Relationships between physical and immunological tumor microenvironment in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is physically palpated as a hard tumor with an unfavorable prognosis. Assessing physical features and their association with pathological features could help to elucidate the mechanism of physical abnormalities in cancer tissues. A total of 93 patients who underwent radical surgery for pancreatic and bile duct cancers at a single center hospital during a 28-month period were recruited for this study that aimed to estimate the stiffness of PDAC tissues compared to the other neoplasms and assess relationships between tumor stiffness and pathological features. Physical alterations and pathological features of PDAC, with or without preoperative therapy, were analyzed. The immunological tumor microenvironment was evaluated using multiplexed fluorescent immunohistochemistry. The stiffness of PDAC correlated with the ratio of Azan-Mallory staining, α-smooth muscle actin, and collagen I-positive areas of the tumors. Densities of CD8+ T cells and CD204+ macrophages were associated with tumor stiffness in cases without preoperative therapy. Pancreatic ductal adenocarcinoma treated with preoperative therapy was softer than that without, and the association between tumor stiffness and immune cell infiltration was not shown after preoperative therapy. We observed the relationship between tumor stiffness and immunological features in human PDAC for the first time. Immune cell densities in the tumor center were smaller in hard tumors than in soft tumors without preoperative therapies. Preoperative therapy could alter physical and immunological aspects, warranting further study. Understanding of the correlations between physical and immunological aspects could lead to the development of new therapies.

Hyaluronic acid/ carboxymethyl cellulose-based adhesion barrier reduces surgical difficulty and complication in repeat hepatectomy.

BACKGROUND: There has been no solid evidence regarding the actual efficacy of adhesion barriers in liver surgery. METHODS: Difficulty grade of lysis of adhesion was evaluated in 122 patients who underwent repeat hepatectomy (ReHx) using the TORAD score. Technical difficulty of lysis of adhesion and incidence of complication were then compared between the group of patients who received a sheet-type adhesion barrier (Seprafilm®) in the previous hepatectomy (n = 70) and those who did not (n = 52) using the inverse probability weighting method. RESULTS: Use of Seprafilm was significantly associated with lower grade of difficulty of lysis of adhesion according to the TORAD score (P < 0.001). Postoperative morbidity rate was lower and postoperative stay was shorter in the Seprafilm group in the propensity-score adjusted population (37% vs. 74%, P < 0.001 and 12 days vs. 14 days in median, P = 0.048). Multivariate analysis confirmed that use of Seprafilm was independent predictor for severity of adhesion (odds ratio [OR] 0.24, 95% CI, 0.09-0.65, P = 0.005) and decreased incidence of postoperative morbidity at ReHx (OR, 0.34; 95% CI, 0.14-0.84, P = 0.020). CONCLUSIONS: Use of Seprafilm may be associated with decreased technical difficulty of lysis of adhesion and may correlate with lower risk of postoperative morbidity in patients undergoing ReHx.

A novel scoring system for evaluating the difficulty of lysis of adhesion and surgical risk at repeat hepatectomy.

BACKGROUND: Repeat hepatectomy (ReHx) for recurrent hepatic malignancies reportedly provides oncological benefit for patients. However, severe adhesions at the time of ReHx may preclude safe and curative resection and there has been no reliable measure to estimate the surgical risk at ReHx. This study sought to create a new scoring system for evaluating the severity of adhesion after hepatectomy and tested its performance looking at the correlation with morbidity rate. METHODS: Operative videos of 66 patients undergoing a second hepatectomy were reviewed and the difficulty levels in lysis of adhesion around the hepatic hilum (A score) and surrounding the liver (B score) were scored by two examiners and validated by two additional reviewers. RESULTS: Very high interobserver agreement was confirmed between the two examiners (κ value, 0.960-0.963) and reproducibility of results were validated with weighted kappa values of >0.8 in both surgical resident and hepatobiliary surgeon. Linear correlation was confirmed between the difficulty score and postoperative morbidity rate. Multivariate analyses confirmed that previous cholecystectomy or transection of visceral surface of segment 4 or 5 was an independent factor predicting hard to extreme adhesions at the hepatic hilum regardless of the use of anti-adhesion materials. CONCLUSIONS: The new difficulty scoring system for the lysis of adhesion at ReHx showed good interobserver agreement and reproducibility of the results. Given the strong correlation with postoperative morbidity rate, the present score could be used for evaluating the technical difficulties in ReHx and may offer a reliable measure for estimating the efficacy of anti-adhesion materials in future analysis.

Anasarca, steatorrhea, and hypoalbuminemia 18 years after total gastrectomy: a case report.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) is known to occur after total gastrectomy. We experienced a case of PEI occurring 18 years after surgery, leading to a potentially fatal condition of capillary leak syndrome (CLS). CASE PRESENTATION: The case is a 58-year-old man on a healthy diet who underwent total gastrectomy 18 years before. He was admitted for a 3-month history of anasarca, steatorrhea, and hypoalbuminemia. An episode of fever occurred during workup, followed by pulmonary edema and shock. The patient was transferred to the intensive care unit and was started on fluid management with albumin infusion. A multidisciplinary team meeting was held, and a clinical diagnosis of PEI resulted in CLS was made and we started administration of oral pancrelipase to show clinical improvement. The patient was discharged, and he remained asymptomatic for 13 months. CONCLUSION: In a post-gastrectomy patient with malnutrition, PEI should be suspected regardless of the period since surgery. When recognized, immediate replenishment of albumin and pancreatic enzymes should be initiated to prevent clinical deterioration.

A case of typhoidal tularemia in a male Japanese farmer.

In Japan, most tularemia cases occur after contact with hares (hunting, cooking) and involve the glandular or ulceroglandular form. Here, we present a case of typhoidal tularemia in a 72-year-old Japanese male farmer who presented with fever, fatigue, and right lower abdominal pain. Computed tomography revealed intestinal wall thickening at the ascending colon, pleural effusion, and ascites. Following an initial diagnosis of bacterial enteric infection, his symptoms deteriorated after a week-long cephalosporin treatment course. The patient lived in an area endemic for scrub typhus; the antibiotic was changed to a tetracycline on suspicion of scrub typhus infection. His symptoms rapidly improved after initiation of minocycline treatment. Later, blood tests revealed marked increases in serological tests against Francisella tularensis exclusively, and the patient was diagnosed with typhoidal tularemia. Typhoidal tularemia may be characterized by any combination of general symptoms, but does not exhibit the local manifestations associated with other forms of tularemia. The patient, in this case, had no direct contact with hares or other wild animals and did not present with local manifestations of tularemia. Physicians should consider this disease, especially when tick-borne disease is suspected in the absence of local wounds, eschar, ulcers, or lymphadenopathy.