Surgeon-Dependent Variability in Cost of Gastrointestinal Operations in a Single Cancer Center.

INTRODUCTION: Cancer operations are increasingly utilizing specialized equipment and technology. Related costs are often not known to the responsible surgeon. We seek to evaluate cost aspects of care episodes attributable to the surgeon's management decisions. METHODS: Financial cost data in a tertiary academic cancer center were queried over 3 y. Consecutive patients undergoing gastrointestinal operations followed by inpatient admission of two or more days were included, excluding patients with 40+ d admissions. Analysis of variance, Kruskal-Wallis, and multiple regression statistics were utilized. RESULTS: The study population included 1540 patients: 54% men and 46% women, with a median age of 64 y (range 15-95). Eight surgeons conducted major (82%) and minor (18%) operations, with a minimally invasive surgical approach in 60.4%. Procedures included colorectal (37%), pancreatic (19%), esophagogastric (18%), hepatobiliary (18%), and small bowel resections (8%). Total direct costs differed between surgeons with an analysis of variance coefficient range between -$3265 and +$6163 (P < 0.001). Surgeons' cost differences were observed for central medical supply, operating room (OR) supply, total OR, inpatient room, laboratory, pharmacy, supportive care (P < 0.001), and radiology costs (P < 0.02). OR supply cost was the dominant consistent domain with significant differences between surgeons in all case subcategories. When controlled for case category and minimally invasive surgical approach, multiple regression showed the most significant variations between surgeons in ORs, medical supply, and nutrition costs (P < 0.001), followed by laboratory costs (P < 0.01). Top OR supply costs were staplers and energy devices. CONCLUSIONS: Even in a highly subspecialized surgical environment, surgeons' variable utilization of ORs and medical supplies is strongly linked to variations in care-related costs. Specific queries into supply items should reduce costs and optimize value generated.

Perioperative Chemotherapy is Associated with Superior Overall Survival in Patients with Synchronous Colorectal Liver Metastases.

BACKGROUND: The sequence of localized and systemic treatment for colorectal liver metastases (CRLM) remains debated. Our objective is to analyze the effect of treatment sequence on overall survival (OS) in patients with CRLM using a large cancer database. PATIENTS AND METHODS: The national cancer database (NCDB) was utilized to identify patients with stage IV colorectal cancer (CRC) diagnosed between 2004 and 2016. OS was analyzed using standard univariate and multivariate methods. RESULTS: We identified 72,376 patients with synchronous CRLM, of whom 43,039 had liver-only metastases. Patients with liver-only CRLM had a median OS of 18.9 months, versus those with CRLM plus extrahepatic sites (11.3 months). In patients with liver-only CRLM, resection of both the primary and metastatic site was associated with median OS 38.9 months versus 30.2 months after resection of the metastatic site alone, and resection of the primary tumor alone (22.3 months, all p < 0.001). Receipt of perioperative chemotherapy correlated with a median OS of 44.7 months versus preoperative chemotherapy only (38.4 months) or postoperative chemotherapy only (27.9 months, all p < 0.001). Patients who received chemotherapy alone had a median OS of 16.4 months versus those who underwent resection without chemotherapy (9.5 months, p < 0.001). CONCLUSIONS: This study reveals a correlation between perioperative chemotherapy and superior OS in patients with liver-only CRLM, and shows that resection of the metastatic site was linked to better OS. Despite obvious cohort heterogeneity, the data can support a resection approach with additional, preferably peri- or preoperative systemic therapy for patients with CRLM.

Low incisional hernia incidence using a large-bite, low-tension technique for celiotomy closure.

Background: Incisional herniae (IH) are reported in 5->20 % of patients undergoing open celiotomy, and can be linked to closure technique. The STITCH randomized trial favors a small bite technique for midline celiotomy closure with a 1-year IH rate of 13 % over larger bites (23 %). Methods: A continuous musculofascial mass closure with absorbable looped #1 PDS suture with 2-cm bite size was used for all open celiotomies. IH frequency and associated clinicopathologic factors were retrospectively analyzed from prospective data in 336 consecutive patients undergoing visceral resections by a single surgeon. Results: The study population included 192 men and 144 women, 81 % of whom had a cancer diagnosis, who underwent hepatobiliary, pancreatic, gastroesophageal, and colorectal resections, or a combination. The majority of patients (84 %) had subcostal incisions, and 10 % received a midline incision. At a median follow-up of 19.5 months, the overall IH rate was 3.3 %. Hernia rates were 2.5 % for subcostal margin, 2.9 % for midline, and 5.5 % for other incisions (p = 0.006). Median time to hernia detection was 492 days. Factors associated with IH were increased weight, abdominal depth/girth, male sex, spleen size, visceral fat, and body height (p ≤ 0.04 for all), but not type of resection, prior operations, underlying diagnosis, weight loss, adjuvant chemotherapy or radiation, incision length or suture to incision ratio. Conclusions: The described technique leads to a low IH rate of <3 % in subcostal or midline incisions, and can be recommended for routine use. The observed results appear superior to those of the STITCH trial, even for the smaller midline incision cohort.

Enhancing gastric cancer conventional chemotherapy effects by triple angiokinase inhibitor nintedanib in preclinical models.

Background: Gastric adenocarcinoma (GAC) is the fourth leading cause of cancer death worldwide. Systemic chemotherapy is a preferred treatment option for advanced and recurrent GAC, but response rates and survival prolongation remain limited. Tumor angiogenesis plays a critical role in GAC growth, invasion and metastasis. We investigated the antitumor efficacy of nintedanib, a potent triple angiokinase inhibitor for VEGFR-1/2/3, PDGFR-α/ß and FGFR-1/2/3, alone or in combination with chemotherapy, in preclinical models of GAC. Methods: Animal survival studies were performed in peritoneal dissemination xenografts in NOD/SCID mice using human GAC cell lines MKN-45 and KATO-III. Tumor growth inhibition studies were performed in subcutaneous xenografts in NOD/SCID mice using human GAC cell lines MKN-45 and SNU-5. The mechanistic evaluation involved Immunohistochemistry analyses in tumor tissues obtained from subcutaneous xenografts. In vitro cell viability assays were performed using a colorimetric WST-1 reagent. Results: In MKN-45 GAC cell-derived peritoneal dissemination xenografts, animal survival was improved by nintedanib (33%), docetaxel (100%) and irinotecan (181%), while oxaliplatin, 5-FU and epirubicin had no effect. The addition of nintedanib to docetaxel (157%) or irinotecan (214%) led to a further extension in animal survival. In KATO-III GAC cell-derived xenografts carrying FGFR2 gene amplification, nintedanib extended survival by 209%. Again, the addition of nintedanib further enhanced the animal survival benefits of docetaxel (273%) and irinotecan (332%). In MKN-45 subcutaneous xenografts, nintedanib, epirubicin, docetaxel and irinotecan reduced tumor growth (range: 68-87%), while 5-FU and oxaliplatin had a smaller effect (40%). Nintedanib addition to all chemotherapeutics demonstrated a further reduction in tumor growth. Subcutaneous tumor analysis revealed that nintedanib attenuated tumor cell proliferation, reduced tumor vasculature and increased tumor cell death. Conclusion: Nintedanib showed notable antitumor efficacy and significantly improved taxane or irinotecan chemotherapy responses. These findings indicate that nintedanib, alone and in combination with a taxane or irinotecan, has the potential for improving clinical GAC therapy.

Augmenting Experimental Gastric Cancer Activity of Irinotecan through Liposomal Formulation and Antiangiogenic Combination Therapy.

Gastric adenocarcinoma (GAC) is the third most common cause of cancer-related deaths worldwide. Combination chemotherapy remains the standard treatment for advanced GAC. Liposomal irinotecan (nal-IRI) has improved pharmacokinetics (PK) and drug biodistribution compared with irinotecan (IRI, CPT-11). Angiogenesis plays a crucial role in the progression and metastasis of GAC. We evaluated the antitumor efficacy of nal-IRI in combination with novel antiangiogenic agents in GAC mouse models. Animal survival studies were performed in peritoneal dissemination xenografts. Tumor growth and PK studies were performed in subcutaneous xenografts. Compared with controls, extension in animal survival by nal-IRI and IRI was >156% and >94%, respectively. The addition of nintedanib or DC101 extended nal-IRI response by 13% and 15%, and IRI response by 37% and 31% (MKN-45 xenografts); nal-IRI response by 11% and 3%, and IRI response by 16% and 40% (KATO-III xenografts). Retardation of tumor growth was greater with nal-IRI (92%) than IRI (71%). Nintedanib and DC101 addition tend to augment nal-IRI or IRI response in this model. The addition of antiangiogenic agents enhanced tumor cell proliferation inhibition effects of nal-IRI or IRI. The tumor vasculature was decreased by nintedanib (65%) and DC101 (58%), while nal-IRI and IRI alone showed no effect. PK characterization in GAC xenografts demonstrated that compared with IRI, nal-IRI treatment groups had higher retention, circulation time, and tumor levels of CPT-11 and its active metabolite SN-38. These findings indicate that nal-IRI, alone and in combination with antiangiogenic agents, has the potential for improving clinical GAC therapy.

Targeted FGFR/VEGFR/PDGFR inhibition with dovitinib enhances the effects of nab-paclitaxel in preclinical gastric cancer models.

Standard chemotherapy regimens for gastric adenocarcinoma (GAC) have limited efficacy and considerable toxicity profiles. Nab-paclitaxel has shown promising antitumor benefits in previous GAC preclinical studies. Dovitinib inhibits members of the receptor tyrosine kinase family including FGFR, VEGFR and PDGFR, and has exhibited antitumor effects in many solid tumors including GAC. Based on the antimitotic, antistromal and EPR effects of nab-paclitaxel, we investigated augmentation of nab-paclitaxel response by dovitinib in multiple GAC preclinical models. In MKN-45 subcutaneous xenografts, inhibition in tumor growth by nab-paclitaxel and dovitinib was 75% and 76%, respectively. Dovitinib plus nab-paclitaxel had an additive effect on tumor growth inhibition and resulted in tumor regression (85% of its original value). Dovitinib monotherapy resulted in minimal improvement in animal survival (25 days) compared to control (23 days), while nab-paclitaxel monotherapy or dovitinib plus nab-paclitaxel combination therapy led to a clinically significant lifespan extension of 83% (42 days) and 187% (66 days), respectively. IHC analysis of subcutaneous tumors exhibited reduced tumor cell proliferation and tumor vasculature by dovitinib. In vitro studies demonstrated that dovitinib and nab-paclitaxel individually reduced tumor cell proliferation, with an additive effect from combination therapy. Immunoblot analyses of MKN-45 and KATO-III cells revealed that dovitinib decreased phospho-FGFR, phospho-AKT, phospho-ERK, phospho-p70S6K, phospho-4EBP1, Bcl-2 and increased cleaved PARP-1, cleaved-caspase-3, p27, Bax, Bim, with an additive effect from combination therapy. These results demonstrate that the FGFR/VEGFR/PDGFR inhibitor, dovitinib, has the potential to augment the antitumor effects of nab-paclitaxel, with implications for use in the advancement of clinical GAC therapy.

A case from the future of HPB surgical oncology: resection of biliary tract cancer after immunotherapy.

Biliary tract cancers (BTCs) have limited response to systemic therapy and poor prognosis. Immunotherapy in BTCs has been investigated in recent years. Here, we report a case of locally advanced, unresectable gallbladder adenocarcinoma that progressed on chemotherapy. The patient was then treated with ipilimumab and nivolumab, which resulted in tumor shrinkage and autoimmune hepatitis, but established technical resectability. He underwent complete resection through extended right hepatectomy with en bloc cholecystectomy bile duct resection, hepatic and portal lymphadenectomy and Roux-Y hepaticojejunostomy reconstruction. The final pathology revealed a pathologic complete response. The scope of operative intervention after immunotherapy is still evolving for BTCs. Establishing resectability in tumors not susceptible to cytotoxic agents but responding to immunotherapy not only facilitates curative intent resection but also enhances the importance of infection prevention through operative stent-free long-term biliary decompression. Immunotherapy may also carry a unique risk profile for post-operative morbidity potential as in this case with autoimmune hepatitis.

Targeted dual inhibition of c-Met/VEGFR2 signalling by foretinib improves antitumour effects of nanoparticle paclitaxel in gastric cancer models.

Elevated expression of multiple growth factors and receptors including c-Met and VEGFR has been reported in gastric adenocarcinoma (GAC) and thus provides a potentially useful therapeutic target. The therapeutic efficacy of foretinib, a c-Met/VEGFR2 inhibitor, was determined in combination with nanoparticle paclitaxel (NPT) in GAC. Animal studies were conducted in NOD/SCID mice in subcutaneous and peritoneal dissemination xenografts. The mechanism of action was assessed by Immunohistochemical and Immunoblot analyses. In c-Met overexpressing MKN-45 cell-derived xenografts, NPT and foretinib demonstrated inhibition in tumour growth, while NPT plus foretinib showed additive effects. In c-Met low-expressing SNU-1 or patient-derived xenografts, the foretinib effect was smaller, while NPT had a similar effect compared with MKN-45, as NPT plus foretinib still exhibited an additive response. Median mice survival was markedly improved by NPT (83%), foretinib (100%) and NPT plus foretinib (230%) in peritoneal dissemination xenografts. Subcutaneous tumour analyses exhibited that foretinib increased cancer cell death and decreased cancer cell proliferation and tumour vasculature. NPT and foretinib suppressed the proliferation of GAC cells in vitro and had additive effects in combination. Further, foretinib caused a dramatic decrease in phosphorylated forms of c-Met, ERK, AKT and p38. Foretinib led to a decrease in Bcl-2, and an increase in p27, Bax, Bim, cleaved PARP-1 and cleaved caspase-3. Thus, these findings highlight the antitumour impact of simultaneous suppression of c-Met and VEGFR2 signalling in GAC and its potential to enhance nanoparticle paclitaxel response. This therapeutic approach might lead to a clinically beneficial combination to increase GAC patients' survival.

Combination effect of lapatinib with foretinib in HER2 and MET co-activated experimental esophageal adenocarcinoma.

Recent studies have demonstrated that HER2 and MET receptor tyrosine kinases are co-overexpressed in a subset esophageal adenocarcinoma (EAC). We therefore studied the usefulness of combining HER2 and MET targeting by small-molecule inhibitors lapatinib and foretinib, respectively, both in in-vitro and in-vivo models of experimental EAC. We characterized MET and HER2 activation in a panel of human EAC cell lines, and the differential susceptibility of these EAC cell lines to single agent or combination of foretinib and lapatinib. We then explored the antitumor efficacy with survival advantage following foretinib and lapatinib monotherapy and in combination in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. The OE33 EAC cell line with strong expression of phosphorylated both MET and HER2, demonstrated reduced sensitivity to foretinib and lapatinib when used as a single agent. The co-administration of foretinib and lapatinib effectively inhibited both MET and HER2 phosphorylation, enhanced inhibition of cell proliferation and xenograft tumor growth by inducing apoptosis, and significantly enhanced mouse overall survival, overcoming single agent resistance. In the OE19 EAC cell line with mainly HER2 phosphorylation, and the ESO51 EAC cell line with mainly MET phosphorylation, profound cell growth inhibition with induction of apoptosis was observed in response to single agent with lack of enhanced growth inhibition when the two agents were combined. These data suggest that combination therapy with foretinib and lapatinib should be tested as a treatment option for HER2 positive patients with MET-overexpressing EAC, and could be a novel treatment strategy for specific EAC patients.

Dual inhibition of the PI3K and MAPK pathways enhances nab-paclitaxel/gemcitabine chemotherapy response in preclinical models of pancreatic cancer.

Standard chemotherapy for pancreatic ductal adenocarcinoma (PDAC), nab-paclitaxel (NPT) plus gemcitabine (Gem), has led to an average survival of 8.5 months. Presently, no therapeutics exist that effectively target the KRAS oncogene, activated in 95% of PDACs, but alternative strategies focus on inhibition of downstream effectors of KRAS signaling. Through combined inhibition of PI3K and MAPK signaling with MK-2206 (MK) and trametinib (Tra), enhancement of NPT + Gem response was evaluated. Median animal survival was significantly improved by the NPT + Gem combination (67% increase). Addition of MK-2206 or trametinib further increased median survival: NPT + Gem + MK (86%), NPT + Gem + Tra (105%), and NPT + Gem + MK + Tra (129%). In cell line-derived xenografts, the net tumor growth (in mm3) compared to controls (878.5) was significantly reduced by NPT + Gem (191.2), NPT + Gem + MK (150.7), NPT + Gem + Tra (62.2) and NPT + Gem + MK + Tra (49.9) therapies. In patient-derived xenografts, the combination of MK-2206 and trametinib with chemotherapy had an additive response in reducing tumor growth. Effects of therapy on tumor cell proliferation and apoptosis corresponded with tumor growth inhibition. These findings suggest that the standard chemotherapy response of PDAC can be enhanced through dual targeting of PI3K and MAPK signaling, which could lead to improved PDAC therapy.

Therapeutic efficacy of anti-MMP9 antibody in combination with nab-paclitaxel-based chemotherapy in pre-clinical models of pancreatic cancer.

Matrix metalloproteinase 9 (MMP9) is involved in the proteolysis of extracellular proteins and plays a critical role in pancreatic ductal adenocarcinoma (PDAC) progression, invasion and metastasis. The therapeutic potential of an anti-MMP9 antibody (αMMP9) was evaluated in combination with nab-paclitaxel (NPT)-based standard cytotoxic therapy in pre-clinical models of PDAC. Tumour progression and survival studies were performed in NOD/SCID mice. The mechanistic evaluation involved RNA-Seq, Luminex, IHC and Immunoblot analyses of tumour samples. Median animal survival compared to controls was significantly increased after 2-week therapy with NPT (59%), Gem (29%) and NPT+Gem (76%). Addition of αMMP9 antibody exhibited further extension in survival: NPT+αMMP9 (76%), Gem+αMMP9 (47%) and NPT+Gem+αMMP9 (94%). Six-week maintenance therapy revealed that median animal survival was significantly increased after NPT+Gem (186%) and further improved by the addition of αMMP9 antibody (218%). Qualitative assessment of mice exhibited that αMMP9 therapy led to a reduction in jaundice, bloody ascites and metastatic burden. Anti-MMP9 antibody increased the levels of tumour-associated IL-28 (1.5-fold) and decreased stromal markers (collagen I, αSMA) and the EMT marker vimentin. Subcutaneous tumours revealed low but detectable levels of MMP9 in all therapy groups but no difference in MMP9 expression. Anti-MMP9 antibody monotherapy resulted in more gene expression changes in the mouse stroma compared to the human tumour compartment. These findings suggest that anti-MMP9 antibody can exert specific stroma-directed effects that could be exploited in combination with currently used cytotoxics to improve clinical PDAC therapy.

A Simplified Two-Step Technique for Extended Lymphadenectomy During Resection of Gastroesophageal Malignancy: Early Results Compared to En Bloc Dissection.

BACKGROUND: Extended lymph node dissection (ELND) remains an important component of curative intent resection of mid-stage gastric cancer (GC). Benefits include enhanced staging accuracy, extending regional disease control, and optimizing potential curability. ELND during gastrectomy remains underutilized in US centers due to a low prevalence of GC operations. METHODS: The traditional en bloc ELND was modified into a two-step technique to facilitate greater ease of dissection with better exposure. After completion of the gastrectomy component, retrogastric nodes are dissected in a separate, contiguous specimen. Resulting data were compared to outcomes after en bloc resection. RESULTS: Of 179 consecutive patients undergoing gastrectomy, 129 underwent an ELND (73%). There were 97 men and 32 women, with a median age of 64 years (range 24-98). The median total LN count was 25 (3-86). The two-step dissection yielded an average of 18.3 (± 8.5 S.D.) perigastric and 12.1 (± 5.8) retrogastric nodes. Two-step LND was associated with lower estimated blood loss (265 vs. 448 ml, p = 0.0005), lower transfusion requirements (6 vs. 28%, p = 0.007), greater mean total LN counts (30 vs. 26, p = 0.03), and a greater rate of obtaining at least 15 or 20 LNs (91 vs. 77% and 83 vs. 65%, p = 0.05). Major morbidity (overall 16%), length of stay, and survival outcomes were not different. CONCLUSIONS: The two-step LND technique as described was found to be associated with favorable operative and postoperative outcome parameters and an excellent LN yield. It can be recommended for standard ELND indications in the absence of macroscopically abnormal LNs.

Physician derived versus administrative data in identifying surgical complications. Fact versus Fiction.

BACKGROUND: Administrative data are widely used as determinants of surgical quality. We compared surgical complications identified in a structured surgical review to coding and billing data of over a 19-month period. METHODS: A retrospective review of monthly morbidity and mortality conference reports was compared to a report over the same time period generated from hospital coding and billing data. RESULTS: 807 sequential operative procedures were included. Physician derived data compared to administrative data identified a complication of any severity in 205 (25.4%) versus 111 (13.8%) cases (r = 0.39), and major complications in 68 (8.4%) versus 46 (5.7%) cases (r = 0.36). Review of the administrative data regarding major complications identified 80 false negatives, 52 false positives, and 38 true positive designations. Overall sensitivity, specificity, positive and negative predictive values, and accuracy for administrative data in identifying major complications was 0.32, 0.99, 0.42, 0.99, and 0.99. CONCLUSIONS: The correlation between physician determined and administrative data with regard to identifying surgical complications is poor. Administrative data are insensitive and lack positive predictive value.

Augmentation of Nab-Paclitaxel Chemotherapy Response by Mechanistically Diverse Antiangiogenic Agents in Preclinical Gastric Cancer Models.

Gastric adenocarcinoma (GAC) remains the third most common cause of cancer-related deaths worldwide. Systemic chemotherapy is commonly recommended as a fundamental treatment for metastatic GAC; however, standard treatment has not been established yet. Angiogenesis plays a crucial role in the progression and metastasis of GAC. We evaluated therapeutic benefits of mechanistically diverse antiangiogenic agents in combination with nab-paclitaxel, a next-generation taxane, in preclinical models of GAC. Murine survival studies were performed in peritoneal dissemination models, whereas tumor growth studies were performed in subcutaneous GAC cell-derived or patient-derived xenografts. The mechanistic evaluation involved IHC and Immunoblot analysis in tumor samples. Nab-paclitaxel increased animal survival that was further improved by the addition of antiangiogenic agents ramucirumab (or its murine version DC101), cabozantinib and nintedanib. Nab-paclitaxel combination with nintedanib was most effective in improving animal survival, always greater than 300% over control. In cell-derived subcutaneous xenografts, nab-paclitaxel reduced tumor growth while all three antiangiogenic agents enhanced this effect, with nintedanib demonstrating the greatest inhibition. Furthermore, in GAC patient-derived xenografts the combination of nab-paclitaxel and nintedanib reduced tumor growth over single agents alone. Tumor tissue analysis revealed that ramucirumab and cabozantinib only reduced tumor vasculature, whereas nintedanib in addition significantly reduced tumor cell proliferation and increased apoptosis. Effects of nab-paclitaxel, a promising chemotherapeutic agent for GAC, can be enhanced by new-generation antiangiogenic agents, especially nintedanib. The data suggest that nab-paclitaxel combinations with multitargeted antiangiogenic agents carry promising potential for improving clinical GAC therapy. Mol Cancer Ther; 17(11); 2353-64. ©2018 AACR.

Pancreatic ductal adenocarcinoma cell secreted extracellular vesicles containing ceramide-1-phosphate promote pancreatic cancer stem cell motility.

The high mortality rate associated with pancreatic ductal adenocarcinoma (PDAC) is in part due to lack of effective therapy for this highly chemoresistant tumor. Cancer stem cells, a subset of cancer cells responsible for tumor initiation and metastasis, are not targeted by conventional cytotoxic agents, which renders the identification of factors that facilitate cancer stem cell activation useful in defining targetable mechanisms. We determined that bioactive sphingolipid induced migration of pancreatic cancer stem cells (PCSC) and signaling was specific to ceramide-1-phosphate (C1P). Furthermore, PDAC cells were identified as a rich source of C1P. Importantly, PDAC cells express the C1P converting enzyme ceramide kinase (CerK), secrete C1P-containing extracellular vesicles that mediate PCSC migration, and when co-injected with PCSC reduce animal survival in a PDAC peritoneal dissemination model. Our findings suggest that PDAC secrete C1P-containing extracellular vesicles as a means of recruiting PCSC to sustain tumor growth therefore making C1P release a mechanism that could facilitate tumor progression.

Clinical trends and effects on quality metrics for surgical gastroesophageal cancer care.

BACKGROUND: Surgical therapy of mid-stage gastric cancer (GC) and other neoplastic conditions requiring gastric resection remains at the center of curative outcomes, while epidemiologic changes and multimodality treatment options have evolved rapidly. Putative quality metrics for gastrectomy such as R0 rate, total lymph node (LN) count or postoperative morbidity may depend partly on changing disease and treatment patterns, and deserve evaluation under various practice conditions. METHODS: Data within a U.S.-based single surgical oncologist's practice over 15 years were prospectively recorded and retrospectively analyzed for clinicopathologic factors, operative treatment aspects and outcomes. Trends and spectrum changes over three time intervals were analyzed with contingency analysis and continuous data comparative statistics. RESULTS: Of 179 patients undergoing gastric resection, 119 were male and 60 female, with a median age of 63 years (range, 24-98 years). Resections included 56 total, 56 subtotal/distal, 30 proximal and 37 segmental gastrectomies. Diagnoses included 96 GCs, 31 gastroesophageal (GE) junction (GEJ) cancers, 21 GI stromal tumors (GISTs), and 31 other conditions. Significant trends from first towards last time interval were observed for resection type (16% to 32% proximal, 9% to 30% segmental, P=0.0003), curative intent (76% to 98%, P=0.002), diagnosis (5% to 42% GEJ cancer, P<0.0001) and preoperative therapy use (0% to 58%, P<0.0001), among others. Intraoperative aspects showed significantly reduced blood loss (median: 500 to 150 mL) and transfusion requirements (39% to 4%), and an increased use of minimally invasive techniques over time (all at P<0.001). Among patients undergoing curative intent GC resection with LN dissection, total LN counts remained steady (mean: 26), while the number of involved LNs decreased (9.0 to 3.7, P=0.0003) and the R0 resection rate increased from 74% to 85% (P=0.05). The number of specimens with >15 LNs examined increased from 69.0% to 92.5% (P=0.022). At the same time, spleen preservation rate (91% overall) and major morbidity (16%) remained unchanged throughout. Postoperative length of stay decreased from a median of 12 to 8 days (P<0.0001). CONCLUSIONS: This experience represents some variable practice patterns within a clinicopathologic spectrum of GE diseases. Postoperative or oncologic quality metrics have been sustained or did improve, which would support their utility for various practice settings; they compare favorably to other published U.S. experiences during the same time period.

Experience with a simplified feeding jejunostomy technique for enteral nutrition following major visceral operations.

BACKGROUND: Background: Perioperative nutrition support has been shown to impact on outcomes for patients with gastrointestinal cancer. Postoperative benefits of feeding tubes must be weighed against morbidity related to placement and use. A simplified jejunostomy tube technique was evaluated for outcomes. METHODS: A 16-Fr rubber tube is secured at the jejunal entry site without Witzel tunnel, followed by a continuous, circumferential and alternating suture between jejunal wall and parietal peritoneum. Prospectively collected data were analyzed. RESULTS: The technique was performed in 343 of 803 major hepatopancreatobiliary and upper gastrointestinal (GI) resections (43%). Of these patients (male =57%, median age: 65.8 years, range, 24.0-98.0 years), 89% had a cancer diagnosis. The procedures included pancreatectomy (n=189, 55%), gastrectomy (n=109, 32%), esophagectomy (n=19, 6%) and others (n=26, 7%). The operative intent was curative in 78%, palliative in 10%, or combined in 12% of patients. Postoperative morbidity rate was 40%, with 19 lethal events (5.5%), and a median length of stay of 10 days (range, 4-111 days). Tube feeds were administered in 139 patients (41%), and in 17% continued beyond discharge. Use of the feeding tube was linked to treatment interval, length of stay, major complication grade (all at P<0.0001), metastatic stage (P=0.0007) and noncurative intent (P=0.001). Tube feeds beyond discharge were associated with time interval (P<0.0001), length of stay (P=0.0006) and noncurative intent (P=0.014). Tube-specific events in 38 patients (11%) were all minor, without any intraabdominal leak, infection or obstruction. CONCLUSIONS: The technique described is safe and expedient, and the overall tube-related morbidity is low. This procedure can be recommended in cases at risk for major morbidity and nutrition support needs.

Managing the Unmanageable: A Two-Staged Palliative Resection to Control Life-Threatening Duodenal Bleeding Due to Recurrent Paraganglioma.

BACKGROUND This report presents therapeutic decision-making and management of refractory, life-threatening duodenal bleeding in a young man with recurrent metastatic retroperitoneal paraganglioma. CASE REPORT The patient had been symptom free for 8 years after radioactive MIBG (metaiodobenzylguanidine) therapy. Failure of endoscopic or angiographic bleeding control led to urgent need to evaluate possible endocrine functional status, tumor curability, safety of incomplete resection, intra- and postoperative support needs, and anticipated recovery potential and postoperative function. Aside from these considerations, impact of tumor biology, alternative therapeutic options, current management guidelines, and ethical challenges of resource utilization for such complex palliative operative intervention were reviewed. CONCLUSIONS Based on the observed outcomes after an urgent presentation of an unusual tumor-related complication, palliation-intent therapy was justifiable even if significant treatment-related risks were expected and complex resources were required.