Organ-specific variations in tumor marker dynamics in postoperative pancreatic cancer recurrence: Trends in lung and liver recurrence highlighting biological heterogeneity.

BACKGROUND/OBJECTIVES: Although tumor recurrence after surgical resection in pancreatic cancer (PC) is generally considered incurable, it is well-accepted that clinical presentations and outcomes vary according to the recurrent sites (e.g., liver vs. lung recurrence), suggesting a possible biological inhomogeneity of PC recurrence. Understanding the behavior of biological factors, specifically tumor markers (TMs), at different recurrence sites may contribute to individualized treatment strategies. Therefore, this study aimed to compare the dynamics of pre-recurrence TMs at liver and lung recurrence sites. METHODS: Patients with isolated postoperative liver or lung recurrence as their first recurrence were enrolled. Starting from the recurrence date confirmed by imaging examinations, the values of TMs (carbohydrate antigen 19-9: CA19-9; carcinoembryonic antigen: CEA) were retrospectively evaluated 6 and 3 months before recurrence and at the time of recurrence. RESULTS: Patients with liver recurrence displayed a significant increase in CA19-9 and CEA levels from as early as 6 months before recurrence. Contrastingly, patients with lung recurrence demonstrated a significant elevation of CA19-9 levels starting from 3 months before recurrence, with no increase in CEA levels, even at the time of recurrence. The relative change in CA19-9 and CEA levels during each period were significantly lower in patients with lung recurrence. CONCLUSIONS: Both TMs exhibited organ-specific variations in patients with postoperative PC recurrence. This disparity may reflect the biological heterogeneity of PC between recurrence patterns, thereby highlighting the importance of conducting postoperative follow-up with consideration of this fact.

Prognostic Significance of Biologic Factors in Patients with a Modest Radiologic Response to Neoadjuvant Treatment for Resectable and Borderline Resectable Pancreatic Cancers: Impact of the Combination Index of Sialyl-Lewis Antigen-Related Tumor Markers.

BACKGROUND: Appropriate re-evaluation after neoadjuvant treatment (NAT) is important for optimal treatment selection. Nonetheless, determining the operative eligibility of patients with a modest radiologic response remains controversial. This study aimed to assess the prognostic significance of biologic factors for patients showing a modest radiologic response to NAT and investigate the tumor markers (TMs), CA19-9 alone, DUPAN-II alone, and their combination, to create an index that combines these sialyl-Lewis antigen-related TMs associated with treatment outcomes. METHODS: This study enrolled patients deemed to have a "stable disease" by RECIST classification with slight progression (tumor size increase rate, ≤20%) as their radiologic response after NAT. A sialyl-Lewis-related index (sLe index), calculated by adding one fourth of the serum DUPAN-II value to the CA19-9 value, was created. The prognostic significances of CA19-9, DUPAN-II, and the sLe index were assessed in relation to postoperative outcomes. RESULTS: An sLe index lower than the cutoff value (45.25) was significantly associated with favorable disease-free survival. Moreover, the post-NAT sLe index had a higher area under the curve value for recurrence within 24 months than the post-NAT levels of CA19-9 or DUPAN-II alone. Multivariable analysis showed that a post-NAT sLe index higher than 45.25 was the single independent predictive factor for recurrence within 24 months. CONCLUSIONS: Additional evaluation of biologic factors can potentially enhance patient selection, particularly for patients showing a limited radiologic response to NAT. The authors' index is a simple indicator for the biologic evaluation of multiple combined sialyl-Lewis antigen-related TMs and may offer a better predictive significance.

Hybrid approach with laparoscopic wall-inversion surgery and single-incision intragastric surgery for intraluminal gastrointestinal stromal tumor: A case report.

Laparoscopic wedge resection (LWR) for intraluminal gastrointestinal stromal tumor (GIST) leads to excessive resection of normal gastric wall. We report a case of GIST around the cardia successfully treated with full-thickness partial resection using a hybrid approach of laparoscopic surgery and single-incision intragastric surgery (SIIGS). A 69-year-old woman had a 5 cm intraluminal GIST at the posterior wall around the cardia. Submucosal injection of glycerin and indigo carmine was performed with transoral endoscopy. Circumferential seromuscular incision followed by placement of seromuscular sutures to invert the lesion into the stomach was performed under laparoscopy. By SIIGS, resection of the inverted mucosa and retrieval of the tumor were completed. A hybrid approach consisting of laparoscopic wall-inversion surgery and SIIGS was useful for intraluminal GIST and may expand the indications for laparoscopic wall-inversion surgery by removing size limitations.

Effects of odorants on the hypothalamic-pituitary-adrenal axis and interleukin-6 (IL-6) and IL-6 receptor mRNA expression in rat hypothalamus after restraint stress.

We recently reported that stress alters interleukin (IL)-6 and IL-6 receptor (IL-6R) mRNA levels in the hypothalamus. Odorants are reported to exert anti-stress effects. The aim of our study was to determine the effects of odorants on IL-6 and IL-6R mRNA expression in the hypothalamus, using reverse transcriptase-polymerase chain reaction and on serum levels of adrenocorticotropic hormone (ACTH) and corticosterone in rats exposed to stress. Control rats were not exposed to stress; test control rats were exposed to 4 h stress then immediately killed. In other groups, rats were exposed to the same stress followed by 30 min exposure air, dimethoxymethylbenzene (DMMB), or citralva. In the air group, IL-6 and IL-6R mRNA levels were significantly reduced and serum levels of ACTH and corticosterone significantly increased relative to the control. Exposure to DMMB significantly augmented IL-6 mRNA expression but restored that of IL-6R mRNA, did not change serum corticosterone level relative to that of the air group and significantly reduced ACTH. In comparison, citralva restored the expression of IL-6 and IL-6R mRNAs and significantly increased serum ACTH and corticosterone levels. Our results indicate that citralva enhances stress-induced activation of the hypothalamic-pituitary-adrenal axis by corticotropin-releasing hormone (CRH)-mediated stimulation of IL-6, while DMMB enhances the beneficial action of IL-6 without affecting CRH.

Effects of single and repeated prolonged stress on mu-opioid receptor mRNA expression in rat gross hypothalamic and midbrain homogenates.

This study tested the hypothesis that stress-induced opioid peptides may have stimulative and inhibitive influence on mu opioid receptor (MOR) mRNA expression and hypothalamus. Several studies have investigated the effects of stress on MOR mRNA expression in rat brain, but almost none compared the response to single versus repeated stresses. Here, we examined the effects of single and repeated stress on MOR mRNA expression in different rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR). Following a single episode of restraint stress for 4 h (1R) or 4 h per day on 2 (2R) or 3 (3R) consecutive days, the hypothalamus and midbrain were removed immediately and MOR mRNA levels in both regions were determined by RT-PCR. Blood samples were also collected for simultaneous measurement of serum adrenocorticotropic hormone (ACTH) and corticosterone (CS). MOR mRNA expression was significantly higher in both regions in the 2R group, whereas expression levels in the 3R group did not differ from controls. In the 1R group, hypothalamic MOR expression was equivalent to that in controls, but expression was significantly higher in the midbrain. Serum ACTH levels were significantly higher only in the 1R group, whereas serum CS was significantly higher in both the 1R and 3R groups. Our findings indicate that the influence of restraint stress on MOR mRNA expression in the hypothalamus is different than in the midbrain region in rats. Endogenous opioid peptides released in response to stress may paradoxically have an effect on the HPA axis.

Effects of single and repeated restraint stresses on the expression of beta(1)-adrenoceptor mRNA in the rat hypothalamus and midbrain.

We examined the effects of single and repeated restraint stresses on the expression of beta(1)-adrenoceptor mRNA in the rat midbrain and hypothalamus using reverse transcriptase-polymerase chain reaction (RT-PCR). After the rats had been restrained for 4 h (single stress), or for 4 h per day during 2 or 3 consecutive days, the hypothalamus and midbrain were removed immediately and beta(1)-adrenoceptor mRNA levels in these regions were determined by RT-PCR. Single stress significantly decreased the mRNA level in the hypothalamus, but the mRNA level was near control levels after 2 and 3 days of stress. In the midbrain, single stress had no effect on the mRNA level, but 2 days of stress significantly increased it.