Genetic influence of cytokine polymorphisms on the clinical outcome of Japanese gastrointestinal cancer patients in palliative care.

Gastrointestinal cancer is one of the most common causes of mortality globally. The present study examined the influence of cytokine genetic polymorphisms [interleukin (IL)-1B C-31T, IL-1RN VNTR, IL-6 C-634G, IL-8 T-251A, IL-10 T-819C and IL-10 A-1082G] on clinical outcomes in patients with gastrointestinal cancer in palliative care. A total of 59 patients with gastrointestinal cancer who were admitted to Iga City General Hospital were analyzed. Genotyping was conducted using a polymerase chain reaction with confronting two-pair primers. Patients with at least one IL-1RN 2 allele demonstrated a significantly better survival (P=0.0275) while those with IL-6-634 G/G demonstrated a worse survival (P=0.0024). Multivariate analyses using the Cox proportional hazard model revealed that those with at least one IL-1RN 2 allele, IL-6-634 G/G or IL-10-1082 A/G had a significantly elevated adjusted hazard ratio of 9.20 (P=0.014), 41.01 (P=0.001) or 6.49 (P=0.046), respectively, compared with those with each homozygous wild-type polymorphism. In addition, the evaluation of weight loss by genotype revealed the potential influence of IL-10 T-819C genotype (P=0.072). IL-1RN, IL-6 and IL-10 polymorphisms were associated with the survival of patients with gastrointestinal cancer, suggesting the clinical feasibility of genetic testing in patients with gastrointestinal cancer in palliative care.

Polymorphisms in folic acid metabolism genes do not associate with cancer cachexia in Japanese gastrointestinal patients.

We used clinical data from Iga General Hospital to examine the association between polymorphisms in MTR (methionine synthase) A2756G (rs1805087), MTRR (methionine synthase reductase) His595Tyr (rs10380), MTHFR (methylenetetrahydrofolate reductase) C677T (rs1801133), MTHFR A1298C (rs1801131) and SHMT (serine hydroxymethyltransferase) C1420T (rs1979277), which are genes involved in folate metabolism, and the risk of weight loss in patients with gastrointestinal cancers, with the aim of establishing personalized palliative care for each patient based on genetic information. The data from 59 patients (37 males and 22 females) with gastrointestinal cancers who visited the outpatient clinic for cancer chemotherapy and palliative care at Iga General Hospital from December 2011 to August 2015 were analyzed. There was no significant association between the single nucleotide polymorphisms (SNPs) in the folate metabolizing genes examined and weight loss defined as weight loss of more than 5 percent or more than 10 percent during the first 6 months after initiation of chemotherapy. We did not detect any significant association between any of the SNPs examined and overall survival of patients. The present study indicated that these SNPs have relatively limited or no roles in the genesis of cachexia in patients with gastrointestinal cancers; however, further investigations into the roles of these folate metabolizing genes in the context of cancer palliative care, from clinical, biological and epidemiological viewpoints are warranted.

Fish oil-enriched nutrition combined with systemic chemotherapy for gastrointestinal cancer patients with cancer cachexia.

Despite recent advances in chemotherapy for gastrointestinal cancer, a crucial factor related to poor prognosis is reduced tolerance to chemotherapy induced by cancer cachexia. Fish oil (FO)-derived eicosapentaenoic acid (EPA) modulates inflammation in patients with various malignancies; however, the impact of FO-enriched nutrition as a combined modality therapy on clinical outcomes remains controversial. We systemically analysed chronological changes in biochemical and physiological status using bioelectrical impedance analysis in 128 gastrointestinal cancer patients provided with or without FO-enriched nutrition during chemotherapy. Furthermore, we evaluated the clinical significance of FO-enriched nutrition and clarified appropriate patient groups that receive prognostic benefits from FO-enriched nutrition during treatment of gastrointestinal cancer. The control group showed significant up-regulation of serum CRP) levels and no significant difference in both skeletal muscle mass and lean body mass. In contrast, the FO-enriched nutrition group showed no changes in serum CRP concentration and significantly increased skeletal muscle mass and lean body mass over time. Furthermore, high CRP levels significantly correlated with reduced tolerance to chemotherapy, and FO-enriched nutrition improved chemotherapy tolerance and prognosis, particularly in gastrointestinal cancer patients with a modified Glasgow prognostic score (mGPS) of 1 or 2. We conclude that FO-enriched nutrition may improve the prognosis of patients with cancer cachexia and systemic inflammation (i.e., those with a mGPS of 1 or 2).

Objective Predictive Score as a Feasible Biomarker for Short-term Survival in TerminalIy Ill Patients with Cancer.

BACKGROUND: In palliative care, prediction of life expectancy is one of the most crucial issues for patients, family and medical staff, in order to provide appropriate end-of-life care. The aim of this study was to formulate a new objective score to predict life expectancy within 1 week for terminally ill patients with cancer. PATIENTS AND METHODS: Medical records were obtained from 187 terminally-ill patients with cancer who were admitted for palliative care. The biomarkers for a potential 'Objective Predictive Score' were assessed. RESULTS: Profiling of blood parameters demonstrated that elevated levels of alanine aminotransferase (ALT), total bilirubin (T-bil), blood urea nitrogen (BUN), creatinine (Cr) and a decreased platelet count were significantly correlated with death within 1 week in a training cohort. Our formulated Objective Predictive Score was able to predict death within 1 week with high accuracy in a training and a validation cohort. CONCLUSION: Our scoring system might enable the assessment of prognostication with higher accuracy in a terminal care setting.

[Pneumomediastinum Due to the Fracture of the Maxillary Antrum].

A 47-year-old man was admitted to the emergency room, half a day after having fallen down on his right cheek drunkenly onto a concrete block. Physical examination revealed that the contusion was limited to the right side of his face, only around the cheek, without trauma to the neck, chest or abdomen. But wide ranging tactile crepitus with severe swelling was present on his face and neck due to widely spread emphysema. Computed tomography (CT) scan revealed some fractures of maxillary antrum, facial and cervical emphysema spreading to the lower part of mediastinum. After a conservative treatment, he recovered without any severe systematic complication. It was found that the facial and cervical emphysema and pneumomediastimum completely disappeared on the follow-up CT scan, 18 days after the event.

Seprafilm does not aggravate intraperitoneal septic conditions or evoke systemic inflammatory response.

PURPOSE: To determine whether Seprafilm aggravates the systemic inflammatory response and adversely affects the outcome of postoperative intraperitoneal septic conditions. METHODS: We retrospectively analyzed the relationship between the intraperitoneal placement of Seprafilm and the rate of intraperitoneal septic complications in 278 consecutive patients. Experimentally, 40 rats were subjected to laparotomy with or without the intraperitoneal placement of Seprafilm. Bacterial peritonitis was induced by cecal ligation and puncture (CLP) and the serum cytokine levels were measured. RESULTS: Seprafilm did not increase the rate of septic complications or aggravate inflammatory responses in patients with or without postoperative intraperitoneal inflammatory complications. Experimentally, there was no significant difference between the serum inflammatory cytokine levels after CLP with or without Seprafilm. CONCLUSIONS: Seprafilm did not adversely affect postoperative inflammatory response or clinical outcomes, even in patients with intraperitoneal septic complications.

Strategy for the treatment of unresectable hepatoblastoma: neoadjuvant chemotherapy followed by delayed primary operation or liver transplantation.

We present our experience in using neoadjuvant regional and systemic chemotherapy together with surgical resection as a strategy for the treatment of unresectable hepatoblastoma. Neoadjuvant chemotherapy was given prior to surgical treatment in six children with unresectable hepatoblastoma. Furthermore, the neoadjuvant chemotherapy was intensified according to response to the initial treatment. Surgical resection was performed when the tumor was judged to be resectable. The adjuvant chemotherapy was given after delayed primary operation. Five of six children receiving neoadjuvant chemotherapy responded to the treatment and subsequently received delayed primary operation or living donor liver transplantation. All five children who had successful surgery have completed treatment and show no evidence of disease to date (27-115 months after surgery). It is concluded that neoadjuvant chemotherapy given as a combination of regional and systemic chemotherapy was effective for tumor reduction in cases with early stage or stage III disease. Also, to increase the cure rate of children with localized disease that was still unresectable after chemotherapy, living donor liver transplantation, which offers some advantage in timing of transplant compared with cadaveric liver transplantation, seems to be a possible procedure.

Predicting factor of quality of life in long-term jaundice-free survivors after the Kasai operation.

BACKGROUND/PURPOSE: The aim of this study was to determine simple predictors for quality of life (QOL) in long-term jaundice-free survivors after the Kasai operation. METHODS: Kasai's original portoenterostomy was performed on 55 patients with biliary atresia. Among them, records were reviewed retrospectively of 35 long-term (at least 5 years) and jaundice-free (clearance in bilirubin level less than 1.0 mg/dL after Kasai operation) survivors. The patients were divided into 2 groups based on QOL, and the differences in clinical and laboratory data were analyzed statistically. RESULTS: The ages at Kasai operation, histologic, fibrosis grade of liver biopsy specimen at operation, the first onset and frequency of postoperative cholangitis, and postoperative clearance speed of jaundice after Kasai operation were not significantly different between the 2 groups. The aspartate aminotransferase (AST) level at 1 year was significantly correlated with the serum concentration of hyaluronic acid and an independent predictor for QOL in long-term jaundice-free survivors of the Kasai operation. CONCLUSIONS: The serum AST level at 1 year was a simple, strong predicting factor of QOL and liver dysfunction in long-term jaundice-free survivors after Kasai operation and may prove useful in planning liver transplantation.