Outcomes of a Phase II Study of Intraperitoneal Paclitaxel plus Systemic Capecitabine and Oxaliplatin (XELOX) for Gastric Cancer with Peritoneal Metastases.

BACKGROUND: Adding intraperitoneal paclitaxel (IP-PTX) to paclitaxel/5-fluoropyrimidine has shown promising results in patients with gastric cancer peritoneal metastases (GCPM) but has not been studied with standard-of-care platinum/fluoropyrimidine combinations. Our goal to was evaluate IP-PTX with capecitabine/oxaliplatin (XELOX) in GCPM. METHODS: Forty-four patients with GCPM received IP PTX (40 mg/m2, Days 1, 8), oral capecitabine (1000 mg/m2 twice daily, Days 1-14) and intravenous oxaliplatin (100 mg/m2, Day 1) in 21-day cycles. Patients with synchronous GCPM underwent conversion surgery if they had good response after chemotherapy, conversion to negative cytology, no extraperitoneal metastasis, and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were compared against a matched cohort of 39 GCPM patients who received systemic chemotherapy (SC) comprising platinum/fluoropyrimidine. RESULTS: The median OS for the IP and SC groups was 14.6 and 10.6 months (hazard ratio [HR] 0.44; 95% confidence interval [CI], 0.26-0.74; p = 0.002). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI 0.25-0.66; p < 0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p = 0.021) and had better performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p = 0.007) compared with the IP cohort. In IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95% CI 13.1-35.3) months and 1-year OS of 84.6%. CONCLUSIONS: IP PTX with XELOX is a promising treatment option for GCPM patients. In patients with good response, conversion surgery was feasible with favourable outcomes.

A secondary learning curve in 3D versus 2D imaging in laparoscopic training of surgical novices.

BACKGROUND: Stereoscopic (3D) imaging can be used to facilitate the learning of basic laparoscopic tasks. Its advantages over traditional endoscopic (2D) imaging include better depth perception and spatial orientation. However, the transition between 3D and 2D imaging systems has not been previously studied. This study compares the acquisition of basic laparoscopic skills in a laparoscopic-naïve population using both imaging systems, and explores the possibility of a secondary learning curve in the transition between systems. METHODS: 26 novice learners were randomly allocated into two arms and taught to perform two basic laparoscopic tasks adopted from the fundamentals of laparoscopic surgery (FLS) curriculum, peg transfer (T1) and pattern cutting (T2) using either 2D or 3D imaging systems. These tasks were repeated until proficiency was achieved. Participants in each arm then repeated the tasks in the other viewing system (2D/3D vs 3D/2D). The parameters measured were: (a) time taken to complete the task and (b) number of attempts to achieve proficiency. RESULTS: There was a significant shortening of time required to achieve proficiency in T2 using a 3D system (mean difference-in-differences = - 65.4, 95% CI - 103.6 to - 27.2, t(24) = - 3.5, p value = 0.002) but no difference between 2D and 3D imaging systems for T1, a simpler task. Sub-group analysis of T1 and T2 between the 2D/3D and 3D/2D arms showed the presence of a secondary learning curve in the 2D/3D arm for both tasks, (T1: ß-estimate - 2.68, 95% CI - 3.68 to - 1.68, p value = 0.0003; T2: ß-estimate - 2.45, 95% CI - 3.75 to - 1.14, p value 0.004), but in the 3D/2D arm there was a secondary learning curve only for T2. (ß-estimate 2.60, 95% CI 1.45-3.76, p value 0.001) CONCLUSION: 3D imaging can be an effective tool to speed the acquisition of proficiency in basic laparoscopic tasks for novice learners, especially in more complex tasks such as pattern cutting. The skills learned in 3D imaging can translate into 2D, albeit with a secondary learning curve.

A case report of bleeding from a duodenal varix: Rare cause of upper gastrointestinal bleeding.

INTRODUCTION: Ectopic variceal bleeding is uncommon, accounts for 2-5% of variceal bleeding, of which 17% is in duodenum. PRESENTATION OF CASE: 62-year-old lady with newly diagnosed liver cirrhosis on admission, presented with severe upper gastrointestinal bleeding (UGIB), was ultimately diagnosed with bleeding duodenal varices with single-balloon enteroscopy, after multiple oesophagogastroduodenoscopies (OGDs) and CT scans which failed to identify the varices. She was treated successfully with duodenectomy. DISCUSSION: Endoscopy and CT angiography remain the diagnostic modalities of choice. However, diagnosis can be difficult as evidenced by three OGDs and two CTMAs yielding negative findings in this case. Endoscopic diagnosis is challenging and often delayed due to its rarity and unusual location. CONCLUSION: Ectopic variceal bleeding is a rare but important cause of UGIB. Diagnosis is challenging and management of this condition should take a multidisciplinary approach, involving experienced gastroenterologists, interventional radiologists and surgeons. Endoscopic ligation or sclerotherapy is the first-line of treatment.

MicroRNA-5p and -3p co-expression and cross-targeting in colon cancer cells.

BACKGROUND: Two mature miRNA species may be generated from the 5' and 3' arms of a pre-miRNA precursor. In most cases, only one species remains while the complementary species is degraded. However, co-existence of miRNA-5p and -3p species is increasingly being reported. In this work, we aimed to systematically investigate co-expression of miRNA-5p/3p in colon cancer cells in a genome-wide analysis, and to examine cross-targeting of the dysregulated miRNAs and 5p/3p species. RESULTS: Four colon cancer cell lines were examined relative to two normal colon tissues. Of the 1,190 miRNAs analyzed, 92 and 36 were found to be up- or down-regulated, respectively, in cancer cells. Nineteen co-expressed miRNA-5p/3p pairs were further identified suggesting frequent 5p/3p co-accumulation in colon cancer cells. Of these, 14 pairs were co-up-regulated and 3 pairs were co-down-regulated indicating concerted 5p/3p dysregulation. Nine dysregulated miRNA pairs fell into three miRNA gene families, namely let-7, mir-8/200 and mir-17, which showed frequent cross-targeting in the metastasis process. Focusing on the let-7d-5p/3p pair, the respectively targeted IGF1R and KRAS were shown to be in a reverse relationship with expression of the respective miRNA, which was confirmed in transient transfection assays using let-7d mimic or inhibitor. Targeting of KRAS by let-7d was previous reported; targeting of IGF1R by let-7d-5p was confirmed in luciferase assays in this study. The findings of let-7d-5p/3p and multiple other miRNAs targeting IGF1R, KRAS and other metastasis-related factors suggest that 5p/3p miRNAs contribute to cross-targeting of multiple cancer-associated factors and processes possibly to evade functional abolishment when any one of the crucial factors are inactivated. CONCLUSIONS: miRNA-5p/3p species are frequently co-expressed and are coordinately regulated in colon cancer cells. In cancer cells, multiple cross-targeting by the miRNAs, including the co-existing 5p/3p species, frequently occurs in an apparent safe-proof scheme of miRNA regulation of important tumorigenesis processes. Further systematic analysis of co-existing miRNA-5p/3p pairs in clinical tissues is important in elucidating 5p/3p contributions to cancer pathogenesis.

Barrett's oesophagus: Evidence from the current meta-analyses.

Guidelines have been published regarding the management of Barrett's oesophagus (columnar-lined oesophagus). These have examined the role of surveillance in an effort to detect dysplasia and early cancer. The guidelines have provided criteria for enrolment into surveillance and some risk stratification with regard to surveillance interval. The research basis for the decisions reached with regard to cancer risk is weak and this manuscript has examined the available data published from meta-analyses up to 25(th) April 2013 (much of which has been published since the guidelines and their most recent updates have been written). There were 9 meta-analyses comparing patients with Barrett's oesophagus to control populations. These have demonstrated that Barrett's oesophagus is more common in males than females, in subjects who have ever smoked, in subjects with obesity, in subjects with prolonged symptoms of gastro-oesophageal reflux disease, in subjects who do not have infection with Helicobacter pylori and in subjects with hiatus hernia. These findings should inform public health measures in reducing the risk of Barrett's oesophagus and subsequent surveillance burden and cancer risk. There were 8 meta-analyses comparing different groups of patients with Barrett's oesophagus with regard to cancer risk. These have demonstrated that there was no statistically significant benefit of antireflux surgery over medical therapy, that endoscopic ablative therapy was effective in reducing cancer risk that there was similar cancer risk in patients with Barrett's oesophagus independent of geographic origin, that the adenocarcinoma incidence in males is twice the rate in females, that the cancer risk in long segment disease showed a trend to be higher than in short segment disease, that there was a trend for higher cancer risk in low-grade dysplasia over non-dysplastic Barrett's oesophagus, that there is a lower risk in patients with Helicobacter pylori infection and that there is a significant protective effect of aspirin and statins. There were no meta-analyses examining the role of intestinal metaplasia. These results demonstrate that guidance regarding surveillance based on the presence of intestinal metaplasia, segment length and the presence of low-grade dysplasia has a weak basis, and further consideration should be given to gender and helicobacter status, ablation of the metaplastic segment as well as the chemoprotective role of aspirin and statins.

Single port Billroth I gastrectomy.

INTRODUCTION: Experience has allowed increasingly complex procedures to be undertaken by single port surgery. We describe a technique for single port Billroth I gastrectomy with a hand-sewn intracorporeal anastomosis in the resection of a benign tumour diagnosed incidentally on a background of cholelithiasis. MATERIALS AND METHODS: Single port Billroth I gastrectomy and cholecystectomy was performed using a transumbilical quadport. Flexible tipped camera and straight conventional instruments were used throughout the procedure. The stomach was mobilised including a limited lymph node dissection and resection margins in the proximal antrum and duodenum were divided with a flexible tipped laparoscopic stapler. The lesser curve was reconstructed and an intracorporal hand sewn two layer end-to-end anastomosis was performed using unidirectional barbed sutures. Intraoperative endoscopy confirmed the anastomosis to be patent without leak. RESULTS: Enteral feed was started on the day of surgery, increasing to a full diet by day 6. Analgesic requirements were a patient-controlled analgesia morphine pump for 4 postoperative days and paracetamol for 6 days. There were no postoperative complications and the patient was discharged on the eighth day. Histology confirmed gastric submucosal lipoma. DISCUSSION: As technology improves more complex procedures are possible by single port laparoscopic surgery. In this case, flexible tipped cameras and unidirectional barbed sutures have facilitated an intracorporal hand-sewn two layer end-to-end anastomosis. Experience will allow such techniques to become mainstream.

A literature review on the role of totally extraperitoneal repairs for groin pain in athletes.

A literature review was made on the role of totally extraperitoneal (TEP) hernia repairs for groin pain in athletes. Electronic databases were searched for literature published from January 1993 to November 2011. There were 10 articles incorporating 196 patients included in this review. Thirty percent of patients were reported to have direct inguinal hernias, 22% had indirect inguinal hernias, and 41% had dilated internal rings. Of note, 30% of cases had no macroscopic abnormality. Four studies reported on an early follow-up ranging between 3 and 6 weeks. Only minimal or mild symptoms were reported. Up to 33% of patients had impaired ability to perform at peak levels. Up to 53% of patients had persistence of symptoms at the early follow-up. Total follow-up time ranged from 3 to 80 months, and most patients were active (90%-100%). At long-term follow-up, 3% to 10% were unable to play, and 5% were reported as being unable to train. Two studies from the same center reported on TEP surgery for osteitis pubis, and most patients returned to sporting activity after 4 to 8 weeks. TEP repair is a good operative intervention in athletes with chronic groin pain not relieved by conservative measures. Athletes recover quickly and return to sport early.

Two-phase laparoscopic-assisted oesophago-gastrectomy: a single-unit experience of 111 consecutive cases and outcomes.

BACKGROUND: Minimal access surgery for oesophago-gastric cancer is topical and demanding, and approaches vary significantly. There is little data on the hybrid technique of laparoscopic-assisted two-phase oesophago-gastrectomy (LA2OG). Here we aim to review our experience, which exceeds 10 years, of this technique for oesophageal malignancy. METHODS: From June 1998 to May 2009, 111 patients underwent LA2OG. Patients included 84 men and 27 women with mean age 65 years (range 35-85 years). Retrospective analysis of indications, outcome, staging, complications and survival was performed. RESULTS: The majority of resections (96%) were performed for gastro-oesophageal junction or distal oesophageal pathology. Indications included adenocarcinoma (84.7%), squamous cell carcinoma (7.2%) and high-grade dysplasia (5.4%). Of patients, 67.6% received neoadjuvant chemotherapy. The median time for the laparoscopic phase was 207 min (range 105-600 min), and 420 min (range 210-780 min) overall. Estimated blood loss was 330 ml (range 100-1,200 ml). Median critical care and post-operative stays were 3 and 14 days, respectively. Over time, the radicality of surgery increased. From 1998 to 2001 median lymph node yield was 5, from 2002 to 2005 it was 12 nodes, and from 2006 to 2009 it was 28 nodes (p < 0.001). The overall complication rate was 38.7%, minor in 24.3%, with anastomotic leak rate of 5.5%. Median survival was 38.5 ± 5.4 months. Thirty-day and in-hospital mortality were 1.8 and 2.7%, respectively. CONCLUSIONS: Two-stage laparoscopic-assisted oesophago-gastrectomy is a safe staged method of developing minimal access surgery for oesophago-gastric cancer. This study provides a useful reference for comparison with other minimally invasive methods.

Single-port laparoscopic subtotal gastrectomy with DIα lymphadenectomy.

BACKGROUND: "Conventional multiport" laparoscopic gastrectomy for early stage gastric cancer is an increasingly frequently performed procedure. The authors describe their experience of the first reported single-port laparoscopic subtotal gastrectomy in an 88-year-old lady with early antral gastric adenocarcinoma. METHOD: Single-port laparoscopic subtotal gastrectomy with D1α lymphadenectomy was successfully performed using a transumbilical multichannel single port. Straight and flexible tipped laparoscopes were used to obtain off-axis views of the operative field. A flexible tipped stapler and curved instruments were used to reconstruct the Polya-type gastrojejunostomy. The procedure was performed without compromising standard, oncological principles. RESULTS: Specimen histology revealed moderately to poorly differentiated adenocarcinoma infiltrating the submucosa. Proximal and distal resection margins were tumor free. Furthermore, 41 tumor-free lymph nodes were harvested. The patient was discharged on postoperative day 6. CONCLUSIONS: Single-port gastrectomy for cancer is technically and oncologically feasible when performed by experienced minimally invasive surgical oncologists with extensive experience of benign single-port laparoscopic procedures. The advantages to the patient in terms of cosmesis and shorter hospital stay are clear. However, further studies are required to assess this technique when treating gastric and other malignancies.

Single-port laparoscopy for the drainage of abdominal infected fluid collections in children, with the TriPort system: initial experience of 2 cases.

Single-port or single-incision laparoscopic surgery has been reported for a number of surgical procedures, including cholecystectomy, appendicectomy, and urological procedures. Single-port thoracoscopic procedures for evacuation of empyema have been described. However, to the authors' knowledge, there has been no report of single-port laparoscopic drainage of abdominal infected fluid collections, especially in children, in the relevant world literature. The authors report the first use of single-port laparoscopy with the TriPort system for drainage of abdominal infected fluid collections in children using the previous open appendicectomy wound. This approach was successfully completed in 2 consecutive children without conversion to open surgery. The operative duration was less than 30 minutes in each case. Both patients had no intraoperative or postoperative complications on follow-up at 8 weeks. Single-port laparoscopy with the TriPort system is safe and technically feasible for the management of pelvic collection and/or abscesses. Also, this technique is useful in multiloculated collections and allows for a washout of the peritoneal cavity at the same time, which is not the case for image-guided drainage. In addition, it also allows checking for the blowout of the appendicectomy stump as the cause for the collection. Finally, it has the advantage of reduced wound morbidity and better cosmesis.

[Not Available].

Laparoscopic cholecystectomy is the gold standard method for treating gallstone related disease. Despite its widespread and well established application, clear consensus is not arrived at regarding the comparative risks and benefits of acute versus interval cholecystectomy. The complications of this technique are well known, with respect to both the operative intervention and the technique used. This case describes a case of cholecystitis in a 76-year-old man, who underwent acute laparoscopic cholecystectomy for cholecystitis refractory to antibiotic therapy. Postoperative complications included subhepatic collections bilaterally, eventually leading to the formation of an enterocutaneous fistula to the left chest wall - a previously undocumented phenomenon. The protracted course of the disease is discussed, with reference to investigations performed and the eventual successful outcome.

Systematic review of the costs of laparoscopic colorectal surgery.

PURPOSE: Recent studies have confirmed the clinical efficacy of laparoscopic colorectal surgery; however, its use has not become widespread. One reason for this is perceived economic implications. A systematic review was undertaken examining the costs of laparoscopic colorectal surgery. METHODS: Electronic databases were searched for articles comparing laparoscopic colorectal surgery and open surgery. Primary outcome measures were operating room, direct hospital, and indirect costs. Secondary outcomes were conversion rates and length of hospital stay. The percentage difference in costs was used for comparisons between studies. RESULTS: Twenty-nine articles were identified in which cost data were presented (total number of patients 3,681); the economic data in most studies was limited. Operating room costs were greater for laparoscopic colorectal surgery than open surgery in all studies (median difference, 50 percent; interquartile range, 27-78 percent; P < 0.001). There was no overall difference in total hospital costs (median difference, 0 percent; interquartile range, -17.5 to 21 percent). Only two articles collected data on indirect costs, with both in favor of laparoscopic colorectal surgery. Hospital stay was shorter for laparoscopic colorectal surgery in all studies (median difference, 2.8 days; interquartile range, 1.3-3.7; P < 0.001). Median conversion rate was 7.8 percent (mean, 14 percent; interquartile range, 6-21 percent). CONCLUSIONS: Operating room costs are greater for laparoscopic colorectal surgery than open surgery. Total hospital costs are similar. There may be societal benefits associated with lower indirect costs for laparoscopic colorectal surgery. Cost should not be a deterrent to performing laparoscopic colorectal surgery.

Prevention of acute mountain sickness by acetazolamide in Nepali porters: a double-blind controlled trial.

OBJECTIVE: This study aimed to determine the efficacy, tolerability, and practicality of acetazolamide for the prevention of acute mountain sickness (AMS) in Nepali trekking porters early in the trekking season. METHODS: This study was a randomized, double-blind controlled trial with 400 male Nepali porters in the Mount Everest region of Nepal, trekking from Namche Bazaar (3440 m) to Lobuche (4930 m), the study endpoint. Participants were randomized to receive 250 mg acetazolamide daily or placebo, and AMS symptom scores (Lake Louise) were compared in highlanders vs lowlanders. RESULTS: Only 109 (27.2%) of the 400 porters completed the trial (28 highlanders, 81 lowlanders). The rest either dropped out (275/400 porters, 68.8%) or were excluded (16/400 porters, 4%). Acute mountain sickness occurred in 13 (11.9%) of 109 porters; all were lowlanders; 7 were taking acetazolamide, 6 taking placebo. Birthplace, acclimatization in the week before the trial, ascent rate, and rest days were the most important variables affecting the incidence of AMS. No highlanders, but 13 (16.1%) of 81 lowlanders had AMS (P = .016). Acclimatization in the pretrial week reduced AMS incidence (P = .013), as did a slower ascent rate (P = .0126), but rest days were the most potent prophylactic variable (P = .0001). Side effects were more frequent in porters taking acetazolamide than in the placebo group (P = .0001), but there were no serious side effects. CONCLUSIONS: Acetazolamide was tolerable, but impractical for the routine prevention of AMS in Nepali porters. A good trekking schedule and adequate acclimatization remain the most effective preventive measures. This study identified lowland porters as a high-risk group for developing AMS.