[Standardized and quality-assured predictive PD-L1 testing in the upper gastrointestinal tract. German version]. / Standardisierte und qualitätsgesicherte prädiktive PD-L1-Testung im oberen Gastrointestinaltrakt.

As a result of the high approval dynamics and the growing number of immuno-oncological therapy concepts, the complexity of therapy decisions and control in the area of carcinomas of the esophagus, gastroesophageal junction and stomach is constantly increasing. Since the treatment indication for PD­1 inhibitors that are currently approved in the European Union is often linked to the expression of PD-L1 (programmed cell death-ligand 1), the evaluation of tissue-based predictive markers by the pathologist is of crucial importance for treatment stratification. Even though the immunohistochemical analysis of the PD-L1 expression status is one of the best studied, therapy-relevant biomarkers for an immuno-oncological treatment, due to the high heterogeneity of carcinomas of the upper gastrointestinal tract, there are challenges in daily clinical diagnostic work with regard to implementation, standardization and interpretation of testing. An interdisciplinary group of experts from Germany has taken a position on relevant questions from daily pathological and clinical practice, which concern the starting material, quality-assured testing and the interpretation of pathological findings, and has developed recommendations for structured reporting.

Trauma Surgeon and Palliative Care Physician Attitudes Regarding Goals-of-Care Delineation for Injured Geriatric Patients.

BACKGROUND: The value of defining goals of care (GoC) for geriatric patients is well known to the palliative care community but is a newer concept for many trauma surgeons. Palliative care specialists and trauma surgeons were surveyed to elicit the specialties' attitudes regarding (1) importance of GoC conversations for injured seniors; (2) confidence in their own specialty's ability to conduct these conversations; and (3) confidence in the ability of the other specialty to do so. METHODS: A 13-item survey was developed by the steering committee of a multicenter, palliative care-focused consortium and beta-tested by trauma surgeons and palliative care specialists unaffiliated with the consortium. The finalized instrument was electronically circulated to active physician members of the American Association for the Surgery of Trauma and American Academy for Hospice and Palliative Medicine. RESULTS: Respondents included 118 trauma surgeons (8.8%) and 244 palliative care specialists (5.7%). Palliative physicians rated being more familiar with GoC, were more likely to report high-quality training in performing conversations, believed more palliative specialists were needed in intensive care units, and had more interest in conducting conversations relative to trauma surgeons. Both groups believed themselves to perform GoC discussions better than the other specialty perceived them to do so and favored their own specialty leading team discussions. CONCLUSIONS: Both groups believe themselves to conduct GoC discussions for injured seniors better than the other specialty perceived them to do so, which led to disparate views on the optimal leadership of these discussions.

Burn Surgeon and Palliative Care Physician Attitudes Regarding Goals of Care Delineation for Burned Geriatric Patients.

Palliative care specialists (PCS) and burn surgeons (BS) were surveyed regarding: 1) importance of goals of care (GoC) conversations for burned seniors; 2) confidence in their own specialty's ability to conduct these conversations; and 3) confidence in the ability of the other specialty to do so. A 13-item survey was developed by the steering committee of a multicenter consortium dedicated to palliative care in the injured geriatric patient and beta-tested by BS and PCS unaffiliated with the consortium. The finalized instrument was electronically circulated to active physician members of the American Burn Association and American Academy for Hospice and Palliative Medicine. Forty-five BS (7.3%) and 244 PCS (5.7%) responded. Palliative physicians rated being more familiar with GoC, were more comfortable having a discussion with laypeople, were more likely to have reported high-quality training in performing conversations, believed more palliative specialists were needed in intensive care units, and had more interest in conducting conversations relative to BS. Both groups believed themselves to perform GoC discussions better than the other specialty perceived them to do so. BS favored leading team discussions, whereas palliative specialists preferred jointly led discussions. Both groups agreed that discussions should occur within 72 hours of admission. Both groups believe themselves to conduct GoC discussions for burned seniors better than the other specialty perceived them to do so, which led to disparate views on perceptions for the optimal leadership of these discussions.

A comparison of prognosis calculators for geriatric trauma: A Prognostic Assessment of Life and Limitations After Trauma in the Elderly consortium study.

BACKGROUND: The nine-center Prognostic Assessment of Life and Limitations After Trauma in the Elderly consortium has validated the Geriatric Trauma Outcome Score (GTOS) as a prognosis calculator for injured elders. We compared GTOS' performance to that of the Trauma Injury Severity Score (TRISS) in a multicenter sample. METHODS: Three Prognostic Assessment of Life and Limitations After Trauma in the Elderly centers not submitting subjects to the GTOS validation study identified subjects aged 65 years to 102 years admitted from 2000 to 2013. GTOS was specified using the formula [GTOS = age + (Injury Severity Score [ISS] × 2.5) + 22 (if transfused packed red cells (PRC) at 24 hours)]. TRISS uses the Revised Trauma Score (RTS), dichotomizes age (<55 years = 0 and ≥55 years = 1), and was specified using the updated 1995 beta coefficients. TRISS Penetrating was specified as [TRISSP = -2.5355 + (0.9934 × RTS) + (-0.0651 × ISS) + (-1.1360 × Age)]. TRISS Blunt was specified as [TRISSB = -0.4499 + (0.8085 × RTS Total) + (-0.0835 × ISS) + (-1.7430 × Age)]. Each then became the sole predictor in a separate logistic regression model to estimate probability of mortality. Model performances were evaluated using misclassification rate, Brier score, and area under the curve. RESULTS: Demographics (mean + SD) of subjects with complete data (N = 10,894) were age, 78.3 years ± 8.1 years; ISS, 10.9 ± 8.4; RTS = 7.5 ± 1.1; mortality = 6.9%; blunt mechanism = 98.6%; 3.1 % of subjects received PRCs. The penetrating trauma subsample (n = 150) had a higher mortality rate of 20.0%. The misclassification rates for the models were GTOS, 0.065; TRISSB, 0.051; and TRISSP, 0.120. Brier scores were GTOS, 0.052; TRISSB, 0.041; and TRISSP, 0.084. The area under the curves were GTOS, 0.844; TRISSB, 0.889; and TRISSP, 0.897. CONCLUSION: GTOS and TRISS function similarly and accurately in predicting probability of death for injured elders. GTOS has the advantages of a single formula, fewer variables, and no reliance on data collected in the emergency room or by other observers. LEVEL OF EVIDENCE: Prognostic, level II.

Inflammatory bowel disease and the elderly: a review.

Inflammatory bowel disease among the elderly is common, with growing incident and prevalence rates. Compared with younger IBD patients, genetics contribute less to the pathogenesis of older-onset IBD, with dysbiosis and dysregulation of the immune system playing a more significant role. Diagnosis may be difficult in older individuals, as multiple other common diseases can mimic IBD in this population. The clinical manifestations in older-onset IBD are distinct, and patients tend to have less of a disease trajectory. Despite multiple effective medical and surgical treatment strategies for adults with Crohn's disease and ulcerative colitis, efficacy studies typically have excluded older subjects. A rapidly ageing population and increasing rates of Crohn's and ulcerative colitis make the paucity of data in older adults with IBD an increasingly important clinical issue.

From diagnosis through survivorship: health-care experiences of colorectal cancer survivors with ostomies.

PURPOSE: The journey from diagnosis through treatment to survivorship can be challenging for colorectal cancer (CRC) survivors with permanent ostomies. Memories of both the positive and negative health-care interactions can persist years after the initial diagnosis and treatment. The purpose of this paper is to describe the health-care experiences of long-term (>5 years) CRC survivors with ostomies. METHODS: Thirty-three CRC survivors with ostomies who were members of Kaiser Permanente, an integrated care organization, in Oregon, southwestern Washington and northern California participated in eight focus groups. Discussions from the focus groups were recorded, transcribed, and analyzed for potential categories and themes. RESULTS: Health-care-related themes described CRC survivors' experiences with diagnosis, treatment decision-making, initial experiences with ostomy, and survivorship. Participants discussed both positive and negative health-care-related experiences, including the need for continued access to trained nurses for ostomy self-care, access to peer support, and resources related to managing persistent, debilitating symptoms. CONCLUSIONS: Long-term CRC survivors with ostomies have both positive and negative health-care experiences, regardless of health-related quality of life (HRQOL) and gender. Long-term support mechanisms and quality survivorship care that CRC survivors with ostomies can access are needed to promote positive adjustments and improved HRQOL. The current literature in CRC survivorship suggests that HRQOL concerns can persist years after treatment completion. The coordination of care to manage persistent late- and long-term effects are still lacking for CRC survivors living with an ostomy. Findings from this qualitative analysis will aid in the development of support strategies that foster more positive adjustments for CRC survivors living with an ostomy and support their ongoing ostomy-related needs.

Inverse correlation of serum inflammatory markers with metabolic parameters in healthy, Black and White prepubertal youth.

OBJECTIVE: To examine for the first time the associations between pro-inflammatory cytokines and obesity-related metabolic biomarkers in, exclusively prepubertal, otherwise healthy obese and non-obese Black and White children, 7-9 years of age. DESIGN AND METHODS: Body mass index (BMI), homeostasis model assessment-estimated insulin resistance, visceral adipose tissue and subcutaneous adipose tissue (SAT (magnetic resonance imaging)); total body fat (dual-energy X-ray absorptiometry), ectopic, intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) fat (proton magnetic resonance spectroscopy) and serum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 were measured in 40 obese and non-obese children. Relationships between inflammatory cytokines and obesity were assessed by analysis of variance and Spearman's rank correlation. RESULTS: Significant inverse correlations were found between BMI z-score, SAT, total BF, and IHL and levels of TNF-α (Spearman's ρ=-0.36, -0.39, -0.43 and -0.39, respectively; P<0.05). Levels of IL-8 were significantly and inversely correlated with IMCL (-0.39; P=0.03) and remained significant after adjusting for race. IMCL was inversely associated with TNF-α only after adjusting for race (-0.37; P=0.04). CONCLUSIONS: Relationships between pro-inflammatory and metabolic markers commonly observed in adults are reversed in healthy, Black and White children before puberty. Prospective studies are warranted to determine how these inverse relationships modify chronic disease risk later in life.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

Surviving colorectal cancer: long-term, persistent ostomy-specific concerns and adaptations.

PURPOSE: The purpose of this article was to describe persistent ostomy-specific concerns and adaptations in long-term (>5 years) colorectal cancer survivors with ostomies. SUBJECTS AND SETTINGS: Thirty-three colorectal cancer survivors who participated in 8 gender- and health-related quality of life stratified focus groups and 130 colorectal cancer survivors who provided written comments to 2 open-ended questions on ostomy location and pouch problems participated in the study. Data were collected on health maintenance organization members in Oregon, southwestern Washington, and northern California. METHODS: Qualitative data were analyzed for the 8 focus groups and written comments from 2 open-ended survey questions. Discussions from the focu s groups were recorded, transcribed, and analyzed using content analysis. Written content from the open-ended questions was derived from a mailed questionnaire on health-related quality of life in survivors with ostomies and analyzed using content analysis. RESULTS: Discussions related to persistent ostomy-related issues more than 5 years after formation were common. Persistent ostomy-related issues were focused on clothing restrictions and adaptations, dietary concerns, issues related to ostomy equipment and self-care, and the constant need to find solutions to adjust and readjust to living with an ostomy. CONCLUSIONS: Ostomy-specific concerns persist 5 years and more for long-term colorectal cancer survivors after initial ostomy formation. Adaptations tend to be individualized and based on trial and error. Findings underscore the need to develop long-term support mechanisms that survivors can access to promote better coping and adjustment to living with an ostomy.

[Diagnosis and treatment of esophageal cancer]. / Diagnostik und Therapie des Ösophaguskarzinoms.

The prognosis for patients with advanced esophageal cancer is poor. Proper risk assessment and knowledge of tumor biology may facilitate early diagnosis of adenocarcinomas and squamous cell cancer of the esophagus. New endoscopic techniques are available (e.g., (virtual) chromoendoscopy, autofluorescence, and endomicroscopy) for the early detection of cancer. Endoscopic therapy with complete resection of mucosal cancers offers long-term survival.En bloc resection combined with the removal of locoregional lymph nodes is the surgical option of choice for locally advanced cancer. In this respect, minimally invasive surgery offers the patient numerous advantages. Multimodal therapy results in better outcome for defined cancer stages and includes surgery, chemotherapy and chemoradiation. Multimodal treatment should always be individualized and requires cooperation of all subspecialties (tumor board conference). New chemotherapeutic strategies may offer improved survival but may also include new side effects. Patients with inoperable esophageal cancer also benefit from multimodal treatment.

[Current S3 guidelines on surgical treatment of gastric carcinoma]. / Aktuelle S3-Leitlinie zur Chirurgie des Magenkarzinoms.

The current S3 guidelines on the diagnosis and treatment of gastric carcinoma including those of the esophagogastric junction describe optimal clinical practice based on a high level of evidence and expert consensus from different medical disciplines. Endoscopy and performance of multiple biopsies is the standard approach to detect malignant tumors in the upper gastrointestinal tract. Further diagnostic procedures are necessary to evaluate the tumor stage. With the exception of mucosal carcinomas, surgical therapy is the cornerstone of curative treatment in all potentially resectable stages. In locally advanced carcinomas perioperative chemotherapy should be carried out and in high-seated tumors preoperative radiochemotherapy might be an alternative option. Palliative surgical resection should be avoided in disseminated asymptomatic stages. In a palliative situation complications of the tumor should primarily be treated by interventional or conservative procedures.

Gender differences in quality of life among long-term colorectal cancer survivors with ostomies.

PURPOSE/OBJECTIVES: To describe how gender shapes the concerns and adaptations of long-term (i.e., more than five years) colorectal cancer survivors with ostomies. DESIGN: Qualitative study using content analysis of focus group content. SETTING: Oregon, southwestern Washington, and northern California. SAMPLE: Four female and four male focus groups (N = 33) selected from 282 quantitative survey participants with health-related quality-of-life (HRQOL) scores in the highest or lowest quartile. METHODS: Eight focus groups discussed the challenges of living with an ostomy. Content was recorded, transcribed, and analyzed using directive and summative content analysis. MAIN RESEARCH VARIABLES: HRQOL domains of physical, psychological, social, and spiritual well-being. FINDINGS: All groups reported avoiding foods that cause gas or rapid transit and discussed how limiting the amount of food eaten controlled the output. All groups discussed physical activities, getting support from friends and family, and the importance of being resilient. Both genders identified challenges with sexuality and intimacy. Coping and adjustment difficulties mostly were discussed by women, with men only discussing these issues to a small extent. Difficulties with sleep primarily were identified by women with low HRQOL. Problems with body image and depression were discussed only by women with low HRQOL. CONCLUSIONS: Common issues included diet management, physical activity, social support, and sexuality. Although both genders identified challenges, women described more specific psychological and social issues than men. IMPLICATIONS FOR NURSING: Application of these gender-based differences can inform educational interventions for colorectal cancer survivors with ostomies.

Complications among colorectal cancer survivors: SF-6D preference-weighted quality of life scores.

BACKGROUND: Societal preference-weighted health-related quality of life (HRQOL) scores enable comparing multidimensional health states across diseases and treatments for research and policy. OBJECTIVE: To assess the effects of living with a permanent intestinal stoma, compared with a major bowel resection, among colorectal cancer (CRC) survivors. RESEARCH DESIGN: Cross-sectional multivariate linear regression analysis to explain preference-weighted HRQOL scores. SUBJECTS: In all, 640 CRC survivors (≥ 5 years) from 3 group model health maintenance organizations; ostomates and nonostomates with colorectal resections for CRC were matched on gender, age (± 5 years), time since diagnosis, and tumor site (rectum vs. colon). MEASURES: SF-6D scoring system was applied to Medical Outcomes Study Short Form-36 version 2 (SF-36v2); City of Hope Quality of Life-Ostomy; and Charlson-Deyo comorbidity index. METHODS: Survey of CRC survivors linked to respondents' clinical data extracted from health maintenance organization files. RESULTS: Response rate was 52%. Ostomates and nonostomates had similar sociodemographic characteristics. Mean SF-6D score was 0.69 for ostomates, compared with 0.73 for nonostomates (P < 0.001), but other factors explained this difference. Complications of initial cancer surgery, and previous year comorbidity burden, and hospital use were negatively associated with SF-6D scores, whereas household income was positively associated. CONCLUSIONS: CRC survivors' SF-6D scores were not associated with living with a permanent ostomy after other factors were taken into account. Surgical complications, comorbidities, and metastatic disease lowered the preference-weighted HRQOL of CRC survivors with and without ostomies. Further research to understand and reduce late complications from CRC surgeries as well as associated depression is warranted.

Overcoming challenges: life with an ostomy.

BACKGROUND: Studies have demonstrated decreased health-related quality of life in patients with stomas. METHODS: Using US Department of Veterans Affairs electronic medical records, veterans with stomas were surveyed using the City of Hope Quality of Life-Ostomy questionnaire. Focus groups were conducted segregated by type of stoma (ileostomy vs colostomy) and quality-of-life score (high vs low). Qualitative analysis was performed on the basis of the City of Hope Quality of Life for Ostomates format of health-related quality of life (physical, psychological, social, and spiritual). The findings of the colostomy focus groups are reported. RESULTS: Two new domains emerged: colostomy specific and health care specific. The most common domains discussed were colostomy specific, psychological, and social. The most frequently discussed colostomy-specific theme was effective and ineffective solutions to colostomy care. Family and spousal relationships were the main theme from the psychological category. The predominant social issue was sexual relationships. CONCLUSIONS: Awareness of patients' social, psychological, and medical status allows surgeons to identify those likely to have problems and devote resources to those veterans.

Treatment of metachronous and simultaneous liver metastases of pancreatic cancer.

AIM: Patients were analyzed who underwent treatment of liver metastases from pancreatic cancer. METHODS: Selection criteria were the possibility of R0 resection of the primary and/or the liver metastases, no other sites of metastases, and the presentation of liver metastases. A comparison of treatment by surgery versus chemotherapy regarding overall survival and disease-free interval was performed. RESULTS: Between 1996 and 2008, a total number of 23 patients were retrospectively identified from a prospective database of 193 cases of pancreatic cancer. In 14 cases, liver metastases were found simultaneously, and in 9 cases metachronously, fulfilling the abovementioned selection criteria. Of these, 13 patients underwent surgery and 10 were treated by gemcitabine. There were no differences in survival in patients with synchronous liver metastases of pancreatic cancer treated by resection of the primary combined with partial hepatectomy versus treatment by gemcitabine (8 vs. 11 months). In patients with metachronous liver metastases, the median survival was increased after liver resection compared to patients who were treated with gemcitabine (31 vs. 11 months). CONCLUSIONS: Simultaneous resection of pancreatic cancer and liver metastases cannot be recommended. Resection of metachronous liver metastases of pancreatic cancer seems to improve survival in highly selected patients.

[Detection of hepatic micrometastases in the context of adjuvant chemotherapy and surgery for hepatic metastases]. / Nachweis hepatischer Mikrometastasen.

Colorectal cancer is one of the three most frequent malignancies in humans. Survival is mainly determined by local recurrence, lymphatic and hematogenous dissemination. Primary liver resection for metastases is possible in ~20-25% of patients with hepatic metastases and results in a 50% recurrence rate within 23 months. The five-year survival without treatment in patients with UICC stage IV is only 5%, the mean survival 6-9 months. As a result of promising developments in chemotherapy and targeted therapies in the last decade, the mean survival rate has significantly improved to over more than two years. Furthermore, the use of polychemotherapy in combination with anti-angiogenic and anti-proliferative biologicals has resulted in a significant increase of secondary resectability of liver metastases. Despite of a R0-resection (i.e. resection with clear margins) of liver metastases, only 30% of patients remain free of recurrence in the long-term. Prognostic scores are used for optimal patient selection, e.g. the Fong-Score. Resection is often limited by a high number of recurrences: intrahepatic micrometastases and disseminated tumor cells (DTC) are suspected as the cause of their development. In this connection the load of disseminated tumor cells correlates significantly with the survival and recurrence rate after resection. These micrometastases are targets in current adjuvant treatment studies (e.g. MT 201) by using anti-EpCam antibodies. The detection of DTC can supplement the previously used scores and represents the indication for an adjuvant antibody-based treatment (e.g. anti-EpCam) in the context of clinical trials.

Health-related quality of life among long-term rectal cancer survivors with an ostomy: manifestations by sex.

PURPOSE: Intestinal stomas can pose significant challenges for long-term (> or = 5 years) rectal cancer (RC) survivors. Specifying common challenges and sociodemographic or clinical differences will further the development of tailored interventions to improve health-related quality of life (HRQOL). PATIENTS AND METHODS: This was a matched cross-sectional study of long-term RC survivors conducted in three Kaiser Permanente regions. The mailed questionnaire included the modified City of Hope Quality of Life-Ostomy (mCOH-QOL-Ostomy) and Medical Outcomes Study 36-Item Short-Form Health Survey, version 2 (SF-36v2). Groups surveyed were permanent ostomates (cases) and those who did not require an ostomy (controls). RC survivors were matched on sex, age, and time since diagnosis. Comparisons between groups used regression analysis with adjustment for age, comorbidity score, history of radiation therapy, income, and work status. RESULTS: Response rate was 54% (491 of 909). Cases and controls had similar demographic characteristics. On the basis of the mCOH-QOL-Ostomy, both male and female cases had significantly worse social well-being compared with controls, while only female cases reported significantly worse overall HRQOL and psychological well-being. For younger females (< age 75 years), ostomy had a greater impact on physical well-being compared with older females. Based on the SF-36v2, statistically significant and meaningful differences between female cases and controls were observed for seven of the eight scales and on the physical and mental component summary scores. CONCLUSION: Men and women report a different profile of challenges, suggesting the need for targeted or sex-specific interventions to improve HRQOL in this population. This may include focus on physical HRQOL for female ostomy survivors younger than age 75.

[Gastrointestinal oncology - therapy update 2008 / 2009]. / Gastrointestinale Onkologie - Therapieupdate 2008 / 2009.

As a consequence of recent studies the treatment of gastrointestinal cancers has become challenging and is undergoing constant changes on the basis of the results of new trials. The steering committee of the working group on gastrointestinal cancers of the Deutsche Gesellschaft für Verdauungs- und Stoffwechselkrankheiten has decided to summarise and present recent updates of the current treatment guidelines and recommendations for the most relevant gastrointestinal malignancies. In this review we have included recent findings from large trials on esophageal, gastric, pancreatic, cholangiocellular and liver cancers, as well as colorectal cancers, neuroendocrine tumours and lymphomas. This includes an update on the combination with novel targeted agents and the introduction of potential predictive biomarkers in the selection of the appropriate treatment strategy.