Endoscopic clipping of gastrojejunostomy leakage following Whipple procedure: A case report.

BACKGROUND: Currently, perioperative complications of classic Whipple surgery occur at a rate of approximately 40%. Common complications include delayed gastric emptying, pancreatic fistula, and bile leakage, whereas gastrojejunostomy (GJ) leakage is rare. CASE SUMMARY: This case report will assess the management of a GJ leak in a 71-year-old male patient following the Whipple procedure. After surgery, the patient was transferred to the clinic after four days of intensive care, where vacuum therapy was used to handle a developing subcutaneous collection. The patient, who had bile in the drains and incision during follow-up, underwent endoscopic examination on the 21st day after the operation. An opening of approximately 4 mm was observed in the GJ anastomosis during endoscopy. Five titanium clips were used to close the openings. The drainage of bile decreased to less than 50 mL on the first day after the procedure, and the patient's oral intake was opened. CONCLUSION: Current literature reports a GJ leakage rate of 0. 54% following Whipple surgery, with clinical findings lasting on average between 4-34 days. Surgery was the main form of therapy for this case, with a success rate of 84%, and percutaneous drainage was also utilized as a treatment option. This case report is the first to document endoscopic treatment of GJ leaks following the classic Whipple procedure.

Carbohydrate antigens Lewis a and Lewis b act as tumor markers cooperating with CA19.9 in the management of PDAC patients.

BACKGROUND: CA19.9 is the unique marker recommended for the preoperative staging and the follow-up of patients suffering from pancreatic ductal adenocarcinoma (PDAC) but up to 30% of PDAC patients maintain normal CA19.9 values and cannot be monitored in this way. Lewis a (Lea Galß1,3[Fucα1,4]GlcNAc) and b (Leb, Fucα1,2Galß1,3[Fucα1,4]GlcNAc) are antigens which are structurally similar to sialyl-Lewis a (Siaα2,3Galß1,3[Fucα1,4]GlcNAc), the epitope of CA19.9. METHODS: We set an ELISA procedure determining the levels of Lea, Leb, and CA19.9 in the blood of healthy individuals or PDAC patients. Moreover, such antigens were also detected in cancer resections by immunofluorescence microscopy, and the levels of glycosyltransferase transcripts involved in Lewis antigen biosynthesis were determined by RT-qPCR. RESULTS: In our cohort of 116 healthy individuals, the distribution of circulating Lea and Leb was similar to that of CA19.9, allowing us to set putative cutoff values for both antigens. In a cohort of 115 PDAC patients, the differential distribution with respect to the controls was statistically significant for both antigens (p < 0.001). Out of 37 patients presenting normal CA19.9 values, 15 patients presented Lea or Leb above the cutoffs. By immunofluorescence, Lea, Leb and CA19.9 were all detected in cancer resections and expression levels were heterogeneous among patients in terms of intensity, localization and diffusion. The levels of relevant glycosyltransferase transcripts were found to be heterogeneous between cancers of different patients and no association was detectable with the levels of any circulating antigen. CONCLUSIONS: The concurrent quantification of Lea and Leb together with CA19.9 improves the management of PDAC patients.

Pancreatic Cancer Screening among High-risk Individuals.

Pancreatic ductal adenocarcinoma (PDAC) continues to remain one of the leading causes of cancer-related death. Unlike other malignancies where universal screening is recommended, the same cannot be said for PDAC. The purpose of this study is to review which patients are at high risk of developing PDAC and therefore candidates for screening, methods/frequency of screening, and risk for these groups of patients.

Impact of proton pump inhibitors on pathologic response rates following fluoropyrimidine-based neoadjuvant chemotherapy in pancreatic cancer patients.

BACKGROUND: Proton pump inhibitors (PPIs) negatively impact fluoropyrimidine-based chemotherapy efficacy in colorectal cancer. This study assessed PPI impact on major pathologic response (mPR) rates of pancreatic adenocarcinoma (PDAC) patients receiving fluoropyrimidine-based chemotherapy. METHODS: An institutional retrospective review of resected PDAC patients receiving neoadjuvant fluoropyrimidine-based chemotherapy (98% FOLFIRINOX) from 2011 to 2021 was conducted. Outcomes were stratified by use or nonuse of PPIs within 6 months of neoadjuvant chemotherapy initiation. Primary outcome was mPR defined as complete or near complete response. RESULTS: Among 540 patients included, the median age was 64 (IQR: 60-70) years, 297 (55%) were male, and 202 (37%) were PPI users. 170 (31%) patients had mPR with similar rates among PPI users and nonusers (29% vs. 33%, p = 0.38). No difference in mPR was seen between PPI users and nonusers receiving chemoradiation (35% vs. 36%, p = 0.89) or ≥8 cycles of NAC (33% vs. 36%, p = 0.55). Median OS for PPI users was 30.9 versus 31.7 months for nonusers (p = 0.62). On multivariable analysis, PPI therapy was not associated with decreased survival. CONCLUSION: PPI usage did not significantly influence mPR or OS following neoadjuvant fluoropyrimidine-based chemotherapy in resected PDAC patients. Further analysis of all patients, not just those who underwent resection, is required.

Data privacy-aware machine learning approach in pancreatic cancer diagnosis.

PROBLEM: Pancreatic ductal adenocarcinoma (PDAC) is considered a highly lethal cancer due to its advanced stage diagnosis. The five-year survival rate after diagnosis is less than 10%. However, if diagnosed early, the five-year survival rate can reach up to 70%. Early diagnosis of PDAC can aid treatment and improve survival rates by taking necessary precautions. The challenge is to develop a reliable, data privacy-aware machine learning approach that can accurately diagnose pancreatic cancer with biomarkers. AIM: The study aims to diagnose a patient's pancreatic cancer while ensuring the confidentiality of patient records. In addition, the study aims to guide researchers and clinicians in developing innovative methods for diagnosing pancreatic cancer. METHODS: Machine learning, a branch of artificial intelligence, can identify patterns by analyzing large datasets. The study pre-processed a dataset containing urine biomarkers with operations such as filling in missing values, cleaning outliers, and feature selection. The data was encrypted using the Fernet encryption algorithm to ensure confidentiality. Ten separate machine learning models were applied to predict individuals with PDAC. Performance metrics such as F1 score, recall, precision, and accuracy were used in the modeling process. RESULTS: Among the 590 clinical records analyzed, 199 (33.7%) belonged to patients with pancreatic cancer, 208 (35.3%) to patients with non-cancerous pancreatic disorders (such as benign hepatobiliary disease), and 183 (31%) to healthy individuals. The LGBM algorithm showed the highest efficiency by achieving an accuracy of 98.8%. The accuracy of the other algorithms ranged from 98 to 86%. In order to understand which features are more critical and which data the model is based on, the analysis found that the features "plasma_CA19_9", REG1A, TFF1, and LYVE1 have high importance levels. The LIME analysis also analyzed which features of the model are important in the decision-making process. CONCLUSIONS: This research outlines a data privacy-aware machine learning tool for predicting PDAC. The results show that a promising approach can be presented for clinical application. Future research should expand the dataset and focus on validation by applying it to various populations.

Prognostic value of ABO blood groups in upfront operated pancreatic ductal adenocarcinomas.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has been shown to have a lower incidence in patients with blood group O. It is currently uncertain if patients with group O have a better prognosis after pancreatectomy. This study assessed the overall survival (OS) and disease-free survival (DFS) of PDAC patients who underwent upfront pancreatoduodenectomy based on ABO blood groups. METHODS: A cross-sectional study was performed including patients from two university centers. All consecutive head PDAC patients who underwent upfront pancreatoduodenectomy from 2000 to 2016 were included. OS and DFS were compared between blood groups A, B, AB, and O using Kaplan-Meier curves and log-rank tests. RESULTS: A total of 438 patients were included (215 women, median age 67). Pre- and intraoperative details were comparable between all subgroups. Median OS did not differ between the four blood groups (A: 23 months, 95% CI 18-28; B: 32, 95% CI 20-44; AB: 37, 95% CI 18-56 and O: 26, 95% CI 20-32, p = 0.192). Median DFS were also similar (A: 19 months, 95% CI 15-23; B: 26, 95% CI 19-33; AB: 35, 95% CI 15-55 and O: 22, 95% CI 15-29, p = 0.441). There was no OS difference between O and non-O groups (median: 26 months, 95% CI 20-33 vs. 25 months, 95% CI 20-30, p = 0.773). On multivariable analysis blood groups were not prognostic of OS. Only lymph node involvement, tumor differentiation, and adjuvant chemotherapy were independent prognostic factors. CONCLUSION: OS and DFS were similar between all four blood groups after pancreatoduodenectomy. Independent predictors of OS were associated with tumor characteristics and adjuvant treatment.

First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase I dose exploration.

BACKGROUND: Homozygous deletion of methylthioadenosine phosphorylase (MTAP) occurs in ∼10%-15% of solid tumors. AMG 193, a CNS-penetrant methylthioadenosine-cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor, selectively induces synthetic lethality in MTAP-deleted tumor cells. Here, we report results of the completed monotherapy dose exploration evaluating AMG 193 in patients with MTAP-deleted solid tumors. PATIENTS AND METHODS: In this first-in-human, multicenter, open-label, phase I study, patients with advanced CDKN2A-deleted and/or MTAP-deleted solid tumors received AMG 193 orally [once (o.d.) or twice (b.i.d.) daily] continuously in 28-day cycles. Primary objectives were safety and tolerability assessed by dose-limiting toxicities and determination of the maximum tolerated dose; secondary objectives included pharmacokinetics and preliminary antitumor activity measured by RECIST v1.1. RESULTS: As of 23 May 2024, 80 patients in dose exploration received AMG 193 at doses 40-1600 mg o.d. or 600 mg b.i.d. The most common treatment-related adverse events were nausea (48.8%), fatigue (31.3%), and vomiting (30.0%). Dose-limiting toxicities were reported in eight patients at doses ≥240 mg, including nausea, vomiting, fatigue, hypersensitivity reaction, and hypokalemia. The maximum tolerated dose was determined to be 1200 mg o.d. Mean exposure of AMG 193 increased in a dose-proportional manner from 40 mg to 1200 mg. Among the efficacy-assessable patients treated at the active and tolerable doses of 800 mg o.d., 1200 mg o.d., or 600 mg b.i.d. (n = 42), objective response rate was 21.4% (95% confidence interval 10.3% to 36.8%). Responses were observed across eight different tumor types, including squamous/non-squamous non-small-cell lung cancer, pancreatic adenocarcinoma, and biliary tract cancer. At doses ≥480 mg, complete intratumoral PRMT5 inhibition was confirmed in paired MTAP-deleted tumor biopsies, and molecular responses (circulating tumor DNA clearance) were observed. CONCLUSIONS: AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP-deleted solid tumors was observed based on objective response rate and circulating tumor DNA clearance.

Development and Preclinical Evaluation of 18F-Labeled PEGylated Sansalvamide A Decapeptide for Noninvasive Evaluation of Hsp90 Status in Pancreas Cancer.

Heat shock protein 90 (Hsp90) is a promising target for cancer therapy and imaging. Accurate detection of Hsp90 levels in tumors via noninvasive PET imaging might be beneficial for management. To achieve this, the precursor compound Dimer-Sansalvamide A (Dimer-San A) was PEGylated and modified by conjugating it with the bifunctional chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The 18F-labeled PEGylated Dimer-SanA decapeptide (18F-PEGylated San A) was completed within 30 min using a two-step process. In vitro stability and specificity were assessed, including competition studies with the Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG). MicroPET imaging was performed on PL45 tumor-bearing mice to evaluate probe accumulation and tumor-to-muscle ratios. Biodistribution studies determined the route of excretion. The probe resulted in a radiochemical yield of 23.11% with a purity exceeding 95%. In vitro, 18F-PEGylated San A exhibited high stability and selectively accumulated in Hsp90-positive PL45 cells, with binding effectively blocked by the Hsp90 inhibitor 17AAG, confirming its specificity. MicroPET imaging of PL45 tumor-bearing mice showed significant probe accumulation in tumor tissues at 1 and 2 h postinjection (4.06 ± 0.30 and 3.72 ± 0.61%ID/g, respectively), with optimal tumor-to-muscle ratios observed at 2 h postinjection (6.09 ± 1.92). While 18F-PEGylated San A demonstrates enhanced water solubility, as indicated by increased kidney uptake relative to liver accumulation. The study successfully incorporated PEG units to create the novel probe 18F-PEGylated San A targeting to Hsp90 without affecting its targeting capability, aimed at improving the pharmacokinetics and PET imaging of Hsp90 expression noninvasively.

Current landscape of gastrointestinal radiation oncology in Spain: a multicenter real-life survey and comparison with key clinical guidelines.

Background: The GI Tumors Workgroup, a division of the Spanish Society of Radiation Therapy, conducted a survey in December 2020 to assess the adherence of radiation oncologists in Spain to international guidelines for gastrointestinal tumors. Materials and methods: Using Google Forms, we designed a survey covering treatments for esophageal, gastric, pancreatic, and rectal cancers. Results: In esophageal cancer treatment, neoadjuvant chemoradiation was the standard in 76.7% of institutions. Radiation doses range from 41.1 to 50.4 Gy in conventional fractionation. Planning positron emission tomography-computed tomography (PET-CT) was performed in 83.3% of centers, and intensity-modulated radiation therapy/volumetric-arc radiation therapy (IMRT/VMAT) was the preferred technique in 86.7% of institutions. For gastric cancer, 71.4% followed perioperative chemotherapy guidelines. In the case of adjuvant radiotherapy, the majority prescribed 45-50.4 Gy, and 82.1% used IMRT/VMAT for treatment. For pancreas cancer, neoadjuvant chemotherapy followed by surgery in borderline resectable tumors and induction chemotherapy followed by radical radiotherapy for non-resectable tumors were the most frequent approaches. IMRT/VMAT was the primary technique. Locally advanced rectal cancer treatment is mainly based on neoadjuvant radiotherapy in all institutions. The preferred radiation doses typically range from 45 to 50 Gy in conventional fractionation. IMRT/VMAT was standard in most Institutions. Conclusions: Spain's radiotherapy practices among respondents generally align with international guidelines for GI tumors highlighting Spain's commitment to evidence-based medical practice.

Venous thromboembolism in patients with pancreatic adenocarcinoma: Disease burden and initiation of ambulatory thromboprophylaxis.

BACKGROUND/OBJECTIVES: Ambulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times. METHODS: Patients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation. RESULTS: The cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021). CONCLUSION: VTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation.

Investigation of Pulmonary Saddle Embolism Caused by Metastasis-Induced Hypercoagulability Originating From Pancreatic Cancer.

An adult male cadaver, approximately 60 years of age, was dissected as part of an eight-week didactic course. It was found that the subject had evidence of pancreatic cancer with signs of metastasis as well as significant bilateral pulmonary artery clotting. In particular, a saddle embolism was observed, and the cause of death was listed as sudden pulmonary failure. Malignant tumors are often accompanied by hypercoagulable states and increased risk of thromboembolism. Because the clots showed lines of Zahn on histology, we can infer that this hypercoagulable state preceded death and may have been related to the presence of pancreatic carcinoma. There are few recorded cases of pulmonary saddle embolism being the fatal event in cases of underlying pancreatic cancer. The extensive clotting observed in the inferior vena cava and pulmonary arteries demonstrates to clinicians that patients, especially those with pancreatic cancer, are at higher risk for thromboembolic events. This case report also serves as a reminder that instances of pulmonary failure or sudden death because of pulmonary saddle embolism may be caused by underlying visceral neoplasms, such as pancreatic cancer.

Preoperative neutrophil-to-C-reactive protein ratio as a predictor of post-operative complications of pancreas cancer.

OBJECTIVE: We would like to investigate the prognostic utility of the previously described factors and offer a new parameter called neutrophil-to-C-reactive protein ratio (NCR) as a predictor of post-operative complications of pancreas cancer. METHODS: 92 patients underwent pancreaticoduodenectomy for the pancreatic head tumor were enrolled in this study. Receiver operating curve analysis was performed to detect the cutoff values, and logistic regression analyses were performed to identify the independent risk factors of complications. RESULTS: In univariate analysis, complications were observed in lymphocyte-to-C-reactive protein ratio levels below 0.06 (Odds Ratio [OR]: 3.92, 95% confidence interval [CI] = 1.08-14.21, p = 0.037). In multivariate analysis, albumin < 3.6 (OR: 3.25, 95% CI: 1.16-9.06, p = 0.024) and NCR < 0.28 (OR: 2.81, 95 % CI: 1.07-7.63, p = 0.042) were the independent and significant predictors of the overall survival. DISCUSSION: Quantification of preoperative NCR and albumin may help surgeons to settle an effective perioperative management, take extra caution, and be aware of post-operative complications of pancreatic cancer patients.

OBJETIVO: Se investigó la proporción de neutrófilos a proteína C reactiva (NCR) como predictor de complicaciones posoperatorias del cáncer de páncreas. MATERIAL Y MÉTODOS: 92 pacientes fueron sometidos a pancreaticoduodenectomía (PD) por el tumor de la cabeza del páncreas incluidos en este estudio. Se realizaron análisis de curva operativa del receptor (ROC) y análisis de regresión logística para detectar los valores de corte y los factores de riesgo independientes de complicaciones. RESULTADOS: En análisis univariado; se observaron complicaciones en niveles de LCR por debajo de 0,06 (OR: 3.92, IC 95%: 1.08-14.21, p = 0.037). En análisis multivariado; albúmina < 3.6 (OR: 3.25, IC 95 %: 1.16-9.06, p = 0.024), NCR < 0.28 (OR: 2.81, IC 95 %: 1.07-7.63, p = 0.042) fueron los predictores independientes y significativos de la supervivencia. CONCLUSIÓN: La cuantificación de la NCR y la albúmina preoperatorias puede ayudar a los cirujanos a establecer un manejo perioperatorio efectivo, tomar precauciones adicionales y estar atentos a las complicaciones posoperatorias.

Prognostic significance of lymph node metastasis in pancreatic tail cancer: A multicenter retrospective study.

Background: Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt-PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt-PDAC. Patients and method: This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt-PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt-PDAC prognosis were investigated. Results: There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt-PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence-free survival (HR = 2.01, 95% CI = 1.33-3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence-free survival. Conclusions: LN dissection along the hepatic artery for Pt-PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short-term outcomes and preservation of pancreatic function is required.

Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting.

INTRODUCTION: Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities. METHODS: Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables. Statistical significance was set at p < 0.05. RESULTS: A total of 286 patients met inclusion criteria. Eighty-nine patients (31.1%) were underrepresented minorities (URM). Fifty-seven (64.0%) URMs presented during an EP versus 100 (50.8%) non-URMs (p = 0.037). Forty-one (46.1%) URMs were reviewed at PMDC versus 71 (36.0%) non-URMs (p = 0.10). No differences in clinical and pathologic stage between the cohorts (p = 0.28) were present. URMs took 22 days longer on average to receive treatment (66.5 days vs. 44.8 days, p = 0.003) in the EP cohort and 18 days longer in OP cohort (58.0 days vs. 40.5 days, p < 0.001) compared with non-URMs. Pancreatic Multidisciplinary Clinic enrollment in EP cohort eliminated the difference in time to treatment between cohorts (48.3 days vs. 37.0 days; p = 0.151). RESULTS: Underrepresented minorities were more likely to be diagnosed via EP and showed delayed times to treatment compared with non-URM counterparts. Our PMDC alleviated some of these observed disparities. Future studies are required to elucidate the specific factors that resulted in these findings and to identify solutions.

Sphingosine is involved in PAPTP-induced death of pancreas cancer cells by interfering with mitochondrial functions.

Pancreas ductal adenocarcinoma belongs to the most common cancers, but also to the tumors with the poorest prognosis. Here, we pharmacologically targeted a mitochondrial potassium channel, namely mitochondrial Kv1.3, and investigated the role of sphingolipids and mutated Kirsten Rat Sarcoma Virus (KRAS) in Kv1.3-mediated cell death. We demonstrate that inhibition of Kv1.3 using the Kv1.3-inhibitor PAPTP results in an increase of sphingosine and superoxide in membranes and/or membranes associated with mitochondria, which is enhanced by KRAS mutation. The effect of PAPTP on sphingosine and mitochondrial superoxide formation as well as cell death is prevented by sh-RNA-mediated downregulation of Kv1.3. Induction of sphingosine in human pancreas cancer cells by PAPTP is mediated by activation of sphingosine-1-phosphate phosphatase and prevented by an inhibitor of sphingosine-1-phosphate phosphatase. A rapid depolarization of isolated mitochondria is triggered by binding of sphingosine to cardiolipin, which is neutralized by addition of exogenous cardiolipin. The significance of these findings is indicated by treatment of mutated KRAS-harboring metastasized pancreas cancer with PAPTP in combination with ABC294640, a blocker of sphingosine kinases. This treatment results in increased formation of sphingosine and death of pancreas cancer cells in vitro and, most importantly, prolongs in vivo survival of mice challenged with metastatic pancreas cancer. KEY MESSAGES: Pancreatic ductal adenocarcinoma (PDAC) is a common tumor with poor prognosis. The mitochondrial Kv1.3 ion channel blocker induced mitochondrial sphingosine. Sphingosine binds to cardiolipin thereby mediating mitochondrial depolarization. Sphingosine is formed by a PAPTP-mediated activation of S1P-Phosphatase. Inhibition of sphingosine-consumption amplifies PAPTP effects on PDAC in vivo.

Meta-analysis of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy.

The role of surgical resection in patients with recurrent pancreatic cancer is unclear. We aimed to evaluate the survival outcomes of pancreatic re-resection for locally recurrent pancreatic cancer following index pancreatectomy. A literature search was carried out in CENTRAL, EMBASE, MEDLINE, CINAHL, and Web of Science. Proportion meta-analysis model was constructed to quantify 1 to 5-year survival after pancreatic re-resection for locally recurrent pancreatic cancer. Random-effects modelling was applied to calculate pooled outcome data. Fifteen retrospective studies were included, reporting a total of 250 patients who underwent pancreatic re-resection for locally recurrent pancreatic cancer following their index pancreatectomy. Pancreatic re-resection was associated with 1-year survival 70.6% (95% confidence interval [CI], 65.0-76.2), 2-year survival 38.8% (95% CI, 28.6-49.0), 3-year survival 20.2% (95% CI, 13.8-26.7), and 5-year survival 9.2% (95% CI, 5.5-12.8). The between-study heterogeneity was insignificant in all outcome syntheses. Repeat pancreatectomy for local recurrence of pancreatic cancer in the remnant pancreas following the index pancreatectomy is associated with acceptable overall patient survival. We recommend selective re-resection of such recurrences in younger patients with favorable tumor size and location. Our findings may encourage more robust studies to be conducted in this context to provide stronger evidence.

Theranostics: Timing is Everything.

On stage, and in real life, timing is critical for success. Theranostic cancer care epitomizes the central role of timing in the evolution of efficacious molecular targeted radioligand therapy and its incorporation into routine clinical practice of oncology. Nuclear medicine has returned to its therapeutic roots, having been founded as a medical specialty, over three-quarters of a century ago, with radioiodine therapy of thyroid cancer. The very recent oncologist acceptance of 68Ga/177Lu/225Ac-PSMA effectiveness in treating prostate cancer has re-established the role of the physician in nuclear medicine. This article addresses various important issues in respect of timing related to this resurgence. Training of the required new workforce in technical -omics expertise and physicianly virtues is an urgent priority. Precision in radioligand therapy requires definition of individual radiation absorbed dose (Gy) to tumor and to critical normal organs, preferably prospectively. It is time to abandon one-size-fits-all administration of fixed activities (GBq) in arbitrary cycle intervals and duration. The time has also come to design combination sequenced theranostic-immuno-chemotherapeutic approaches to metastatic cancer to address unmet needs, particularly in pancreatic carcinoma; exploiting the potential of new fibroblast activation protein inhibitor radioligands targeting the tumor microenvironment. Public perception of all things "nuclear," including nuclear medicine, has recently recovered from the general opprobrium and radiophobia of the last half-century. Nuclear is the new green. At last, there have arisen propitious circumstances for the future development of theranostics: The timing is right, now.

Preliminary Investigation of the Efficacy and Indications of Proton Beam Therapy for Stage IV Pancreatic Adenocarcinoma.

BACKGROUND: The present study aimed to evaluate proton beam therapy (PBT) for stage IV pancreatic adenocarcinoma and its metastases and define the criteria for eligibility. Materials and methods: We retrospectively evaluated the patients who had a histopathological diagnosis of pancreatic adenocarcinoma, had progressed to stage IV, and underwent PBT for both the primary and some metastatic lesions between 2017 and 2022. PBT was performed using the passive scattering technique. RESULTS: Sixteen patients (median age, 72 years; range, 55-85 years) were enrolled. All patients had stage IV pancreatic cancer at the initiation of PBT. The median duration from the date of stage IV diagnosis to the initiation of PBT was 5.8 (range, 0.4-13.5) months. Three patients had been diagnosed as having recurrent stage IV cancer at other institutions before their referral to our hospital because they had local recurrence and distant metastases after the resection of the primary tumor. Chemotherapy was as follows: pre-PBT, 0, 1, 2, and 3 lines in 4, 7, 4, and 1 patients, respectively; concurrent with PBT, 0 and 1 line in 11 and 5 patients, respectively; post-PBT, 0 and 1 line in 5 and 5 patients, respectively; and unknown, 6 patients. The median survival times (MSTs) from the date of stage IV diagnosis for the with or without non-irradiated active metastatic tumor were 11.4 and 20.1 months, respectively. Univariate analysis revealed that the performance status (PS) levels (p < 0.01), the carbohydrate antigen (CA) 19-9 tumor marker levels (p < 0.01), active tumors not treated with irradiation (p = 0.02), and with or without post-PBT chemotherapy (p < 0.01) were statistically significant factors. Multivariate analysis revealed that the CA 19-9 tumor marker levels (p= 0.04), the number of metastatic lesions (p = 0.049), and with or without non-irradiated active metastatic tumors (p = 0.02) were significant factors. CONCLUSION: PBT is indicated when the number of metastases is limited to ≤ 4 lesions and all tumors can be irradiated within the smallest possible number of irradiation fields that can be performed within the patient's tolerable time, which is a subjective duration that depends on the patient's reaction during each session. It may be a viable treatment option for patients with oligometastatic pancreatic cancer.