Prognostic relevance of tertiary lymphoid organs following neoadjuvant chemoradiotherapy in pancreatic ductal adenocarcinoma.

The efficacy of preoperative neoadjuvant chemoradiotherapy (NAC) in cases of pancreatic cancer with extremely poor prognoses has been reported. In this study, we aimed to identify novel biomarkers that reflect prognoses following chemoradiotherapy using tertiary lymphoid organs (TLO) expressed in the tumor microenvironment. Resected tumor specimens were obtained from 140 pancreatic cancer patients. We retrospectively investigated the clinical relevance of TLO by categorizing patients into those who underwent upfront surgery (surgery first [SF]) and those who received NAC. The immunological elements within TLO were analyzed by immunohistochemistry (IHC). In the IHC analysis, the proportions of CD8+ T lymphocytes, PNAd+ high endothelial venules, CD163+ macrophages and Ki-67+ cells within the TLO were higher in the NAC group than in the SF group. In contrast, the proportion of programmed cell death-1+ immunosuppressive lymphocytes within TLO was lower in the NAC group than in the SF group. The NAC group demonstrated favorable prognoses compared with the SF group. In the multivariate analysis, the TLO/tumor ratio was determined as an independent predictive prognostic factor. In conclusion, the administration of preoperative chemoradiotherapy may influence the immunological elements in the tumor microenvironment and result in favorable prognoses in pancreatic ductal adenocarcinoma patients.

Postoperative nutritional benefits of proximal parenchymal pancreatectomy for low-grade malignant lesions in the pancreatic head.

BACKGROUND: Outcomes of proximal parenchymal pancreatectomy (PPP) as compared to pancreatoduodenectomy (PD) have not been reported. The aim of this study was to describe the short- and long-term outcomes of patients with low-grade pancreatic head lesions who underwent PPP or PD. METHODS: Patients who underwent PPP or PD for low-grade lesions between 2009 and 2017 were included. Operative factors including postoperative complications and nutritional indicators during the first-year postoperatively were compared. RESULTS: A total of 13 and 14 patients underwent PPP and PD respectively. The PPP group demonstrated significantly less intraoperative blood loss and shorter postoperative hospital stay than the PD group. No significant differences were noted in the incidence of postoperative complications between the two groups. Nutritional indices were significantly better in the PPP group at 3 months post-surgery, but these nutritional indices were not significantly different at 6 months and 1-year. None of 12 patients who underwent PPP and did not require biliary resection developed postoperative cholangitis. None of the 12 PPP patients without preoperative diabetes developed impaired glucose tolerance after surgery. DISCUSSION: The complication rate of PPP is equivalent to that of PD. PPP demonstrated better short-term nutritional status than PD. Moreover, preservation of the total duodenum and bile duct may reduce the risk of developing postoperative diabetes and cholangitis.

[Transmanubrial Osteomuscular-sparing Approach for Resection of Superior Mediastinal Schwannoma].

Various approaches can be applied to resect superior mediastinal tumor. It is important to choose the procedure according to the location, size, and characteristics of the tumor in order to perform safe procedure surgery because of distinctive anatomy of this site. We hereby report on a case of Schwannoma of the superior mediastinum resected by the transmanubrial approach. A 67-year-old woman was referred to our department to examine an abnormal chest shadow found at a regular health checkup. Computed tomography revealed a tumor 58×52 mm in size extending from the left supraclavicular fossa to the upper border of the aortic arch. The surgery was performed under the diagnosis of neurogenic tumor using the transmanubrial approach. The tumor was resected safely and the pathological diagnosis was a Schwannoma. Transmanubrial approach was found to be quite useful in securing an adequate visual field and enabling the safe separation of blood vessels and nerves from the tumor.

The preoperative SOFA score and remnant small intestine length are postoperative risk factors for mortality in patients with non-occlusive mesenteric ischemia: a case-control study.

Aim: Non-occlusive mesenteric ischemia (NOMI) is a fatal condition with a low survival rate in most cases. The risk factors for perioperative mortality in NOMI cases are unclear. The purpose of this study was to define the risk factors for mortality in patients with NOMI undergoing surgery. Methods: Thirty-eight consecutive patients who underwent surgery for NOMI at Teine Keijinkai Hospital between 2012 and 2020 were included in the study. Patient information, including age, sex, physical findings, comorbidities, laboratory data, and computed tomography and surgical findings were retrospectively analyzed. Results: Of the 38 patients, 18 (47%) died before discharge. Significant univariate predictors of mortality were a high Sequential Organ Failure Assessment (SOFA) score, high lactate level, low blood pH, and short intestinal length after surgery. In the multivariate analysis, a high SOFA score (odds ratio 1.33, P = 0.036) and short intestine length after surgery (odds ratio 34.7, P = 0.003) were identified as independent risk factors for perioperative mortality. Conclusion: The preoperative SOFA score and postoperative residual intestinal length may be predictors of death in NOMI surgical patients, not age and the content of comorbidities.

Tumor Growth Suppression of Pancreatic Cancer Orthotopic Xenograft Model by CEA-Targeting CAR-T Cells.

Chimeric antigen receptor engineered T cell (CAR-T) therapy has high therapeutic efficacy against blood cancers, but it has not shown satisfactory results in solid tumors. Therefore, we examined the therapeutic effect of CAR-T therapy targeting carcinoembryonic antigen (CEA) in pancreatic adenocarcinoma (PDAC). CEA expression levels on the cell membranes of various PDAC cell lines were evaluated using flow cytometry and the cells were divided into high, medium, and low expression groups. The relationship between CEA expression level and the antitumor effect of anti-CEA-CAR-T was evaluated using a functional assay for various PDAC cell lines; a significant correlation was observed between CEA expression level and the antitumor effect. We created orthotopic PDAC xenograft mouse models and injected with anti-CEA-CAR-T; only the cell line with high CEA expression exhibited a significant therapeutic effect. Thus, the therapeutic effect of CAR-T therapy was related to the target antigen expression level, and the further retrospective analysis of pathological findings from PDAC patients showed a correlation between the intensity of CEA immunostaining and tumor heterogeneity. Therefore, CEA expression levels in biopsies or surgical specimens can be clinically used as biomarkers to select PDAC patients for anti-CAR-T therapy.

PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy: study protocol for the PYNI-GAREREO phase III randomized controlled trial.

BACKGROUND: After esophagectomy for esophageal and esophagogastric cancer, more than half of patients have lost > 10% of their body weight at 12 months. In most cases, the gastric remnant is used for reconstruction after esophagectomy. One of the most serious nutritional complications of this technique is delayed gastric emptying caused by gastric remnant mobilization and denervation of the vagus nerve. The aim of the PYloroplasty versus No Intervention in GAstric REmnant REconstruction after Oesophagectomy (PYNI-GAREREO) trial is to analyze the clinical outcome of modified Horsley pyloroplasty (mH-P) as a method of preventing delayed gastric emptying. METHODS: The PYNI-GAREREO trial is designed as an open randomized, single-center superiority trial. Patients will be randomly allocated to undergo gastric remnant reconstruction with mH-P (intervention group) or no intervention (control group) in parallel groups. All patients with esophageal cancer or esophagogastric cancer planning to undergo curative minimally invasive esophagectomy will be considered for inclusion. A total of 140 patients will be included in the study and randomized between the groups in a 1:1 ratio. The primary outcome is the body weight change at 6 months postoperatively, and the secondary outcomes are the nutritional status, postoperative complications, functional outcome, and quality of life until 1 year postoperatively. DISCUSSION: We hypothesize that mH-P after minimally invasive esophagectomy more effectively maintains patients' nutritional status than no pyloroplasty. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000045104. Registered on 25 August 2021. https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051346 .

Appropriate Lymph Node Dissection Sites for Cancer in the Body and Tail of the Pancreas: A Multicenter Retrospective Study.

Distal pancreatectomy (DP) with lymphadenectomy is the standard surgery for pancreatic body-tail cancer. However, the optimal lymph node (LN) dissection area for DP remains controversial. Thus, we evaluated the frequency and patterns of LN metastasis based on the tumor site. In this multicenter retrospective study, we examined 235 patients who underwent DP for pancreatic cancer. Tumor sites were classified as confined to the pancreatic body (Pb) or pancreatic tail (Pt). The efficacy index (EI) was calculated by multiplying the frequency of metastasis to each LN station by the five-year survival rate of patients with metastasis to that station. LN metastasis occurred in 132/235 (56.2%) of the patients. Patients with Pb tumors showed no metastasis to the splenic hilum LN. Distal splenic artery LNs and anterosuperior/posterior common hepatic artery LNs did not benefit from dissection for Pb and Pt tumors, respectively. In multivariate analysis, splenic artery LN metastasis was identified as an independent predictor of poor overall survival in patients with pancreatic body-tail cancer. In conclusion, differences in metastatic LN sites were evident in pancreatic body-tail cancers confined to the Pb or Pt. Spleen-preserving pancreatectomy might be feasible for Pb cancer.

Carbon dioxide embolism during transanal total mesorectal excision: A hint of prevention from a case report.

Transanal total mesorectal excision is a relatively new approach for treating lower rectal cancer. Carbon dioxide embolism is a critical complication of this procedure. We report the case of a 69-year-old man with lower rectal cancer who underwent transanal total mesorectal excision followed by laparoscopic low anterior resection. He had a sudden intraoperative carbon dioxide embolism during the transanal mesorectal excision. During the ventral dissection of the rectum, end-tidal carbon dioxide and blood oxygen saturation suddenly decreased. We stopped the insufflation of carbon dioxide and suspended the procedure. There was no circulatory collapse, and the vital signs gradually recovered; therefore, we resumed the surgery approximately 30 minutes later and completed it without additional complications. Upon reviewing the video, we found a small injured vein that would aspirate carbon dioxide. These findings suggested that careful hemostasis is essential to prevent carbon dioxide embolus during transanal total mesorectal excision.

Laparoscopic parastomal herniorrhaphy utilizing transversus abdominis release and a modified Sugarbaker technique: A case report.

A 69-year-old woman was referred to our department with complaints of abdominal discomfort in the standing position. She had undergone robot-assisted radical cystectomy and ileal conduit urinary diversion for bladder cancer 10 months earlier. Abdominal CT revealed a parastomal hernia. Laparoscopic parastomal hernia repair using the Pauli technique was performed successfully with no recurrence after a 4-month follow-up. Although there are concerns about potential mesh-related complications and long-term results, this novel approach can be a successful option for parastomal hernia repair. As far as we know, this is the first English-language report on the application of Pauli parastomal hernia repair combined with a pure laparoscopic approach.

Central pancreatic body-preserving pancreatoduodenectomy for pancreatic head cancer following a combined total gastrectomy and distal pancreatectomy: a case report.

BACKGROUND: Following a total pancreatectomy and a total gastrectomy procedure, patients often present with nutritional and diabetes-related disorders, along with a corresponding decrease in their quality of life. Consequently, an appropriate surgical procedure should be selected, with which an R0 resection can be achieved while conserving optimum pancreatic function, in order to prevent adverse sequelae. CASE PRESENTATION: We present a case of a 66-year-old female, with a history of primary gastric cancer, for which, she underwent total gastrectomy combined with a distal pancreatectomy, 21 years ago. She presented to us with a primary cancer of the head of the pancreas. We performed a central pancreatic body-preserving pancreatoduodenectomy, in order to conserve the pancreatic function. Since the splenic artery had already been resected in the earlier surgery, conserving the blood flow to the preserved pancreatic body was an important concern. By utilizing the techniques of preoperative angiography and intraoperative indocyanine green fluorescence imaging, the pancreatic body could be accurately resected while leaving its vascular supply intact and undamaged. Thus, the patient's pancreatic endocrine function could be preserved. CONCLUSIONS: An accurate evaluation of the pancreatic vascular supply enabled the operating surgeon to perform a safe, central pancreatic body-preserving pancreatoduodenectomy, even in patients who have undergone a combined total gastrectomy along with a distal pancreatectomy.

Laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor located in the second portion of the duodenum: A case report.

Gastrointestinal stromal tumors of the duodenum are rare. For benign tumors, premalignant lesions, or malignant potential tumors located in the second portion of the duodenum close to the papilla of Vater, pancreaticoduodenectomy is sometimes performed. A case of laparoscopic segmental duodenectomy for a gastrointestinal stromal tumor at the second portion of the duodenum is reported. The surgical procedure was performed as follows: first, the second portion of the duodenum was separated from the pancreatic head; second, the duodenum was cut off with the linear stapler after having confirmed preservation of the papilla by intraoperative endoscopy; and third, reconstruction was carried out by a side-to-side duodenojejunostomy. Laparoscopic segmental duodenectomy for duodenal gastrointestinal stromal tumors is thought to be advantageous compared with pancreaticoduodenectomy in terms of low burden and organ function preservation. The present procedure is feasible for benign or low-malignant tumors that do not infiltrate outside of the duodenal walls.

Molecular targeting of cell-permeable peptide inhibits pancreatic ductal adenocarcinoma cell proliferation.

BACKGROUND: Chromosome 16 open reading frame 74 (C16orf74) is highly expressed in pancreatic ductal adenocarcinoma (PDAC) and is involved in cancer cell proliferation and invasion through binding to calcineurin (CN). Therefore, C16orf74 is a good target for the development of a PDAC treatment. A cell-permeable dominant-negative (DN) peptide that can inhibit the C16orf74/CN interaction was designed to examine whether this peptide can inhibit PDAC cell proliferation in vitro and in vivo. METHOD: TheDN-C16orf74 peptide, which corresponds to the portion of C16orf74 that interacts with CN, was synthesized, and we assessed its anti-tumor activity in proliferation assays with human PDAC cells and the underlying molecular signaling pathway. Using an orthotopic xenograft model of PDAC, we treated mice intraperitoneally with phosphate-buffered saline (PBS), control peptide, or DN-C16orf74 and analyzed the tumor-suppressive effects. RESULT: DN-C16orf74 inhibited the binding of C16orf74 to CN in an immunoprecipitation assay. DN-C16orf74 suppressed PDAC cell proliferation, and the level of suppression depended on the expression levels of C16orf74 in vitro. DN-C16orf74 also exhibited anti-tumor effects in orthotopic xenograft model. Furthermore, the tumor-suppressive effect was associated with inhibition of the phosphorylation of Akt and mTOR. CONCLUSION: The cell-permeable peptide DN-C16orf74 has a strong anti-tumor effect against PDAC in vitro and in vivo.