Development of a Reliable Surgical Quality Assurance System for 2-stage Esophagectomy in Randomized Controlled Trials.

OBJECTIVE: The aim was to develop a reliable surgical quality assurance system for 2-stage esophagectomy. This development was conducted during the pilot phase of the multicenter ROMIO trial, collaborating with international experts. SUMMARY OF BACKGROUND DATA: There is evidence that the quality of surgical performance in randomized controlled trials influences clinical outcomes, quality of lymphadenectomy and loco-regional recurrence. METHODS: Standardization of 2-stage esophagectomy was based on structured observations, semi-structured interviews, hierarchical task analysis, and a Delphi consensus process. This standardization provided the structure for the operation manual and video and photographic assessment tools. Reliability was examined using generalizability theory. RESULTS: Hierarchical task analysis for 2-stage esophagectomy comprised fifty-four steps. Consensus (75%) agreement was reached on thirty-nine steps, whereas fifteen steps had a majority decision. An operation manual and record were created. A thirty five-item video assessment tool was developed that assessed the process (safety and efficiency) and quality of the end product (anatomy exposed and lymphadenectomy performed) of the operation. The quality of the end product section was used as a twenty seven-item photographic assessment tool. Thirty-one videos and fifty-three photographic series were submitted from the ROMIO pilot phase for assessment. The overall G-coefficient for the video assessment tool was 0.744, and for the photographic assessment tool was 0.700. CONCLUSIONS: A reliable surgical quality assurance system for 2-stage esophagectomy has been developed for surgical oncology randomized controlled trials. ETHICAL APPROVAL: 11/NW/0895 and confirmed locally as appropriate, 12/SW/0161, 16/SW/0098.Trial registration number: ISRCTN59036820, ISRCTN10386621.

Multi-omic molecular comparison of primary versus metastatic pancreatic tumours.

BACKGROUND: Molecular profiling is increasingly used to match patients with metastatic cancer to targeted therapies, but obtaining a high-quality biopsy specimen from metastatic sites can be difficult. METHODS: Patient samples were received by Perthera to coordinate genomic, proteomic and/or phosphoproteomic testing, using a specimen from either the primary tumour or a metastatic site. The relative frequencies were compared across specimen sites to assess the potential limitations of using a primary tumour sample for clinical decision support. RESULTS: No significant differences were identified at the gene or pathway level when comparing genomic alterations between primary and metastatic lesions. Site-specific trends towards enrichment of MYC amplification in liver lesions, STK11 mutations in lung lesions and ATM and ARID2 mutations in abdominal lesions were seen, but were not statistically significant after false-discovery rate correction. Comparative analyses of proteomic results revealed significantly elevated expression of ERCC1 and TOP1 in metastatic lesions. CONCLUSIONS: Tumour tissue limitations remain a barrier to precision oncology efforts, and these real-world data suggest that performing molecular testing on a primary tumour specimen could be considered in patients with pancreatic adenocarcinoma who do not have adequate tissue readily available from a metastatic site.

Biweekly cisplatin and gemcitabine in patients with advanced biliary tract cancer.

Treatment with cisplatin and gemcitabine demonstrates a survival benefit in patients with advanced biliary tract cancer (ABTC). However, the weekly administration can add significant toxicities that may prohibit prolonged treatment. Based on previous studies, we implemented a modified biweekly regimen of GC in an attempt to optimize the prescribed regimen with an improved toxicity profile, added convenience to patients while maintaining efficacy. Patients with ABTC were treated with fixed dose rate (FDR) gemcitabine (1,000 mg/m2 /min) and cisplatin 20 mg/m2 on days 1 and 15 of every 28-day cycle. Patients received treatment until time of progression, death, or discontinuation due to intolerance. Collected data included demographics, clinico-pathologic features, toxicities, and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). The study included 107 evaluable pts with unresectable ABTC who received the biweekly regimen. Sites of tumor included gallbladder (21.5%), ampullary (3.7%), and bile duct (74.8%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade ≥3 adverse events included neutropenia (11%), fatigue (10%), and thrombocytopenia (6.4%). Biweekly FDR GC in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many patients. Further prospective trials should consider evaluating the role of biweekly GC regimen in ABTC, including a potentially more favorable platform in novel experimental strategies.

Surgical resection of hepatic metastases from gastric cancer: outcomes from national series in England.

BACKGROUND: The objectives of this national study were to examine the short-term safety and long-term survival benefit associated with surgical resection of hepatic metastases from gastric cancer. METHODS: Patients from the Hospital Episode Statistics database were classified by disease and treatment approach. Gastric cancer: 1. Without liver metastases treated by gastrectomy (GG). 2. With liver metastases treated by gastrectomy and hepatectomy (GGH). 3. With liver metastases treated by gastrectomy without hepatectomy (GGNH). 4. With liver metastases treated with no surgery (GNS). Propensity score matching and multivariable analyses were used to compensate for differences in some baseline characteristics. RESULTS: During the study period, 87,482 were patients diagnosed with gastric cancer, of whom 13,841 underwent partial or total gastrectomy. Of those who underwent gastrectomy, 336 had a diagnosis of liver metastases and 78 of these had a hepatectomy. Propensity-matched analysis showed no significant differences in 30- or 90-day mortality between the GGH and GG groups. The GGH group had significantly improved 1-year mortality (35.9 % vs. 50.0 %, p = 0.049) and 5-year mortality (61.5 % vs. 75.7 %, p = 0.031) compared to the GGNH group, and compared to the GNS group, the GCH group had 1-year mortality (35.9 % vs. 84.6 %, p < 0.001) and 5-year mortality (61.5 % vs. 90.8 %, p < 0.001). CONCLUSIONS: This study showed that hepatectomy for synchronous gastric cancer hepatic metastases may carry survival benefits in selected patients. The data presented should not be a rationale to change current clinical practice but rather a stimulus to prospectively study the role of surgery in a selected group of patients who are currently treated with palliative chemotherapy.

Randomized Phase 2 Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront Treatment of Metastatic Pancreatic Adenocarcinoma.

Pelareorep causes oncolysis in tumor cells with activated Ras. We hypothesized that pelareorep would have efficacy and immunomodulatory activity in metastatic pancreatic adenocarcinoma (MPA) when combined with carboplatin and paclitaxel. A randomized phase 2 study (NCT01280058) was conducted in treatment-naive patients with MPA randomized to two treatment arms: paclitaxel/carboplatin + pelareorep (Arm A, n = 36 evaluable patients) versus paclitaxel/carboplatin (Arm B, n = 37 evaluable patients). There was no difference in progression-free survival (PFS) between the arms (Arm A PFS = 4.9 months, Arm B PFS = 5.2 months, P = 0.6), and Kirsten rat sarcoma viral oncogene (KRAS) status did not impact outcome. Quality-adjusted Time without Symptoms or Toxicity analysis revealed that the majority of PFS time was without toxicity or progression (4.3 months). Patient immunophenotype appeared important, as soluble immune biomarkers were associated with treatment outcome (fractalkine, interleukin (IL)-6, IL-8, regulated on activation, normal T cell expressed and secreted (RANTES), and vascular endothelial growth factor (VEGF)). Increased circulating T and natural killer (NK)-cell subsets were also significantly associated with treatment outcome. Addition of pelareorep was associated with higher levels of 14 proinflammatory plasma cytokines/chemokines and cells with an immunosuppressive phenotype (Tregs, cytotoxic T lymphocyte associated protein 4 (CTLA4)(+) T cells). Overall, pelareorep was safe but does not improve PFS when administered with carboplatin/paclitaxel, regardless of KRAS mutational status. Immunologic studies suggest that chemotherapy backbone improves immune reconstitution and that targeting remaining immunosuppressive mediators may improve oncolytic virotherapy.

Molecular biology of gastroesophageal cancers: opportunities and challenges.

Gastroesophageal (GE) malignancies make up a significant and growing segment of newly diagnosed cancers. Approximately 80% of patients who have GE cancers die within 5 years of diagnosis, which means that effective treatments for these malignancies need to be found. Currently, targeted therapies have a minimal role in this disease group. Intensive study of the molecular biology of GE cancers is a relatively new and ongoing venture, but it has already led to a significant increase in our understanding of these malignancies. This understanding, although still limited, has the potential to enhance our ability to develop targeted therapies in conjunction with the ability to identify actionable gene mutations and perform genomic profiling to predict drug resistance. Several cell surface growth factor receptors have been found to play a prominent role in GE cancer cell signaling. This discovery has led to the approval of 2 agents within the last few years: trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody used in the first-line treatment of HER2-positive GE cancers, and ramucirumab, an anti-vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody that is currently used in later lines of therapy. This review discusses the current state of molecular testing in GE cancers, along with the known molecular biology and current and investigational treatments. The development of trastuzumab and ramucirumab represents a significant advance in our ability to make use of GE tumor molecular profiles. As our understanding of the impact of molecular aberrations on drug effectiveness and disease outcomes increases, we anticipate improved therapy for patients with GE cancers.

Outcomes of definitive chemoradiation in patients with esophageal cancer.

The incidence of esophageal cancer has risen dramatically in the Western world. Although surgical resection of esophageal tumors is considered the cornerstone of curative approaches in localized esophageal cancer, approximately 40% of patients who undergo chemoradiation followed by surgery will experience a recurrence. Additionally, surgical resection is not a viable option for many patients with locally advanced unresectable disease, poor general condition or whose condition deteriorated following chemoradiation. Several investigators have, therefore, attempted to evaluate the outcomes of definitive chemoradiation in patients with localized or locally advanced esophageal cancer. The outcomes of concurrent chemoradiation remain a matter of debate given the heterogenous study design and treatment regimens used in recent trials. Understanding the clinical benefit of chemoradiation is essential prior to recommending it as an alternative to surgery. In our review, we present the most recent studies evaluating the role of chemoradiation to better define the clinical outcomes of patients with special attention to overall survival.

Next-generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance.

BACKGROUND: Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance. METHODS: Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS). RESULTS: When genes with an incidence > 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached. CONCLUSIONS: In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.

Influence of Surgical Resection of Hepatic Metastases From Gastric Adenocarcinoma on Long-term Survival: Systematic Review and Pooled Analysis.

OBJECTIVES: The objectives of this systematic review and pooled analysis were to examine long-term survival, morbidity, and mortality following surgical resection of gastric cancer hepatic metastases and to identify prognostic factors that improve survival. BACKGROUND: Patients with hepatic metastases from gastric cancer are traditionally treated with palliative chemotherapy. METHODS: A systematic literature search was undertaken (1990 to 2015). Publications were included if they studied more than 10 patients undergoing hepatectomy for hepatic metastasis from gastric adenocarcinoma in the absence of peritoneal disease or other distant organ involvement. The primary outcome was the hazard ratio (HR) for overall survival. The influence of liver metastasis related factors; multiple vs single and metachronous vs synchronous upon survival was also assessed. RESULTS: The median number of resections for the 39 studies included was 21 (range 10 to 64). Procedures were associated with a median 30-day morbidity of 24% (0% to 47%) and mortality of 0% (0% to 30%). The median 1-year, 3-year, and 5-year survival were 68%, 31%, and 27%, respectively. Survival was improved in Far Eastern compared with Western studies; 1-year (73% vs 59%), 3-year (34% vs 24.5%), and 5-year (27.3% vs 16.5%). Surgical resection of hepatic metastases was associated with a significantly improved overall survival (HR = 0.50; P < 0.001). Meta-analysis confirmed the additional survival benefit of solitary compared with multiple hepatic metastases (odds ratio = 0.31; P = 0.011). CONCLUSIONS: The observed improved survival rates following the resection of hepatic metastasis from gastric adenocarcinoma in selected patients merit a prospective study to formally address the survival benefits and the influence on quality of life of such approach.

Cyclin-dependent kinase inhibitors and the treatment of gastrointestinal cancers.

The cell cycle is a highly conserved and tightly regulated biological system that controls cellular proliferation and differentiation. The cell cycle regulatory proteins, which include the cyclins, the cyclin-dependent kinases (CDKs), and the CDK inhibitors, are critical for the proper temporal and spatial regulation of cellular proliferation. Conversely, alterations in cell cycle regulatory proteins, leading to the loss of normal cell-cycle control, are a hallmark of many cancers, including gastrointestinal cancers. Accordingly, overexpression of CDKs and cyclins and by contrast loss of CDK inhibitors, are all linked to gastrointestinal cancers and are often associated with less favorable prognoses and outcomes. Because of the importance that the cell cycle regulatory proteins play in tumorigenesis, currently there is a broad spectrum of cell-cycle inhibitors under development that, as a group, hold promise as effective cancer treatments. In support of this approach to cancer treatment, the growing availability of molecular diagnostics techniques may help in identifying patients who have driving abnormalities in the cell-cycle machinery and are thus more likely to respond to cell-cycle inhibitors. In this review, we discuss the prevalence of cell-cycle abnormalities in patients with gastrointestinal cancers and provide a preclinical and clinical overview of new agents that target cell-cycle abnormalities with a special emphasis on gastrointestinal cancers.

Sofosbuvir plus ribavirin for the treatment of chronic genotype 4 hepatitis C virus infection in patients of Egyptian ancestry.

BACKGROUND & AIMS: We conducted an open-label phase 2 study to assess the efficacy and safety of the oral nucleotide polymerase inhibitor sofosbuvir in combination with ribavirin in patients of Egyptian ancestry, chronically infected with genotype 4 hepatitis C virus (HCV). METHODS: Treatment-naive and previously treated patients with genotype 4 HCV were randomly allocated in a 1:1 ratio to receive sofosbuvir 400mg and weight-based ribavirin, for 12 or 24 weeks. The primary efficacy endpoint was the proportion of patients with sustained virologic response (HCV RNA <25IU/ml) 12 weeks after cessation of therapy (SVR12). RESULTS: Thirty treatment-naive and thirty previously treated patients were enrolled and treated for 12 weeks (n=31) or 24 weeks (n=29). Overall, 23% of patients had cirrhosis and 38% had diabetes. 14% of treatment-naive patients were interferon ineligible and 63% of treatment-experienced patients had prior non-response. SVR12 was achieved by 68% of patients (95% CI, 49-83%) in the 12-week group, and by 93% of patients (95% CI, 77-99%) in the 24-week group. The most common adverse events were headache, insomnia, and fatigue. No patient discontinued treatment due to an adverse event. CONCLUSIONS: The findings from the present study suggest that 24 weeks of sofosbuvir plus ribavirin is an efficacious and well tolerated treatment in patients with HCV genotype 4 infection.

Improving the standard of lymph node retrieval after gastric cancer surgery.

AIMS: To examine factors that influence lymph node count and to study the relationship between nodal size and metastatic involvement in gastric cancer. METHODS AND RESULTS: Observational study comparing lymph node retrieval by manual nodal dissection (MND) and systematic fat blocking (SFB) from 114 gastrectomy specimens. The influence of lymph node retrieval method, patient characteristics, oncological factors and surgical approach on lymph node count were examined using regression models. The risk-adjusted cumulative sum chart method was also used to analyse lymph node count. The lymph node count increased during the course of this study (P < 0.005). Both pathologist and lymph node retrieval method were independent predictors for lymph node count. MND yielded lower lymph node counts than SFB (58 versus 66, P < 0.05). The pathologist influenced lymph node retrieval by MND (R(2) : 0.297-0.518, P < 0.0001), but not SFB (R(2) : 0.340-0.344, P > 0.05). The percentage of positive lymph nodes below 5 mm was 24.2% and 44.1% for MND and SFB, respectively, resulting in cancer upstaging (P = 0.037). CONCLUSIONS: Systematic fat blocking is associated with a higher total and positive lymph node yield compared to MND and is independent of the pathologist. Ignoring small lymph nodes can be a major cause for missing positive nodes, leading in turn to cancer down-staging.

The effect of bariatric surgery on echocardiographic indices: a review of the literature.

Obesity is the new epidemic and is associated with an increased risk of diastolic and systolic heart failure. Effective treatment options with drastic results such as bariatric surgery have raised interest in the possible reversal of some of the cardiovascular sequelae. Many studies have assessed individually the effect of weight loss on specific echocardiographic indices, mostly employing nonhomogeneous groups. The purpose of this narrative review is to summarise the effect of bariatric surgery on echocardiographic indices of biventricular function and to help in the understanding of the expected echocardiographic changes in bariatric patients after weight-loss surgery.

Towards cost saving in surgery without compromising safety: stapleless laparoscopic splenectomy in a developing country-a prospective cohort study.

BACKGROUND: Minimally invasive surgery has been steadily growing in popularity. Control of splenic hilar vessels is the most delicate step during laparoscopic splenectomy (LS). In the earlier eras of LS, hilar vessels were controlled using clips and/or ligation. Laparoscopic staples were later introduced and have arguably led to an increase in popularity of LS. They do not abolish potential complications of splenectomy and theoretically represent an added operative cost.In this study, we aimed to assess the safety and efficacy of stapleless LS (using knots, haemostatic devices and clips) compared with the now more conventional stapled LS. METHODS: A pilot randomised prospective study was conducted in a university hospital between September 2018 and April 2020. It included 40 patients randomly assigned to two equal groups: (1) 20 patients: stapleless LS and (2) 20 patients: LS using laparoscopic staples.We compared operative time, intra and postoperative complications and postoperative recovery. RESULTS: There was no statistically significant difference between both groups across all comparative outcomes. CONCLUSION: Both techniques are comparable in terms of safety and operative time. In terms of cost efficiency, we recommend more comprehensive analyses of hospital costs.

One Anastomosis Gastric Bypass Versus Long Biliopancreatic Limb Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is one of the most effective bariatric procedures. The study aimed to explore the value of lengthening the biliopancreatic limb (BPL) in RYGB compared to the outcome of one-anastomosis gastric bypass (OAGB). METHODS: This prospective study included morbidly obese patients divided into two groups. The RYGB group (n = 36) was subjected to long biliary limb Roux-en-Y gastric bypass (LPRYGB), and the OAGB Group (n = 36) had one anastomosis gastric bypass. During follow-up, weight, BMI, percentage of excess body weight loss (%EBWL), resolution of obesity-related comorbidities, and quality of life (QoL) were evaluated. RESULTS: There was no significant difference in weight and BMI after 3 and 6 months. At 12-month follow-up, weight loss was significantly higher in the OAGB group. After 12 months, the two groups showed significant improvement of comorbid conditions without significant difference between the two groups. The Qol was significantly higher in the LPRYGB group 3, 6, and 12 months after surgery compared to the OAGB group. CONCLUSIONS: Extending the BPL length in RYGB to 150 cm is as effective as OAGB in remission of comorbidities, including diabetes. It was also equally effective in weight reduction in the short term. OAGB was more efficient in weight reduction and a significantly faster operation. LPRYGB showed a better QoL of life 1 year after surgery.

Radiofrequency-assisted hepatic resection.

BACKGROUND: The only curative procedure to date for liver tumors is surgical resection, which remains a major procedure with marked morbidity and mortality. Radiofrequency (RF) has increasingly been used for both ablation and resection. On the basis of this technique, a new bipolar RF device, Habib 4X, has been developed and used clinically. We present our technique of liver resection with this device in a patient with colorectal liver metastases. METHODS: A patient with situs inversus who had colorectal liver metastases in her left lobe underwent left lateral segmentectomy with the new device, a four-electrode bipolar resection device that uses RF energy for tissue necrosis. After laparotomy and intraoperative ultrasound, the plane resection was marked 1 cm away from the edge of the lesion. Coagulative desiccation was performed along this plane using this sealer connected to a RF generator. The necrosed band of parenchyma was then divided with a scalpel and resection completed. RESULTS: The length of the procedure was 105 minutes; resection time was 35 minutes. Total blood loss was 100 ml. No blood transfusions were required, and the patient was not admitted to the intensive care unit after surgery. The patient was discharged 10 days after surgery without any surgical complications. CONCLUSIONS: We think that RF-assisted liver resection with this new device is safe and effective. It is quicker than conventional RF and may reduce overall hospital stay in liver resection patients.

Early Effects of Laparoscopic Sleeve Gastrectomy and Laparoscopic One-Anastomosis Gastric Bypass on Portal Venous Flow: a Prospective Cohort Study.

BACKGROUND: Portal vein thrombosis (PVT) is an infrequent, yet potentially lethal, complication of bariatric surgery. The aim of this prospective, non-randomized, cohort study is to compare between laparoscopic sleeve gastrectomy (LSG) and laparoscopic one-anastomosis gastric bypass (LOAGB) in terms of their early postoperative effects on portal venous flow and patency. METHODS: Forty-nine morbidly obese patients were allocated to one of 2 groups (A or B). Group A patients underwent LSG, whereas group B patients underwent LOAGB. Portal venous Doppler ultrasound scanning was performed preoperatively and 2 weeks postoperatively in all cases, in order to assess the portal venous flow (PVF) in terms of flow direction and peak systolic velocity (PSV); as well as to assess the portal venous patency and exclude PVT. The mean change in PSV (ΔPSV) and the mean percentage change in PSV (%ΔPSV) were determined in both groups. RESULTS: In all cases (group A (n = 26); group B (n = 23)), the direction of PVF was "hepatopetal" both preoperatively and 2 weeks postoperatively. The mean ΔPSV and the mean %ΔPSV were higher in LSG patients "group A" (- 0.84 cm/s and 3.25% respectively) compared with LOAGB patients "group B"(- 0.06 cm/s and 0.27% respectively); P = 0.038 and 0.039 respectively. The mean change in PSV was in the negative direction in both groups, i.e., "deceleration." No cases of PVT were reported in the study. CONCLUSIONS: Laparoscopic sleeve gastrectomy is associated with greater reduction in portal venous peak systolic flow velocity in the early postoperative period, compared with laparoscopic one-anastomosis gastric bypass.

Phase I Trial of Trametinib with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer.

PURPOSE: The RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and KRAS, NRAS, and BRAF mutations foster resistance to radiation. We performed a phase I trial to determine the safety of trametinib, a potent MEK1/2 inhibitor, with 5-fluorouracil (5-FU) chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC). PATIENTS AND METHODS: Patients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m2/day and radiation dose of 28 daily fractions of 1.8 Gy (total 50.4 Gy). The primary endpoint was to identify the MTD and recommended phase II dose. IHC staining for phosphorylated ERK (pERK) and genomic profiling was performed on the tumor samples. RESULTS: Patients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses. CONCLUSIONS: The combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a RAS/RAF-mutant selected population.

Food Tolerance After Laparoscopic Sleeve Gastrectomy with Total Antral Resection.

BACKGROUND: Among the controversial points in laparoscopic sleeve gastrectomy (LSG) is how much of the antrum to be resected. This study aimed to evaluate food tolerance after preservation or resection of the antrum during LSG. METHODS: Prospective randomized study included 50 patients scheduled for LSG. Participants were randomly allocated into one of two groups. In antral resection (AR-LSG) group (n = 25), resection started 2 cm from the pylorus. In antral sparing (AS-LSG) group (n = 25), it started 6 cm from the pylorus. Percentage of excess weight loss (%EWL) and percentage of excess BMI loss (%EBL) were evaluated after 3 and 6 months. Quality of life (QOL) was evaluated by using the Bariatric Analysis and Reporting Outcome System (BAROS). Food tolerance was assessed using the Quality of Alimentation questionnaire. Primary outcome measure was food tolerance and %EWL. RESULTS: Food tolerance was significantly better in the antral sparing group compared to the antral resection group after 3 and 6 months. The two groups were comparable in %EWL and BMI change after 3 and 6 months. Six months after surgery, the majority of patients had a very good quality of life, with no significant difference between the two groups (p = 0.877). There was no significant difference between the two groups in operative time, intraoperative blood loss, and hospital stay. CONCLUSIONS: Preservation of the pyloric antrum during LSG is associated with significantly better food tolerance and comparable effect of weight loss up to 6 months postoperatively when compared with total antral resection.

Conventional Versus Distal Laparoscopic One-Anastomosis Gastric Bypass: a Randomized Controlled Trial with 1-Year Follow-up.

BACKGROUND: There is no consensus on the ideal small bowel length that should be bypassed in laparoscopic one-anastomosis gastric bypass (OAGB). This study aimed to compare the safety and efficacy of conventional versus distal techniques of laparoscopic OAGB. METHODS: This randomized controlled trial involved 60 adults with morbid obesity scheduled for laparoscopic OAGB randomly assigned to one of the two techniques; conventional technique (fixed anastomosis 200 cm from the ligament of Treitz) and distal technique (anastomosis 400 cm from the ileocecal valve). Total small bowel length (TSBL) was measured in all cases. Quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI). Outcome measures were excess body weight loss percentage (EBWL%), resolution of associated comorbidities, frequency of nutritional deficiencies, and quality of life. RESULTS: No patients were lost to follow-up. The two groups were comparable in TSBL, EBWL%, and complete resolution of comorbidities up to 12 months. The percentage of afferent loop length to TSBL was significantly higher in the distal group (p < 0.001) but was not correlated with EBWL%. The levels of hemoglobin, cholesterol, triglycerides, iron, and albumin were significantly lower and parathormone hormone was higher in the distal group. The GIQLI score was significantly higher in the conventional group during follow-up. CONCLUSION: OAGB achieves optimum results when the afferent loop length is 200 cm; bypassing more than 200 cm does not improve weight loss or comorbidity resolution. Measuring TSBL is recommended to avoid excessive small bowel shortening that increases the risk of nutritional consequences.