Surgery For Gastrointestinal Malignancies Research Articles

Audit of Pain Management After Colorectal Surgeries in a Tertiary Care Cancer Hospital.

Surgery for gastrointestinal malignancy is associated with severe post-operative pain, which if inadequately treated, can lead to pulmonary complications and, in addition, delayed mobilization leading to delayed recovery and discharge. We audited our practices looking at the various pain modalities used and their effects on the post-operative recovery in colorectal surgeries, in a tertiary care cancer centre during the era of ERAS. The primary aim of the study was to assess the average pain score on movement in the first 72 h of post-operative period among patients. The secondary aim was to study the various modalities of pain management used and complications, perioperative vasopressor requirement, post-operative resumption of enteral feeding, ambulation, duration of hospital stay, duration of ICU/HDU stay, and worst pain scores in the first 72 h. We analyzed a total of 174 patients who underwent colorectal surgeries for the period of 1 year from 1st January 2018 till 31st December 2018. Out of the 174 patients, 86 (49.4%) patients received epidural analgesia and 88 (50.6%) patients who did not receive epidural analgesia, belong to the non-epidural group. Average pain scores on movement at 72 h in the epidural group was 2 [2, 3] and 2 [1, 2] in the non-epidural group (p < 0.001). Worst pain score at post-operative 72 h in epidural group was 3 [3, 4] and 3 [2, 4] in the non-epidural group (p = 0.016). In conclusion, we conclude, that the analgesic efficacy of epidural analgesia was not found to be superior in our study in patients undergoing major colorectal surgeries.

COVID-19 Effect on Surgery for Gastrointestinal Malignancies: Have Operative Volumes Recovered?

BackgroundCOVID-19 disrupted elective operations, cancer screening, and routine medical care while simultaneously overwhelming hospital staff and supplies. Operations for gastrointestinal (GI) malignancies rely on endoscopic screening, staging, and neoadjuvant therapy (NAT), each of which was disrupted by the pandemic. The aim was to evaluate the effect of the COVID-19 pandemic on the US national rates of gastrointestinal oncologic operations. MethodsThe Vizient Clinical Data Base® was queried for oncologic operations for esophageal, gastric, and colorectal malignancies with and without NAT from March 2019 to March 2022. Control chart analysis examined operative volume over time while Wilcoxon rank sum tests were used to compare mean monthly volume before and during the pandemic. ResultsA total of 95,912 patients were identified over 36 months; 5.8% esophageal, 6.3% gastric, 77.5% colonic, and 10.4% rectal operations. Esophageal operative volume decreased for 9 months during the pandemic and was significantly lower during than before the pandemic (p=0.002). Gastric operations decreased for 10 months early in the pandemic, but rebounded so that after 2 years volumes were unchanged (p=0.49). Colonic operations experienced a sharp decrease for 4 months at the beginning of the pandemic, but volumes quickly increased and overall were unchanged (p=0.29). Rectal operations decreased for 13 months and were significantly lower during than before the pandemic (p=0.018). Oncologic operations for patients receiving NAT varied. ConclusionCOVID-19 significantly disrupted the volume of gastrointestinal oncologic operations in the USA. Esophageal and rectal oncologic operations experienced prolonged and significant reductions while gastric and colonic oncologic operations transiently decreased but rebounded during the pandemic.

ASO Visual Abstract: Chronologic Age, Independent of Frailty, is the Strongest Predictor of Failure-to-Rescue After Surgery for Gastrointestinal Malignancies.

ASO Visual Abstract: Chronologic Age, Independent of Frailty, is the Strongest Predictor of Failure-to-Rescue After Surgery for Gastrointestinal Malignancies.

Chronologic Age, Independent of Frailty, is the Strongest Predictor of Failure-to-Rescue After Surgery for Gastrointestinal Malignancies.

Prior studies of older cancer patients undergoing large operations have reported similar rates of complications to the general population but higher rates of mortality, suggesting higher rates of failure-to-rescue (FTR) with advanced age. Whether age is a marker for frailty, or an independent predictor of FTR, is not clear. The ACS-NSQIP database was queried from 2015-19 for patients undergoing surgery for gastrointestinal (GI) malignancy. Patients were divided into age-stratified cohorts: C1 (18-55), C2 (56-65), C3 (66-75), C4 (76-89). Adjusted odds ratios (aOR) were computed to assess the relationship of the FTR rate and age, while controlling for potential confounders. A second analysis was specified with all covariates converted to Z-scores, which generated scaled adjusted odds ratios (saOR) to determine the strongest predictor of FTR. Multivariable analysis suggests that age is an independent predictor of FTR: C2:C1 aOR = 1.87 (p < 0.001); C3:C1 aOR = 3.33 (p < 0.001); C4:C1 aOR = 5.71 (p < 0.001). The scaled analysis demonstrated that age is the strongest predictor of FTR (saOR = 1.92, p < 0.001); a one standard deviation increase in age was associated with a 92% increased odds of FTR. The saOR for frailty (1.18, p < 0.001) and for number of comorbidities (1.10, p = 0.005) also were statistically significant. Chronologic age was independently associated with increased FTR after surgery for GI malignancy and was the strongest predictor of FTR. These results suggest that chronologic age must be carefully considered when evaluating the fitness of a patient for GI cancer surgery.

The impact of myosteatosis on outcomes following surgery for gastrointestinal malignancy: a meta-analysis.

The aim of this review was to evaluate the impact of preoperative myosteatosis on long-term outcomes following surgery for gastrointestinal malignancy. We conducted a systematic search of the electronic information sources, including PubMed MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL and AMED. Studies were included if they reported the impact of preoperatively defined myosteatosis, or a similar term, on long-term survival outcomes following surgery for gastrointestinal malignancy. A subgroup analysis was performed for those studies reporting outcomes for colorectal cancer patients only. Thirty-nine full-text articles were reviewed for inclusion, with 19 being retained after the inclusion criteria were applied. The total number of included patients across all studies was 14,481. Patients with myosteatosis had significantly poorer overall survival, according to univariate (hazard ratio (HR) 1.82, 95% confidence interval (CI) 1.67-1.99) and multivariable (HR 1.66, 95% CI 1.49-1.86) analysis. This was also demonstrated for cancer-specific survival (univariate HR 1.62, 95% CI 1.18-2.22; multivariable HR 1.73, 95% CI 1.48-2.03) and recurrence-free survival (univariate HR 1.28, 95% CI 1.10-1.48; multivariable HR 1.38, 95% CI 1.07-1.77). This meta-analysis demonstrates that patients with preoperative myosteatosis have poorer long-term survival outcomes following surgery for gastrointestinal malignancy. Therefore, myosteatosis should be used for preoperative optimisation and as a prognostic tool before surgery. More standardised definitions of myosteatosis and further cohort studies of patients with non-colorectal malignancies are required.

The impact of myosteatosis on outcomes following surgery for gastro-intestinal malignancy: A systematic review and meta-analysis.

e15540 Background: Recent research has demonstrated the impact that body composition parameters can have on the outcomes following cancer surgery. Adipose tissue deposition in muscle, known as myosteatosis, can be detected on pre-operative imaging. This systematic review aims to analyse the impact of pre-operative myosteatosis on long-term outcomes following surgery for gastro-intestinal malignancy. Methods: Using MeSH terms, a systematic search of the databases PubMed MEDLINE, EMBASE, Cochrane, CINAHL and AMED was performed. Studies were included if they reported hazard ratios (HR) analysing the impact of pre-operatively defined myosteatosis, or similar term, on the long-term outcomes following surgery for gastro-intestinal malignancy. A total of 39 full texts articles were reviewed for inclusion, with 19 being included after the inclusion criteria were applied. A sub-group analysis was performed for those studies reporting outcomes for colorectal cancer patients only. Results: The total number of included patients across all studies was 14,481. Patients with myosteatosis had a significantly poorer overall survival, according to univariate (HR 1.82, 95% CI 1.67 – 1.99) and multivariable (HR 1.66, 95% CI 1.49 – 1.86) analysis. This was also demonstrated with regards to cancer-specific survival (univariate HR 1.62, 95% CI 1.18 – 2.22, multivariable HR 1.73, 95% CI 1.48 – 2.03) and recurrence-free survival (univariate HR 1.28, 95% CI 1.10 – 1.48, multivariable HR 1.38, 95% CI 1.07 – 1.77). Conclusions: This review demonstrates that patients with pre-operative myosteatosis have poorer long-term outcomes following surgery for gastro-intestinal malignancy. Therefore, myosteatosis should be used for pre-operative optimisation and as a prognostic tool before surgery. More standardised definitions of myosteatosis and further cohort studies of patients with non-colorectal malignancies are required.

Combined use of advanced practice providers and care pathways reduces the duration of stay after surgery for gastrointestinal malignancies

BackgroundThe gastrointestinal surgical oncology service at our comprehensive cancer center sought to improve the quality of postsurgical inpatient care while increasing discharge efficiency. MethodsA stakeholder team established standard postsurgical care pathways and dedicated inpatient advanced practice provider positions. We compared postsurgical length of stay before (July 2017 to April 2018) and after (May 2018 to April 2019) the interventions using Wilcoxon rank-sum tests. We benchmarked length of stay to National Surgical Quality Improvement Project and Centers for Medicare and Medicaid Services geometric mean length of stay. We also compared readmission rates and surgeon-specific Hospital Consumer Assessment of Health Care Provider and Systems and Press-Ganey scores. ResultsThere were 462 cases before and 563 after the interventions. Postintervention, median length of stay decreased from 6.50 to 6.00 days (P = .017). There was a ≥1-day reduction for 10 of 14 case types with significant length of stay decreases for robotic esophagectomy (P = .001), liver resection (P = .023), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (P = .030). More case types met or exceeded Centers for Medicare and Medicaid Services and National Surgical Quality Improvement Project benchmarks after the interventions. Readmission rates were stable (preintervention 9.3%, postintervention 10.3%, P = .585). Press-Ganey and HCAHPS measures were stable or improved in all evaluated domains. ConclusionIncorporating advanced practice providers and care pathways into gastrointestinal surgical oncology inpatient care was associated with reduced length of stay without declination in readmission rates or patient experience measures.

Abstract B77: Low-density neutrophils (LDN) in circulating blood of postoperative patients may participate in the development of distant recurrence through the production of neutrophil extracellular traps (NETs)

Abstract Background: Low density neutrophils (LDN) which are co-purified with mononuclear cells by Ficoll-Hypaque density gradient preparations, have been reported to be increased in circulating blood in patients with autoimmune diseases, sepsis and cancer. Recent studies have suggested the LDN contributes to lupus pathogenesis as well as the development of organ damage in sepsis. Method: In patients who underwent curative surgery for gastrointestinal malignancy, peripheral blood was obtained at the timing of laparotomy (preoperative) and just before wound closure (postoperative) and the ratios of LDN were evaluated with flowcytometry. The LDN and mononuclear cells (MNC) in postoperative samples were separated using CD66b microbeads and MACS column and the proliferation of T cells were evaluated by in vitro culture on anti-CD3 coated plate using CFSE dilution method. The LDN were cultured for 2 hours and neutrophil extracellular traps (NETs) were observed with the addition of SYTOX green, dye for extracellular double strand (ds)-DNA. In adhesion experiments, human colon cancer, DLD-1, were stained by PKH-26 and added on the cultured LDN for 5 min. After gentle washing, the remaining cells were counted under fluorescein microscope. Results: 1. Ratios of CD66b(+) LDG in CD45(+) leukocytes were markedly increased in postoperative as compared with preoperative blood samples. 2. Division of CD3(+) T cells were significantly suppressed by the addition autologous CD66b(+) LDN. 3. Short term culture of the LDN produced massive thread-like structures stained with SYTOX green. Immunostaining with specific mAbs revealed that histone and myeloperoxidase (MPO) were colocalized on the fibrous structure, indicating NETs 3. DLD-1, selectively attached to the NETs, which was totally abrogated by the pretreatment with 100u/ml DNAse. Conclusion: During abdominal surgery, immunosuppressive LDN are markedly increased in circulating blood. The LDN extensively produces NETs which support the metastasis formation by trapping the circulating tumor cells in target organ. Functional blockade of the LDN might effectively reduce the recurrence rate after curative surgery. Citation Format: Yuko Kumagai, Rihito Kanamaru, Hideyuki Ohzawa, Hisanaga Horie, Yoshinori Hosoya, Naohiro Sata, Joji Kitayama. Low-density neutrophils (LDN) in circulating blood of postoperative patients may participate in the development of distant recurrence through the production of neutrophil extracellular traps (NETs) [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2017 Oct 1-4; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2018;6(9 Suppl):Abstract nr B77.

Abstract 3784: Intraoperative changes of low density granulocyte (LDG) in gastrointestinal cancer surgery

Abstract Background: Low density granulocytes (LDG) have been shown to be increased in peripheral blood of autoimmune disease, severe sepsis and cancer. In this study, we examined the frequency and function of the LDG in patients who received abdominal surgery for gastrointestinal malignancy. Method: In 57 patients who received laparotomy due to the gastrointestinal cancer ( 5 esophageal, 25 gastric , 27 colorectal cancer), peripheral blood was collected before and after operative procedure in operation room. After Ficoll-Hypaque centrifugation, intermediate layer which consists mainly of mononuclear cells was collected and immunestained with mAbs to CD66b, CD45 as well as 7AAD and their expressions were examined with flow cytometer. CD66b(+) CD45(+) cells were defined as LDG and the ratios of LDG in total CD45(+) leukocytes were calculated in 7AAD(-) live cell fraction. Next, CD66b(+) LDG and CD66b(-) mononuclear cells were separated with MACS method, and LDG were cultured and examined for extracellular traps (NETs) formation in vitro. Finally, CD66b(-) mononuclear cells were cultured on anti-CD3 mAb coated plate with or without autologous LDG, and proliferation of T lymphocytes was examined with CFSE dilution method. Results: The ratio of the LDG is low (median= 1.14%, 0.62 ~1.66%, n=57) at a beginning of surgery. In contrast, the ratio was markedly increased (median= 8.10%, 5.91~10.3%, n=57, p&amp;lt;0.001) at the end of surgery. The ratio of postoperative LDG showed significant correlation with operation time and positive trend with intraoperative bleeding. The LDG showed relatively week expression of CD11b and CD66b, but highly expressed in IL8 receptor and CD62L, suggesting immature LDG. The short-term culture of the LDG produced massive SYTOX-positive web like stricture which was characteristic for NETs. The mixture of tumor cells on the LDG culture demonstrated that many tumor cells were trapped in the NETs within 5 min incubation and vigorously grew thereafter. Finally, addition of the LDG on mononuclear cell culture strongly suppressed the anti-CD3 stimulated T cell division. Conclusion: LDG with immature phenotype increase in circulating blood of the patients who underwent gastrointestinal cancer surgery, probably due to the surgical stress. The LDG produce NETs which may efficiently trap circulating tumor cells, and can inhibit T lymphocyte mediated-immune reaction. Thus, the LDG provide tumor permissive microenvironment in target organ and have supportive roles on the development of postoperative hematogenous metastasis in gastrointestinal cancer. Citation Format: Yuko Kumagai. Intraoperative changes of low density granulocyte (LDG) in gastrointestinal cancer surgery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3784.

Incidence and risk factor analysis of the postoperative delirium after gastrointestinal surgery: An exploratory analysis of a prospective, randomized phase II trial.

30 Background: The postoperative complications, delirium are a particularly common morbidity after gastrointestinal surgery. Postoperative delirium makes patient management much more difficult, increases costs, and causes severe discomfort to the patient. The aim of this study was to evaluate the incidence of the postoperative delirium and a predictor for postoperative delirium using phase II clinical trial data. Methods: We analyzed the cases that were enrolled to randomized clinical trials of the efficacy and safety of TJ-54 (Yokukansan; a traditional Japanese medicine [Kampo]) for the prevention and/or treatment of postoperative delirium in a randomized phase II trial of patients receiving surgery for gastrointestinal and lung malignancies (UMIN000005423). The American Psychiatric Association’s the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) was used to assess. A uni- and multivariate logistic regression analyses was performed to identify risk factors for morbidity. Results: Between October 2009 and July 2011, a total of 186 patients were registered to the Yokukansan trial. Among them, 167 patients received surgery for gastrointestinal malignancy and were eligible for the present study. The incidence of postoperative delirium was 9.0% (15 patients) and postoperative delirium was the most common postoperative complication in the study. Risk factors for postoperative delirium were analyzed by uni- and multi-variate analyses using clinical factors determined before the enrollment of the study. Among these, high patients’ age ( &gt; 80 years) and low MMSE score ( &lt; 27) were identified as significant independent risk factor for postoperative delirium (Odds ratio: 3.90, 95% CI; 1.25-12.16, p = 0.013 and Odds ratio: 0.24, 95% CI; 0.08-0.73, p = 0.013). Conclusions: The major of the findings were that high patients’ age (≥ 80 years) and low MMSE score ( &lt; 27) were significant independent risk factors for predicting postoperative delirium. Careful attention for postoperative delirium is required in patients with high patients’ age and MMSE score when surgeons perform surgery for gastrointestinal malignancies. Clinical trial information: 000005423.

Randomized phase II study of TJ-54 (Yokukansan) for postoperative delirium in gastrointestinal malignancy patients.

115 Background: Delirium is one of the common postoperative complications. When postoperative delirium occurred, the patient management becomes much more difficult, leading to functional recovery delay, and is also associated with postoperative mortality and morbidity. Although many attempts to prevent and treat delirium have been developed, a higher level of evidence is needed. In the present study, we evaluated the efficacy and safety of TJ-54 (Yokukansan; one of the traditional Japanese medicines, Kampo) for the prevention and/or treatment of postoperative delirium in a randomized phase III trial for the patients receiving surgery for gastrointestinal malignancy. Methods: Patients 70 years of age or older, who were received surgery for gastrointestinal malignancy were eligible in this study. The 167 eligible patients were randomly assigned on a 1:1 ratio to receive TJ-54 or control during their perioperative care (between day 7 before surgery and day 4 after surgery). The signs and symptoms of delirium were assessed with using Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV by the investigator during perioperative period. Results: We analyzed 167 eligible gastrointestinal malignancy patients (TJ-54; 83, control; 84). There were no disparities between the two PPS randomized groups. The incidence of delirium was 7.2% (6 patients) in the TJ-54 group and 10.7% (9 patients) in the control group with no significant difference (p=0.431), also no significant difference was observed in duration of delirium between the two groups (p=0.477). The ratio of patients who needed some kind of the medication which including treatment of delirium were significantly less in the TJ-54 group than in the control group (p=0.037). Conclusions: In this study, TJ-54 did not demonstrate the contribution to prevention of occurring delirium in the patients receiving surgery for gastrointestinal malignancy. However, TJ-54 might be effective in reducing the medication for treating delirium after surgery for gastrointestinal malignancy. Clinical trial information: 000005423.

MP60-08 SARCOPENIA PREDICTS POSTOPERATIVE OUTCOMES FOLLOWING RADICAL CYSTECTOMY

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2014MP60-08 SARCOPENIA PREDICTS POSTOPERATIVE OUTCOMES FOLLOWING RADICAL CYSTECTOMY Timothy Lyon, Nicholas Farber, Thomas Fuller, Jeffrey Gingrich, and Tatum Tarin Timothy LyonTimothy Lyon More articles by this author , Nicholas FarberNicholas Farber More articles by this author , Thomas FullerThomas Fuller More articles by this author , Jeffrey GingrichJeffrey Gingrich More articles by this author , and Tatum TarinTatum Tarin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1762AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Introduction and Objectives Sarcopenia, or the loss of skeletal muscle mass, is an indicator of overall nutritional status and can be quantified by measuring skeletal muscle volume on axial imaging. Total psoas area (TPA) has been shown to correlate with postoperative outcomes following surgery for gastrointestinal malignancies. There is limited available data supporting the relationship of TPA to outcomes following radical cystectomy. We sought to further clarify the predictive role of TPA in patients undergoing radical cystectomy for bladder cancer. Methods Following institutional review board approval, a retrospective chart review for all patients who underwent radical cystectomy at our institution in 2011 and 2012 was completed. TPA was measured on preoperative computed tomography (CT) scans at the L3 vertebral level and was then normalized for patient size using body surface area. We performed multivariate logistic regression analysis to evaluate TPA as a predictor of outcomes including postoperative complication rate, length of stay, and overall mortality. Variables including age, gender, BMI, American Society of Anesthesiologists class, diversion type, pathologic stage and TPA were analyzed. Patients were then grouped into TPA tertiles to facilitate comparative analysis. Results A total of 128 patients had data available for analysis. Of these, 20 (15.6%) underwent neoadjuvant chemotherapy. Average total psoas area was 8.43 cm2/m2. On multivariate analysis, TPA was a significant independent predictor of complication rate during the initial postoperative hospitalization (OR 0.726, 95% confidence interval (CI) 0.589 - 0.895, p = 0.002). In comparative analysis, patients in the lowest TPA tertile were significantly more likely to experience a complication than those in the highest tertile (RR 1.61, 95% CI 1.06 – 2.45, p = 0.021). Further, patients in the lowest tertile experienced a significantly longer length of stay (LOS) than those in the highest tertile (8.1 vs. 7.5 days, p = 0.047). Conclusions Low total psoas area was associated with increased complication rate and LOS following cystectomy. TPA is an easily measurable biometric parameter that may be useful in preoperative risk stratification by helping to identify patients most at risk for adverse postoperative outcomes. Future research should focus on further defining the role of sarcopenia in identifying patients who may benefit from preoperative nutritional supplementation. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e635-e636 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Timothy Lyon More articles by this author Nicholas Farber More articles by this author Thomas Fuller More articles by this author Jeffrey Gingrich More articles by this author Tatum Tarin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A case with ipsilateral upper and lower extremities deep venous thrombosis developed after surgery for gastrointestinal malignancy

A case with ipsilateral upper and lower extremities deep venous thrombosis developed after surgery for gastrointestinal malignancy

Single-Photon Emission Computed Tomography in the Screening for Postoperative Pulmonary Embolism

The aim of the study was to evaluate the usefulness of serial lung perfusion scintigraphy prospectively using single-photon emission computed tomographic image (SPECT) in screening for pulmonary embolism (PE) after elective surgery for gastrointestinal malignancy. PE was examined pre- and postoperatively with SPECT. Diagnosis of PE was based on segmental perfusion defect visualization in at least two of three planes on a SPECT image compared with preoperative SPECT images. Final diagnosis was determined by detection of embolus with multidetector helical CT (MDCT). No perioperative anticoagulant was used. Thirty-four patients were enrolled. One patient was excluded because of thrombophilia. In preoperative scans, nonsegmental defects were detected in 11 and a segmental defect in 1 patient, who was then diagnosed as PE preoperatively. Among 21 patients with normal preoperative SPECT, 2 had nonsegmental and 5 had segmental defects postoperatively. Among 11 patients with nonsegmental preoperative SPECT, 7 had nonsegmental and 4 had segmental defects postoperatively. Postoperative segmental defects were differentiated by their shape only and there was no need to compare pre- and postoperative SPECT. MDCT confirmed four patients with PE among nine with segmental defects postoperatively. Our results of screening for PE by visualization at least two planes of SPECT images suggest that postoperative SPECT scan is suitable for the diagnosis of postoperative PE.

Dextran sulfate inhibits injured abdominal wall-specific tumor implantation in mice.

Tumor recurrence is often seen at sites where the peritoneum has been injured during surgery for gastrointestinal malignancies. It is thought that malignant cells released from the tumor during surgery implant in the sites of injury in the abdominal wall and cause tumor recurrence. Here we use dextran sulfate (DS) as an antagonist to cell adhesion for preventing implantation of i.p. seeded malignant cells, thus suppressing the recurrent tumor formation often observed at the site of injury in postoperative abdominal walls. DS was tested for anti-adherent activity against B-16 melanoma cells to injured abdominal wall specimens ex vivo and showed the capacity to significantly impair B-16 melanoma cell adherence compared to controls without DS. DS was also tested for the activity to prevent i.p. seeded B-16 melanoma cells from implanting in the site of injury in the abdominal wall in vivo and DS prevented B-16 melanoma cells from implanting in the sites of injury in the abdominal wall. In the test for the activity to improve survival in mice after B-16 melanoma was inoculated i.p., DS improved the survival of mice as compared to the controls without DS. We conclude that DS may be useful in preventing surgically promoting tumor implantation at sites of injury in post-operative abdominal wall treated for gastrointestinal malignancies.

Incidental Cholecystectomy Does Not Increase the Risk of Surgery for Gastrointestinal Malignancy

From 1975 to 1994, 291 incidental cholecystectomies were performed in our department, 143 of them during surgery for gastrointestinal tumors. The number of incidental cholecystectomies has increased gradually each year, mainly after preoperative sonographic screening of the gallbladder became routine in our department. We have found that mortality, morbidity and duration of surgery were not significantly influenced by the addition of incidental cholecystectomy. The risk of the gallbladder becoming symptomatic during the expected survival of the patients who were operated upon for gastrointestinal tumors is higher than the added risk, morbidity or mortality as well as additional cost of incidental cholecystectomy. Therefore, the authors recommend the performance of incidental cholecystectomy during elective laparotomies for gastrointestinal tumors.

Inhibitory effect of nafamostat mesilate on metastasis into the livers of mice and on invasion of the extracellular matrix by cancer cells.

Although many agents that interfere with clotting mechanisms have been investigated for their potential to inhibit metastasis, their toxicity has prevented administration of sufficiently high doses to achieve inhibition of metastasis in clinical trials. Nafamostat mesilate (FUT-175), a synthetic serine protease inhibitor, inhibited liver metastasis in a CDF1 mice model with colon 26 adenocarcinoma cells. The apparently dose-dependent inhibitory effect was seen 21 days after all of the doses tested (0.3, 1.0, 3.0 and 10.0 mg/kg for 7 days) but the effect was only statistically significant (P less than 0.01) at the highest dose. The blood concentrations 3 min after dosing were less than 10(-6) M for all of the doses tested. At a concentration of 10(-5) M or less nafamostat mesilate was not cytotoxic towards colon 26 cells in vitro. The results indicate that it may not be difficult to achieve blood nafamostat mesilate concentrations that inhibit metastasis in mouse liver. Possible mechanisms of nafamostat mesilate are inhibition of extravasation and invasion of cancer cells, inactivation of collagenase due to inhibition of plasmin activity and inhibition of the formation of the cancer cell thrombus, and arrest in the capillaries through inhibition of thrombin activity. These preliminary results suggest that peri-operative administration of nafamostat mesilate may prevent metastasis into the liver after surgery for gastrointestinal malignancies.