Outcomes of surgical treatment of non-metastatic gastric cancer in patients aged 70 and older: A systematic review and meta-analysis.

The optimal surgical treatment strategy for gastric cancer in older patients needs to be carefully evaluated due to increased vulnerability of older patients. We performed a database search for randomized controlled trials (RCTs) and cohort studies that included patients ≥70 years with potentially resectable stage I-III gastric cancer. Postoperative and survival outcomes were compared between groups undergoing 1) gastrectomy vs conservative treatment (best supportive care or non-operative treatment), 2) minimally invasive (MIG) vs open gastrectomy (OG), or 3) extended vs limited lymphadenectomy. When possible, results were pooled using risk ratios (RR). Thirty-one studies were included. Six retrospective studies compared overall survival (OS) between gastrectomy (N = 2332) and conservative treatment (N = 246). Longer OS was reported in the gastrectomy group in all studies, but study quality was low and meta-analysis was not feasible. Eighteen cohort studies compared MIG (N = 3626) and OG (N = 5193). MIG was associated with fewer complications (pooled RR 0.68, 95% confidence interval 0.54-0.84). OS was not different between the groups. Two RCTs and five cohort studies compared outcomes between extended (N = 709) and limited lymphadenectomy (N = 1323). Complication rates were comparable between the groups. Two cohort studies found longer OS or cancer-specific survival after extended lymphadenectomy. No quality of life (QoL) or functional outcomes were reported. In older patients with gastric cancer, there is low-quality evidence for better OS after gastrectomy vs conservative treatment. Compared to OG, MIG was associated with less postoperative morbidity. The evidence to support extended lymphadenectomy is limited. QoL and functional outcomes should be addressed in future studies.

Prognostic implications of occult nodal tumour cells in stage I and II colon cancer: The correlation between micrometastasis and disease recurrence.

INTRODUCTION: Occult nodal tumour cells should be categorised as micrometastasis (MMs) and isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, but not ITCs, are prognostic for disease recurrence in patients with stage I/II colon cancer. AIMS & METHODS: The objective of this retrospective multicenter study was to correlate MMs and ITCs to characteristics of the primary tumour, and to determine their prognostic value in patients with stage I/II colon cancer. RESULTS: One hundred ninety two patients were included in the study with a median follow up of 46 month (IQR 33-81 months). MMs were found in eight patients (4.2%), ITCs in 37 (19.3%) and occult tumour cells were absent in 147 patients (76.6%). Between these groups, tumour differentiation and venous or lymphatic invasion was equally distributed. Advanced stage (pT3/pT4) was found in 66.0% of patients without occult tumour cells (97/147), 72.9% of patients with ITCs (27/37), and 100% in patients with MMs (8/8), although this was a non-significant trend. Patients with MMs showed a significantly reduced 3 year-disease free survival compared to patients with ITCs or patients without occult tumour cells (75.0% versus 88.0% and 94.8%, respectively, p = 0.005). When adjusted for T-stage, MMs independently predicted recurrence of cancer (OR 7.6 95% CI 1.5-37.4, p = 0.012). CONCLUSION: In this study, the incidence of MMs and ITCs in patients with stage I/II colon cancer was 4.2% and 19.3%, respectively. MMs were associated with an reduced 3 year disease free survival rate, but ITCs were not.

Lower muscle density is associated with major postoperative complications in older patients after surgery for colorectal cancer.

BACKGROUND: Reduced muscle density is associated with an increased risk of postoperative complications. We examined the prognostic value of muscle density as a predictor of postoperative complications in elderly patients undergoing surgery for colorectal cancer. METHODS: Patients (≥70 years) who underwent surgery for colorectal cancer between 2006 and 2013 were selected from a prospective single centre database. The Hounsfield Unit Average (HUA or HU/mm2) of the psoas muscles at the level of the third lumbar vertebra was calculated on the scan. High and low muscle density groups were identified based on the lowest gender specific HUAC quartile. Major postoperative complications (Clavien-Dindo (CD) ≥3) within 30 days after surgery were retrospectively documented. Logistic regression analysis was used to identify risk factors for postoperative complications. RESULTS: A total of 373 patients (median age = 78 years) were included in this study. The mean muscle density score was 24.5 ± 4.3 HU/mm2 for males and 26.3 ± 5.0 HU/mm2 for females. The cut-off point for the lowest gender specific quartile was ≤22.0 HU/mm2 for males and ≤23.5 HU/mm2 for females. After multivariable regression, there was a statistically significant association between muscle density and CD ≥ 3 (OR = 1.84 (95% CI 1.11-3.06), p = 0.019). Anastomotic leakage in patients with a primary anastomosis (n = 287) occurred more often in patients with low muscle density (11.7% vs 23.3%, p = 0.016). The associations remained significant after correction for confounders. CONCLUSION: Low muscle density is associated with major postoperative complications in older patients who undergo surgery for colorectal cancer.

The effects of physical prehabilitation in elderly patients undergoing colorectal surgery: a systematic review.

AIM: Prehabilitation, defined as enhancement of the preoperative condition of a patient, is a possible strategy for improving postoperative outcome. Lack of muscle strength and poor physical condition, increasingly prevalent in older patients, are risk factors for postoperative complications. Eighty-five per cent of patients with colorectal cancer are aged over 60 years. Since surgery is the cornerstone of their treatment, this review systemically examined the literature on the effect of physical prehabilitation in older patients undergoing colorectal surgery. METHOD: Trials and case-control studies investigating the effect of physical prehabilitation in patients over 60 years undergoing colorectal surgery were retrieved from MEDLINE, EMBASE, CINAHL and the Cochrane library. Patient characteristics, the type of intervention and outcome measurements were recorded. The risk of bias and heterogeneity was assessed. RESULTS: Five studies including 353 patients were identified. They were small, containing an average of 77 patients and were of moderate methodological quality. Compliance rates of the prehabilitation programme varied from 16 to 97%. None of the studies could identify a significant reduction of postoperative complications or length of hospital stay. Four studies showed physical improvement (walking distance, respiratory endurance) in the prehabilitation group. Clinical heterogeneity precluded a meta-analysis. CONCLUSION: Prehabilitation is a possible means of enhancing the physical condition of patients preoperatively. The quality of studies in older patients undergoing colorectal surgery is poor, despite the increase in elderly people with colorectal cancer. Defining specific patient groups at risk and standardizing the outcome are essential for improving the results of treatment.

Bridge-to-surgery stent placement versus emergency surgery for acute malignant colonic obstruction.

BACKGROUND: Endoscopic self-expanding metal stent (SEMS) placement as a bridge to surgery is an option for acute malignant colonic obstruction. There is ongoing debate regarding the superiority and oncological safety of SEMS placement compared with emergency surgery. This retrospective study aimed to compare outcomes of these treatment approaches. METHODS: Patients were identified from cohorts treated between 2005 and 2012 in two teaching hospitals, of which one used emergency surgery only in patients with large bowel obstruction, whereas the other attempted SEMS placement. Only patients treated with curative intent were included. RESULTS: The study included 59 patients in whom SEMS placement was attempted and 51 who underwent surgery alone. The successful primary anastomosis rate was higher in the SEMS group than in the surgery-alone group among patients with left-sided obstruction (30 of 43 versus 10 of 34 respectively; P = 0.001), whereas stoma formation was less common (11 of 43 versus 23 of 34; P < 0.001). Such differences were not apparent in patients with right-sided obstruction. Secondary stoma rates were comparable between treatment approaches (left-sided: 11 of 43 versus 13 of 34, P = 0.322; right-sided: 1 of 16 versus 1 of 17, P = 1.000). There were no significant differences in morbidity, mortality, recurrence or survival. CONCLUSION: Endoscopic SEMS placement increased the primary anastomosis rate in patients with left-sided large bowel obstruction.

Lymph node size as a predictor of lymphatic staging in colonic cancer.

BACKGROUND: In colonic cancer, the number of harvested lymph nodes is associated with prognosis. The aim of this study was to determine the contribution of small lymph nodes to pathological staging, and to analyse the hypothesis that node size is a confounder in the relationship between prognosis and nodal harvest. METHODS: Nodal harvest and size were analysed in patients who underwent elective surgery for colonic cancer. Visible and palpable nodes were harvested without fat clearance techniques, and conventional histology was performed. RESULTS: Metastases were found in 99 of 2043 measured lymph nodes in 150 patients. Lymph nodes smaller than 3 mm were positive in 8.0 per cent of patients (12 of 150), but were the sole reason for upstaging in only 1.3 per cent (2 of 150). No metastases were found among 95 nodes of 1 mm or less. Metastatic nodes were larger than those without metastasis (median (i.q.r.) 5.0 (3.2-7.0) versus 3.8 (2.4-5.2) mm; P < 0·001), but a receiver operating characteristic (ROC) curve did not identify a relevant cut-off point to predict metastatic involvement. A hazard ratio of 0.71 (95 per cent confidence interval 0.50 to 1.01) was suggestive of an association between disease recurrence and increased node size, although not significant (P = 0.056). In patients with N0 disease, there was a correlation between node size and harvest (Pearson's correlation 0.317, P = 0.002), and a nodal yield of at least 12 was associated with a larger median node size (4.3 (3.3-5.0) versus 3.4 (2.7-4.0) mm; P = 0.015). CONCLUSION: The contribution of lymph nodes smaller than 3 mm to nodal staging is limited. Increased node size is associated with increased nodal yield, and could be a confounder in the relationship between prognosis and nodal harvest in patients with N0 disease.

The prognostic value of micrometastases and isolated tumour cells in histologically negative lymph nodes of patients with colorectal cancer: a systematic review and meta-analysis.

INTRODUCTION: Detection of occult tumour cells in lymph nodes of patients with stage I/II colorectal cancer is associated with decreased survival. However, according to recent guidelines, occult tumour cells should be categorised in micrometastases (MMs) and isolated tumour cells (ITCs). This meta-analysis evaluates the prognostic value of MMs and of ITCs, separately. METHODS: PubMed, Embase, Biosis and the World Health Organization International Trials Registry Platform were searched for papers published until April 2013. Studies on the prognostic value of MMs and ITCs in lymph nodes of stage I/II colorectal cancer patients were included. Odds ratios (ORs) for the development of disease recurrence were calculated to analyse the predictive value of MMs and ITCs. RESULTS: From five papers, ORs for disease recurrence could be calculated for MMs and ITCs separately. In patients with colorectal cancer, disease recurrence was significantly increased in the presence of MMs in comparison with absent occult tumour cells (OR 5.63; 95%CI 2.4-13.13). This was even more pronounced in patients with colon cancer (OR 7.25 95% CI 1.82-28.97). In contrast, disease recurrence was not increased in the presence of ITCs (OR 1.00 95% CI 0.53-1.88). CONCLUSION: Patients with stage I/II colorectal cancer and MMs have a worse prognosis than patients without occult tumour cells. However, ITCs do not have a predictive value. The distinction between ITCs and MMs should be made if the detection of occult tumour cells is incorporated in the clinical decision for adjuvant treatment.

Implications of sentinel lymph node mapping on nodal staging and prognosis in colorectal cancer.

AIM: Sentinel lymph node (SN) mapping for staging in colorectal cancer remains controversial and needs to be validated before it can be implemented in daily practice. We prospectively assessed the effect of SN mapping on nodal staging and its implication on survival in patients with colorectal cancer. METHOD: Between November 2005 and July 2009, 331 patients underwent a resection for colorectal cancer. In 189 patients (group A) an ex-vivo SN procedure was performed with immunohistochemical analysis of the SN. Tumour cell deposits between 0.2 mm and 2.0 mm were referred to as micrometastases (pN1mi+). The remaining patients (n = 142, group B) had standard nodal staging. Multivariate Cox regression analysis was performed to identify prognostic factors for disease recurrence. RESULTS: The average number of harvested lymph nodes was higher in group A than in group B (15.5 ± 7.3 vs 12.1 ± 5.2, P < 0.0001). After conventional staging, 81 (43%) patients of group A were judged to have nodal metastasis. This increased to 89 (47%) patients when immunohistochemically detected micrometastases were included. In group B, 50 (35%) patients had nodal metastasis. During follow up, a lower recurrence rate was seen in N0 patients after SN mapping compared with the conventional staging group (4%vs 15.2%, P = 0.04). The SN procedure (hazard ratio = 4.1) was an independent predictor of disease recurrence. CONCLUSION: The SN procedure results in a more accurate staging of patients with colorectal cancer. This is reflected by a better prognosis of N0 patients after SN mapping.

Decreased incidence of isolated tumor cells in lymph nodes after laparoscopic resection for colorectal cancer.

BACKGROUND: Laparoscopic surgery has potential for less tumor cell spread because of the no-touch technique. We assessed the effect of the surgical approach (open versus no-touch laparoscopic) on the presence of tumor cells in sentinel lymph nodes (SN) of patients with stage I and II colorectal cancer. METHODS: A single-center consecutive prospective series of patients operated on for colorectal cancer was analyzed. After conventional hematoxylin and eosin (H&E) staining, 107 patients without lymphatic metastases were included; 59 patients had open surgery, and 48 patients underwent laparoscopic resection. Patients in the laparoscopic group underwent a no-touch medial to lateral approach, whereas the conventional lateral to medial approach was applied in open surgery. A SN procedure was performed in all patients. The SNs were immunohistochemically analyzed for presence of occult tumor cells (OTC). According to the American Joint Committee on Cancer (AJCC) these tumor cells were divided into micrometastases (0.2-2 mm) or isolated tumor cells (ITC, < 0.2 mm). RESULTS: In ten patients micrometastases were found, equally distributed between the two groups. However, ITC were more often found after open surgery (18 versus 5 patients, p = 0.03). Presence of OTC was related to depth of tumor invasion and tumor diameter > 3.5 cm. Logistic regression analysis identified lymphovascular invasion as a predictor for micrometastases [odds ratio (OR) 18.4], whereas open resection was predictive for presence of ITC (OR 3.3). CONCLUSIONS: No-touch medial to lateral laparoscopic surgery results in less isolated tumor cells in lymph nodes compared with open lateral to medial surgery in patients with stage I and II colorectal cancer.

The persisting presacral sinus after anastomotic leakage following anterior resection or restorative proctocolectomy.

AIM: Despite improvements in anastomotic technique, anastomotic leakage is frequently encountered following anterior resection. This can eventually evolve into a presacral sinus. This study assessed the incidence, the natural course and the outcome of persisting presacral sinus. METHOD: Patients who underwent low anterior resection (LAR) for cancer or restorative proctocolectomy (RPC) for ulcerative colitis or familial polyposis were eligible. Patients with anastomotic leakage or a presacral abscess were included. Outcome parameters included a persistent presacral sinus, or its closure and average time to closure and the stoma closure rate. RESULTS: Twenty-five patients were identified with a sinus after LAR (n = 20) or RPC (n = 5). A persistent sinus was present in nine (1%) of 834 patients after LAR and two (0.9%) of 229 patients after RPC. Definitive resolution of the sinus occurred in 12 (52%) of 23 assessable patients. This was achieved at a median of 340 days (range 23-731 days). At final follow-up, nine of the 23 patients had permanent faecal diversion because of recurrent abscess or persistent sinus formation, seven after LAR and two after RPC. CONCLUSION: A significant proportion of patients with anastomotic leakage after rectal surgery develop a chronic sinus, of which only half heal over time. Persisting sinus is the main reason for a permanent stoma.

Diagnosing occult tumour cells and their predictive value in sentinel nodes of histologically negative patients with colorectal cancer.

PURPOSE: Most studies on the sentinel node (SN) procedure in patients with colorectal cancer include immunohistochemical analysis of the SN only. To evaluate the real diagnostic accuracy of the SN procedure with immunohistochemical analysis, the presence of occult tumour cells in all histologically negative lymph nodes was compared to the presence of these cells in SNs. Also the reproducibility of diagnosing occult tumour cells (OTC) and the sensitivity of three different antibodies was assessed. METHODS: Between November 2006 en July 2007, an ex vivo SN procedure was performed in 58 histologically N0 patients with colorectal cancer. All lymph nodes (n = 908, mean 15.7) were step-sectioned and immunohistochemistry was performed using two antibodies against cytokeratins (Cam5.2, and CK 20) and one antibody against BerEp-4. RESULTS: OTC were identified in 19 of 58 patients, with micrometastases (0.2-2 mm) in 7 and isolated tumour cells (ITC)(<0.2 mm) in 12 patients. The overall agreement in diagnosing OTC between two independent pathologists was 86%. An SN was identified in 53 of 58 patients. All micrometastases were found in SNs. In two patients with negative SNs, ITC's were demonstrated in non-SNs (sensitivity 88%, and overall accuracy 96%). CONCLUSION: Additional immunohistochemical analysis of histologically negative lymph nodes demonstrates occult tumour cells in 33% of the patients resulting in an upstaging rate of 12%. Occult tumour cells are predominantly found in the SN, therefore SN mapping has the potential to refine the staging system for patients with colorectal cancer.

Improving staging accuracy in colon and rectal cancer by sentinel lymph node mapping: a comparative study.

AIM: To compare the predictive value of sentinel lymph node (SN) mapping between patients with colon and rectal cancer. PATIENTS AND METHODS: An ex vivo SN procedure was performed in 100 patients with colon and 32 patients with rectal cancer. If the sentinel node was negative, immunohistochemical analyses using two different antibodies against cytokeratins (Cam5.2 and CK 20) and one antibody against BerEp-4 were performed to detect occult tumour cells. Isolated tumour cells (<0.2mm) were discriminated from micrometastases (0.2-2mm). RESULTS: An SN was identified in 117 patients (89%), and accurately predicted nodal status in 106 patients (accuracy 91%). Both sensitivity and negative predictive value were higher in colon carcinomas than in rectal carcinomas (83% versus 57%, p=0.06 and 93% versus 65%, p=0.002 respectively). In patients with extensive lymph node metastases the SN procedures were less successful. Eleven of the 13 unsuccessful SN procedures were performed in patients with rectal cancer who had pre-operative radiotherapy. After immunohistochemical analysis 21 of the 73 N0 patients had occult tumour cells in their SN; eight patients had micrometastases and 13 patients had isolated tumour cells. CONCLUSION: SN mapping accurately predicts nodal status in patients with colonic cancer. Immunohistochemical analysis demonstrates micrometastatic disease in eight out of 73 N0 patients, with a true upstaging rate of 11%. SN mapping is less reliable in patients with rectal cancer after pre-operative radiotherapy.

Angioplasty or bypass for superficial femoral artery disease? A randomised controlled trial.

AIM: To evaluate whether angioplasty or above-knee bypass is the best treatment for symptomatic superficial femoral artery occlusive lesions, we performed a multicentre randomised trial. PATIENTS AND METHODS: Between October 1995 and August 1998, 56 patients were enrolled, all with symptoms related to a 5-15 cm long occlusive lesion of the superficial femoral artery. Thirty-one patients were randomly assigned to percutaneous transluminal angioplasty (PTA); 25 patients to bypass surgery. All patients were followed at 1, 6 and 12 months after the procedure. The primary outcome of our study was re-occlusion of the femoral artery. RESULTS: Thirty patients underwent the allocated PTA and 24 patients underwent bypass surgery. Cumulative 1-year primary patency after PTA was 43 and 82% after bypass surgery. After PTA more than half of the patients had a re-occlusion with an absolute risk reduction of 31% (CI: 6-56%) in favour of bypass surgery. The hazard ratio for occlusion comparing PTA with bypass surgery is 2.24 (95% CI: 0.9-5.58). CONCLUSION: Despite 18 participating centres only 56 patients were randomised to PTA our bypass surgery. Based on our results, for every three patients treated with bypass surgery instead of PTA, one additional re-occlusion is prevented. Therefore, we conclude that with respect to patency, for long superficial femoral artery (SFA) stenoses or occlusions, surgery is better than PTA.

Aortoiliac reconstructive surgery based upon the results of duplex scanning.

OBJECTIVE: To evaluate whether duplex scanning can replace angiography in patients operated for aortoiliac obstructive disease. DESIGN: Retrospective. MATERIALS AND METHODS: Between January 1995 and October 1996, 44 patients underwent vascular surgery of the aortoiliac tract. The study population was divided into two groups; patients operated upon the results of duplex scanning only and patients who also underwent angiography prior to surgery. The additional value of angiography and the differences between both groups concerning unexpected peroperative findings, early postoperative failures and the need for additional radiological or surgical interventions in the first three postoperative months were studied. RESULTS: Duplex scan group: 22 patients were operated upon the results of duplex scanning only. In two patients surgical strategy had to be changed. Early postoperative graft occlusion occurred in one case. A haemodynamically significant graft stenosis within 3 months of surgery occurred in one patient. Duplex/angiography group: 22 patients underwent both duplex scanning and angiography. Six patients underwent diagnostic angiography after failed duplex scanning. In 10 patients angiography was part of percutaneous transluminal angioplasty prior to surgery. In six patients angiograms were performed after successful duplex scanning. Angiography failed in two patients and added information in four of 16 patients. Unexpected findings at operation occurred in four patients. Graft stenosis within 3 months was detected in three patients. CONCLUSION: After successful duplex scanning information obtained by angiography has only a limited impact on therapeutic decision-making. In the majority of patients vascular reconstructive surgery of aortoiliac arteries can be planned based on duplex scanning only.

Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile.

Increased biliary bile salt and phospholipid hydrophobicity may promote nucleation of cholesterol crystals and gallstone formation. We therefore compared bile salt composition (determined by gas-liquid chromatography) in patients with cholesterol (n = 35) and pigment (n = 16) gallstones (group A). Bile salt composition and cumulative bile salt hydrophobicity index were not different between both stone types. Hydrophobicity index or % of individual bile salts did not correlate with cholesterol saturation index or nucleation time. In an additional 21 cholesterol stone patients (group B) biliary bile salt and phospholipid hydrophobicity as determined by high-pressure liquid chromatography did not correlate with cholesterol saturation index or nucleation time. In both group A and group B, cholesterol stone patients with cholesterol crystals in their fresh biles had a higher % deoxycholic acid, a lower % cholic acid and a higher bile salt hydrophobicity index than crystal-negative patients. This study indicates the need for further research on the role of bile salt hydrophobicity in the pathogenesis of gallstones.