparoscopic examination (control or laparoscopy plus LUS) in three Danish centres. Neither participants nor staff were blinded to the group assignment. RESULTS: Three hundred patients were randomized, 150 in each group. After randomization, 43 patients were excluded, leaving 128 in the control group and 129 in the LUS group. Intraoperative T and N categories were not altered by LUS, but laparoscopy alone identified previously undetected M1 disease in one patient (0·8 per cent) in the control group and three (2·3 per cent) in the LUS group. In the latter group, LUS suggested that an additional six patients (4·7 per cent) had M1 disease with liver (4) or para-aortal lymph node (2) metastases. The change in treatment strategy was greater in the LUS than in the control group (7·8 (95 per cent c.i. 3·8 to 13·8) and 0·8 (0 to 4·2) per cent respectively; P = 0·010), but the suspected M1 disease was benign in half of the patients. CONCLUSION: Routine LUS during resection of colorectal cancer is not recommended. Registration number: NCT02079389 (http://www.clinicaltrials.gov).

Renal impairment and late toxicity in germ-cell cancer survivors.

BACKGROUND: Treatment with bleomycin-etoposide-cisplatin (BEP) impairs renal function and increases the risk of late cardiovascular disease (CVD) and death. We investigated the influence of BEP on glomerular filtration rate (GFR) and assessed the importance of GFR changes on CVD and death in a large cohort of germ-cell cancer survivors. PATIENTS AND METHODS: BEP-treated patients (N = 1206) were identified in the Danish DaTeCa database, and merged with national registers to identify late toxicity. GFR were measured (51Cr-EDTA clearance) before and after treatment and at 1, 3 and 5-year follow-up. The influence of BEP on GFR was evaluated with a linear mixed model. Risk factors for late toxicity were identified by a landmark analysis adjusting for covariates. The cohort was compared with the background population with standardized hospitalization/mortality rates. RESULTS: GFR changed (ΔGFR) -11.3%, -15.4% and -25.9% after three, four and five+ cycles of BEP. For patients with impaired renal function before treatment the changes were 4.3%, 0.0% and -12.8%, respectively. During follow-up a significant rebound of GFR was documented. Compared with the background population, all patients, irrespective of renal function, had an increased risk of CVD and death. This risk depended on chronic kidney disease stage before treatment but not after treatment. ΔGFR had no influence on risk of late toxicity [death: hazard ratio (HR) 1.06, P = 0.50; CVD: HR 0.97, P = 0.61]. CONCLUSIONS: Renal function after BEP is closely related to number of cycles, but the changes in GFR are partly reversible and have no impact on risk of CVD or death.

Screening for carcinoma in situ in the contralateral testicle in patients with testicular cancer: a population-based study.

BACKGROUND: Screening programmes for contralateral carcinoma in situ (CIS) testis in patients with unilateral germ-cell cancer (GCC) have never been evaluated. We investigated the effect of screening for contralateral CIS in a large nation-wide, population-based study. PATIENTS AND METHODS: A contralateral single-site biopsy was offered to 4130 patients in whom GCC had been diagnosed in 1984-2007 (screened cohort); 462 patients in whom GCC was diagnosed in 1984-1988 comprised the unscreened cohort. Cases with CIS were offered radiotherapy. Initially CIS-negative biopsies in patients with metachronous GCC were revised according to today's standards. Risk for metachronous GCC was estimated using cumulative incidence and the Cox proportional hazards model. RESULTS: In the screened cohort, contralateral CIS was found in 181 (4.4%) patients. The cumulative incidence of metachronous GCC after 20 years was 1.9% in the screened cohort and 3.1% in the unscreened cohort (P = 0.097), hazard ratio (HR) for the unscreened cohort: 1.59 (P = 0.144). Expert revision with contemporary methodology of CIS-negative biopsy samples from patients with metachronous cancer revealed CIS in 17 out of 45 (38%) cases. Decreased risks for metachronous GCC were related to older age at diagnosis (HR 0.52 per 10 years, P < 0.001) and chemotherapy (HR 0.35, P = 0.002). Limitations include the small number of patients in the unscreened cohort and the retrospective study design. CONCLUSIONS: Our evaluation of a national population-based screening programme for contralateral CIS in patients with testicular cancer showed no significant difference in the risk for metachronous GCC between a screened and an unscreened cohort. Single-site biopsy including modern immunohistochemistry does not identify all cases of CIS.

Randomized clinical trial of prevention of seroma formation after mastectomy by local methylprednisolone injection.

BACKGROUND: Seroma formation, the most prevalent postoperative complication after mastectomy, is an inflammatory process that is potentially preventable via local steroid administration. This study investigated the effect of local steroid administration on seroma formation. METHODS: This was a double-blind randomized placebo-controlled intervention study of a single dose of 80 mg methylprednisolone versus saline on seroma formation after mastectomy. Patients were further classified according to the surgical axillary procedure: mastectomy with sentinel lymph node biopsy (M + SLNB) or mastectomy with level I-II axillary lymph node dissection (M + ALND). Treatments were administered into the wound cavity via the drain orifice following removal of the drain on the first day after surgery. The primary endpoint was seroma formation; secondary endpoints included the frequency of side-effects and complications. RESULTS: A total of 212 women scheduled for mastectomy for primary breast cancer were included. After M + SLNB, 32 (46 per cent) of 69 women developed a seroma in the methylprednisolone group, compared with 52 (78 per cent) of 67 in the saline group (P < 0.001). The mean cumulative seroma volume in the intention-to-treat population for the first 10 and 30 days was significantly lower in the methylprednisolone group (24 ml versus 127 ml in the saline group, and 177 versus 328 ml respectively) (P < 0.001). After M + ALND, similar proportions of patients developed a seroma in the methylprednisolone (35 of 37, 95 per cent) and saline (34 of 36, 94 per cent) groups, and methylprednisolone administration had no significant effect on seroma formation. No differences in infection rate were observed. CONCLUSION: Methylprednisolone administered into the wound cavity on the first day after M + SLNB exerted a highly significant preventive effect against seroma formation during the next 30 days. This effect was not seen in the M + ALND group. Future studies may clarify whether higher or repeated methylprednisolone doses increase the efficacy.

A randomised crossover comparison of manikin ventilation through Soft Seal®, i-gel™ and AuraOnce™ supraglottic airway devices by surf lifeguards.

Forty surf lifeguards attempted to ventilate a manikin through one out of three supraglottic airways inserted in random order: the Portex® Soft Seal®; the Intersurgical® i-gel™; and the Ambu® AuraOnce™. We recorded the time to ventilate and the proportion of inflations that were successful, without and then with concurrent chest compressions. The mean (SD) time to ventilate with the Soft Seal, i-gel and AuraOnce was 35.2 (7.2)s, 15.6 (3.3)s and 35.1 (8.5) s, respectively, p < 0.0001. Concurrent chest compression prolonged the time to ventilate by 5.0 (1.3-8.1)%, p = 0.0072. The rate of successful ventilations through the Soft Seal (100%) was more than through the AuraOnce (92%), p < 0.0001, neither of which was different from the i-gel (97%). The mean (SD) tidal volumes through the Soft Seal, i-gel and AuraOnce were 0.65 (0.14) l, 0.50 (0.16) l and 0.39 (0.19) l, respectively. Most lifeguards (85%) preferred the i-gel. Ventilation through supraglottic airway devices may be considered for resuscitation by surf lifeguards.

A randomised crossover comparison of mouth-to-face-shield ventilation and mouth-to-pocket-mask ventilation by surf lifeguards in a manikin.

Thirty surf lifeguards (mean (SD) age: 25.1 (4.8) years; 21 male, 9 female) were randomly assigned to perform 2 × 3 min of cardiopulmonary resuscitation on a manikin using mouth-to-face-shield ventilation (AMBU LifeKey) and mouth-to-pocket-mask ventilation (Laerdal Pocket Mask). Interruptions in chest compressions, effective ventilation (visible chest rise) ratio, tidal volume and inspiratory time were recorded. Interruptions in chest compressions per cycle were increased with mouth-to-face-shield ventilation (mean (SD) 8.6 (1.7) s) compared with mouth-to-pocket-mask ventilation (6.9 (1.2) s, p < 0.0001). The proportion of effective ventilations was less using mouth-to-face-shield ventilation (199/242 (82%)) compared with mouth-to-pocket-mask ventilation (239/240 (100%), p = 0.0002). Tidal volume was lower using mouth-to-face-shield ventilation (mean (SD) 0.36 (0.20) l) compared with mouth-to-pocket-mask ventilation (0.45 (0.20) l, p = 0.006). No differences in inspiratory times were observed between mouth-to-face-shield ventilation and mouth-to-pocket-mask ventilation. In conclusion, mouth-to-face-shield ventilation increases interruptions in chest compressions, reduces the proportion of effective ventilations and decreases delivered tidal volumes compared with mouth-to-pocket-mask ventilation.

The Nordic prescription databases as a resource for pharmacoepidemiological research--a literature review.

PURPOSE: All five Nordic countries have nationwide prescription databases covering all dispensed drugs, with potential for linkage to outcomes. The aim of this review is to present an overview of therapeutic areas studied and methods applied in pharmacoepidemiologic studies using data from these databases. METHODS: The study consists of a Medline-based structured literature review of scientific papers published during 2005-2010 using data from the prescription databases in Denmark, Finland, Iceland, Norway, and Sweden, covering 25 million inhabitants. Relevant studies were analyzed in terms of pharmacological group, study population, outcomes examined, type of study (drug utilization vs. effect of drug therapy), country of origin, and extent of cross-national collaboration. RESULTS: A total of 515 studies were identified. Of these, 262 were conducted in Denmark, 97 in Finland, 4 in Iceland, 87 in Norway, and 61 in Sweden. Four studies used data from more than one Nordic country. The most commonly studied drugs were those acting on the nervous system, followed by cardiovascular drugs and gastrointestinal/endocrine drugs. A total of 228 studies examined drug utilization and 263 focused on the effects and safety of drug therapy. Pregnant women were the most commonly studied population in safety studies, whereas prescribers' adherence to guidelines was the most frequent topic of drug utilization studies. CONCLUSIONS: The Nordic prescription databases, with their possibility of record-linkage, represent an outstanding resource for assessing the beneficial and adverse effects of drug use in large populations, under routine care conditions, and with the potential for long-term follow-up.

Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo.

Timely elimination of damaged mitochondria is essential to protect cells from the potential harm of disordered mitochondrial metabolism and release of proapoptotic proteins. In mammalian red blood cells, the expulsion of the nucleus followed by the removal of other organelles, such as mitochondria, are necessary differentiation steps. Mitochondrial sequestration by autophagosomes, followed by delivery to the lysosomal compartment for degradation (mitophagy), is a major mechanism of mitochondrial turnover. Here we show that mice lacking the essential autophagy gene Atg7 in the hematopoietic system develop severe anemia. Atg7(-/-) erythrocytes accumulate damaged mitochondria with altered membrane potential leading to cell death. We find that mitochondrial loss is initiated in the bone marrow at the Ter119(+)/CD71(High) stage. Proteomic analysis of erythrocyte ghosts suggests that in the absence of autophagy other cellular degradation mechanisms are induced. Importantly, neither the removal of endoplasmic reticulum nor ribosomes is affected by the lack of Atg7. Atg7 deficiency also led to severe lymphopenia as a result of mitochondrial damage followed by apoptosis in mature T lymphocytes. Ex vivo short-lived hematopoietic cells such as monocytes and dendritic cells were not affected by the loss of Atg7. In summary, we show that the selective removal of mitochondria by autophagy, but not other organelles, during erythropoeisis is essential and that this is a necessary developmental step in erythroid cells.

Avoiding complications in esophageal cancer surgery.

Modern handling of esophageal cancer patients is based on a multidisciplinary concept, but surgery remains the primary curative treatment modality. Improvements in the perioperative care have reduced the overall morbidity and mortality, but 2-7% of the patients may still die within 30 days as a direct consequence of complications related to the esophagectomy procedure. Primarily based on results from randomized studies published after 2000 this review describes some of the factors that may contribute to the development of postoperative complications following esophageal cancer surgery as well as studies intended to finding ways of reducing the complication rate.

Endoscopic ultrasound, endoscopic sonoelastography, and strain ratio evaluation of lymph nodes with histology as gold standard.

BACKGROUND AND STUDY AIMS: Accurate lymph node staging is essential for the selection of an optimal treatment in patients with upper gastrointestinal cancer. Endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) are considered to be the most accurate method for locoregional staging. Endoscopic sonoelastography (ESE) assesses the elasticity of lymph nodes and has been used to differentiate lymph nodes with promising results. The aim of this study was to evaluate the use of EUS, EUS - FNA, ESE, and ESE-strain ratio using histology as the gold standard. PATIENTS AND METHODS: Patients with upper gastrointestinal cancer who were referred for EUS examination were enrolled if surgical treatment was planned and the patient had a lymph node that was accessible for EUS - FNA and EUS-guided fine-needle marking (FNM). The lymph node was classified using EUS, ESE, and ESE-strain ratio. Finally, EUS - FNA and EUS - FNM were performed. The marked lymph node was isolated during surgery for histological examination. RESULTS: The marked lymph node was isolated for separate histological examination in 56 patients, of whom 22 (39 %) had malignant lymph nodes and 34 (61 %) had benign lymph nodes. There were no complications of EUS - FNM. The sensitivity of EUS for differentiation between malignant and benign lymph nodes was 86 % compared with 55 % - 59 % for the different ESE modalities. The specificity of EUS was 71 % compared with 82 % - 85 % using ESE modalities. CONCLUSION: The use of the EUS - FNM technique enabled the identification of a specific lymph node and thereby the use of histology as gold standard. ESE and ESE-strain ratio were no better than standard EUS in differentiating between malignant and benign lymph nodes in patients with resectable upper gastrointestinal cancer.

Treatment options for carcinoma in situ testis.

Carcinoma in situ testis (CIS) is known as the precursor of germ cell cancer of the testis. International guidelines on diagnosis and treatment are inconsistent. Some countries offer routine biopsies of the contralateral testicle in relation to orchidectomy for testicular cancer, whereas other countries only offer this to high-risk patients. The treatment options range from orchidectomy and chemotherapy to radiotherapy and in rare cases surveillance. Results of the different treatment strategies are presented in this review. The optimal radiation dose is still not clarified. Most patients have been treated in the dose range of 16-20 Gy. Higher doses involve a higher risk of androgen insufficiency. Radiotherapy is recommended in patients with contralateral CIS. Orchidectomy should be offered in extragonadal germ cell cancer and CIS in one testicle, whereas patients with bilateral CIS should be offered radiation therapy. Patients who have undergone chemotherapy for testicular cancer are still at risk of developing CIS and we also recommend radiotherapy to the affected testicle in these patients. Cryopreservation should be offered before treatment is initiated and all patients should have their androgen status measured on a regular basis to find those cases where hormone substitution is needed.