Background Obstructive jaundice is a common presenting symptom among patients with pancreatic cancer. While benefits of preoperative biliary drainage have been suggested by previous studies, recent ...evidence has shown no significant improvements of preoperative biliary drainage on the postoperative outcome but rather an increase of complications. There is no clear consensus on whether to treat malignant obstructive jaundice with preoperative biliary drainage prior to operative intervention or to proceed directly to resection. Thus, our aim was to elucidate the impact of preoperative biliary drainage of obstructive jaundice due to malignant pancreatic head tumors on postoperative morbidity and mortality. Methods We conducted a meta-analysis in accordance with the PRISMA guidelines and carried out a systematic search of medical databases. The results were analyzed according to predefined criteria. We pooled the incidence of overall complications, wound infection, pancreatic fistula, intra-abdominal abscess, and death within the perioperative time period. Results We initially identified 1,816 studies, and 25 of these (22 retrospective studies, 3 randomized controlled trials) were finally included in the analysis with a total number of 6,214 patients. Analysis revealed an increased incidence of overall complications (odds ratio: 1.40; 95% confidence interval: 1.14–1.72; P = .002) and wound infections (odds ratio: 1.94; 95% confidence interval: 1.48–2.53; P < .00001) in patients receiving preoperative biliary drainage compared to operative intervention first. Mortality, incidence of pancreatic fistula, or intra-abdominal abscess formation were not affected by preoperative biliary drainage. Conclusion Preoperative biliary drainage does not have a beneficial effect on postoperative outcome. The increase of postoperative overall complications and wound infections urges for precise indications for preoperative biliary drainage and against routine preoperative biliary decompression.
Pancreatic nerves undergo prominent alterations during the evolution and progression of human chronic pancreatitis and pancreatic cancer. Intrapancreatic nerves increase in size (neural hypertrophy) ...and number (increased neural density). The proportion of autonomic and sensory fibres (neural remodelling) is switched, and are infiltrated by perineural inflammatory cells (pancreatic neuritis) or invaded by pancreatic cancer cells (neural invasion). These neuropathic alterations also correlate with neuropathic pain. Instead of being mere histopathological manifestations of disease progression, pancreatic neural plasticity synergizes with the enhanced excitability of sensory neurons, with Schwann cell recruitment toward cancer and with central nervous system alterations. These alterations maintain a bidirectional interaction between nerves and non-neural pancreatic cells, as demonstrated by tissue and neural damage inducing neuropathic pain, and activated neurons releasing mediators that modulate inflammation and cancer growth. Owing to the prognostic effects of pain and neural invasion in pancreatic cancer, dissecting the mechanism of pancreatic neuroplasticity holds major translational relevance. However, current in vivo models of pancreatic cancer and chronic pancreatitis contain many discrepancies from human disease that overshadow their translational value. The present Review discusses novel possibilities for mechanistically uncovering the role of the nervous system in pancreatic disease progression.
Pancreatic cancer is known to be the deadliest of all common cancers. Despite all efforts in pancreatic cancer treatment, the five-year survival rates at diagnosis over the past 20 years have only ...increased from 5% to 8%. Assuming that pancreatic cancer is going to become the second most frequent cause of cancer related death in the next 20 years, we are all encouraged to treat patients in clinical trials to gain improvements in this devastating disease. Areas covered: This review will provide a summary of pancreatic cancer treatment over the last 20 years, starting with the pivotal study in 1997 which showed the superiority of gemcitabine over 5-FU in advanced pancreatic cancer and is marked as the beginning of a new era in pancreatic cancer treatment. This review will also focus on improvements in different areas of treatment, including pancreatic surgery, adjuvant treatment, neoadjuvant therapy and palliative therapy. Expert commentary: The treatment of pancreatic cancer has changed substantially in the last 20 years compared to almost no improvements in the decades before. This provides hope that more effective treatment options will become available in the near future. Particularly, new concepts such as neoadjuvant therapy in resectable and borderline-resectable tumors may potentially shift treatment strategies.
Pancreatic cancer has an extremely poor prognosis and prolonged survival is achieved only by resection with macroscopic tumor clearance. There is a strong rationale for a neoadjuvant approach, since ...a relevant percentage of pancreatic cancer patients present with non-metastatic but locally advanced disease and microscopic incomplete resections are common. The objective of the present analysis was to systematically review studies concerning the effects of neoadjuvant therapy on tumor response, toxicity, resection, and survival percentages in pancreatic cancer.
Trials were identified by searching MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1966 to December 2009 as well as through reference lists of articles and proceedings of major meetings. Retrospective and prospective studies analyzing neoadjuvant radiochemotherapy, radiotherapy, or chemotherapy of pancreatic cancer patients, followed by re-staging, and surgical exploration/resection were included. Two reviewers independently extracted data and assessed study quality. Pooled relative risks and 95% confidence intervals were calculated using random-effects models. Primary outcome measures were proportions of tumor response categories and percentages of exploration and resection. A total of 111 studies (n = 4,394) including 56 phase I-II trials were analyzed. A median of 31 (interquartile range IQR 19-46) patients per study were included. Studies were subdivided into surveys considering initially resectable tumors (group 1) and initially non-resectable (borderline resectable/unresectable) tumors (group 2). Neoadjuvant chemotherapy was given in 96.4% of the studies with the main agents gemcitabine, 5-FU (and oral analogues), mitomycin C, and platinum compounds. Neoadjuvant radiotherapy was applied in 93.7% of the studies with doses ranging from 24 to 63 Gy. Averaged complete/partial response probabilities were 3.6% (95% CI 2%-5.5%)/30.6% (95% CI 20.7%-41.4%) and 4.8% (95% CI 3.5%-6.4%)/30.2% (95% CI 24.5%-36.3%) for groups 1 and 2, respectively; whereas progressive disease fraction was estimated to 20.9% (95% CI 16.9%-25.3%) and 20.8% (95% CI 14.5%-27.8%). In group 1, resectability was estimated to 73.6% (95% CI 65.9%-80.6%) compared to 33.2% (95% CI 25.8%-41.1%) in group 2. Higher resection-associated morbidity and mortality rates were observed in group 2 versus group 1 (26.7%, 95% CI 20.7%-33.3% versus 39.1%, 95% CI 29.5%-49.1%; and 3.9%, 95% CI 2.2%-6% versus 7.1%, 95% CI 5.1%-9.5%). Combination chemotherapies resulted in higher estimated response and resection probabilities for patients with initially non-resectable tumors ("non-resectable tumor patients") compared to monotherapy. Estimated median survival following resection was 23.3 (range 12-54) mo for group 1 and 20.5 (range 9-62) mo for group 2 patients.
In patients with initially resectable tumors ("resectable tumor patients"), resection frequencies and survival after neoadjuvant therapy are similar to those of patients with primarily resected tumors and adjuvant therapy. Approximately one-third of initially staged non-resectable tumor patients would be expected to have resectable tumors following neoadjuvant therapy, with comparable survival as initially resectable tumor patients. Thus, patients with locally non-resectable tumors should be included in neoadjuvant protocols and subsequently re-evaluated for resection.
Pancreatic ductal adenocarcinoma (PDAC) is one of the five most lethal malignancies worldwide and survival has not improved substantially in the past 30 years. Desmoplasia (abundant fibrotic stroma) ...is a typical feature of PDAC in humans, and stromal activation commonly starts around precancerous lesions. It is becoming clear that this stromal tissue is not a bystander in disease progression. Cancer-stroma interactions effect tumorigenesis, angiogenesis, therapy resistance and possibly the metastatic spread of tumour cells. Therefore, targeting the tumour stroma, in combination with chemotherapy, is a promising new option for the treatment of PDAC. In this Review, we focus on four issues. First, how can stromal activity be used to detect early steps of pancreatic carcinogenesis? Second, what is the effect of perpetual pancreatic stellate cell activity on angiogenesis and tissue perfusion? Third, what are the (experimental) antifibrotic therapy options in PDAC? Fourth, what lessons can be learned from Langton's Ant (a simple mathematical model) regarding the unpredictability of genetically engineered mouse models?
The role of a defunctioning stoma in patients undergoing low anterior resection for rectal cancer is still the subject of controversy. Recent studies suggest reduced morbidity after low anterior ...rectal resection with a defunctioning stoma.
Retrospective and prospective studies published between 1966 and 2007 were systematically reviewed. Randomized controlled trials (RCTs) comparing anterior resections with or without defunctioning stoma were included in a meta-analysis. The pooled estimates of clinically relevant anastomotic leakages and of reoperations were analyzed using a random effects model (odds ratio and 95% confidence interval, CI).
Relevant retrospective single (n = 18) and multicenter (n = 9) studies were identified and included in the systematic review. Analysis of incoherent data of the leakage rates in these nonrandomized studies demonstrated that a defunctioning stoma did not influence the occurrence of anastomotic failure but seemed to ameliorate the consequences of the leak. Four RCTs were included in the meta-analysis. The odds ratio for clinically relevant anastomotic leakage was 0.32 (95% CI 0.17-0.59), revealing a statistically significant benefit conferred through a defunctioning stoma (Z = 3.65, P = 0.0003). The odds ratio for reoperation because of leakage-caused complications was 0.27 (95% CI 0.14-0.51), with significantly fewer reoperations in patients with a defunctioning stoma (Z = 3.95, P < 0.0001). Overall mortality rates were comparable regardless of the presence of a defunctioning stoma.
A defunctioning stoma reduces the rate of clinically relevant anastomotic leakages and is thus recommended in surgery for low rectal cancers.
Background
Preoperative radio(chemo)therapy (pR(C)T) significantly reduces the local recurrence risk and is therefore recommended in stage II/III rectal cancer. However, this multimodal treatment ...approach may be associated with late adverse effects. To determine the impact of pR(C)T on long-term anorectal, sexual, and urinary function, we performed a systematic review and meta-analysis.
Methods
PubMed, Embase, and the Cochrane Library were systematically searched for studies reporting on long-term functional outcome after rectal cancer resection with pR(C)T. Only studies that reported anorectal, sexual, and/or urinary function after rectal cancer resection in TME-technique with pR(C)T were eligible for inclusion.
Results
Twenty-five studies, including 6,548 patients, were identified. Methodological quality of the eligible studies was low. The majority of studies reported higher rates of anorectal (14/18 studies) and male sexual dysfunction (9/10 studies) after pR(C)T. Few studies examined female sexual dysfunction (
n
= 4). Meta-analysis revealed that stool incontinence occurred more often in irradiated patients (risk ratio (RR) = 1.67; 95 % confidence interval (CI), 1.36, 2.05;
p
< 0.0001) and manometric results were significantly worse after pR(C)T (mean resting pressures (weighted mean difference (WMD) = 15.04; 95 % CI, 0.77, 29.31;
p
= 0.04) and maximum squeeze pressures (WMD = 30.39; 95 % CI, 21.48, 39.3;
p
< 0.0001)). Meta-analysis of erectile dysfunction revealed no statistical significance (RR = 1.41; 95 % CI, 0.74, 2.72;
p
= 0.3). Six of eight studies and meta-analysis demonstrated no negative effect of pR(C)T on urinary function (RR = 1.05; 95 % CI, 0.67, 1.65;
p
= 0.82).
Conclusions
Although quality of studies on long-term functional outcome is limited, current evidence demonstrates that pR(C)T negatively affects anorectal function after TME.
To define the prognostic value of different histological subtypes of colorectal cancer.
Most colorectal cancers are classical adenocarcinomas (AC). Less frequent subtypes include mucinous ...adenocarcinomas (MAC) and signet-ring cell carcinomas (SC). In contrast to established prognostic factors such as TNM and grading, the histological subtype has no therapeutical consequences so far, although it may reflect different biological behavior.
Between 1982 and 2012, a total of 3479 consecutive patients underwent surgery for primary colorectal cancer (AC, MAC, or SC). Clinical, histopathological, and survival data were analyzed.
Of all 3479 patients, histological subtype was AC in 3074 cases (88%), MAC in 375 cases (11%), and SC in 30 cases (0.9%). MAC (51%, P < 0.001) and SC (50%, P = 0.029) occurred more frequently in right-sided tumors than AC (28%). Compared with AC, tumor stages and histological grading were higher in MAC and SC (P < 0.001 for each). Rates of angioinvasion were lower in MAC than in AC (5% vs 9%, P = 0.011). Rates of lymphatic invasion were higher in SC than in AC (67% vs 25%, P < 0.001). Five-year cause-specific survival was 67 ± 1% for AC, 61 ± 3% for MAC, and 21 ± 8% for SC (P < 0.001 for difference between the groups). In multivariable analysis, survival did not differ significantly between AC and MAC after correction for tumor stage. However, SC remained an independent prognostic factor associated with worse survival (hazard ratio = 2.5, 95% confidence interval = 1.6-3.8, P < 0.001).
MAC and SC are histological subtypes of colorectal cancer with different characteristics than classical AC. Both are diagnosed in more advanced tumor stages, but the dismal prognosis of SC seems to be caused by its intrinsic tumor biology.
Hepatocellular carcinoma (HCC) is a global health issue with increasing incidence and high mortality rate. Depending on the tumor load and extent of underlying liver cirrhosis, aggressive surgical ...treatment by hepatectomy or liver transplantation (LT) may lead to cure, whereas different modalities of liver-directed locoregional or systemic tumor treatments are currently available for a noncurative approach. Apart from tumor burden and grade of liver dysfunction, assessment of prognostic relevant biological tumor aggressiveness is vitally important for establishing a promising multimodal therapeutic strategy and improving the individual treatment-related risk/benefit ratio. In recent years, an increasing body of clinical evidence has been presented that 18 F-fludeoxyglucose ( 18 F-FDG) positron emission tomography (PET), which is a standard nuclear imaging device in oncology, may serve as a powerful surrogate for tumor invasiveness and prognosis in HCC patients and, thereby, impact individual decision making on most appropriate therapy concept. This review describes the currently available data on the prognostic value of 18 F-FDG PET in patients with early and advanced HCC stages and the resulting implications for treatment strategy.
Abstract
Aim of this study was to validate the prognostic impact of clinical parameters and baseline
18
F-FDG-PET/CT derived textural features to predict histopathologic response and survival in ...patients with esophageal squamous cell carcinoma undergoing neoadjuvant chemoradiation (nCRT) and surgery. Between 2005 and 2014, 38 ESCC were treated with nCRT and surgery. For all patients, the
18
F-FDG-PET-derived parameters
metabolic tumor volume
(
MTV
),
SUVmax, contrast
and
busyness
were calculated for the primary tumor using a SUV-threshold of 3. The parameter
uniformity
was calculated using contrast-enhanced computed tomography. Based on histopathological response to nCRT, patients were classified as good responders (< 10% residual tumor) (R) or non-responders (≥ 10% residual tumor) (NR). Regression analyses were used to analyse the association of clinical parameters and imaging parameters with treatment response and overall survival (OS). Good response to nCRT was seen in 27 patients (71.1%) and non-response was seen in 11 patients (28.9%). Grading was the only parameter predicting response to nCRT (Odds Ratio (OR) = 0.188, 95% CI: 0.040–0.883;
p
= 0.034). No association with histopathologic treatment response was seen for any of the evaluated imaging parameters including
SUVmax, MTV, busyness, contrast
and
uniformity
. Using multivariate Cox-regression analysis, the heterogeneity parameters
busyness
(Hazard Ratio (HR) = 1.424, 95% CI: 1.044–1.943;
p
= 0.026) and
contrast
(HR = 6.678, 95% CI: 1.969–22.643
;
p
= 0.002) were independently associated with OS, while no independent association with OS was seen for
SUVmax
and
MTV
. In patients with ESCC undergoing nCRT and surgery, baseline
18
F-FDG-PET/CT derived parameters could not predict histopathologic response to nCRT. However, the PET/CT derived features
busyness
and
contrast
were independently associated with OS and should be further investigated.
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