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Retrospective analysis of systemic chemotherapy and total parenteral nutrition for the treatment of malignant small bowel obstruction.

ABSTRACT: Malignant small bowel obstruction (MSBO) that does not resolve with conservative measures frequently leaves few treatment options other than palliative care. This single-institution retrospective study assesses the outcomes of a more aggressive approach-concurrent systemic chemotherapy and total parenteral nutrition (TPN)-in the treatment of MSBO. The MD Anderson pharmacy database was queried to identify patients who received concurrent systemic chemotherapy and TPN between 2005 and 2013. Only patients with MSBO secondary to peritoneal carcinomatosis requiring TPN for ≥8 days were included. Survival and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazard models. The study included 82 patients. MSBO resolution was observed in 10 patients. Radiographic assessments showed a response to chemotherapy in 19 patients; 6 of these patients experienced MSBO resolution. Patients spent an average of 38% of their remaining lives hospitalized, and 28% of patients required admission to the intensive care unit. In multivariate modeling, radiographic response to chemotherapy correlated with MSBO resolution (odds ratio [OR] 6.81; 95% confidence interval [CI], 1.68-27.85, P = 0.007). Median overall survival (OS) was 3.1 months, and the 1-year OS rate was 12.6%. Radiographic response to chemotherapy (HR 0.30; 95% CI, 0.16-0.56, P < 0.001), and initiation of new chemotherapy during TPN (HR 0.55; 95% CI, 0.33-0.94, P = 0.026) independently predicted for longer OS. Concurrent treatment with systemic chemotherapy and TPN for persistent MSBO results in low efficacy and a high morbidity and mortality, and thus should not represent a standard approach.

SUBMITTER: Chouhan J

PROVIDER: S-EPMC4735773 | biostudies-other | 2016 Feb

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:Total parenteral nutrition (TPN) provides all nutritional needs intravenously. Although lifesaving, enthusiasm is significantly tempered due to side effects of liver and gut injury, as well as lack of mechanistic understanding into drivers of TPN injury. We hypothesized that the state of luminal nutritional deprivation with TPN drives alterations in gut-systemic signaling, contributing to injury, and tested this hypothesis using our ambulatory TPN model. METHODS:A total of 16 one-week-old piglets were allocated randomly to TPN (n = 8) or enteral nutrition (EN, n = 8) for 3 weeks. Liver, gut, and serum were analyzed. All tests were two-sided, with a significance level of 0.05. RESULTS:TPN resulted in significant hyperbilirubinemia and cholestatic liver injury, p = 0.034. Hepatic inflammation (cluster of differentiation 3 (CD3) immunohistochemistry) was higher with TPN (p = 0.021). No significant differences in alanine aminotransferase (ALT) or bile ductular proliferation were noted. TPN resulted in reduction of muscularis mucosa thickness and marked gut atrophy. Median and interquartile range for gut mass was 0.46 (0.30-0.58) g/cm in EN, and 0.19 (0.11-0.29) g/cm in TPN (p = 0.024). Key gut-systemic signaling regulators, liver farnesoid X receptor (FXR; p = 0.021), liver constitutive androstane receptor (CAR; p = 0.014), gut FXR (p = 0.028), G-coupled bile acid receptor (TGR5) (p = 0.003), epidermal growth factor (EGF; p = 0.016), organic anion transporter (OAT; p = 0.028), Mitogen-activated protein kinases-1 (MAPK1) (p = 0.037), and sodium uptake transporter sodium glucose-linked transporter (SGLT-1; p = 0.010) were significantly downregulated in TPN animals, whereas liver cholesterol 7 alpha-hydroxylase (CyP7A1) was substantially higher with TPN (p = 0.011). CONCLUSION:We report significant alterations in key hepatobiliary receptors driving gut-systemic signaling in a TPN piglet model. This presents a major advancement to our understanding of TPN-associated injury and suggests opportunities for strategic targeting of the gut-systemic axis, specifically, FXR, TGR5, and EGF in developing ameliorative strategies.

Project description:BackgroundAdhesive small bowel obstruction (ASBO) is one of the most common causes of postoperative morbidity. According to Boyle's law, decreased barometric pressure expands the volume of intestinal gas. We aimed to elucidate the relationship between barometric pressure and ASBO.MethodsWe divided 215 admissions of 120 patients with ASBO into three groups: the fasting group, which responded to fasting (n = 51); the decompression group, which was successfully treated with gastrointestinal decompression (n = 104); and the surgery group which required emergency or elective surgery to treat ASBO (n = 60). We compared and examined clinical backgrounds, findings on admission, and barometric pressure during the peri-onset period (29 days: from 14 days before to 14 days after the onset of ASBO).ResultsThere were significant differences among the three groups regarding gender, history of ASBO, hospital length of stay, and barometric pressure on the onset day of ASBO. Barometric pressure on the onset day was significantly higher in the fasting group than in the decompression group (p = 0.005). During pre-onset day 5 to post-onset day 2, fluctuations in the barometric pressure in the fasting and decompression groups showed reciprocal changes with a symmetrical axis overlapping the median barometric pressure in Matsumoto City; the fluctuations tapered over time after onset. In the fasting group, the barometric pressure on the onset day was significantly higher than that on pre-onset days 14, 11, 7, 4, 3, and 2; post-onset days 3 and 10; and the median pressure in Matsumoto City. Conversely, in the decompression group, the barometric pressure on the onset day was lower than that on pre-onset days 14, 5-2; post-onset days 1, 2, 7, 8, 11, 13, and 14; and the median pressure in Matsumoto City. In the surgery group, the barometric pressure on the onset day was equivalent to those on the other days.ConclusionsASBO with response to conservative treatment is vulnerable to barometric pressure. Additionally, ASBO that is successfully treated with fasting and decompression is associated with a different barometric pressure on the onset day and reciprocal fluctuations in the barometric pressure during the peri-onset period.

Project description:BackgroundMetastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Due to its rarity, high-quality data are lacking to guide treatment. This retrospective analysis was conducted to help characterize the treatment options for patients with metastatic SBA while providing clinically meaningful prognostic information.Patients and methodsIn total, 437 patients who initially presented with or developed metastatic SBA between September 1977 and September 2019 were identified from the MD Anderson Tumor Registry. Clinical data were collected from review of the medical record. Overall response rates (ORR), time to progression (TTP), and overall survival (OS) were assessed across various treatments and treatment lines.ResultsThe median OS from diagnosis of metastatic disease was 15.9 months [95% confidence interval (CI): 14.3-17.9]. Seventy-five patients (17.1%) underwent metastasectomy, which was associated with a median OS of 34.5 versus 17.1 months among patients who received chemotherapy alone (P < 0.001). Fluoropyrimidine plus platinum (n = 164) was the most common first-line chemotherapy, associated with an ORR of 59% and TTP of 8.1 months. Irinotecan with 5-FU (n = 101) was the most common second-line therapy associated with an ORR of 31% and TTP of 4.0 months. Twenty-two patients received immunotherapy; 5 of 6 patients with deficient mismatch repair (dMMR) responded, while 0 of 16 with proficient mismatch repair (pMMR) responded. Taxane-based chemotherapy was given to 34 patients with an ORR of 21% and a median TTP of 2.4 months. Among 11 patients who received anti-epidermal-growth-factor-receptor (EGFR) monotherapy, the best response was stable disease (SD) in 1 patient.ConclusionsIn well-selected patients with SBA, metastasectomy appears to be associated with improved OS. This improvement was seen across metastasectomy sites, including liver, lung and peritoneal. Anti-programmed cell death protein 1 (PD-1) based immunotherapy was active for dMMR SBA but not pMMR SBA. While taxane-based chemotherapy demonstrates therapeutic activity, the activity of anti-EGFR therapy was limited.

Project description:BackgroundHyperglycemia is associated with poor clinical outcomes and mortality in several patients. However, studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition (TPN) are scarce. The aim of this study was to assess the relationship between glycemia and tumor kinds with TPN by monitoring glycemic variation in tumor patients.MethodsThis retrospective clinical trial selected 312 patients with various cancer types, whose unique nutrition treatment was TPN during the monitoring period. All patients had blood glucose (BG) values assessed at least six times daily during the TPN infusion. The glycemic variation before and after TPN was set as the indicator to evaluate the factors influencing BG.ResultsThe clinical trial lasted 7.5 ± 3.0 days adjusted for age, gender, family cancer history and blood types. There were six cancer types: Hepatic carcinoma (HC, 21.8%), rectal carcinoma (17.3%), colon carcinoma (CC, 14.7%), gastric carcinoma (29.8%), pancreatic carcinoma (11.5%), and duodenal carcinoma (DC, 4.8%). The patients were divided into diabetes and nondiabetes groups. No statistical differences in TPN glucose content between diabetes and nondiabetes groups were found; however, the tumor types affected by BG values were obvious. With increasing BG values, DC, HC and CC were more represented than other tumor types in this sequence in diabetic individuals, as well as in the nondiabetic group. BG was inclined to be more easily influenced in the nondiabetes group. Other factors did not impact BG values, including gender, body mass index, and TPN infusion duration time.ConclusionsWhen tumor patients are treated with TPN, BG levels should be monitored according to different types of tumors, besides differentiating diabetes or nondiabetes patients. Special BG control is needed for DC, HC and CC in both diabetic and nondiabetic patients. If BG overtly increases, positive measurements are needed to control BG values. The ClinicalTrials.gov ID is NCT02024321.

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Retrospective analysis of systemic chemotherapy and total parenteral nutrition for the treatment of malignant small bowel obstruction.

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