Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia.

BACKGROUND & AIMS: The international cancer cachexia criteria with a cutoff of 5% weight loss (WL) was proposed in Western patients. The Asian Working Group for Cachexia (AWGC) developed new criteria in Asian patients. The AWGC criteria are not cancer-specific and employ a cutoff of 2% WL. However, it is unclear whether both criteria are useful in patients with very advanced cancer because WL can be underestimated owing to fluid retention. Therefore, this study aimed to investigate the impacts of fluid retention on the prognostic abilities of both criteria in cancer patients with weeks of survival. METHODS: This study involved a secondary analysis of a prospective cohort study. The inclusion criteria constrained the study to adult patients with advanced cancer. Patients were divided into Non-cachexia and Cachexia groups using the international criteria and AWGC criteria. We performed time-to-event analyses using the Kaplan-Meier method and log-rank tests, and by conducting univariate and multivariate Cox regression analyses. RESULTS: A total of 402 patients were included in the analysis. Using the international criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.55 and 0.18, respectively. Using the AWGC criteria, the p-values for the log-rank test and stratified log-rank test for the mixed patients with and without fluid retention were 0.38 and 0.12, respectively. Without considering the impacts of fluid retention, no significant differences were observed between the Non-cachexia and Cachexia groups for both criteria. After adjusting for the status of fluid retention, significantly higher risks of mortality were not observed in the Cox proportional hazard model for the Cachexia group compared with the Non-cachexia group, for both criteria. However, significant associations were observed between fluid retention and overall survival. CONCLUSIONS: The international criteria and AWGC criteria lost their prognostic abilities in cancer patients with weeks of survival. Since measurements of %WL were significantly confounded by fluid retention, fluid retention-adjusted criteria for cachexia need to be developed for cancer patients with refractory cachexia.

Fluid retention and weight loss in refractory cancer cachexia.

OBJECTIVES: It is unknown to what extent the fluid retention (FR) status disrupts the detection of weight loss rate (WLR) in adult patients with advanced cancer. This study aimed to determine the association of FR status with WLR. METHODS: This study was a secondary analysis of a prospective cohort study. FR was evaluated as follows: oedema (0, no; 1, yes), pleural effusion (0, no; 1, yes but asymptomatic; 2, symptomatic) and ascites (0, no; 1, yes but asymptomatic; 2, symptomatic). Patients were divided into three groups according to their FR scores: no-FR (0), moderate-FR (1-2) and high-FR (3-5). Multiple regression analysis was performed. RESULTS: Four hundred and twenty patients were categorised: no-FR group (n=164), moderate-FR group (n=158) and high-FR group (n=98). The prevalence of oedema, pleural effusion and ascites was 63.9%, 27.8% and 36.7% in the moderate-FR group, and 93.9%, 61.3% and 82.6% in high-FR group. The means of WLR were 9.2, 8.4 and 3.8 in the groups. The high-FR group and the FR score of 5 were correlated with WLR (estimate -4.71, 95% CI -7.84 to -1.58; estimate -10.29, 95% CI -17.84 to -2.74). CONCLUSIONS: The coexistence of FR was significantly correlated with WLR.

Cancer-related breathlessness: opioids other than morphine - comprehensive literature review.

INTRODUCTION: Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine. METHODS: The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded. RESULTS: A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs. CONCLUSION: As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.

Validity of the diagnostic criteria from the Asian Working Group for Cachexia in advanced cancer.

BACKGROUND: Recently, the Asian Working Group for Cachexia (AWGC) published a consensus statement on diagnostic criteria for cachexia in Asians. We aimed to validate the criteria in adult patients in Japan with advanced cancer. METHODS: We conducted a single-institution retrospective cohort study between April 2021 and October 2022. The AWGC criteria include chronic comorbidities and either a weight loss of >2% over 3-6 months or a body mass index (BMI) of <21 kg/m2 . In addition, any of the following items were required: anorexia as a subjective symptom, decreased grip strength as an objective measurement and an elevated C-reactive protein (CRP) level as a biomarker. We used the cut-off value of grip strength of 28/18 kg for male/female individuals and CRP level of 5 mg/L. RESULTS: Of the 449 consecutive patients, 85 of those who could not be evaluated because of end-of-life or refractory symptoms (n = 41) or missing data (n = 44) were excluded from the primary analysis. The prevalence of the AWGC-defined cachexia was 76% (n = 277), and the median survival time (MST) for all patients was 215 (95% confidence interval [CI] 145-270) days. The prevalence of the following criteria was significantly higher in patients with cachexia than in those without cachexia: a BMI of <21 kg/m2 (65% vs. 15%, P < 0.001), a weight loss of >2% in 6 months (87% vs. 14%, P < 0.001), anorexia (75% vs. 47%, P < 0.001), a grip strength of <28 kg in male individuals (63% vs. 28%, P < 0.001) and CRP level of >5 mg/L (85% vs. 56%, P < 0.001). Overall survival was significantly shorter in patients with cachexia than in those without cachexia (MST 157 days, 95% CI 108-226 days vs. MST 423 days, 95% CI 245 days to not available, P = 0.0023). The Cox proportional hazards analysis showed that best supportive care (hazard ratio [HR] 2.91, P ≤ 0.001), lung cancer (HR 1.67, P = 0.0046), an Eastern Cooperative Oncology Group Performance Status score of ≥3 (HR 1.58, P = 0.016), AWGC-defined cachexia (HR 1.56, P = 0.015), an age of ≥70 years (HR 1.53, P = 0.0070), oedema (HR 1.31, P = 0.022) and head/neck cancer (HR 0.44, P = 0.023) were found to be the significant predictors for mortality. CONCLUSIONS: We demonstrated that AWGC-defined cachexia has a significant prognostic value in advanced cancer.

Survival impact of occult liver metastasis and peritoneal dissemination compared with radiologically defined distant organ metastasis in pancreatic ductal adenocarcinoma.

BACKGROUND: Characteristics and prognoses of patients with occult metastases (OM) of pancreatic ductal adenocarcinoma (PDAC) compared with radiologically defined metastases (RM) have been rarely reported. OBJECTIVE: We aimed to clarify the prognosis of OM compared with RM and to establish a treatment strategy for PDAC patients with OM. METHODS: This single-institution, retrospective study evaluated patients with unresectable PDAC between 2008 and 2018. OM was defined as abdominal metastasis that was detected by staging laparoscopy or open laparotomy but not in the initial assessment of radiological images. RESULTS: OM and RM were identified in 135 and 112 patients, respectively. Eastern Cooperative Oncology Group Performance Status (ECOG PS), neutrophil to lymphocyte ratio (NLR), tumor diameter, and rate of local unresectability were significantly lower in the OM group. Median overall survival (OS) of OM was significantly better than that of RM (13.0 vs 8.9 months, p < 0.001). In multivariate analysis of OS, ECOG PS ≥ 1 (HR 1.64, p = 0.009), NLR ≥5 (HR 1.97, p = 0.004), carbohydrate antigen (CA) 19-9 ≥1000 (HR 1.68, p = 0.001), tumor diameter ≥40 mm (HR 1.40, p = 0.027), conversion surgery (HR 0.12, p < 0.001), and multiple lines of chemotherapy (HR 0.38, p < 0.001) were independent predictors. However, type of metastasis (OM vs RM) not an independent predictor (HR 1.10, p = 0.590). CONCLUSION: The prognosis of PDAC with OM was relatively better than that with RM, but general and nutritional statuses, primary tumor size and CA19-9, conversion surgery and multiple lines of chemotherapy were independent predictors but not tumor burden.

Levosimendan Increases Survival in a D-Galactosamine and Lipopolysaccharide Rat Model.

Levosimendan, a calcium sensitizer, has an organ protective profile through the inhibition of inflammatory mediators and cytokines in critical conditions, such as heart failure, ischemia-reperfusion injury, and sepsis. The survival effect of levosimendan for acute liver failure has not been examined yet. Male Sprague-Dawley rats were examined in the D-galactosamine hydrochloride and lipopolysaccharide (GalN/LPS) model. Levosimendan was injected intraperitoneally before GalN/LPS treatment. Survival was monitored for 7 days. For biochemical analyses, liver and blood samples were collected from the rats at 1 and 8 h after GaIN/LPS treatment. The pretreatment of levosimendan at 4 mg/kg significantly increased survival in GalN/LPS rats. In the liver specimen, levosimendan significantly inhibited the activation of nuclear factor-κB (NF-κB) at 1 h, and significantly decreased the mRNA expression of inflammatory mediators, including inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α), at 8 h. In serum, levosimendan decreased the levels of nitrite, a metabolite of nitric oxide, and TNF-α protein, as well as aspartate aminotransferase and alanine aminotransferase. These results indicated that Levosimendan ameliorated liver dysfunction and survival in acute liver failure model rats through the suppression of NF-κB activation.

Hydromorphone for dyspnoea in terminally ill patients with cancer: case series.

OBJECTIVE: Opioids can mitigate dyspnoea, but the efficacy of hydromorphone use for dyspnoea in patients with cancer is not well known. METHODS: Patients with cancers with more than mild dyspnoea treated with subcutaneous injection of hydromorphone between March 2020 and February 2022 at Kitano Hospital (Osaka, Japan) were reviewed retrospectively. Only patients who could self-report their symptoms ≥3 days after the start of hydromorphone therapy were included. Dyspnoea severity was rated on a five-point scale (0: 'not bothersome'; 1: 'mild'; 2: 'moderate'; 3: 'severe'; 4: 'overwhelming'). RESULTS: Fifteen patients (2 with moderate, 12 with severe and 1 with overwhelming dyspnoea) were deemed eligible. The median interval from the start of hydromorphone initiation to death was 19 (IQR, 11-37) days. Thoracic drainage and palliative sedation after the start of hydromorphone therapy was undertaken in three and two patients, respectively. At 3 days, the median score of the Dyspnoea Rating Scale was improved significantly from 3 to 2 compared with that at baseline (p=0.0023). The intensity of dyspnoea was improved in 11 patients (73%). Opioid-related adverse events were not observed within 3 days. CONCLUSIONS: Using hydromorphone for dyspnoea in patients with cancer seems to be appropriate if morphine use is contraindicated.

Fentanyl titration for cancer pain: continuous subcutaneous injection and a once-daily transdermal patch - case series.

OBJECTIVES: Continuous subcutaneous injection (CSCI) followed by a once-daily transdermal patch is a reasonable strategy for rapid titration of fentanyl in patients with cancer pain who are unable to take oral medication or have renal impairment, but the effectiveness and safety have not been demonstrated. METHODS: Medical records of patients with moderate to severe cancer pain who underwent titration of fentanyl by CSCI between October 2019 and October 2021 at Kitano Hospital, Osaka, Japan, were retrospectively reviewed. The dose of fentanyl was increased to a maximum of 0.05 mg/hour. If the dose was inadequate, the fentanyl patch was added on CSCI. When pain relief was adequate, CSCI was completely converted to the patch. RESULTS: Thirty-three patients were enrolled. Titration was completed successfully in 28 patients (85%) over a median of 2 days. The average Numeric Rating Scale for pain decreased by at least 66% in 22 patients (67%) and by at least 33% in 7 (21%). After conversion to the patch, two patients (6.1%) required to increase the dose of fentanyl within a week. Two patients (6.1%) experienced moderate drowsiness during titration. CONCLUSIONS: Fentanyl titration by CSCI is an effective and safe method for achieving rapid pain control.

Peritonitis caused by group A streptococcus: A case report and literature review.

BACKGROUND: Group A streptococcus (GAS) occasionally causes life-threatening infections. We encountered a case of GAS peritonitis associated with bilateral salpingitis. CASE PRESENTATION: A 56-year-old previously healthy woman suddenly experienced a fever of 40 °C and lower abdominal pain, and was taken to the emergency room. She exhibited a condition of severe sepsis with pan-peritonitis. Although an intra-peritoneal source of infection was not detected preoperatively, an exploratory laparotomy was performed at 3 h after her arrival. During the surgery, bilateral salpingitis was observed. Peritoneal drainage was performed. Meropenem was administered and she was extubated on the next day. GAS was detected in the vaginal fluid culture and ascitic fluid culture. Antibiotics therapy was completed on postoperative day 9 and the patient was discharged on day 10 without any complications. METHODS: A literature review was performed using the following algorithm: "(group A streptococcus OR streptococcus pyogenes) AND (peritonitis)". All case reports and case series published in English after 1990 were reviewed. RESULTS: Fifty-six reports including 65 cases were eligible. There was a strong sex difference, with 80% of cases being female. All patients had symptoms of peritonitis, 80% had high-grade fever, and 74% had shock. The average time from onset to start of treatment was 3.8 days. Abdominal surgeries were required in 80% of cases. Multiple organ failure developed in 23%, and the mortality rate was 4.6%. DISCUSSION: GAS peritonitis is a rare but life-threatening disease. Emergency surgical exploration and drainage are required to prevent progression to multiple organ failure.

High tumor budding predicts a poor prognosis in resected duodenal adenocarcinoma.

PURPOSE: Tumor budding is a histological characteristic defined as the presence of small clusters of cancer cells at the invasion front. Its significance in duodenal adenocarcinoma (DA) has not been fully described. METHODS: A single-center, retrospective study was conducted. Patients who underwent curative surgery for histologically diagnosed DA from January 2006 to December 2018 at Kansai Medical University Hospital were included. Tumor budding was counted per 0.785 mm2 and classified as low (0-4 buds), intermediate (5-9 buds), or high (≥ 10 buds). RESULTS: In total, 47 patients were included. The 5-year overall survival and relapse-free survival rates were 77% and 72%, respectively. High tumor budding was seen in 15 patients (32%). Excluding patients with superficial type (pT1) DA (n = 22), high tumor budding [hazard ratio (HR) 13.4, p = 0.028], regional lymph node metastasis (HR 19.9, p = 0.039), and adjuvant chemotherapy (HR 0.056, p = 0.036) were independent factors related to the overall survival in multivariate analyses. Distant metastases occurred significantly more often in patients who had high tumor budding than in others (p = 0.039). CONCLUSION: The data suggest that high tumor budding is a predictor of a poor prognosis in resected DA.

Estimation of the degree of surgical difficulty anticipated for pancreatoduodenectomy: Preoperative and intraoperative factors.

BACKGROUND: Pancreatoduodenectomy (PD) is a technically complex procedure. Preoperative anticipation of the degree of difficulty could contribute to patient safety during trainee surgical education. METHODS: We prospectively administered a questionnaire to the chief surgeon after each PD performed between 2016 and 2018 at our institution (99 consecutive patients). The surgeon rated the difficulty of the procedure; we then analyzed this information against perioperative data. RESULTS: The difficulty of PD was ranked as simple (29.3%), moderate (40.4%), or difficult (30.3%). The difficult procedures required an operative time of 2 h longer than the simple procedures and involved an additional 800 mL of intraoperative blood loss. Postoperative complications were similar in all groups. Multivariate analysis revealed that an unrecognized tissue plane for dissection was an independent determinant of a difficult PD (odds ratio [OR]: 89.2, 95% confidence interval [CI]: 9.2-861.2; P < .001). Independent predictors of a difficult PD were a pretreatment status of borderline resectable or unresectable (OR: 21.9, CI: 5.3-90.6; P < .001) and cholangitis during the preoperative period (OR: 4.1, CI: 1.3-13.0; P = .017). CONCLUSIONS: Surgeons deem the PD procedure to be difficult when the proper tissue plane for dissection is unrecognized. Preoperative assessment of the anticipated difficulty could contribute to better operative management.

A simple risk score for detecting radiological occult metastasis in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: We advocated carbohydrate antigen (CA) 19-9 ≥ 150 U/mL and tumor size ≥30 mm as "high-risk markers" for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC. METHODS: Predictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020. RESULTS: Five hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P < .0001) and "high-risk markers" (OR 2.07, P = .011) as independent predictors of OAM. A scoring system consisting of body/tail (yes: 1, no: 0) and "high-risk markers" (yes: 1, no: 0) was constructed. In the validation cohort, when staging laparoscopy (SL) was performed for patients with scores 1/2, the eligibility for SL, sensitivity, and negative predictive value of OAM were 55%, 91%, and 96%, respectively. CONCLUSIONS: Tumor location of body/tail and "high-risk markers" were independent predictors of OAM, composing our simple and reproducible risk scoring system.

Validation of the triple-checked criteria for drain management after pancreatectomy.

BACKGROUND: Drain management is important for the detection and treatment of clinically relevant postoperative pancreatic fistula (CR-POPF). We previously established the triple-checked criteria for drain removal: drain fluid amylase (DFA) <5000 U/L on postoperative day (POD) 1 and DFA <3000 U/L on POD 3, or C-reactive protein <15 mg/dL on POD 3. This study aimed to validate the efficacy of the triple-checked criteria. METHODS: In this study, 681 patients who underwent pancreatectomy were included. Drains were removed according to our previous criteria (sequentially checked criteria: DFA <5000 U/L on POD 1 and DFA <3000 U/L on POD 3) from 2012 to 2016 (control group) and the triple-checked criteria from 2017 to 2019 (intervention group). RESULTS: The control group included 406 patients, and the intervention group included 275 patients. Significantly more patients (n = 237, 86.2%) met the triple-checked criteria in the intervention group, relative to the sequentially checked criteria for early drain removal policy (n = 309, 76.1%; P = .001). Sensitivity, accuracy, and negative predictive value were significantly higher in the intervention group than in the control group (P < .001). The incidence of CR-POPF was not significantly different (11.1% vs 13.8%, P = .285). CONCLUSIONS: The triple-checked criteria contributed to effective drain removal after pancreatectomy without increasing CR-POPF.

Risk factors and treatment strategy for clinical hepatico-jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy: A retrospective study.

BACKGROUNDS/PURPOSE: The purpose of this study was to identify risk factors and establish a treatment strategy for clinical hepatico-jejunostomy stenosis defined with intrahepatic bile duct dilatation after pancreaticoduodenectomy. METHODS: The 443 patients who underwent PD from April 2006 to December 2015 were analyzed. Clinical characteristics were compared between patients with and without clinical HJ stenosis, and risk factors for clinical HJ stenosis were analyzed. In addition, the treatment and clinical course of patients with clinical HJ stenosis were retrospectively reviewed. RESULTS: Clinical HJ stenosis defined with intrahepatic bile duct dilatation was identified in 40 patients (9.0%). Multivariate analysis revealed that the independent risk factor for clinical HJ stenosis was the hepatic duct at surgery ≤8 mm. Endoscopic HJ stenosis was identified in 36 patients, and 31 patients were treated successfully with double balloon endoscopic retrograde cholangiography; five patients required re-anastomosis (n = 3) and percutaneous transhepatic biliary drainage (n = 2). Complete obstruction of HJ was found in five patients, and treatment with DB-ERC was successful in only one patient. CONCLUSION: The independent risk factor for clinical HJ stenosis was hepatic duct diameter ≤8 mm. Most cases of endoscopic HJ stenosis were treated successfully with DB-ERC, except in patients with complete obstruction.

Management of incidentally detected idiopathic pneumoperitoneum: A case report and literature review.

INTRODUCTION: Pneumoperitoneum usually requires emergency surgery. Asymptomatic idiopathic pneumoperitoneum is a rare subgroup of pneumoperitoneum for which a management algorithm has not been established. PRESENTATION OF CASE: In an 88-year-old female patient, pneumoperitoneum was found incidentally by chest computed tomography during a periodic follow-up for sarcoidosis. Emergency admission was ordered for conservative treatment. Upper gastrointestinal endoscopy revealed edematous mucosa in the entire gastric vestibule. After being discharged on the 7th day, her clinical course was uneventful over 2 months of follow-up. DISCUSSION: The initial clinical manifestations of pneumoperitoneum are variable and range widely from asymptomatic to septic shock. The etiology of pneumoperitoneum in our patient implied a subclinical visceral perforation that resolved without treatment. We advocate an algorithm for the initial management of pneumoperitoneum according to the extent of peritonitis and impaired conditions. CONCLUSION: Incidentally found asymptomatic pneumoperitoneum does not always require intervention. Careful and repeated physical assessment with investigation of underlying etiology is important in the management of pneumoperitoneum.

Hepatic actinomycosis after total pancreatectomy: A case report.

INTRODUCTION AND IMPORTANCE: Hepatic actinomycosis (HA) is a rare infection mimicking a malignancy. HA after total pancreatectomy for a pancreatic tumor has not been reported. CASE PRESENTATION: A 70-year-old woman with a history of gastrectomy and sigmoidectomy for benign lesions, underwent a total pancreatectomy for a non-invasive, intraductal papillary mucinous carcinoma (IPMC). She required partial resection of the transverse colon due to insufficient blood flow and had an anastomotic failure. Four months later, she developed a fever and effusion from the upper abdominal midline incision. No bacteria were cultured from the effusion. Contrast-enhanced computed tomography demonstrated an 80-mm iso-vascular liver mass. A slightly high-signal intensity on T2-weighted magnetic resonance imaging was demonstrated. Positron emission tomography (PET) showed a standardized uptake value of 11.9 at the liver mass. The percutaneous liver biopsy did not establish a diagnosis. Because a malignancy could not be ruled out, an exploratory laparotomy was performed. A tissue sample revealed aggregates of branched filamentous microorganisms; actinomycosis was diagnosed. Oral amoxicillin for 4 months resolved the mass. CLINICAL DISCUSSION: This patient had several causative factors for HA, including multiple surgical procedures involving the gastrointestinal tract, reconstruction of the biliary tract, anastomotic failure of the transverse colon, and diabetes mellitus following total pancreatectomy. Based on the past treatment history for IPMC and PET findings mimicking a malignancy, a laparotomy was performed to biopsy the lesion. Typically, penicillin is recommended for >6 months. CONCLUSION: A rare case of HA mimicking a malignancy after a total pancreatectomy for IPMC is presented.

Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Does direct invasion of peripancreatic lymph nodes impact survival in patients with pancreatic ductal adenocarcinoma? A retrospective dual-center study.

BACKGROUND: Pancreatic ductal adenocarcinoma can directly invade the peripancreatic lymph nodes; however, the significance of direct lymph node invasion is controversial, and it is currently classified as lymph node metastasis. This study aimed to identify the impact of direct invasion of peripancreatic lymph nodes on survival in patients with pancreatic ductal adenocarcinoma. METHODS: A total of 411 patients with resectable/borderline resectable pancreatic ductal adenocarcinoma who underwent pancreatic resection at two high-volume centers from 2006 to 2016 were evaluated retrospectively. RESULTS: Sixty (14.6%) patients had direct invasion of the peripancreatic lymph nodes without isolated lymph node metastasis (N-direct group), 189 (46.0%) had isolated lymph node metastasis (N-met group), and 162 (39.4%) had neither direct invasion nor isolated metastasis (N0 group). There was no significant difference in median overall survival between the N-direct group (35.0 months) and the N0 group (45.6 month) (p = 0.409), but survival was significantly longer in the N-direct compared with the N-met group (25.0 months) (p = 0.003). Similarly, median disease-free survival was similar in the N-direct (21.0 months) and N0 groups (22.7 months) (p = 0.151), but was significantly longer in the N-direct compared with the N-met group (14.0 months) (p < 0.001). Multivariate analysis identified resectability, adjuvant chemotherapy, and isolated lymph node metastasis as independent predictors of overall survival. However, direct lymph node invasion was not a predictor of survival. CONCLUSION: Direct invasion of the peripancreatic lymph nodes had no effect on survival in patients undergoing pancreatic resection for pancreatic ductal adenocarcinoma, and should therefore not be classified as lymph node metastasis.