[Show abstract][Hide abstract] ABSTRACT: Objective: To determine whether circular plastic wound edge protectors (CWEPs) significantly reduce the rate of surgical site infections (SSIs) in comparison to standard surgical towels in patients undergoing laparotomy. Background: SSIs cause substantial morbidity, prolonged hospitalization, and costs and remain one of themost frequent surgical complications. CWEPs have been proposed as a measure to reduce the incidence of SSIs. Methods: In this randomized controlled, multicenter, 2-arm, parallel-group design, patient-and observer-blinded trial patients undergoing open elective abdominal surgery were assigned to either intraoperative wound coverage with a CWEP or standard coverage with surgical towels. Primary endpoint was superiority of intervention over control in terms of the incidence of SSIs within a 30-day postoperative period. Results: Between September 2010 and November 2012, 608 patients undergoing laparotomy were randomized at 16 centers across Germany. Three patients in the device group and 11 patients in the control group did not undergo laparotomy. Patients' and procedural characteristics were well balanced between the 2 groups. Forty-eight patients discontinued the study prematurely, mainly because of relaparotomy (control, n = 9; intervention, n = 9) and death (control, n = 4; intervention, n = 7). A total of 79 patients experienced SSIs within 30 days of surgery, 27 of 274 (9.9%) in the device group and 52 of 272 (19.1%) in the control group (odds ratio = 0.462, 95% confidence interval: 0.281-0.762; P = 0.002). Subgroup analyses indicate that the effect could be more pronounced in colorectal surgery, and in cleancontaminated/contaminated surgeries. Conclusions: Our trial shows that CWEPs are effective at reducing the incidence of SSIs in elective and clean or clean-contaminated open abdominal surgery.
Full-text · Article · Nov 2014 · Annals of Surgery
[Show abstract][Hide abstract] ABSTRACT: Objectives: Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. Background: The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain. Materials and Methods: NI was characterized in approximately 16,000 hematoxylin and eosin tissue sections from 2050 patients with adenocarcinoma of the esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC), cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic cancer (PC). NI prevalence and severity was determined and related to patient's prognosis and survival. Results: NI prevalence largely varied between HCC/6%, CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG-III/65% to PC/100%. NI severity score was uppermost in PC (24.9 +/- 1.9) and lowest in AEG-I (0.8 +/- 0.3). Multivariable analyses including age, sex, TNM stage, and grading revealed that the prevalence of NI was significantly associated with diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity impaired survival in AEG-II/III and PC only. Conclusions: NI prevalence and NI severity strongly vary within GIMs. Determination of NI severity in GIMs is amore precise tool than solely recording the presence of NI and revealed dismal prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a concomitant side feature in GIMs and, therefore, deserves special attention for improved patient stratification and individualized therapy after surgery.
No preview · Article · Nov 2014 · Annals of Surgery
[Show abstract][Hide abstract] ABSTRACT: Routine placement of intraperitoneal drains has been shown to be ineffective or potentially harmful in various abdominal surgical procedures. Studies assessing risks and benefits of abdominal drains for pancreatic resections have demonstrated inconsistent results. We thus performed a systematic review of the literature and meta-analyzed outcomes of pancreatic resections with and without intraoperative placement of drains.
A database search according to the PRISMA guidelines was performed for studies on pancreatic resection with and without intraperitoneal drainage. The subgroup ‘pancreaticoduodenectomy’ was analyzed separately. The quality of studies was assessed using the MINORS and STROBE criteria. Pooled estimates of morbidity, mortality and length of hospital stay were calculated using random effects models.
Only two randomized trials were identified. Their results were contradictory. We thus included six further, retrospective studies in the meta-analysis. However, with I2 = 68% for any kind of complication, the estimate of inter-study heterogeneity was high. While overall morbidity after any kind of pancreatic resection was lower without drains (p = 0.04), there was no significant difference in mortality rates. In contrast, pooled estimates of outcomes after pancreaticoduodenectomy demonstrated no differences in morbidity (p = 0.40) but increased rates of intraabdominal abscesses (p = 0.04) and mortality (p = 0.04) without intraperitoneal drainage.
Although drains are associated with slightly increased morbidity for pancreatic resections, routine omission of drains cannot be advocated, especially after pancreaticoduodenectomy. While selective drainage seems reasonable, further efforts to generate more reliable data are questionable because of the current studies and the presumed small differences in outcomes.
Systematic review registration number CRD42014007497.
[Show abstract][Hide abstract] ABSTRACT: Background
The lymph node (Ln) status of patients with resectable pancreatic ductal adenocarcinoma is an important predictor of survival. The survival benefit of extended lymphadenectomy during pancreatectomy is, however, disputed, and there is no true definition of the optimal extent of the lymphadenectomy. The aim of this study was to formulate a definition for standard lymphadenectomy during pancreatectomy.
During a consensus meeting of the International Study Group on Pancreatic Surgery, pancreatic surgeons formulated a consensus statement based on available literature and their experience.
The nomenclature of the Japanese Pancreas Society was accepted by all participants. Extended lymphadenectomy during pancreatoduodenectomy with resection of Ln's along the left side of the superior mesenteric artery (SMA) and around the celiac trunk, splenic artery, or left gastric artery showed no survival benefit compared with a standard lymphadenectomy. No level I evidence was available on prognostic impact of positive para-aortic Ln's. Consensus was reached on selectively removing suspected Ln's outside the resection area for frozen section. No consensus was reached on continuing or terminating resection in cases where these nodes were positive.
Extended lymphadenectomy cannot be recommended. Standard lymphadenectomy for pancreatoduodenectomy should strive to resect Ln stations no. 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a, 14b, 17a, and 17b. For cancers of the body and tail of the pancreas, removal of stations 10, 11, and 18 is standard. Furthermore, lymphadenectomy is important for adequate nodal staging. Both pancreatic resection in relatively fit patients or nonresectional palliative treatment were accepted as acceptable treatment in cases of positive Ln's outside the resection plane. This consensus statement could serve as a guide for surgeons and researchers in future directives and new clinical studies.
[Show abstract][Hide abstract] ABSTRACT: Despite progress in the treatment of pancreatic cancer, there is still a need for improved therapies. In this manuscript, we report clinical experience with a new therapy for the treatment of pancreatic cancer involving the implantation of encapsulated cells over-expressing a cytochrome P450 enzyme followed by subsequent low-dose ifosfamide administrations as a means to target activated ifosfamide to the tumor. The safety and efficacy of the angiographic instillation of encapsulated allogeneic cells overexpressing cytochrome P450 in combination with low-dose systemic ifosfamide administration has now been evaluated in 27 patients in total. These patients were successfully treated in four centers by three different interventional radiologists, arguing strongly that the treatment can be successfully used in different centers. The safety of the intra-arterial delivery of the capsules and the lack of evidence that the patients developed an inflammatory or immune response to the encapsulated cells or encapsulation material was shown in all 27 patients. The ifosfamide dose of 1 g/m2/day used in the first trial was well tolerated by all patients. In contrast, the ifosfamide dose of 2 g/m2/day used in the second trial was poorly tolerated in most patients. Since the median survival in the first trial was 40 weeks and only 33 weeks in the second trial, this strongly suggests that there is no survival benefit to increasing the dose of ifosfamide, and indeed, a lower dose is beneficial for quality of life and the lack of side effects. This is supported by the one-year survival rate in the first trial being 38%, whilst that in the second trial was only 23%. However, taking the data from both trials together, a total of nine of the 27 patients were alive after one year, and two of these nine patients were alive for two years or more.
[Show abstract][Hide abstract] ABSTRACT: Background In neural invasion (NI), cancer cells are classically assumed to actively invade nerves and to cause local recurrence and
pain. However, the opposite possibility, that nerves may reach cancer cells even in their preinvasive stage and thereby promote
cancer spread, has not yet been genuinely considered. The present study analyzes the reaction of Schwann cells of peripheral
nerves to carcinogenesis in pancreatic cancer and colon cancer.
Full-text · Article · Aug 2014 · JNCI Journal of the National Cancer Institute
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma is one of the most common malignancies worldwide. The only curative treatment is surgery. As hepatocellular carcinoma is often associated with liver cirrhosis, patients are at risk for postoperative liver failure. In the recent years, platelets are thought to play an important role in liver regeneration.The aim of this study was to discover the relevance of postoperative platelet counts after liver resection for hepatocellular carcinoma.
Data of 68 patients who underwent liver resection for hepatocellular carcinoma between July 2007 and July 2012 in a single centre were analysed. Postoperative morbidity and mortality were evaluated in regard to postoperative platelet counts. Comparative analysis between patients with platelet counts ≤100 2x109/ l and >100 x109/ l at d1 was performed in regard to postoperative outcome.
Within this cohort, 43 patients (63%) suffered from histologically proven liver cirrhosis. Postoperative mortality was statistically significant associated with postoperative reduced platelet counts. Comparative analysis showed significantly elevated postoperative bilirubin levels and lower prothrombin time in patients with platelet counts ≤ 100 1x109/ l at d1.
Postoperative low platelet counts are associated with poor outcome after hepatic resection for hepatocellular carcinoma.
No preview · Article · Jul 2014 · Hepato-gastroenterology
[Show abstract][Hide abstract] ABSTRACT: Background
Complete macroscopic tumor resection is one of the most relevant predictors of long-term survival in pancreatic ductal adenocarcinoma. Because locally advanced pancreatic tumors can involve adjacent organs, “extended” pancreatectomy which includes the resection of additional organs may be needed to achieve this goal. Our aim was to develop a common consistent terminology to be used in centers reporting results of pancreatic resections for cancer.
An international panel of pancreatic surgeons working in well-known, high-volume centers reviewed the literature on extended pancreatectomies and worked together to establish a consensus on the definition and the role of extended pancreatectomy in pancreatic cancer.
Macroscopic (R1) and microscopic (R0) complete tumor resection can be achieved in patients with locally advanced disease by extended pancreatectomy. Operative time, blood loss, need for blood transfusions, duration of stay in the intensive care unit and hospital, morbidity, and possibly also perioperative mortality are increased with extended resections. Long-term survival is similar compared to standard resections but appears to be better compared to bypass surgery or nonsurgical palliative chemotherapy or chemoradiotherapy. It was not possible to identify any clear prognostic criteria based on the specific additional organ resected.
Despite increased perioperative morbidity, extended pancreatectomy is warranted in locally advanced disease to achieve long-term survival in pancreatic ductal adenocarcinoma if macroscopic clearance can be achieved. Definitions of extended pancreatectomies for locally advanced disease (and not distant metastatic disease) are established which are crucial for comparison of results of future trials across different practices and countries, in particular for those utilizing neoadjuvant therapy.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
With improved chemotherapeutic regimens, metastasized gastric cancer may show a good response rendering an initially unresectable tumor resectable. We performed a retrospective analysis on the outcome of stage IV gastric cancer patients treated by chemotherapy followed by oncologic resection in a western institution.
From August 1988 to December 2010, a total number of 1,817 patients underwent surgery for gastric cancer at the Department of Surgery, Technical University of Munich. A retrospective analysis of our prospective gastric cancer database identified 58 patients with stage IV gastric cancer having undergone induction chemotherapy followed by surgery in an individualized treatment concept. After induction chemotherapy usually consisting of 2 cycles of PLF (cisplatin, 5-fluorouracil, leucovorin), resection was performed with or without removal of metastases in patients without disease progression. Patients were followed up until death or loss to follow up.
The three most common metastatic locations were liver (27.6 %), distant lymph nodes (22.4 %), and peritoneum (19.0 %). Of patients, 13.8 % had metastases in more than one location. Thirty-day mortality was 5.2 %, 90-day mortality was 13.8 %, while overall postoperative morbidity accounted for 24 %. In 19 (32.8 %) patients, a complete resection without any macroscopic tumor residues was achieved. In 39 (67.2 %) patients, tumors could not be completely removed with either local residual disease or residual disease at distant sites. Overall median survival was 20 months, while patients without residual tumor survived significantly longer (72 months) than patients with residual disease (12 months, p = 0.001).
Secondary surgery of metastasized gastric cancer may be justified in selected cases without progression under induction chemotherapy. An achievable complete removal of the primary tumor and metastases appears the main selection criterion for patients benefitting from this approach.
No preview · Article · Jun 2014 · Langenbeck s Archives of Surgery
[Show abstract][Hide abstract] ABSTRACT: Aim:
To systematically characterize specific pain patterns in the most frequent pancreatic diseases.
Pain in patients with chronic pancreatitis (n = 314), pancreatic cancer (n = 469), and other pancreatic tumors (n = 249) including mucinous (n = 20) and serous cystadenoma (n = 31), invasive (n = 37) and non-invasive intraductal papillary mucinous neoplasia (IPMN; n = 48), low stage (n = 18) and high stage neuroendocrine neoplasia (n = 44), and ampullary cancer (n = 51) was registered and correlated with clinicopathological data. Survival times were estimated by the Kaplan-Meier method. Patients alive at the follow-up time were censored. Survival curves were compared statistically using the log-rank test.
Forty-nine point one percent of pancreatic cancer patients revealed no pain, whereas in chronic pancreatitis only 18.3% were pain free. In contrary, moderate/severe pain was registered in 15.1% in pancreatic cancer patients that was increased in chronic pancreatitis with up to 34.2%. Serous cystadenoma was asymptomatic in most cases (58.1%), whereas 78.9% of all mucinous cystadenoma patients suffered pain. In neuroendocrine neoplasia pain was not a key clinical symptom since 64% of low stage neuroendocrine neoplasia and 59% of high stage neuroendocrine neoplasia patients were pain free. Cancer localization in the pancreatic body and patients with malignant pancreatic neoplasms were associated with more severe pain. Tumor grading and stage did not show any impact on pain. Only in pancreatic cancer, pain was directly associated with impaired survival.
Pancreatic pain depicts different patterns of abdominal pain sensation according to the respective pancreatic disorder and does not allow a unification of the term pancreatic pain.
[Show abstract][Hide abstract] ABSTRACT: Background
This position statement was developed in order to expedite a consensus on definition and treatment for borderline resectable pancreatic ductal adenocarcinoma (BRPC) that would have worldwide acceptability.
An international panel of pancreatic surgeons from well-established high-volume centers collaborated on a literature review and development of consensus on issues related to borderline resectable pancreatic cancer.
The International Study Group for Pancreatic Surgery (ISGPS) supports the National Comprehensive Cancer Network (NCCN) criteria for the definition of BRPC. Current evidence supports operative exploration and resection in the case of involvement of the mesenterico-portal venous axis; in addition, a new classification of extrahepatic mesenterico-portal venous resections is proposed by the ISGPS. Suspicion of arterial involvement should lead to exploration to confirm the imaging-based findings. Formal arterial resections are not recommended; however, in exceptional circumstances, individual therapeutic approaches may be evaluated under experimental protocols. The ISGPS endorses the recommendations for specimen examination and the definition of an R1 resection (tumor within 1mm from the margin) used by the British Royal College of Pathologists (RCPath). Standard preoperative diagnostics for BRPC may include: 1) serum levels of CA19-9, because CA19-9 levels predict survival in large retrospective series, and also 2) the modified Glasgow Prognostic Score (mGPS) and the neutrophil/lymphocyte ratio (NLR), because of the prognostic relevance of the systemic inflammatory response. Various regimens of neoadjuvant therapy are recommended only in the setting of prospective trials at high-volume centers.
Current evidence justifies porto-mesenteric venous resection in patients with BRPC. Basic definitions were identified, that are currently lacking but that are needed to obtain further evidence and improvement for this important patient subgroup. A consensus for each topic is given.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with an extremely poor prognosis. Inflammatory processes have emerged as key mediators of pancreatic cancer development and progression. In genetically engineered mouse models, induction of pancreatitis accelerates PDAC development, and patients with chronic pancreatitis are known to have a higher risk of developing pancreatic cancer. In recent years, much effort has been given to identify the underlying mechanisms that contribute to inflammation-induced tumorigenesis. Many inflammatory pathways have been identified and inhibitors have been developed in order to prevent cancer development and progression. In this chapter, we discuss the role of inflammatory pathways in the initiation and progression of pancreatic cancer as well as the role of inhibitors used in treatment and prevention of pancreatic cancer.
Full-text · Article · May 2014 · Advances in Experimental Medicine and Biology
[Show abstract][Hide abstract] ABSTRACT: Neuroplasticity is an inherent feature of the enteric nervous system and gastrointestinal (GI) innervation under pathological conditions. However, the pathophysiological role of neuroplasticity in GI disorders remains unknown. Novel experimental models which allow simulation and modulation of GI neuroplasticity may enable enhanced appreciation of the contribution of neuroplasticity in particular GI diseases such as pancreatic cancer (PCa) and chronic pancreatitis (CP). Here, we present a protocol for simulation of pancreatic neuroplasticity under in vitro conditions using newborn rat dorsal root ganglia (DRG) and myenteric plexus (MP) neurons. This dual-neuron approach not only permits monitoring of both organ-intrinsic and -extrinsic neuroplasticity, but also represents a valuable tool to assess neuronal and glial morphology and electrophysiology. Moreover, it allows functional modulation of supplied microenvironmental contents for studying their impact on neuroplasticity. Once established, the present neuroplasticity assay bears the potential of being applicable to the study of neuroplasticity in any GI organ.
No preview · Article · May 2014 · Journal of Visualized Experiments