Secondary technical resectability of colorectal cancer liver metastases after chemotherapy with or without selective internal radiotherapy in the randomized SIRFLOX trial.

BACKGROUND: Secondary resection of initially unresectable colorectal cancer liver metastases (CRLM) can prolong survival. The added value of selective internal radiotherapy (SIRT) to downsize lesions for resection is not known. This study evaluated the change in technical resectability of CRLM with the addition of SIRT to FOLFOX-based chemotherapy. METHODS: Baseline and follow-up hepatic imaging of patients who received modified FOLFOX (mFOLFOX6: fluorouracil, leucovorin, oxaliplatin) chemotherapy with or without bevacizumab (control arm) versus mFOLFOX6 (with or without bevacizumab) plus SIRT using yttrium-90 resin microspheres (SIRT arm) in the phase III SIRFLOX trial were reviewed by three or five (of 14) expert hepatopancreatobiliary surgeons for resectability. Reviewers were blinded to one another, treatment assignment, extrahepatic disease status, and information on clinical and scanning time points. Technical resectability was defined as at least 60 per cent of reviewers (3 of 5, or 2 of 3) assessing a patient's liver metastases as surgically removable. RESULTS: Some 472 patients were evaluable (SIRT, 244; control, 228). There was no significant baseline difference in the proportion of technically resectable liver metastases between SIRT (29, 11·9 per cent) and control (25, 11·0 per cent) arms (P = 0·775). At follow-up, significantly more patients in both arms were deemed technically resectable compared with baseline: 159 of 472 (33·7 per cent) versus 54 of 472 (11·4 per cent) respectively (P = 0·001). More patients were resectable in the SIRT than in the control arm: 93 of 244 (38·1 per cent) versus 66 of 228 (28·9 per cent) respectively (P < 0·001). CONCLUSION: Adding SIRT to chemotherapy may improve the resectability of unresectable CRLM.

ANTECEDENTES: La resección secundaria de metástasis hepáticas de cáncer colorrectal (colorectal cancer liver metastases, CRLM) inicialmente irresecables puede prolongar la supervivencia. Se desconoce el valor añadido de la radioterapia interna selectiva (selective internal radiation therapy, SIRT). Este estudio evaluó el cambio en la resecabilidad técnica de las CRLM secundario a la adición de SIRT a una quimioterapia tipo FOLFOX. MÉTODOS: Las pruebas de radioimagen basales y durante el seguimiento de pacientes tratados con un régimen FOLFOX modificado (mFOLFOX6: fluorouracilo, leucovorina, oxaliplatino) ± bevacizumab (grupo control) versus mFOLFOX6 (± bevacizumab) más SIRT usando microesferas de resina de yttrium-90, en el ensayo de fase III SIRFLOX, fueron revisadas por 3-5 (de 14) cirujanos expertos hepatobiliares para determinar la resecabilidad. Los expertos efectuaron la revisión de forma ciega unos respecto a otros en relación con la asignación al tratamiento, estado de la enfermedad extra-hepática y situación clínica en el momento del estudio radiológico. La resecabilidad técnica se definió como ≥ 60% de revisores evaluando las metástasis del paciente como quirúrgicamente resecables. RESULTADOS: Fueron evaluables un total de 472 pacientes (control, n = 228; SIRT, n = 244). No hubo diferencias significativas basales en la proporción de metástasis hepáticas técnicamente resecables entre SIRT (29/244; 11,9%) y el grupo control (25/228; 11,0%: P = 0,775). Durante el seguimiento y en ambos brazos de tratamiento, un número significativamente mayor de pacientes se consideraron técnicamente resecables en comparación con la situación basal (54/472 (11,4%) basal y 159/472 (33,7%) al seguimiento). Hubo más pacientes resecables en el grupo SIRT que en el control (93/244 (38,1%) y 66/228 (28,9%); P < 0,001, respectivamente). CONCLUSIÓN: La adición de SIRT a la quimioterapia puede mejorar la resecabilidad de las CRLM irresecables.

Radioablation of adrenal gland malignomas with interstitial high-dose-rate brachytherapy : Efficacy and outcome.

PURPOSE: To assess the efficacy, safety, and outcome of image-guided high-dose-rate (HDR) brachytherapy in patients with adrenal gland metastases (AGM). MATERIALS AND METHODS: From January 2007 to April 2014, 37 patients (7 female, 30 male; mean age 66.8 years, range 41.5-82.5 years) with AGM from different primary tumors were treated with CT-guided HDR interstitial brachytherapy (iBT). Primary endpoint was local tumor control (LTC). Secondary endpoints were time to untreatable progression (TTUP), time to progression (TTP), overall survival (OS), and safety. In a secondary analysis, risk factors with an influence on survival were identified. RESULTS: The median biological equivalent dose (BED) was 37.4 Gy. Mean LTC after 12 months was 88%; after 24 months this was 74%. According to CTCAE criteria, one grade 3 adverse event occurred. Median OS after first diagnosis of AGM was 18.3 months. Median OS, TTUP, and TTP after iBT treatment were 11.4, 6.6, and 3.5 months, respectively. Uni- and multivariate Cox regression analyses revealed significant influences of synchronous disease, tumor diameter, and the total number of lesions on OS or TTUP or both. CONCLUSION: Image-guided HDR-iBT is safe and effective. Treatment- and primary tumor-independent features influenced survival of patients with AGM after HDR-iBR treatment.

[Contralateral hepatic hypertrophy following unilateral yttrium-90 radioembolization : Implications for liver surgery]. / Kontralaterale Leberhypertrophie nach einseitiger Yttrium-90-Radioembolisation : Implikationen für die Leberchirurgie.

BACKGROUND: Preservation of an adequate future liver remnant (FLR) is the principal limitation to liver surgery in patients with primary or secondary liver malignancies. Hence, methods to increase the volume of the FLR in preparation for liver resection are gaining in importance. OBJECTIVE: In addition to the traditional methods for induction of FLR hypertrophy, such as portal vein embolization (PVE) or portal vein ligation (PVL) with or without parenchymal dissection (ALPPS, in situ split), radioembolization (RE) using yttrium-90 microspheres also leads to a volume increase of non-embolized liver parenchyma. This review outlines its potential role as an alternative procedure for induction of liver hypertrophy. MATERIAL AND METHODS: Synopsis and critical discussion of the available literature on the mechanisms of induction of liver hypertrophy, the advantages and drawbacks of the traditional methods, and current research on volume changes associated with RE as well as their implications for possible clinical use in preparation for liver surgery. RESULTS: Both PVE and PVL can achieve a substantial contralateral volume gain of up to 70 %. The development of contralateral hypertrophy can be accelerated by dissecting the liver parenchyma along the intended plane of resection in addition to PVL (in situ split). Compared to these methods, RE achieves less contralateral liver hypertrophy; however, this effect should not be disregarded as RE provides effective treatment of ipsilateral liver tumors along with induction of hypertrophy and may be associated with a reduced risk of tumor progression compared to PVE and PVL. CONCLUSION: The available data suggest that RE can complement the armamentarium of methods for induction of FLR hypertrophy in specific situations. Further studies are needed to establish its definitive role for this indication and are in preparation.

[Management of perioperative complications following tumor resection in the upper gastrointestinal tract]. / Management perioperativer Komplikationen nach Tumorresektionen im oberen Gastrointestinaltrakt.

BACKGROUND: Surgical resection of tumors of the upper gastrointestinal (GI) tract represent complex procedures and are still associated with a relevant morbidity and mortality. A targeted preoperative risk analysis and patient selection with consideration of the nutritional status and comorbidities are important in order to reduce the perioperative complication rate. RESULTS AND DISCUSSION: Anastomotic leaks still remain the most feared surgical complication and in addition to early recognition, immediate initiation of an appropriate therapy are essential. Conservative treatment can be considered for small and adequately drained fistulas as well as in cervical leakages. Indications for surgical reintervention are leaks that occur in the early postoperative course, fulminant defects with diffuse mediastinitis and conduit necrosis. The majority of anastomotic leaks can be successfully managed with minimally invasive endoscopic techniques, e.g. stent placement and endoluminal vacuum therapy. Delayed gastric emptying is frequently observed following esophageal resection and usually shows a satisfactory response to medicinal treatment and endoscopic interventions. The benefits of pyloroplasty in the primary intervention is still a matter of debate. Chylothorax is a rare but serious complication which should initially be managed with conservative measures. CONCLUSIONS: For the successful management of postoperative complications following surgical resection of tumors of the upper GI tract both an interdisciplinary approach and the availability of an appropriate infrastructure with defined algorithms are of paramount importance. Therefore, a concentration of these procedures in specialized centers would be highly desirable.

[Papillary tumors - therapeutic concepts]. / Papillentumoren - therapeutische Konzepte.

Papillary tumors originate from the various structures of the ampulla of Vater; therefore, these rare tumors represent a heterogeneous group of tumor entities. Intestinal differentiated adenomas are the most common benign lesions, whereas intestinal differentiated papillary carcinomas are the most common malignant tumors. Carcinomas with pancreaticobiliary differentiation have a poorer prognosis. Mesenchymal and neuroendocrine tumors are among the least frequent papillary tumors. Diagnosis is performed by side-view upper endoscopy and biopsy. In cases of suspected malignancy a complete staging with computed tomography (CT) and endoscopic ultrasound scanning is indicated to determine local tumor spread.Adenomas are removed by endoscopic snare papillectomy whereas the therapy of choice for papillary carcinomas is pancreatic head resection with systematic lymphadenectomy. Patients with papillary carcinomas are most likely to benefit from adjuvant therapy, which should be determined in an interdisciplinary consensus conference considering the histological differentiation of the tumor.

[Phytobezoar in the common hepatic duct - rare cause of obstructive jaundice following pancreatoduodenectomy: case report and review of the literature]. / Phytobezoar des Ductus hepaticus communis - seltene Differenzialdiagnose einer Cholestase im Langzeitverlauf nach Kausch-Whipple-Operation: Fallbericht und Literaturübersicht.

Obstruction of bile flow following pancreatoduodenectomy can be caused by stenosis of the hepaticojejunostomy created at the time of surgery, obstruction of the bile-draining jejunal loop, stones or, very rarely, ingested foreign bodies in the common hepatic duct. In analogy with endoscopic sphincterotomy or the once popular side-to-side-choledochduodenostomy, the creation of a hepaticojejunostomy eliminates the barrier of the sphincter Oddi, enabling intestinal content such as ingested foreign bodies or food fibers to migrate into the bile duct. We report on the case of a patient developing biliary tract obstruction due to fibrous material in the common hepatic duct 15 years after pancreatoduodenectomy. In addition, an overview of the literature on the rare phenomenon of foreign body-associated obstructive jaundice is given.

Factors influencing the quality of total mesorectal excision.

BACKGROUND: Total mesorectal excision (TME) has become the standard of care for rectal cancer. Incomplete TME may lead to local recurrence. METHODS: Data from the multicentre observational German Quality Assurance in Rectal Cancer Trial were used. Patients undergoing low anterior resection for rectal cancer between 1 January 2005 and 31 December 2009 were included. Multivariable analysis using a stepwise logistic regression model was performed to identify predictors of suboptimal TME. RESULTS: From a total of 6179 patients, complete data sets for 4606 patients were available for analysis. Pathological tumour category higher than T2 (pT3 versus pT1/2: odds ratio (OR) 1.22, 95 per cent confidence interval 1.01 to 1.47), tumour distance from the anal verge less than 8 cm (OR 1.27, 1.05 to 1.53), advanced age (65-80 years: OR 1.25, 1.03 to 1.52; over 80 years: OR 1.60, 1.15 to 2.22), presence of intraoperative complications (OR 1.63, 1.15 to 2.30), monopolar dissection technique (OR 1.43, 1.14 to 1.79) and low case volume (fewer than 20 procedures per year) of the operating surgeon (OR 1.20, 1.06 to 1.36) were independently associated with moderate or poor TME quality. CONCLUSION: TME quality was influenced by patient- and treatment-related factors.

[Gastric stump carcinoma--a surgical and oncological challenge]. / Magenstumpfkarzinom--Herausforderung der Onkochirurgie.

Gastric stump carcinoma after gastric surgery for benign disease is now widely recognized as a distinct clinical entity. An electronic literature search was performed in the MEDLINE database to identify relevant studies concerning epidemiology, prognosis, treatment, aetiology and pathology of gastric stump carcinoma. The references reported in these studies were used to complete the literature search. It can be assumed that approximately 10 % of patients who had undergone a distal gastric resection for benign disease will develop a carcinoma in the gastric remnant about 15 to 20 years after the primary procedure. The incidence is reported to be higher in males and following Billroth II resection. The site of tumour growth is predominantly in the anastomotic area, but may occur anywhere in the stump. Enterogastric reflux, achlorhydria, bacterial overgrowth, and genetic factors appear to be the major factors involved in the aetiopathogenesis of the gastric stump cancer. Unfortunately, a significant proportion of patients presents with synchronous metastases. Clinical symptoms are mainly attributed to locally advanced tumour growth. Surgical therapy comprises total removal of the gastric remnant and the jejunal segment including modified lymphadenectomy (D2 lymphadenectomy and jejunal mesentery). Surveillance of patients with endoscopy and multiple biopsies should be initiated from the tenth postoperative year and may provide the means to diagnose tumours at an early stage.

[Peritoneal splenosis 26 years after traumatic splenic rupture--rare differential diagnosis of a subepithelial gastric mass--case report and review of the literature]. / Peritoneale Splenose 26 Jahre nach traumatischer Milzruptur--seltene Differenzialdiagnose eines submukösen Magentumors--Fallbericht und Literaturübersicht.

Differential diagnoses of subepithelial gastric masses include benign (leiomyoma, lipoma, haemangioma, lymphangioma, neurogenic tumours, glomus tumour) and malignant (leiomyosarcoma, gastric Kaposi's sarcoma, metastases) neoplastic lesions, gastrointestinal stromal tumours (GIST) and lesions of non-neoplastic origin (heterotopic pancreatic tissue, intramural pseudocysts, intramural haematoma). Occasionally, however, suspected gastric wall tumours are caused by extragastral lesions that are not always easily distinguished from genuine gastric wall lesions by endoscopy or radiological imaging. We report the case of a 77-year-old patient undergoing laparoscopy for suspected gastric GIST in our institution in whom splenectomy had been performed 26 years prior to presentation due to traumatic splenic rupture. The tumour revealed to be ectopic splenic tissue located at the parietal peritoneum of the ventral abdominal wall, thereby fulfilling the definition of splenosis. Epidemiology, pathogenesis, diagnostics and therapy of splenosis are discussed in the context of a review of the relevant literature.

[Minimal Residual Disease (MRD) in gastric carcinoma--an overview]. / Minimale Resterkrankung beim Magenkarzinom - eine Übersicht.

Despite recent developments in therapy for gastric cancer, the prognosis of this disease remains poor in advanced stages. In many cases even curatively treated patients without any residual tumour develop metachronous metastases. As in other solid tumours, adjuvant therapies can reduce the metastatic risk, which implies that some of these patients harbour isolated tumour cells or micrometastases (minimal residual disease, MRD) that are undetectable by radiological imaging and conventional histopathology but can still be the cause of tumour recurrence. Therefore, reliable methods for diagnosing MRD would be desirable for individually tailoring therapy for these patients. Unfortunately, testing methods for MRD and interpretation of their results are not standardised and studies published on this topic are difficult to interpret due to methodological differences and small sample sizes. As of now, testing for MRD has not become relevant in clinical routine for any of the anatomic compartments lymph nodes, peritoneal lavage fluid, peripheral blood, and bone marrow in the Western hemisphere. Most reliable data on MRD in gastric cancer patients have been reported for peritoneal lavage fluid. In some centres in Japan, this test is routinely being used for making therapeutic decisions, e. g., on the use of intraperitoneal chemotherapy. MRD in resected lymph nodes will be further evaluated in the context of the sentinel lymph node concept and possibly be employed for designing individualised therapy for patients in early disease stages who are not routinely candidates for multimodal treatment. As for tumour cells in peripheral blood and in bone marrow, studies suggest that these cells are only able to form metastases in the presence of certain molecular factors. Therefore, rather than simply confirming the existence of isolated tumour cells in blood or bone marrow, future studies should concentrate on defining their molecular characteristics and the conditions required for their metastatic potential. This may gain relevance in diagnostics and prognostic evaluation of individual patients as well as in the development of targeted therapies directly interfering with the metastatic process.

[Surgical management of retroperitoneal soft-tissue sarcomas--an overview]. / Chirurgisches Management retroperitonealer Weichteilsarkome--eine Übersicht.

INTRODUCTION: Retroperitoneal soft-tissue sarcomas (RSTS) represent a rare and heterogeneous class of diseases for which the clinical management is still largely non-standardised. Based on a selective review of recent publications, it was the purpose of the present review article to summarize the current concepts of disease classification, diagnostics and surgical as well as multimodal therapy for these tumors. METHOD: A clinically based empirical review derived from a literature search focusing on publications from the past 5  years was carried out. RESULTS: Due to the paucity of randomised-controlled trials, therapy for RSTS is largely based on personal experience, retrospectively gathered data and historical controls. Pre-therapeutic planning requires precise information on the localisation, extension, and texture of the tumor through cross-sectional imaging (CT, MRI) as well as histological diagnosis through percutaneous or open biopsy. Complete tumor resection is crucial. Recent studies have confirmed the importance of microscopically negative resection margins which has subsequently led to a trend towards more radical resection. Chemotherapy does not play a role in the adjuvant setting except in clinical trials; however, radiotherapy has been controversely debated in adjuvant RSTS therapy. Efforts to limit radiation toxicity include modern techniques as well as a strategy of using pre-resection radiotherapy instead of postoperative radiation. Surgery is also the treatment of choice for locally recurrent RSTS and pulmonary metastases. The prognosis of RSTS depends on the quality of surgical care and several disease-specific factors (histological type, grading). CONCLUSION: The clinical management of RSTS is complex and can only partly be considered as evidence-based. Due to the required level of experience in the treatment of these tumor lesions and the involvement of several subspecialties, pre-therapeutic planning, treatment and follow-up should be limited to high-volume surgical centres. In order to achieve microscopically negative resection margins, multivisceral resections are a valuable option after thorough consideration of the risks and benefits. Adjuvant radiotherapy needs to be decided upon on an individual basis, taking into account patient- and tumor-specific factors as well as resection status.

[Laparoscopy for suspected appendicitis. Should an appendix that appears normal be removed?]. / Laparoskopie bei Verdacht auf akute Appendizitis. Soll die makroskopisch unauffällige Appendix entfernt werden?

The question whether an appendix found to be macroscopically normal at laparoscopy for suspected appendicitis should be removed remains open to debate. Potential advantages of appendicectomy in all cases include early diagnosis of neoplastic lesions that cannot be detected macroscopically, diagnosis and cure of neurogenic appendicectomy, avoidance of diagnostic confusion in later episodes of abdominal pain, and prevention of appendicitis developing later in life. Therefore, adopting a strategy of always removing the appendix even if it is found to be uninflamed at laparoscopy seems justified as long as it does not imply an increase in postoperative morbidity. We retrospectively studied all patients undergoing laparoscopic appendicectomy in which a "normal appendix" was found and all patients undergoing diagnostic laparoscopy in our hospital during a 7-year period. Our data as well as a critical review of the literature show that removal of the appendix does not increase morbidity compared to simple diagnostic laparoscopy and should always be done when performing laparoscopy for suspected acute appendicitis.

[APC resistance due to factor V Leiden mutation presenting as acute hemorrhagic jejunal infarction--case report]. / Akuter hämorrhagischer Jejunuminfarkt als Erstmanifestation einer APC-Resistenz bei Faktor-V-Leiden-Mutation--ein Fallbericht.

We report on a 43-year-old patient presenting to the emergency department with acute abdominal pain the source of which turned out to be acute hemorrhagic jejunal infarction due to portal and mesenteric vein occlusion with no apparent cause. In spite of a lacking history of hereditary thrombophilic risk factors, further diagnostic procedures revealed heterozygous factor V Leiden mutation. Diagnosis, therapy and clinical course are described. An overview on acute mesenteric venous occlusion with special reference to genetically determined thrombophilic disorders is given.