Identische onkologische Ergebnisse bei niedrigerer perioperativer Morbidität nach laparoskopischer Leberresektion

Background

Laparoscopic liver resection belongs to the standard repertoire in hepatobiliary surgery. The advantages and disadvantages are still the subject of controversial discussion.

Objective

The aim of the study was to compare the perioperative and long-term outcomes of laparoscopic and open liver resections.

Material and methods

All patients who underwent liver resection in the Department of Surgery at the certified liver center of the  municipal hospital Karlsruhe were analyzed. From a total of 268 hepatic resections 65 laparoscopic liver resections were identified and matched 1:1 with 65 open resections, based primarily on the extent of the resection and secondarily on diagnosis, age and gender of the patients. The demographic data, comorbidities, perioperative and long-term outcomes were compared.

Results

Both groups had comparable demographic parameters and comorbidities. Operation time, duration of intensive care stay and percentage of negative resection margins were comparable in both groups. The 30-day mortality was 0% and 90-day mortality 1.5% in both groups. The laparoscopic group showed lower intraoperative and postoperative transfusion rates (p?<?0.001), shorter hospital stay (p?<?0.001) and lower overall morbidity (p?<?0.001). The 1-, 3- and 5-year overall and tumor-free survival of patients with colorectal liver metastases was comparable (p?=?0.984; p?=?0.947). The same applied for patients with hepatocellular carcinomas (p?=?0.803; p?=?0.935).

Conclusion

Laparoscopic liver resections have identical long-term outcomes with lower overall morbidity. Laparoscopic liver resections offer advantages regarding transfusion rates, length of hospital stay and postoperative complications.

     

Elevated Alkaline Phosphatase Prior to Transarterial Chemoembolization for Neuroendocrine Tumors Predicts Worse Outcomes

Introduction

We hypothesized that an elevated preoperative alkaline phosphatase (AP) predicted worse outcomes for patients undergoing transarterial chemoembolization (TACE) for neuroendocrine tumor (NET) liver metastases.

Methods

We reviewed all patients who underwent TACE for metastatic NET between 2009 and 2013. Survival was evaluated using preprocedure variables.

Results

One hundred and nine patients underwent 210 TACE procedures. The average age was 57.7 years (range 20–78). Primary sites included pancreas (N?=?20), other gastrointestinal (N?=?52), lung (N?=?9), and unknown (N?=?28). The tumor was grade 1 in 68 (62 %), grade 2 in 21 (19 %), and grade 3 in 3 (3 %). Extrahepatic disease was present in 54 (50 %) and greater than 50 % hepatic tumor burden by imaging in 63 (58 %). Elevated bilirubin occurred in 8 (7 %), elevated AP in 22 (20 %), elevated ALT in 21 (19 %), and elevated AST in 41 (38 %). Univariate predictors included tumor grade (43 vs 27 vs 21 months, p?=?0.015), hepatic tumor burden (59 vs 37 months, p?=?0.009), and elevated AP (59 vs 23 months, p?<?0.001). On multivariate analysis, only elevated AP (p?=?0.001) predicted worse survival.

Conclusions

Elevated AP prior to TACE for metastatic NET portends a worse survival outcome, even more so than tumor grade or extent of hepatic disease.

     

Reconstruction in the Metastatic Breast Cancer Patient: Results from the National Cancer Database

Purpose

Modern treatments are prolonging life for metastatic breast cancer patients. Reconstruction in these patients is controversial. The purpose of this study was to characterize de novo metastatic breast cancer patients who undergo mastectomy and reconstruction and to report complication and survival rates.

Methods

We queried the National Cancer Database for de novo metastatic breast cancer patients, who underwent systemic therapy and mastectomy with reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient-tumor characteristics, mortality, and readmissions were compared. Propensity score matched analysis was performed, and survival was calculated using the Kaplan–Meier method.

Results

A total of 8554 patients fulfilled study criteria (n?=?980/11.5% R vs. n?=?7574/88.5% NR). There was a significant increase in reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p?<?0.0001). Compared with the NR patients, R patients were younger (mean age 49 vs. 58 years, p?<?0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p?=?0.0004), had lower grade disease (p?=?0.0082), and fewer sites of metastases (85.7% had 1 metastasis; 14.3% had?≥?2 R vs. 79% had 1; 21% had?≥?2 NR, p?=?0.0002). R patients received more hormonal and chemotherapy than NR but equally received radiation. Median overall survival of the total cohort was 45 months, and median overall survivals of R and NR groups by matched analysis were 56.7 and 55.3 months respectively (p?=?0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p?=?0.56) and readmissions (5.9%-R, 5.8%-NR, p?=?0.81) were similar; 90-day mortality also was similar (1.1%-R vs. 1.6%-NR, p?=?0.796).

Conclusions

There is an increasing trend to reconstruct metastatic breast cancer patients with low complication rates, without survival compromise. Impact on quality of life warrants further assessment.

     

Readmission Following Gastric Cancer Resection: Risk Factors and Survival

Background

This study utilized a multi-institutional database to evaluate risk factors for readmission in patients undergoing curative gastrectomy for gastric adenocarcinoma with the intent of describing both perioperative risk factors and the relationship of readmission to survival.

Methods

Patients who underwent curative resection of gastric adenocarcinoma from 2000 to 2012 from seven academic institutions of the US Gastric Cancer Collaborative were analyzed. In-hospital deaths and palliative surgeries were excluded, and readmission was defined as within 30 days of discharge. Univariate and multivariable logistic regression analyses were employed and survival analysis conducted.

Results

Of the 855 patients, 121 patients (14.2 %) were readmitted. Univariate analysis identified advanced age (p?<?0.0128), American Society of Anesthesiology status ≥3 (p?=?0.0045), preexisting cardiac disease (p?<?0.0001), hypertension (p?=?0.0142), history of smoking (p?=?0.0254), increased preoperative blood urea nitrogen (BUN; p?=?0.0426), concomitant pancreatectomy (p?=?0.0056), increased operation time (p?=?0.0384), estimated blood loss (p?=?0.0196), 25th percentile length of stay (<7 days, p?=?0.0166), 75th percentile length of stay (>12 days, p?=?0.0256), postoperative complication (p?<?0.0001), and total gastrectomy (p?=?0.0167) as risk factors for readmission. Multivariable analysis identified cardiac disease (odds ratio (OR) 2.4, 95 % confidence interval (CI) 1.6–3.3, p?<?0.0001), postoperative complication (OR 2.3, 95 % CI 1.6–5.4, p?<?0.0001), and pancreatectomy (OR 2.2, 95 % CI 1.1–4.1, p?=?0.0202) as independent risk factors for readmission. There was an association of decreased overall median survival in readmitted patients (39 months for readmitted vs. 103 months for non-readmitted). This was due to decreased survival in readmitted stage 1 (p?=?0.0039), while there was no difference in survival for other stages. Stage I readmitted patients had a higher incidence of cardiac disease than stage I non-readmitted patients (58 vs. 24 %, respectively, p?=?0.0002).

Conclusions

Within this multi-institutional study investigating readmission in patients undergoing curative resection for gastric cancer, cardiac disease, postoperative complication, and concomitant pancreatectomy were identified as significant risk factors for readmission. Readmission was associated with decreased overall median survival, but on further analysis, this was driven by differences in survival for stage I disease only.

     

Practical Contribution of Virtual Hepatectomy for Colorectal Liver Metastases: a Propensity-Matched Analysis of Clinical Outcome

Background

Recent improvements in imaging technologies have enabled surgeons to perform precise planning using virtual hepatectomy (VH). However, the practical and clinical benefits of VH remain unclear. This study sought to assess how three-dimensional analysis using a VH contributed to preoperative planning and postoperative outcome in patients undergoing liver surgery for the treatment of colorectal liver metastases (CRLM).

Methods

From 2007 to 2017, a total of 473 CRLM patients who received curative hepatectomy were retrospectively assessed. A 1:1 matched propensity analysis was performed between patients who did not receive a VH (without 3D group: n?=?188) and received a VH (3D(+) group: n?=?285).

Result

The rate of VH increased over the study period (P?<?0.001). After propensity score matching (n?=?150 for each group), no significant differences were observed in the intraoperative and postoperative outcome, including liver transection time, blood loss, or morbidity between the groups. More patients received a small anatomical resection (plus limited resections) in the 3D(+) group (25 vs 11%, [P?=?0.03]). A submillimeter margin was less frequent in the 3D(+) group. No significant differences in the 5-year overall survival and disease-free survival rates were seen between the without 3D group and the 3D(+) group (38.0 vs. 45.9% [P?=?0.99], 11.1 vs. 21.7%, respectively [P?=?0.109]).

Conclusion

Although VH did not significantly influenced on the long-term outcome after hepatectomy, a more parenchymal-sparing operative procedure (anatomical resections, plus limited resections) was selected and the risk of a submillimeter surgical margin was reduced after introduction of VH.

     

Operative time and length of stay is similar between robotic assisted and laparoscopic colon and rectal resections

Robotic-assisted surgery is increasingly being utilized for colorectal surgery. Data are scarce and contradictory when outcomes are compared between robotic and laparoscopic surgery. All patients undergoing minimally invasive colorectal surgery were compared from 2011 to 2016. Outcomes between the two groups were statistically analyzed. p?<?0.05 was considered statistically significant. 185 patients underwent laparoscopic resection and 70 underwent robotic resection. Demographics, ASA score, and BMI were similar between the two groups (p?>?0.05). There was no statistical difference in median length of stay between laparoscopic and robotic colon (both 4 days; p?=?0.5) and rectal (6 vs 4.5 days; p?=?0.2) resections. Median operative times were also similar between the two approaches for colon (150.5 vs 169.5 min, p?=?0.2) and rectal (197.0 vs 231.5 min, p?=?0.9) resections. There was also no difference in operative time between the two approaches for right (median?=?137 vs 130.5 min; p?=?0.9) and left (median?=?162.0 vs 170.5 min; p?=?0.6) colectomies. Robotic surgery results in similar operative times and length of stay as laparoscopic surgery for patients undergoing colon and rectal resections.     

Primary Tumor Resection Following Favorable Response to Systemic Chemotherapy in Stage IV Pancreatic Adenocarcinoma with Synchronous Metastases: a Bi-institutional Analysis

Introduction

Patients with metastatic pancreatic adenocarcinoma have traditionally been offered palliative chemotherapy alone, and the role of surgery in these patients remains unknown.

Methods

A bi-institutional retrospective review was performed for patients with metastatic pancreatic adenocarcinoma who underwent resection of the primary tumor from 2008 to 2013. The primary outcome measured was postoperative overall survival. Secondary outcomes included postoperative disease-free survival and overall survival from the time of diagnosis.

Results

Twenty-three patients were identified who met the study criteria with a median follow-up of 30 months. Metastatic sites included the liver (n?=?16), the lung (n?=?6), and the peritoneum (n?=?2). Chemotherapy included FOLFIRINOX (n?=?14) and gemcitabine-based regimens (n?=?9), with a median of 9 cycles (range 2–31) prior to surgical treatment. Median time from diagnosis to surgery was 9.7 months (IQR 5.8–12.8). Median overall survival (OS) from surgery, disease-free survival, and OS from diagnosis were 18.2 months (95 % CI 11.8–35.5), 8.6 months (95 % CI 5.2–16.8), and 34.1 months (95 % CI 22.5–46.2), respectively. The 1- and 3-year OS from surgery were 72.7 % (95 % CI 49.1–86.7) and 21.5 % (95 % CI 4.3–47.2), respectively.

Conclusion

Resection of the primary tumor in patients with metastatic pancreatic adenocarcinoma may be considered in highly selected patients with favorable imaging and CA 19-9 response following chemotherapy at high-volume centers providing multidisciplinary care. These patients should be enrolled in prospective clinical trials or institutional registries to better quantify the potential benefits of such a strategy.

     

Anterior Approach to Major Resection for Colorectal Liver Metastasis

Purpose

The aim of this study was to examine the merits of the anterior approach, if any, in colorectal liver metastasis (CRLM) resection.

Methods

Data of patients who underwent partial hepatectomy for CRLM were reviewed. Patients treated by the anterior approach were compared with patients treated by the conventional approach.

Results

Ninety-eight patients had right hepatectomy, extended right hepatectomy, or right trisectionectomy. Among them, 71 patients underwent the conventional approach (CA group) and 27 underwent the anterior approach (AA group). The two groups were comparable in demographic, pathological, and perioperative characteristics except that the AA group had higher levels of aspartate transaminase (median, 41 vs. 31 U/L; p?=?0.006) and alanine transaminase (median, 27 vs. 22 U/L; p?=?0.009), larger tumors (median, 7 vs. 4 cm; p?=?0.000), and more extensive resections (p <?0.001). The median overall survival was 40 months (range, 0.69–168.6 months) in the CA group and 33.7 months (range, 0.95–99.8 months) in the AA group (p?=?0.22), and the median disease-free survival was 9.7 months (range, 0.62–168.6 months) in the CA group and 6.2 months (range, 0.72–99.8 months) in the AA group (p?=?0.464). Univariate and multivariate analyses identified 4 independent prognostic factors for overall survival: lymph node status of primary tumor (HR 1.352, 95% CI 0.639–2.862, p =?0.034), intraoperative blood loss (HR 1.253, 95% CI 1.039–1.510, p =?0.018), multiple liver tumor nodules (HR 1.775, 95% CI 1.029–3.061, p =?0.039), and microvascular invasion (HR 2.058, 95% CI 1.053–4.024, p =?0.035).

Conclusions

The two approaches resulted in comparable survival outcomes even though the AA group had larger tumors and more extensive resections. The anterior approach allows better mobilization and easier removal of large tumors once the liver is opened up.

     

Video assisted thoracic surgery vs. thoracotomy for locally advanced lung squamous cell carcinoma after neoadjuvant chemotherapy

Background

Surgery is an important part of multidisciplinary treatment strategy for locally advanced lung squamous cell carcinoma (LSCC), but insufficient evidence supports the feasibility and safety of video assisted thoracic surgery (VATS) following neoadjuvant chemotherapy for locally advanced LSCC. This study aims to compare perioperative data and long-term survival of locally advanced LSCC patients between VATS and thoracotomy after neoadjuvant chemotherapy.

Methods

We retrospectively collected the clinical and pathological information of patients with locally advanced LSCC who underwent surgical resection after neoadjuvant chemotherapy from October 2013 to October 2017. All patients were divided into two groups (thoracotomy and VATS) and were compared the differences in perioperative, oncological and survival outcomes.

Results

A total of 81 patients were analyzed in this study (67 thoracotomy and 14 VATS). VATS provided less postoperative pain (P =?0.005) and produced less volume of chest drainage (P =?0.019) than thoracotomy, but the number of resected lymph nodes was less in VATS group (P =?0.011). However, there was no significant difference in the number of resected lymph node stations and the rate of nodal upstaging between two groups. The mean disease free survival (DFS) was 32.7?±?2.7?months for the thoracotomy group and 31.8?±?3.0?months for the VATS group (P?=?0.335); the corresponding overall survival (OS) was 41.7?±?2.2?months and 36.4?±?4.1?months (P?=?0.925).

Conclusion

In selected patients with locally advanced LSCC, VATS played a positive role in postoperative recovery and associated similar survival outcome compared with thoracotomy after neoadjuvant chemotherapy.

     

Prediction of Residual Nodal Disease at Completion Dissection Following Positive Sentinel Lymph Node Biopsy for Melanoma

Introduction

While recent trial data have demonstrated no survival benefit to immediate completion lymph node dissection (CLND) for positive sentinel lymph node (SLN) disease in melanoma, prediction of non-SLN disease may help risk-stratify patients for more intensive observation of the nodal basin.

Patients and Methods

A retrospective cohort of patients with positive SLN biopsy (SLNB) who underwent CLND was identified (1996–2016). A risk score for likelihood of CLND-positive disease was developed based on factors associated with presence of CLND metastases identified on logistic regression. Survival outcomes were analyzed.

Results

Among 312 patients with positive SLN, 192 underwent CLND and had complete pathologic data for evaluation. The median age of the study cohort was 53 years [interquartile range (IQR) 43–66 years], and 112 (58%) were male. Thirty-one (16%) had non-SLN metastatic disease on CLND. The four factors independently associated with CLND positivity and thus included in the risk score were Breslow thickness?≥?3 mm [odds ratio (OR) 2.56, p?=?0.047], presence of primary tumor-infiltrating lymphocytes (OR 0.33, p?=?0.013),?≥?2/3 positive-to-total SLN ratio (OR 4.35, p?=?0.003), and combined subcapsular and parenchymal metastatic SLN location or metastatic deposit?≥?1 mm (OR 4.45, p?=?0.013). The four-point risk score predicted CLND positivity well with area under the curve of 0.82 (0.80–0.85). Increasing risk score was independently associated with increasingly worse melanoma-specific survival [hazard ratio (HR)?=?1.54, p?=?0.001].

Conclusions

Likelihood of residual nodal disease after positive SLNB and survival can be predicted from primary tumor and SLN characteristics. High-risk patients may warrant more intensive surveillance of the nodal basin to reduce risk of loss of regional control.

     

RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH,primary and metastatic prostate cancer disease

Background

The cytokine system RANKL (receptor activator of NF-κB ligand), its receptor RANK and the antagonist OPG (osteoprotegerin) play a critical role in bone turnover. Our investigation was conducted to describe the gene expression at primary tumour site in prostate cancer patients and correlate the results with Gleason Score and PSA level.

Methods

Seventy-one samples were obtained from prostate cancer patients at the time of radical prostatectomy and palliative prostate resection (n = 71). Patients with benign prostate hyperplasia served as controls (n = 60). We performed real-time RT-PCR after microdissection of the samples.

Results

The mRNA expression of RANK was highest in tumour tissue from patients with bone metastases (p < 0.001) as compared to BPH or locally confined tumours, also shown in clinical subgroups distinguished by Gleason Score (< 7 or ≥ 7, p = 0.028) or PSA level (< 10 or ≥ 10 µg/l, p = 0.004). RANKL and OPG mRNA expression was higher in tumour tissue from patients with metastatic compared to local disease. The RANKL/OPG ratio was low in normal prostate tissue and high tumours with bone metastases (p < 0.05). Expression of all three cytokines was high in BPH tissue but did not exceed as much as in the tumour tissue.

Conclusion

We demonstrated that RANK, RANKL and OPG are directly expressed by prostate cancer cells at the primary tumour site and showed a clear correlation with Gleason Score, serum PSA level and advanced disease. In BPH, mRNA expression is also detectable, but RANK expression does not exceed as much as compared to tumour tissue.

     

Choledochal Cyst Disease in a Western Center: A 30-Year Experience

Background

The aim of this study was to report a Western experience in the diagnosis and management of choledochal cyst disease.

Results

Sixty-seven patients were identified including 15 children and 52 adults; 76.1 % were females. The median age at diagnosis was 3 [inter-quartile range (IQR)?=?6.0–0.7]?years for children, and 46 [IQR?=?55.6–34.3]?years for adults. Forty-eight patients (72 %) were symptomatic. Types of choledochal cyst included: I (n?=?49, 73.1 %), II (n?=?1, 1.5 %), IV (n?=?9, 13.4 %), and V (n?=?8, 12 %). The median diameter of the type I choledochal cyst was 35 [IQR?=?47–25]?mm. All 48 patients underwent excision of cyst with Roux-en-Y hepaticojejunostomy, and eight underwent resection with hepaticoduodenostomy. Six patients underwent liver resection, and five patients underwent orthotopic liver transplantation. Malignancy was concomitant in five adult patients, being identified on preoperative imaging in three cases; and atypia was seen in three additional patients. Early morbidity included Clavien–Dindo classification grades III (n?=?7) and II (n?=?5), while long-term complications consisted of Clavien–Dindo grades V (n?=?5), IV (n?=?2), III (n?=?18), and II (n?=?1).

Conclusions

Presentation and management of choledochal cyst is varied. Malignant transformation is often detected incidentally, and so should be the driving source for resection when a choledochal cyst is diagnosed.

     

Long-Term Outcome Following Surgery for Colorectal Cancers in Octogenarians: A Single Institution’s Experience of 204 Patients

Background

The incidence of colorectal cancer in elderly patients is likely to increase with an aging population. The aims of this study are to review our experience in the surgical management of octogenarians with colorectal cancers and to identify factors that influence the short-term and long-term outcomes.

Methods

A retrospective review of all octogenarians who underwent surgery for colorectal cancer from December 2002 to October 2008 was performed.

Results

We identified 204 patients with a median age of 84 years (range, 80–97 years). The majority of patients had an American Society of Anesthesiologists score ≥3 (n?=?142, 69.6%) and a Charlson Comorbidity Index of ≤3 (n?=?128, 62.7%). Emergency surgery was performed in 83 (40.7%) patients. Left-sided malignancy was seen in 138 patients (67.6%). Most of the patients had either stage II (n?=?75, 36.8%) or III (n?=?69, 33.8%) diseases. The 30-day mortality rate was 16.2% (n?=?33). After multivariate analysis, the independent variables predicting worse perioperative complications and death were age >85 years old, emergency surgery, and Charlson Comorbidity Index >3. The median follow-up for the 171 remaining patients was 27 months (range, 2–92 months). The 30-day readmission rate was 2.9% (n?=?5). Thirty-one (21.2%) of 146 patients who survived curative surgery developed recurrent disease. Seventy (34.3%) patients died from various etiologies after their first 30 days postoperatively (60% cancer-specific with median survival of 15 months and 40% noncancer-related with median survival of 14 months). Overall and disease-free survivals were adversely affected in patients with advanced malignancy and in those with severe perioperative complications.

Conclusions

Surgery for octogenarians with colorectal cancers is associated with significant morbidity and mortality rates which are associated with advanced age, emergency surgery, and Charlson Comorbidity Index >3. Long-term survival is dependent on the stage of the malignancy and the presence of severe perioperative complications.

     

Ten-year follow-up after combined coronary artery bypass grafting and transmyocardial laser revascularization in patients with disseminated coronary atherosclerosis

Coronary artery disease involving heavily calcified lesions has been associated with worse short- and long-term outcomes including increased mortality. This paper aims to evaluate long-term survival benefit when CABG + transmyocardial laser revascularization (TMLR) are performed on the hearts of patients with disseminated coronary atherosclerosis (DCA). This novel retrospective study was conducted between 1997 and 2002 and followed 86 patients with ischemic heart disease and severe DCA who underwent TMLR using a Holmium:YAG laser and/or CABG. There were 46 patients who had CABG plus TMLR on at least one heart wall (“combined therapy group”) and 40 patients who had CABG or TMLR separately on at least one heart wall (“single therapy group”). For the whole group, actuarial survival at 10 years was 78.3% in the combined group compared to 72.5% in the single therapy group (p?=?0.535). Ten-year survival in the combined vs. single therapy group for the anterior heart walls was 100 vs. 72.2% (p?=?0.027). For the lateral and posterior heart walls were 73.7 vs. 73.3% (p?=?0.97) and 84.2 vs. 72% (p?=?0.27), respectively. Kaplan-Meier survival analysis showed benefit only for the anterior heart wall (F Cox test, p?=?0.103). Single therapy procedures on all heart walls (odds ratio 1.736, p?=?0.264) or on the anterior heart wall only (odds ratio 3.286, p?=?0.279) were found to be predictors of 10-year late mortality. Combined therapy (TMLR + CABG) provides benefit for perioperative mortality and long-term survival only when provided on the anterior heart wall. For patients with disseminated coronary atherosclerosis, cardiac mortality was found to be increased when followed up 6 years later, regardless of the therapy applied.     

Short- and Long-Term Oncological Outcome After Rectal Cancer Surgery: a Systematic Review and Meta-Analysis Comparing Open Versus Laparoscopic Rectal Cancer Surgery

Background

While several trials have compared laparoscopic to open surgery for colon cancer showing similar oncological results, oncological quality of laparoscopic versus open rectal resection is not well investigated.

Methods

A systematic literature search for randomized controlled trials was conducted in MEDLINE, the Cochrane Library, and Embase. Qualitative and quantitative meta-analyses of short-term (rate of complete resections, number of harvested lymph nodes, circumferential resection margin positivity) and long-term (recurrence, disease-free and overall survival) oncologic results were conducted.

Results

Fourteen randomized controlled trials were identified including 3528 patients. Patients in the open resection group had significantly more complete resections (OR 0.70; 95% CI 0.51–0.97; p?=?0.03) and a higher number of resected lymph nodes (mean difference ??0.92; 95% CI ??1.08 to 0.75; p?<?0.001). No differences were detected in the frequency of positive circumferential resection margins (OR 0.82; 95% CI 0.62–1.10; p?=?0.18). Furthermore, no significant differences of long-term oncologic outcome parameters after 5 years including locoregional recurrence (OR 0.95; 95% CI 0.44–2.05; p?=?0.89), disease-free survival (OR 1.16; 95% CI 0.84–1.58; p?=?0.36), and overall survival (OR 1.04; 95% CI 0.76–1.41; p?=?0.82) were found. Most trials exhibited a relevant risk of bias and several studies provided no information on the surgical expertise of the participating surgeons.

Conclusion

Differences in oncologic outcome between laparoscopic and open rectal surgery for rectal cancer were detected for the complete resection rate and the number of resected lymph nodes in favor of the open approach. No statistically significant differences were found in oncologic long-term outcome parameters.

     

Metformin Use Is Associated with Improved Survival in Patients Undergoing Resection for Pancreatic Cancer

Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD?=?9.1 years). Roughly one half of patients were female (n?=?1735, 51.1 %); 49.1 % (n?=?1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n?=?664) had diabetes. At the time of surgery, 60.0 % (n?=?2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n?=?1212) a partial/distal pancreatectomy, while 4.3 % (n?=?147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p?=?0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4–67.3 %] vs. 69.2 % [95 % CI 64.2–73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR]?=?0.79, 95 % CI 0.67–0.93, p?=?0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.     

Docetaxel-rechallenge in castration-resistant prostate cancer: defining clinical factors for successful treatment response and improvement in overall survival

Purpose

The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC).

Methods

An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival.

Results

Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84 m [interquartile range (IQR) 64–104 m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9 m (IQR 5–16 m) and 20 m (IQR 16–26 m), respectively. Partial PSA-response at first docetaxel-sequence (n?=?62), rechallenge (n?=?32), and third-sequence (n?=?22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC?>?47 m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p?=?0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58; p?=?0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31; p?=?0.008) and treatment-free interval?>?3 m (Hazard Ratio 3.49; p?=?0.014) were the only independent predictive factors under taxane treatment for overall survival.

Conclusion

Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval?>?3 m benefit most from docetaxel re-exposure.

     

Determinants of Outcomes Following Resection for Pancreatic Cancer—a Population-Based Study

Background

Patient and health system determinants of outcomes following pancreatic cancer resection, particularly the relative importance of hospital and surgeon volume, are unclear. Our objective was to identify patient, tumour and health service factors related to mortality and survival amongst a cohort of patients who underwent completed resection for pancreatic cancer.

Methods

Eligible patients were diagnosed with pancreatic adenocarcinoma between July 2009 and June 2011 and had a completed resection performed in Queensland or New South Wales, Australia, with either tumour-free (R0) or microscopically involved margins (R1) (n?=?270). Associations were examined using logistic regression (for binary outcomes) and Cox proportional hazards or stratified Cox models (for time-to-event outcomes).

Results

Patients treated by surgeons who performed <4 resections/year were more likely to die from a surgical complication (versus ≥4 resections/year, P?=?0.04), had higher 1-year mortality (P?=?0.03), and worse overall survival up to 1.5 years after surgery (adjusted hazard ratio 1.58, 95 % confidence interval 1.07–2.34). Amongst patients who had ≥1 complication within 30 days of surgery, those aged ≥70 years had higher 1-year mortality compared to patients aged <60 years. Adjuvant chemotherapy treatment improved recurrence-free survival (P?=?0.01). There were no significant associations between hospital volume and mortality or survival.

Conclusions

Systems should be implemented to ensure that surgeons are completing a sufficient number of resections to optimize patient outcomes. These findings may be particularly relevant for countries with a relatively small and geographically dispersed population.

     

Oncologic and Perioperative Outcomes Following Selective Application of Laparoscopic Pancreaticoduodenectomy for Periampullary Malignancies

Background

Data are sparse regarding patient selection criteria or evaluating oncologic outcomes following laparoscopic pancreaticoduodenectomy (LPD). Having prospectively limited LPD to patients with resectable disease defined by National Comprehensive Cancer Network (NCCN) criteria, we evaluated perioperative and long-term oncologic outcomes of LPD compared to a similar cohort of open pancreaticoduodenectomy (OPD).

Methods

Consecutive patients (November 2010–February 2014) undergoing pancreaticoduodenectomy (PD) for periampullary adenocarcinoma were reviewed. Patients were excluded from further analysis for benign pathology, conversion to OPD for portal vein resection, and contraindications for LPD not related to their malignancy. Outcomes of patients undergoing LPD were analyzed in an intention-to-treat manner against a cohort of patients undergoing OPD.

Results

These selection criteria resulted in offering LPD to 77 % of all cancer patients. Compared to the OPD cohort, LPD was associated with significant reductions in wound infections (16 vs. 34 %; P?=?0.038), pancreatic fistula (17 vs. 36 %; P?=?0.032), and median hospital stay (9 vs. 12 days; P?=?0.025). Overall survival (OS) was not statistically different between patients undergoing LPD vs. OPD for periampullary adenocarcinoma (median OS 27.9 vs. 23.5 months; P?=?0.955) or pancreatic adenocarcinoma (N?=?28 vs. 22 patients; median OS 20.7 vs. 21.1 months; P?=?0.703).

Conclusions

The selective application of LPD for periampullary malignancies results in a high degree of eligibility as well as significant reductions in length of stay, wound infections, and pancreatic fistula. Overall survival after LPD is similar to OPD.

     

Male Gender Is Associated with a High Risk for Chronic Antibiotic-Refractory Pouchitis and Ileal Pouch Anastomotic Sinus

Background and Aims

The impact of gender on the development of chronic ileal pouch disorders following ileal pouch-anal anastomosis (IPAA) has not been evaluated. This study was aimed to assess the association between gender and pouch outcomes.

Methods

Comparisons of long-term pouch outcomes between male and female patients were performed using both univariate and multivariate analyses.

Results

Of all patients enrolled (n?=?1564), 881(56.3 %) were males. Male patients were older at the time of inflammatory bowel disease (IBD) diagnosis and pouch construction. The frequencies of neoplasia as the indication for colectomy and significant comorbidity were higher in males, while fewer male patients had IBD-related extra-intestinal manifestations or concurrent autoimmune disorders. There was no significant difference between the genders in other clinicopathological characteristics. More male patients (n?=?144, 16.3 %) developed chronic antibiotic-refractory pouchitis (CARP) than females (n?=?73, 10.7 %) (P?=?0.001). Seventy-four males (8.4 %) had ileal pouch anastomotic sinus versus 22 female patients (3.2 %) (P?<?0.001). Multivariate logistic regression analyses confirmed the association between male gender and CARP (odds ratio (OR) 1.64, 95 % confidence interval (CI) 1.21–2.24, P?=?0.002) and male gender and ileal pouch anastomotic sinus (OR 2.85, 95 % CI 1.48–5.47, P?=?0.002). After a median follow-up of 9.0 (interquartile range 4.0–14.0) years, pouch failed in a total of 126 patients (8.1 %). No significant difference was identified between male and female patients in pouch failure (P?=?0.61).

Conclusions

Among the pouch patients referred to our subspecialty Pouch Center, male patients were found to have an increased risk for the CARP and ileal pouch sinus. The pathogenic mechanisms of the association warrant further study.