Meta-analysis of recurrence pattern after resection for pancreatic cancer.

BACKGROUND: Initial recurrence mapping of resected pancreatic ductal adenocarcinoma (PDAC) could help in stratifying patient subpopulations for optimal postoperative follow-up. The aim of this systematic review and meta-analysis was to investigate the initial recurrence patterns of PDAC and to correlate them with clinicopathological factors. METHODS: MEDLINE and Web of Science databases were searched systematically for studies reporting first recurrence patterns after PDAC resection. Data were extracted from the studies selected for inclusion. Pooled odds ratios (ORs) and 95 per cent confidence intervals were calculated to determine the clinicopathological factors related to the recurrence sites. The weighted average of median overall survival was calculated. RESULTS: Eighty-nine studies with 17 313 patients undergoing PDAC resection were included. The weighted median rates of initial recurrence were 20·8 per cent for locoregional sites, 26·5 per cent for liver, 11·4 per cent for lung and 13·5 per cent for peritoneal dissemination. The weighted median overall survival times were 19·8 months for locoregional recurrence, 15·0 months for liver recurrence, 30·4 months for lung recurrence and 14·1 months for peritoneal dissemination. Meta-analysis revealed that R1 (direct) resection (OR 2·21, 95 per cent c.i. 1·12 to 4·35), perineural invasion (OR 5·19, 2·79 to 9·64) and positive peritoneal lavage cytology (OR 5·29, 3·03 to 9·25) were significantly associated with peritoneal dissemination as initial recurrence site. Low grade of tumour differentiation was significantly associated with liver recurrence (OR 4·15, 1·71 to 10·07). CONCLUSION: Risk factors for recurrence patterns after surgery could be considered for specific surveillance and treatments for patients with pancreatic cancer.

ANTECEDENTES: El mapeo del patrón de recidiva inicial tras la resección de un adenocarcinoma ductal pancreático (pancreatic ductal adenocarcinoma, PDAC) podría ayudar a estratificar subpoblaciones de pacientes para un seguimiento postoperatorio óptimo. El objetivo de esta revisión sistemática con metaanálisis fue investigar los patrones de recidiva inicial de PDAC y correlacionarlos con factores clínico-patológicos. MÉTODOS: Se realizaron búsquedas sistemáticas en las bases de datos MEDLINE y Web of Science para seleccionar estudios que presentaran información sobre los patrones de recidiva inicial después de la resección del PDAC. Se extrajeron los datos de los estudios seleccionados para su inclusión en el metaanálisis. Se calcularon las razones de oportunidades agrupadas (pooled odds ratio, OR) y los i.c. del 95% para definir los factores clínico-patológicos relacionados con las localizaciones de la recidiva. Se estimó el promedio ponderado de la mediana de la supervivencia global. RESULTADOS: Se incluyeron 89 estudios con 17.313 pacientes a los que se realizó una resección por PDAC. Las tasas medias ponderadas de las localizaciones de la recidiva inicial fueron del 20,8% para la locorregional, 26,5% para las hepáticas, 11,4% para el pulmón y 13,5% para la diseminación peritoneal. La mediana ponderada de supervivencia global fue de 19,8 meses (locorregional), 15,0 meses (hígado), 30,4 meses (pulmón) y 14,1 meses (diseminación peritoneal). El metaanálisis demostró que la resección R1 (inicial) (OR 2,21, i.c. del 95% 1,12-4,35), la invasión perineural (OR 5,19; i.c. del 95% 2,79-9,64) y la positividad de la citología del lavado peritoneal (OR 5,29; i.c. del 95% 3,03-9,25) se asociaron significativamente con la diseminación peritoneal como localización de recidiva inicial. El bajo grado de diferenciación tumoral se asoció significativamente con la recidiva hepática (OR 4,15; i.c. del 95%: 1,71-10,07). CONCLUSIÓN: Se podrían tener en cuenta estos factores de riesgo de los patrones de recidiva tras la cirugía para realizar un seguimiento y tratamiento específicos en pacientes con cáncer de páncreas.

Meta-analysis of effect of routine enteral nutrition on postoperative outcomes after pancreatoduodenectomy.

BACKGROUND: The optimal nutritional treatment after pancreatoduodenectomy is still unclear. The aim of this meta-analysis was to investigate the impact of routine enteral nutrition following pancreatoduodenectomy on postoperative outcomes. METHODS: RCTs comparing enteral nutrition (regular oral intake with routine tube feeding) with non-enteral nutrition (regular oral intake with or without parenteral nutrition) after pancreatoduodenectomy were sought systematically in the MEDLINE, Cochrane Library and Web of Science databases. Postoperative data were extracted. Random-effects meta-analyses were performed to compare postoperative outcomes in the two arms, and pooled odds ratios (ORs) or mean differences (MDs) were calculated with 95 per cent confidence intervals. In subgroup analyses, the routes of nutrition were assessed. Percutaneous tube feeding and nasojejunal tube feeding were each compared with parenteral nutrition. RESULTS: Eight RCTs with a total of 955 patients were included. Enteral nutrition was associated with a lower incidence of infectious complications (OR 0·66, 95 per cent c.i. 0·43 to 0·99; P = 0·046) and a shorter length of hospital stay (MD -2·89 (95 per cent c.i. -4·99 to -0·80) days; P < 0·001) than non-enteral nutrition. Percutaneous tube feeding had a lower incidence of infectious complications (OR 0·47, 0·25 to 0·87; P = 0·017) and a shorter hospital stay (MD -1·56 (-2·13 to -0·98) days; P < 0·001) than parenteral nutrition (3 RCTs), whereas nasojejunal tube feeding was not associated with better postoperative outcomes (2 RCTs). CONCLUSION: As a supplement to regular oral diet, routine enteral nutrition, especially via a percutaneous enteral tube, may improve postoperative outcomes after pancreatoduodenectomy.

Predictive performance of factors associated with malignancy in intraductal papillary mucinous neoplasia of the pancreas.

BACKGROUND: Estimation of the risk of malignancy in intraductal papillary mucinous neoplasia (IPMN) of the pancreas is a clinical challenge. Several routinely used clinical factors form the basis of the current consensus guidelines. This study aimed to determine the predictive values of the most commonly assessed risk factors. METHODS: A meta-analysis of individual risk factors of malignancy in IPMN was performed. Contingency tables were derived from these data, and sensitivity, specificity, negative and positive predictive values, and diagnostic odds ratios (DOR) were determined. Hierarchical summary receiver operating characteristic (HSROC) curves for each factor were calculated and the respective area under the curve (AUC) was assessed. RESULTS: A total of 3443 studies were screened initially. Analysis of recent literature revealed 60 studies with 13 relevant risk factors including clinical, serological and radiological parameters. The largest area under the HSROC curve was found for weight loss (0·84) and jaundice/raised bilirubin level (0·80), followed by increased carcinoembryonic antigen (CEA) (0·79) or carbohydrate antigen (CA) 19-9 (0·78) levels. The most sensitive factors were patient age (71 per cent) and mural nodules (65 per cent), and jaundice/raised bilirubin level (97 per cent) and increased CEA level (95 per cent) were most specific. None of the analysed factors reached a positive or negative level of prediction beyond 90 per cent. CONCLUSION: None of the established criteria safely distinguishes malignant from non-malignant lesions.

[Gastric stump carcinoma: frequency, treatment, complications and prognosis]. / Magenstumpfkarzinom: Häufigkeit, Therapie, Komplikationen und Prognose.

BACKGROUND: Gastric stump carcinoma develops in the gastric remnant after partial gastrectomy. While the frequency of gastric cancer is declining, the incidence of gastric stump carcinoma has remained stable due to the long latency period. As the surgical treatment of gastric ulcers by partial gastrectomy has become much less important, more and more gastric stump carcinomas develop after oncological resection. AIM: This study compared the surgical therapy of gastric stump carcinoma with the therapy of primary gastric cancer. MATERIAL AND METHODS: From 2001 to 2014 a total of 24 patients were surgically treated for gastric stump carcinoma in the University Hospital of Heidelberg. In the same time 428 patients underwent resection due to primary gastric cancer. Both groups were analyzed and compared with a focus on preoperative therapy, intraoperative differences, complications and overall survival. RESULTS: Patients with gastric stump carcinoma were older at disease onset (68 years vs. 62 years, p = 0.003). Compared with primary gastric cancer, patients with gastric stump carcinoma were more often suspected of having lymph node (cN+) involvement (51.4 % vs. 41.7 %, p < 0.001) but neoadjuvant therapy was applied less often (48.7 % vs. 14.3 %, p < 0.01). For resection of gastric stump carcinoma, extended resections were more often necessary (54.5 % vs. 28.2 %, p < 0.001). There were no significant differences in mean overall survival between the two patient groups (64.4 months vs. 45.8 months, p = 0.34) CONCLUSION: Despite the differences described, the treatment of gastric stump carcinoma does not essentially differ from that of primary gastric cancer. Carcinomas of the gastric stump are more often locally advanced and in our opinion a neoadjuvant therapy should be applied analogue to gastric cancer even if evidence-based data on this point are limited.

[Are There Gender-Specific Differences in Complications Following Abdominal Surgery?]. / Gibt es geschlechterspezifische Unterschiede bei Komplikationen in der offenen Viszeralchirurgie?

Studies in mice indicate gender-specific differences in surgical complications with a distinct advantage for females. In patient care, however, gender has been an underrated aspect of complication management in abdominal surgery as far. Proven differences between the sexes regarding anatomy, hormonal regulation, constitutional polymorphisms, immune response and psychology suggest different types and incidence of complications and seem to justify studies on the topic. This review aims to compare a selection of current original articles reporting on complications following abdominal surgery separately for the genders. However, data in the literature are sparse and in part very heterogeneous. With data on colorectal carcinoma being most comprehensive, for stomach, oesophagus and finally pancreas fewer data can be found. Summing up all organ systems, the following cautious conclusions can be drawn. Men tend to suffer from postoperative complications more frequently. Men have more cases of anastomotic leakage, whereas women suffer from anastomotic stenosis more often. Currently, however, existing data do not justify any adaptation of patient management. Thus, taking gender aspects into account in designing new trials is paramount in order to obtain robust gender-specific data on incidence and types of complications.

[Gender Aspects in Gastrointestinal Tumours and Their Prognosis in Regard to Multimodal Treatment Concepts]. / Genderaspekte bei Tumoren des Gastrointestinaltrakts und ihre Prognose, insbesondere im Rahmen multimodaler Therapiekonzepte.

Systematic analyses of gender effects in gastrointestinal malignancies are currently lacking, partly because sex and gender have not been used as stratification criteria in major studies on the topic. It is, however, indisputable that gastrointestinal tumours differ in risk factors, incidence and prognosis between the genders. This review summarises the most important findings on differences related to biological sex and sociocultural gender and discusses anatomic specifics with immediate significance for surgical interventions. Epidemiological differences in upper gastrointestinal malignancies are most prominent in regard to histological subtypes, directly affecting diagnostics, therapy, and prognosis. Women have a better prognosis in many of these tumour subtypes. For colorectal carcinoma, sex hormones, specifically oestrogens, appear to play a distinct role in tumourigenesis. Histopathological analysis of the expression of oestrogen receptor beta (ERß) in the tumour tissue has attracted interest since it was shown that women with low ERß expression have a better prognosis than men with comparable ERß status. Data on the higher incidence of right-sided colon carcinoma and non-polypoid neoplasms in women could lead to improved screening programmes. Men and women cite differing reasons for avoidance of screening colonoscopies, thus gender specific approaches could improve colon cancer prevention programmes. Data on differing bioavailability of 5-fluorouracil between the genders are useful to minimise adverse effects of chemotherapy and should be accounted for in dosage. Further systematic analysis of gender effects on gastrointestinal tumours is warranted and would be a substantial step towards personalised oncological surgery.

[Total pelvic exenteration]. / Totale Beckenexenteration.

Over the last decades total pelvic exenteration (TPE) has evolved into an established and safe surgical technique for locally advanced pelvic malignancies. Depending on the type of cancer 5 year overall survival rates of up to 66% and a satisfactory postsurgical quality of life have been reported. Currently infiltration of the pelvic side wall and resectable metastases are not necessarily a contraindication to a curative approach; furthermore, TPE can also be useful in palliative surgery. In locally recurrent rectal cancer TPE is the treatment of choice if the tumor is deemed resectable. A multidisciplinary diagnostic and therapeutic approach is of utmost importance, hence patients should be treated in specialized centers.

[Indications for pre- and postoperative treatment with imatinib for gastrointestinal stromal tumors]. / Indikationen zur prä- und postoperativen Therapie mit Imatinib bei gastrointestinalen Stromatumoren.

Imatinib is a tyrosine kinase inhibitor directed against the KIT and the PDGF-alpha receptors. Imatinib has proven efficacy in the treatment of metastatic GIST with a response rate achieving 70%, but treatment with imatinib alone is not curative. The median progression-free survival is about 2 years. In locally advanced GIST, primary treatment with imatinib proved to be safe and feasible in several cohort studies. The goal of any curatively intended surgical treatment for GIST is R0 resection. Therefore, neoadjuvant treatment with imatinib can be recommended if tumor-free margin resection is doubtful. After R0 resection of GISTs with intermediate or high risk of relapse, preliminary data indicate that imatinib administered for at least 1 year reduces the risk of relapse and may improve the prognosis. However, no mature survival data from randomized studies have been published thus far. Therefore adjuvant treatment with imatinib is not yet approved nor is it a standard of care at this stage. The inclusion of patients with intermediate- and high-risk resected GIST into clinical studies is strongly recommended.