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World Journal of Gastroenterology Oct 2023Comprehensive genomic analysis has shown that small bowel adenocarcinoma (SBA) has different genomic profiles from gastric and colorectal cancers. Hence, it is essential...
BACKGROUND
Comprehensive genomic analysis has shown that small bowel adenocarcinoma (SBA) has different genomic profiles from gastric and colorectal cancers. Hence, it is essential to establish chemotherapeutic regimens based on SBA characteristics. The expression of programmed cell death-ligand 1 (PD-L1) and programmed cell death-ligand 2 (PD-L2) in SBA is not fully understood. Anti-PD-L1/PD-1 therapy uses tumor-infiltrating lymphocytes (TILs); therefore, the status of TILs in the tumor microenvironment (TME) may influence their efficacy. The ratio of FoxP3+ to CD8+ T cells has been reported to be useful in predicting the prognosis of digestive system cancers.
AIM
To investigate the clinicopathological significance of PD-L1/2 expression according to the status of TILs in SBA tissues.
METHODS
We performed immunohistochemical analysis for PD-L1, PD-L2, CD8, FoxP3, and DNA mismatch repair (MMR) proteins using formalin-fixed, paraffin-embedded tissues from 50 patients diagnosed with primary SBA. The immunoreactivities of PD-L1 and PD-L2 were determined separately in tumor cells and tumor-infiltrating immune cells throughout the tumor center and invasive margins, and finally evaluated using the combined positive score (CPS). We assessed CD8+ and FoxP3+ T cells in the intratumoral and tumor-surrounding stroma. Subsequently, we calculated and summed the ratio of FoxP3 to CD8+ T cell counts. Immune-related cell densities were graded as low or high. Immunohistochemical results were compared with clinicopathological factors and patient prognosis. The distribution of cancer-specific survival (CSS) was estimated using the Kaplan-Meier method, and the log-rank test was used to test for significant differences in CSS. A Cox proportional hazard model was also used to assess the effect of tumor variables on CSS.
RESULTS
PD-L1 expression was positive in 34% in tumor cells (T-PD-L1) and 54% in tumor-infiltrating immune cells (I-PD-L1) of the cases examined. T-PD-L2 was positive in 34% and I-PD-L2 was positive in 42% of the cases. PD-L1 CPS ≥ 10 and PD-L2 CPS ≥ 10 were observed in 50% and 56% of the cases, respectively. Deficient MMR (dMMR) was 14% of the cases. T-PD-L1, I-PD-L1 and PD-L1 CPS ≥ 10 were all significantly associated with dMMR ( = 0.037, = 0.009, and = 0.005, respectively). T-PD-L1, I-PD-L1, and PD-L1 CPS ≥ 10 were all associated with deeper depth of invasion ( = 0.001, = 0.024, and = 0.002, respectively). I-PD-L2 expression and PD-L2 CPS ≥ 10 were significantly higher in the differentiated histological type ( = 0.015 and = 0.030, respectively). The I-PD-L1 and I-PD-L2 levels were significantly associated with better CSS ( = 0.037 and = 0.015, respectively). CD8-high was significantly associated with less lymph node metastasis ( = 0.047), less distant metastasis ( = 0.024), less peritoneal dissemination ( = 0.034), and earlier TNM stage ( = 0.047). The CD8-high group had better prognosis than the CD8-low group ( = 0.018). FoxP3 expression was not associated with any clinicopathological factors or prognosis. We found that patients with PD-L2 CPS ≥ 10 tended to have worse prognosis in the FoxP3/CD8-low group ( = 0.088).
CONCLUSION
The clinicopathological significance of PD-L1/2 expression may differ depending on the TME status. Immune checkpoint inhibitors may improve the prognosis of SBA patients with low FoxP3/CD8 ratio and PD-L2 expression.
Topics: Humans; B7-H1 Antigen; Tumor Microenvironment; Clinical Relevance; Ligands; Adenocarcinoma; Prognosis; CD8-Positive T-Lymphocytes; Duodenal Neoplasms; Apoptosis; Forkhead Transcription Factors; Lymphocytes, Tumor-Infiltrating
PubMed: 37970475
DOI: 10.3748/wjg.v29.i40.5566 -
BMC Cancer Nov 2023There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving... (Observational Study)
Observational Study
BACKGROUND
There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP).
METHODS
Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts.
RESULTS
In total nine proteins; chemokine (C-C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocyte chemotactic protein-1 (MCP-1) were strongly correlated (Spearman's Rho ≤ -0.6 or ≥ 0.6) with either cognitive functioning (DCN), emotional functioning (DCN, MCP-1), dyspnoea (CD28, GZMB, GZMH) or insomnia (CCL23, CD4, Gal-1, MMP7) during treatment. Associations between routine laboratory parameters (CA 19-9, CA-125, CRP, CEA and albumin) and HRQoL factors were overall weaker. None of the investigated proteins were associated with pain.
CONCLUSIONS
This is, to our knowledge, the first study exploring associations between serum biomarkers and HRQoL in patients with pancreatic or other periampullary cancer, and some findings merit further validation. The associations of DCN and MCP-1with impaired cognitive and/or emotional functioning are of particular interest, given their established link to various neurodegenerative conditions. Chemotherapy is known to cause persistent cognitive dysfunction with effects on memory and executive function, referred to as "chemo brain". It would therefore be of great value to identify biomarkers for early detection and management of this debilitating condition.
TRIAL REGISTRATION
Clinical Trial Registration: NCT03724994.
Topics: Humans; Albumins; Ampulla of Vater; Blood Proteins; CD28 Antigens; Duodenal Neoplasms; Matrix Metalloproteinase 7; Pancreatic Neoplasms; Prospective Studies; Quality of Life
PubMed: 37936126
DOI: 10.1186/s12885-023-11562-2 -
IJU Case Reports Nov 2023Gastric outlet obstruction caused by upper tract urothelial carcinoma is rare.
INTRODUCTION
Gastric outlet obstruction caused by upper tract urothelial carcinoma is rare.
CASE PRESENTATION
A 78-year-old man presented to the hospital with nausea and vomiting. No hematuria was observed. Computed tomography revealed a tumor in the right renal pelvis and duodenal stenosis. Gastrojejunostomy was performed to treat the symptoms of the gastric outlet obstruction so that the patient could resume oral intake and outpatient chemotherapy. Chemotherapy was unsuccessful, and the patient died 9 months after the gastrojejunostomy. Histological assessment of an autopsy specimen revealed plasmacytoid urothelial carcinoma with direct infiltration of the duodenal wall, which caused the stenosis.
CONCLUSION
Autopsy revealed a right renal pelvis cancer causing gastric outlet obstruction. Early gastrojejunostomy enabled oral intake and outpatient visits.
PubMed: 37928298
DOI: 10.1002/iju5.12652 -
DEN Open Apr 2024Underwater endoscopic mucosal resection (UEMR) is a simpler procedure for superficial non-ampullary duodenal epithelial tumors (SNADET) than conventional endoscopic...
OBJECTIVES
Underwater endoscopic mucosal resection (UEMR) is a simpler procedure for superficial non-ampullary duodenal epithelial tumors (SNADET) than conventional endoscopic mucosal resection (cEMR). This study aimed to evaluate whether cEMR can be substituted by UEMR for SNADET in terms of effectiveness, safety, and learning curve.
METHODS
A total of 157 consecutive patients with 203 SNADETs ≤20 mm in diameter, including 107 lesions resected by cEMR and 96 lesions resected by UEMR, between January 2019 and May 2023, were retrospectively recruited. The treatment outcomes were compared between the cEMR and UEMR groups. The risk factors for incomplete resection by UEMR were analyzed using univariate and multivariate analyses. Lesions in the UEMR group were divided chronologically into five periods; thereafter, the en bloc resection rate and procedure time were compared.
RESULTS
No significant differences existed between the cEMR and UEMR groups in the mean procedure time (3.9 min vs. 3.6 min, = 0.1380) or en bloc resection rate (91% vs. 94%, = 0.4138). No perforation was observed in either group. Tumor size was an independent risk factor for incomplete resection using UEMR ( < 0.01). The history of biopsy was not associated with incomplete resection using UEMR. The en bloc resection rate of UEMR was 100% (20/20) in the first period and ranged from 90% to 100% over all periods.
CONCLUSION
UEMR is safe and effective for SNADET ≤20 mm, regardless of a history of biopsy, and is easy to learn. Thus, UEMR can serve as an alternative to cEMR.
PubMed: 37927952
DOI: 10.1002/deo2.312 -
The Journal of International Medical... Oct 2023Duodenal stenosis caused by upper tract urothelial carcinoma (UTUC) is rare. A 70-year-old male patient was diagnosed with a UTUC invading the duodenum 3 months before...
Duodenal stenosis caused by upper tract urothelial carcinoma (UTUC) is rare. A 70-year-old male patient was diagnosed with a UTUC invading the duodenum 3 months before admission. Owing to duodenal stenosis, enteral nutrition was necessary. We performed pancreaticoduodenectomy with right nephroureterectomy and right hemicolectomy using a multi-disciplinary approach. Postoperative pathology revealed a UTUC invading the right kidney, duodenum, pancreas, and transverse colon. The patient underwent chemotherapy and immunotherapy after surgery, which improved his quality of life.
Topics: Male; Humans; Aged; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Quality of Life; Nephroureterectomy
PubMed: 37899573
DOI: 10.1177/03000605231206958 -
Cancers Oct 2023Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but...
Pancreatic neuroendocrine neoplasms (PNENs) affect over 80% of patients with multiple endocrine neoplasia type 1 (MEN1). Surgery is usually the therapy of choice, but the real immediate and long-term therapeutic benefit of a partial extensive pancreatic resection remains controversial. We analyzed, in 43 PNEN MEN1 patients who underwent 19 pancreaticoduodenectomies (PD), 19 distal pancreatectomies (DP), and 5 minimal pancreatectomies, the prevalence of surgery-derived early complications and post-operative pancreatic sequelae, and the PNEN relapse-free survival time after surgery, comparing major (PD+DP) and minimal pancreatic surgeries. No post-operative mortality was observed. Metastatic cancers were found in 12 cases, prevalently from duodenal gastrinoma. Long-term cure of endocrine syndromes, by the 38 major pancreatic resections, was obtained in 78.9% of gastrinomas and 92.9% of insulinomas. In only one patient, hepatic metastases, due to gastrinoma, progressed to death. Out of the 38 major surgeries, only one patient was reoperated for the growth of a new PNEN in the remnant pancreas. No functioning PNEN persistence was reported in the five minimal pancreatic surgeries, PNEN relapse occurred in 60% of patients, and 40% of cases needed further pancreatic resection for tumor recurrence. No significant difference in PNEN relapse-free survival time after surgery was found between major and minimal pancreatic surgeries.
PubMed: 37894286
DOI: 10.3390/cancers15204919 -
Revista Espanola de Enfermedades... Nov 2023Duodenal-type follicular lymphoma is a clinical variant of follicular lymphoma located in the intestine, presenting as multiple small polyps. The estimated frequency is...
Duodenal-type follicular lymphoma is a clinical variant of follicular lymphoma located in the intestine, presenting as multiple small polyps. The estimated frequency is 1/7000 people and extraduodenal involvement is rare. It predominantly affects middle-aged women, although some cases of young patients have been published in the literature. They are usually located in the second periampullary portion of the duodenum. It is diagnosed incidentally or after performing an imaging test due to non-specific digestive symptoms (abdominalgia, diarrhea or hyporexia). The prognosis is usually favorable without specific treatment5.
Topics: Middle Aged; Humans; Female; Lymphoma, Follicular; Duodenal Neoplasms; Duodenum; Cholestasis; Prognosis; Colorectal Neoplasms
PubMed: 37882167
DOI: 10.17235/reed.2023.9929/2023 -
The Korean Journal of Gastroenterology... Oct 2023The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary... (Review)
Review
The ampulla of Vater is a small projection formed by the confluence of the main pancreatic duct and common bile duct in the second part of the duodenum. Primary ampullary adenocarcinoma is a rare malignancy, accounting for only 0.2% of gastrointestinal cancers and approximately 7% of all periampullary cancers. Jaundice from a biliary obstruction is the most common symptom of ampullary adenocarcinoma. In the early stages, radical pancreatoduodenectomy is the standard surgical approach. On the other hand, no randomized controlled trial has provided evidence to guide physicians on the choice of adjuvant/palliative chemotherapy because of the rarity of the disease and the paucity of related research. This paper reports the biology, histology, current therapeutic strategies, and potential future therapies of ampullary adenocarcinoma.
Topics: Humans; Ampulla of Vater; Adenocarcinoma; Pancreatic Neoplasms; Common Bile Duct Neoplasms; Duodenal Neoplasms
PubMed: 37876255
DOI: 10.4166/kjg.2023.110 -
BJS Open Sep 2023The prevalence of different periampullary cancers (pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary cancer and duodenal cancer) is heterogeneous in...
BACKGROUND
The prevalence of different periampullary cancers (pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary cancer and duodenal cancer) is heterogeneous in the literature. During the 2010s, a standardized histopathological protocol for pancreatoduodenectomy specimens based on axial slicing was adopted in Sweden. The present study sought to provide information about periampullary cancers with regard to tumour types in curative and noncurative settings, preoperative diagnostic accuracy and the impact of a standardized evaluation of the surgical specimen on diagnosis, R status and lymph node assessment.
METHODS
Data from patients diagnosed with periampullary cancer from 2010 to 2019 were retrieved from the Swedish National Registry for Pancreatic and Periampullary Cancer.
RESULTS
Among non-curative patients, 3704 (83.6 per cent) were diagnosed with pancreatic ductal adenocarcinoma. Among patients treated with pancreatoduodenectomy, diagnosis was pancreatic ductal adenocarcinoma in 1380 (50.0 per cent), distal cholangiocarcinoma in 284 (10.3 per cent), ampullary cancer in 376 (13.6 per cent), duodenal cancer in 160 (5.8 per cent) and other diagnoses in 560 (20.3 per cent) patients. The preoperative diagnosis corresponded to the postoperative in 1177 (67.5 per cent) patients for pancreatic ductal adenocarcinoma, 162 (37.4 per cent) patients for distal cholangiocarcinoma, 220 (61.3 per cent) patients for ampullary cancer and 120 (53.6 per cent) patients for duodenal cancer. A higher rate of pancreatic ductal adenocarcinoma was seen in surgical specimens who underwent standardized evaluation, from 56.8 per cent to 64.3 per cent (P = 0.003). After standardization, higher rates of R1 resection (31.7 per cent versus 44.6 per cent, P < 0.001) and N1 stage (62.1 per cent versus 77.0 per cent, P < 0.001) were found.
CONCLUSION
The proportion of pancreatic ductal adenocarcinoma was higher in patients in a non-curative setting compared with patients who underwent surgery. The rate of misdiagnosis for periampullary cancers was confirmed to be high. Thus, it should be taken into account when preoperative oncological treatment is considered. Standardized evaluation of the surgical specimen has increased pancreatic ductal adenocarcinoma, R1 and N1 rates.
Topics: Humans; Ampulla of Vater; Duodenal Neoplasms; Cohort Studies; Adenocarcinoma; Common Bile Duct Neoplasms; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Cholangiocarcinoma; Bile Duct Neoplasms; Bile Ducts, Intrahepatic
PubMed: 37864577
DOI: 10.1093/bjsopen/zrad104 -
Scientific Reports Oct 2023Duodenal neuroendocrine tumors (d-NETs) ≤ 10 mm in size, confined to the submucosal layer, without lymph node or distant metastasis, can be treated safely and...
Duodenal neuroendocrine tumors (d-NETs) ≤ 10 mm in size, confined to the submucosal layer, without lymph node or distant metastasis, can be treated safely and effectively by endoscopic management. However, most results are based on limited data and short follow-up outcomes. Herein, we aimed to evaluate the short-term and long-term outcomes of endoscopic resection for d-NETs. We retrospectively analyzed 63 patients with 68 d-NETs who had undergone endoscopic resection at two hospitals between January 2009 and December 2021. En-bloc resection, endoscopically complete resection, and histopathologically complete resection rates were evaluated as short-term outcomes. Furthermore, long-term outcomes were analyzed in 46 patients with 50 d-NETs with a follow-up period of > 1 year. The overall en-bloc, endoscopically complete, and histopathologically complete resection rates were 92.6% (63/68), 100% (68/68), and 69.1% (47/68), respectively. Tumor size (> 5 mm) was the only predictive factor for histopathologically incomplete resection (p = 0.015). The procedure-related bleeding and perforation rates were 0% and 5.9%, respectively. No recurrences were observed in patients with histopathologically complete resection and those with histopathologically incomplete resection at a median follow-up period of 48 months (range 12-132 months). Endoscopic resection for d-NETs ≤ 10 mm in size, limited to the submucosal layer, and without lymph node or distant metastasis provides favorable long-term outcomes when endoscopically complete resection is achieved.
Topics: Humans; Neuroendocrine Tumors; Treatment Outcome; Retrospective Studies; Duodenal Neoplasms
PubMed: 37863959
DOI: 10.1038/s41598-023-45243-8