Prospective Multicenter Study to Clarify the Frequency of Peristomal Skin Disorders and Appropriate Evaluation Time in Patients with Malignant Rectal Tumors.

OBJECTIVE: This study aimed to understand the effectiveness of regular care in reducing the incidence of severe peristomal skin disorders, as well as to identify their risk factors. SUMMARY BACKGROUND DATA: Peristomal skin disorders occur frequently in outpatient settings and require appropriate intervention. It remains, however, to be demonstrated when the need to follow up these patients decreases and whether assessing severity of peristomal skin disorders is useful. METHODS: This prospective, multicenter, observational cohort study was conducted in six regional high-volume Japanese hospitals. The primary endpoint of the study was the effectiveness of regular follow-up in reducing the incidence of severe peristomal skin disorders via a scoring system at a defined regular outpatient visit. Propensity score matching was performed to compare a control group and patients with severe peristomal skin disorders. RESULTS: In total, 217 patients between December 2019 and December 2021 were enrolled, and 191 patients were analyzed. Multivariate analysis showed that loop stoma (odds ratio [OR], 5.017; 95% confidence interval [CI], 1.350-18.639; P=0.016) and stoma height of <10 mm (OR, 7.831; 95% CI, 1.760-34.838; P=0.007) were independent risk factors for all peristomal skin disorders. After propensity score matching, the incidence of the disorders was not significantly different between the specified evaluation timing and historical control groups (75.7% vs. 77.2%, P=0.775), and the incidence of the severe disorders based on the ABCD and DET scores (5.9% vs. 19.1%, P<0.001 and 1.5% vs. 29.4%, P<0.001, respectively) was significantly lower in the specified evaluation timing group than in the historical control group. CONCLUSION: Regular peristomal skin disease follow-up and scoring, as well as appropriate stoma care at the stoma outpatient visit did not change the frequency of peristomal skin disease, but severe peristomal skin disorders were prevented. Additionally, risk factors for peristomal skin disorders were found to be height <10 mm and loop stoma.

Preoperative risk factors for 90-day postoperative mortality outcome in patients with non-occlusive mesenteric ischemia.

PURPOSE: The mortality rate for non-occlusive mesenteric ischemia remains high even after patients survive the acute postoperative period with tremendous treatment efforts, including emergency surgery, which is challenging. The aim of this study was to explore the preoperative risk factors for 90-day postoperative mortality in patients with non-occlusive mesenteric ischemia. METHODS: This single-center, retrospective cohort study included patients diagnosed with non-occlusive mesenteric ischemia who underwent emergency surgery between August 2014 and January 2023. All patients were divided into survival-to-discharge and mortality outcome groups at the 90-day postoperative follow-up. Preoperative factors, including comorbidities, preoperative status of vital signs and consciousness, blood gas analysis, blood test results, and computed tomography, were compared between the two groups. RESULTS: Twenty patients were eligible, and 90-day mortality was observed in 10 patients (50%). The mortality outcome group had significantly lower HCO3- (20.9 vs. 14.6, p = 0.006) and higher lactate (4.4 vs. 9.4, p = 0.023) levels than did the survival outcome group. The median postoperative time to death was 19 [2-69] days, and five patients (50%) died after postoperative day 30, mainly because hemodialysis was discontinued because of hemodynamic instability in patients requiring hemodialysis. CONCLUSION: Low preoperative HCO3- and high lactate levels may be preoperative risk factors for 90-day postoperative mortality in patients with non-occlusive mesenteric ischemia. However, patients on hemodialysis die from discontinuing hemodialysis even after surviving the acute postoperative phase. Therefore, indications for emergency surgery in patients with risk factors for postoperative mortality should be carefully determined.

Total Superior Mesenteric Artery Nerve Plexus Preservation During Pancreaticoduodenectomy for Pancreatic Cancer.

BACKGROUND: Superior mesenteric artery (SMA) nerve plexus (PLsma) dissection has been performed to achieve R0 resection in pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) in high-volume centers. However, full-extent PLsma preservation in PD is employed in our institution. The feasibility of the PLsma preservation strategy was investigated. METHODS: Between January 2010 and December 2020, 156 patients underwent PLsma preservation PD for PDAC at our institution. Of these, 118 patients had resectable PDAC (R group) and 38 patients had borderline resectable artery (BR-A group). Clinical and oncological outcomes focusing on local recurrence, patient prognoses, and morbidities (including postoperative refractory diarrhea) were retrospectively analyzed and our postoperative outcomes were compared with those of other institutions. RESULTS: Pathological R0 resection by PLsma preservation PD was achieved in 96 R group patients (81.4%) and 27 BR-A group patients (71.1%). The median postoperative hospital stay was 15.0 days in both groups. Local site-only recurrence was observed in 10.2% (12/118) of R-group and 10.5% (4/38) of BR-A-group patients, whereas distant site-only recurrence occurred in 21.2% (25/118) of R-group and 28.9% (11/38) of BR-A-group patients. Median survival times were 64.3 months (R group) and 35.4 months (BR-A group, p = 0.07). Median disease-free survival (DFS) times were 31.0 months (R group) and 12.0 months (BR-A group). No diarrhea requiring opioids was observed in either group. These results were equal or superior to those of PLsma dissection PD in other institutions. CONCLUSIONS: PLsma preservation in PD was feasible compared to PLsma dissection in recurrence and overall survival.

A comparative study of stoma-related complications from diverting loop ileostomy or colostomy after colorectal surgery.

PURPOSE: Even though minor, stoma-related complications significantly impact quality of life, they are often excluded from clinical analyses that compare short-term postoperative outcomes of loop ileostomy and loop colostomy. This study compares stoma-related complications between loop ileostomy and loop colostomy after rectal resection, including minor complications, and discusses the characteristics of diverting stoma types. METHODS: A retrospective review was conducted in patients who underwent diverting stoma construction after rectal resection. Data on patient background and postoperative short-term outcomes, including stoma-related complications and morbidity after stoma closure, were collected and compared between loop ileostomy and loop colostomy groups. Morbidities of all severity grades were targeted for analysis. RESULTS: A total of 47 patients (27 loop ileostomy, 20 loop colostomy) underwent diverting stoma construction following rectal resection. Overall stoma-related complications, incidence of skin irritation, high-output stoma, and outlet obstruction were significantly higher in the loop ileostomy group but high-output stoma and outlet obstruction were absent in the loop colostomy group. Regarding morbidity after stoma closure, operation times and surgical site infections were significantly higher in the loop colostomy group while anastomotic leakage after diverting stoma closure occurred (2 cases; 15%) in the loop colostomy group but not the loop ileostomy group. CONCLUSION: Because stoma-related complications were significantly higher in the loop ileostomy group, and even these minor complications may impair QOL, early loop ileostomy closure is recommended. For loop colostomy, stoma-related morbidities are lower but post-closure leakage is a calculated risk.

Clinical advantage of transmediastinal esophagectomy in terms of postoperative respiratory complications.

BACKGROUND: Although the transmediastinal approach as a radical esophagectomy for esophageal carcinoma patients has attracted attention, its advantages over the transthoracic approach remain unclear. This study aimed to evaluate the efficacy of transmediastinal esophagectomy (TME) in terms of postoperative respiratory complications compared to that of open transthoracic esophagectomy (TTE). METHODS: We reviewed patients with thoracic and abdominal esophageal carcinoma who underwent TME or TTE between February 2014 and November 2021. We compared postoperative respiratory complications as the primary outcome. The secondary outcomes included perioperative operation time, blood loss, postoperative complications, and the number of harvested mediastinal lymph nodes. RESULTS: Overall, 60 and 54 patients underwent TME and TTE, respectively. The baseline characteristics were similar between the two groups, except for age and histological type. There were no intraoperative lethal complications in either group. The incidence of respiratory complications was significantly lower in the TME group than in the TTE group (6.7 vs. 22.2%, p = 0.03). The TME group had a shorter operation time (403 vs. 451 min, p < 0.01), less blood loss (107 vs. 253 mL, p < 0.01), and slightly higher anastomotic leakage (11.7 vs. 5.6%, p = 0.33). The number of harvested lymph nodes was similar in both groups (24 vs. 26, p = 0.10). Multivariate analysis revealed that TME is an independent factor in reducing respiratory complications (odds ratio = 0.27, p = 0.04). CONCLUSIONS: TME for esophageal carcinoma was performed safely. TME was superior to TTE in terms of postoperative respiratory complications; however, the relatively higher frequency of anastomotic leakage should be considered and requires further evaluation.

Prevalence of work-related musculoskeletal disorders among general surgeons in Japan.

PURPOSE: General surgeons are at high risk for work-related musculoskeletal disorders (WRMSDs), especially in their neck and back. The prevalence and risk factors for surgeons' WRMSDs in Japan have not been well surveyed. METHODS: A cross-sectional questionnaire survey on WRMSDs was conducted among general surgeons in Japan. Surgeons were asked about the presence and degree of neck, shoulder, and back disability in relation to open and laparoscopic surgery. RESULTS: The questionnaire was sent to 174 general surgeons in 21 hospitals and 106 (60.9%) responded. The prevalence of WRMSDs in the last month was 65.1%, and the prevalence at least once in a lifetime was 79.2%. The rate of WRMSDs of the neck and back was higher after open surgery (44.3%, 42.5%) than after laparoscopic surgery (28.2%, 31.1%), but there was no marked difference in shoulder pain. Age was the strongest risk factor for WRMSDs, and the pain scores, prevalence of chronic pain, and rate of WRMSD-related absence from work tended to increase with age. CONCLUSION: A questionnaire survey of surgeons in Japan showed that about 80% of surgeons suffer from WRMSDs. Countermeasures for WRMSDs among surgeons are urgently desired to ensure that limited numbers of surgeons work in the operating theatre throughout their career. CLINICAL TRIAL REGISTRATION: Registry name: a survey of surgeons' musculoskeletal pain associated with performing surgery. University of Tsukuba Institutional Review Board registration number: 1519.

Pancreatic juice outflow in pancreatojejunostomy monitoring with the inter-anastomosis drainage tube; a retrospective observational study.

BACKGROUND: Pancreatic fistula remains the biggest problem in pancreatic surgery. We have previously reported a new pancreatojejunostomy method using an inter-anastomosis drainage (IAD) suction tube with Blumgart anastomosis for drainage of the pancreatic juice leaking from the branched pancreatic ducts. This study aimed to evaluate the postoperative outcomes of our novel method, in pancreatojejunostomy and investigate the nature of the inter-anastomosis space between jejunal wall and pancreas parenchyma. METHODS: This retrospectively study consist of 282 pancreatoduodenectomy cases, including 86 reconstructions via the Blumgart method plus IAD (B + IAD group) and 196 cases reconstructed using the Blumgart method alone (B group). Postoperative outcomes and the amylase value and the volume of the drainage fluids were compared between the two groups. The IAD tube was placed to collect amylase-rich fluid from the inter-anastomosis space during operative procedure between the jejunal wall and pancreatic stump. RESULTS: The daily IAD drainage volume and the amylase level was significantly higher in patients with a soft pancreas (vs hard pancreas; 16.5 vs. 10.0 mL/day, p = 0.012; 90,900 vs. 1634 IU/L, p < 0.001, respectively). The mean amylase value of IAD collection in 86 cases of B + IAD group was 63,100 IU/L. The incidence of clinically relevant pancreatic fistula grade B and C (23.2% vs. 23.0%, p = 0.55) and the hospital stay was similar between the groups (median 17 vs. 18 days, p = 0.55). In 176 patients with soft pancreas, the incidence of pancreatic fistula grade B and C (33.3% vs. 35.3%, p = 0.67) and the hospital stay was also similar between the groups (median 22.5 vs. 21 days, p = 0.81). CONCLUSIONS: Positive effect of the IAD method observed in the pilot cases was not reproduced in the current study. IAD tube objectively demonstrated the existence of amylase-rich discharge at the anastomosis site, and countermeasures to eliminate this liquid are highly desired for preventing pancreatic fistula, especially in patients with soft pancreatic texture. Trial registration Retrospectively registered.

Characterization of the Human Intestinal Drug Transport with Ussing Chamber System Incorporating Freshly Isolated Human Jejunum.

Intestinal permeability is a critical factor for orally administered drugs. It can be facilitated by uptake transporters or limited by efflux transporters and metabolic enzymes in the intestine. The present study aimed to characterize the Ussing chamber system incorporating human intestinal tissue as an in vitro model for investigating the impact of intestinal uptake/efflux transporters on the intestinal absorption of substrate drugs in humans. We confirmed the functions of major intestinal uptake/efflux drug transporters in freshly isolated human jejunum sections by demonstrating a significant decrease in the mucosal uptake of cefadroxil (peptide transporter 1) and methotrexate (proton-coupled folate transporter), mucosal-to-serosal permeability of ribavirin (concentrative nucleoside transporters/equilibrative nucleoside transporters), and serosal-to-mucosal permeability of P-glycoprotein and breast cancer resistance protein substrates in the presence of their typical inhibitors. The mucosal-to-serosal apparent permeability coefficients (Papp) of 19 drugs, including substrates of drug transporters and cytochrome P450 3A, ranged from 0.60 × 10-6 to 29 × 10-6 cm/s and showed a good correlation with reported fraction of an oral dose that enters the gut wall and passes into the portal circulation with escaping intestinal metabolism (FaFg) values in humans. Furthermore, the Papp values for cefadroxil, methotrexate, and ribavirin in the presence of the corresponding transporter inhibitors underestimated the FaFg of these drugs, which clearly showed that intestinal uptake transporters facilitate their intestinal absorption in humans. In conclusion, the functions of major intestinal uptake/efflux drug transporters could be maintained in freshly isolated human jejunum sections. The Ussing chamber system incorporating human intestinal tissue would be useful for evaluating the impact of intestinal uptake/efflux transporters on the intestinal absorption of various types of drugs in humans. SIGNIFICANCE STATEMENT: Although previous studies have predicted the intestinal absorption of drugs in humans using the Ussing chamber system incorporating human intestinal tissue, there is little systematic information about drug transport mediated by multiple transporters in this system. We confirmed the functions of major intestinal uptake/efflux transporters in freshly isolated human jejunum sections and demonstrated that the mucosal-to-serosal apparent permeability coefficient of various types of drugs showed a good correlation with reported human FaFg values.

Retrospective analysis of neoadjuvant chemotherapy followed by surgery versus definitive chemoradiotherapy with proton beam for locally advanced esophageal squamous cell carcinoma.

BACKGROUND: This is the first study to compare the long-term outcomes between neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy for locally advanced esophageal squamous cell carcinoma. METHODS: We reviewed patients with clinical stage IB-III esophageal squamous cell carcinoma (UICC 7th edition) who underwent neoadjuvant chemotherapy + surgery or definitive chemoradiotherapy with proton beam therapy (2009-2017). Overall survival, progression-free survival, and recurrence or regrowth rates were compared between the two treatment groups. Subgroup analyses of overall survival according to baseline characteristics were also performed. RESULTS: Forty-three patients received neoadjuvant chemotherapy + surgery (median follow-up 47.4 months) and 60 received definitive chemoradiotherapy with proton beam therapy (median follow-up 51.5 months). Baseline characteristics were similar between the groups except for sex, tumor location, and cT classification. The neoadjuvant chemotherapy + surgery and definitive chemoradiotherapy with proton beam therapy groups had similar 3-year overall survival rates (73.1% and 61.7%, respectively, hazard ratio: 0.88, 95% confidence interval 0.49-1.58, p = 0.66), 3-year progression-free survival rates (46.5% and 45%, respectively, hazard ratio: 1.03, 95% confidence interval 0.62-1.70, p = 0.92), and recurrence or regrowth rates (53.5% vs. 50.0%, p = 0.84). In the subgroup analysis, favorable survival was observed after definitive chemoradiotherapy with proton beam therapy for cT1-2 disease (hazard ratio 2.58, 95% confidence interval 0.84-7.99) and after neoadjuvant chemotherapy + surgery for cT3 or higher disease (hazard ratio 0.32, 95% confidence interval 0.15-0.67, p-for-interaction = 0.002). CONCLUSIONS: Long-term outcomes were comparable between the treatments. The choice of the treatment according to cT classification might affect survival.

Intentional internal drainage tube method for nonlocalized persistent pancreatic leakage: a case report.

BACKGROUND: Persistent pancreatic leakage (PL) due to disconnected pancreatic duct syndrome (DPDS) is associated with severe morbidity and mortality and it usually treated with internal drainage. However, in cases without localized fistula formation, internal drainage is challenging to perform. We report an original one-stage surgical approach for nonlocalized persistent PL, namely, the "intentional internal drainage tube method". CASE PRESENTATION: A 49-year-old woman whose main pancreatic duct was penetrated during endoscopic retrograde cholangiopancreatography experienced severe PL. Peritoneal lavage and a second operation involving central pancreatectomy failed to relieve the symptoms, and nonlocalized PL persisted due to DPDS. Although we attempted a radical resection of the pancreatic remnants as a third strategy, the highly inflamed tissue and massive bleeding prevented the completion of the procedure. We sutured the pancreatic head margin and performed a pancreaticojejunostomy to the distal margin. Because these two cut margins could possibly be the source of the persistent PL, we created a hole at the Roux-en-Y jejunal limb, and a silicone drainage tube was inserted into the peritoneal space via this hole. Postoperatively, we continuously suctioned the intentional internal drainage tube, and the residual PL cavity gradually diminished. Even after removal of the tube, the residual PL drained internally into the jejunum through this hole. CONCLUSIONS: We present this intentional internal drainage tube method as a novel alternative approach for the management of nonlocalized PL consequential of DPDS. Due to the simplicity and minimally invasive nature of this method, we propose this technique may also be used to treat various types of nonlocalized persistent PL or be used prophylactically for central pancreatectomy.

Delayed primary fascia closure of Björck grade 4 open abdomen with enteroatmospheric fistulas after repeated surgery for adhesive small bowel obstruction: a case report.

BACKGROUND: An open abdomen with frozen adherent bowels is classified as grade 4 in Björck's open abdomen classification, and skin grafting after wound granulation is a typical closure option. We achieved delayed primary fascia closure for a patient who developed open abdomen with enteroatmospheric fistulas due to severe adherent small bowel obstruction. We present here the details of his management. CASE PRESENTATION: A 52-year-old man suffered acute abdominal pain during a flight and received an emergency laparotomy due to adhesive small bowel obstruction. Repeated laparotomies were required, and later open abdomen and proximal site jejunostomy were selected. After negative pressure wound therapy, he was transferred to our institution. Two enteroatmospheric fistulas emerged on the exposed intestine, and we diagnosed the condition as a Björck grade 4 open abdomen. After 8 months of wound care and parenteral nutrition, we decided to attempt primary wound closure because the patient required permanent oral restriction and total parenteral nutrition due to short bowel syndrome. A circular incision along the circumference of the exposed bowel allowed us to take a safe approach into the abdominal cavity. We removed the intestinal adhesions completely and resected the bowels, including the fistulas and anastomosed parts. Finally, the abdominal wall defect was reconstructed using the component separation technique, and the patient was discharged without an ostomy. CONCLUSIONS: Primary fascia closure for grade 4 open abdomen is hard, but leaving a long interval before radical surgery and applying pertinent wound management may help solve this adverse situation.

Lectin drug conjugate therapy for colorectal cancer.

Drug resistance represents an obstacle in colorectal cancer (CRC) treatment because of its association with poor prognosis. rBC2LCN is a lectin isolated from Burkholderia that binds cell surface glycans that have fucose moieties. Because fucosylation is enhanced in many types of cancers, this lectin could be an efficient drug carrier if CRC cells specifically present such glycans. Therefore, we examined the therapeutic efficacy and toxicity of lectin drug conjugate therapy in CRC mouse xenograft models. The affinity of rBC2LCN for human CRC cell lines HT-29, LoVo, LS174T, and DLD-1 was assessed in vitro. The cytocidal efficacy of a lectin drug conjugate, rBC2LCN-38 kDa domain of pseudomonas exotoxin A (PE38) was evaluated by MTT assay. The therapeutic effects and toxicity for each CRC cell line-derived mouse xenograft model were compared between the intervention and control groups. LS174T and DLD-1 cell lines showed a strong affinity for rBC2LCN. In the xenograft model, the tumor volume in the rBC2LCN-PE38 group was significantly reduced compared with that using control treatment alone. However, the HT-29 cell line showed weak affinity and poor therapeutic efficacy. No significant toxicities or adverse responses were observed. In conclusion, we demonstrated that rBC2LCN lectin binds CRC cells and that rBC2LCN-PE38 significantly suppresses tumor growth in vivo. In addition, the efficacy of the drug conjugate correlated with its binding affinity for each CRC cell line. These results suggest that lectin drug conjugate therapy has potential as a novel targeted therapy for CRC cell surface glycans.

Real-time automatic surgical phase recognition in laparoscopic sigmoidectomy using the convolutional neural network-based deep learning approach.

BACKGROUND: Automatic surgical workflow recognition is a key component for developing the context-aware computer-assisted surgery (CA-CAS) systems. However, automatic surgical phase recognition focused on colorectal surgery has not been reported. We aimed to develop a deep learning model for automatic surgical phase recognition based on laparoscopic sigmoidectomy (Lap-S) videos, which could be used for real-time phase recognition, and to clarify the accuracies of the automatic surgical phase and action recognitions using visual information. METHODS: The dataset used contained 71 cases of Lap-S. The video data were divided into frame units every 1/30 s as static images. Every Lap-S video was manually divided into 11 surgical phases (Phases 0-10) and manually annotated for each surgical action on every frame. The model was generated based on the training data. Validation of the model was performed on a set of unseen test data. Convolutional neural network (CNN)-based deep learning was also used. RESULTS: The average surgical time was 175 min (± 43 min SD), with the individual surgical phases also showing high variations in the duration between cases. Each surgery started in the first phase (Phase 0) and ended in the last phase (Phase 10), and phase transitions occurred 14 (± 2 SD) times per procedure on an average. The accuracy of the automatic surgical phase recognition was 91.9% and those for the automatic surgical action recognition of extracorporeal action and irrigation were 89.4% and 82.5%, respectively. Moreover, this system could perform real-time automatic surgical phase recognition at 32 fps. CONCLUSIONS: The CNN-based deep learning approach enabled the recognition of surgical phases and actions in 71 Lap-S cases based on manually annotated data. This system could perform automatic surgical phase recognition and automatic target surgical action recognition with high accuracy. Moreover, this study showed the feasibility of real-time automatic surgical phase recognition with high frame rate.

Comparison of 2- and 4-week S-1 administration as adjuvant chemotherapy for advanced gastric cancer.

BACKGROUND: A 4-week administration of tegafur/gimeracil/oteracil (S-1) followed by a 2-week rest is the standard adjuvant chemotherapy for surgically resected advanced gastric cancer. This study aimed to evaluate the oncological feasibility of a 2-week S-1 administration followed by a 1-week rest, which is frequently applied in clinical practice to reduce toxicity and improve drug adherence. METHODS: We retrospectively enrolled patients with stage II/III gastric cancer who received S-1 adjuvant chemotherapy following radical gastrectomy from 2006 to 2016 in three institutions. Two-week and 4-week regimen cohorts were compared for relative dose intensity (RDI) as a primary outcome, and treatment completion rate, adverse event incidence, overall survival (OS), and relapse-free survival (RFS) as secondary outcomes. Confounders were adjusted for using propensity score matching (PSM). RESULTS: One hundred and thirty-four patients received the 2-week regimen and 121 patients received the 4-week regimen. Ninety-five patients were extracted from each group after PSM. The RDIs of S-1 in the 2-week and 4-week cohorts were 73.5 and 69.9%, respectively (p = 0.35), which were not significantly different. The treatment completion rate (54.7 vs. 53.7%, p = 1.0), incidence of grade ≥3 adverse events (7.4 vs. 12.6%, p = 0.33), 3-year OS (76.4 vs. 82.7%, p = 0.78), and 3-year RFS (71.3 vs. 73.4%, p = 0.70) did not significantly differ between both cohorts. CONCLUSIONS: The 2-week S-1 adjuvant chemotherapy could not improve drug adherence in terms of RDI, but its relapse rates were not significantly different compared with those of the 4-week regimen. The 2-week regimen might be considered as an option depending on the patient's status.

Novel Pancreatic Cancer Therapy Targeting Cell Surface Glycans by Liposomes Modified with rBC2LCN Lectin.

INTRODUCTION: Since the outermost layer of cancer cells is covered with various glycans, targeting these groups may serve as an effective strategy in cancer therapy. We previously reported that fucosylated glycans are specifically expressed on pancreatic cancer cells, and that a protein specifically binding to these glycans, namely rBC2LCN lectin, is a potential guiding drug carrier. In the present study, a novel type of glycan-targeting nanoparticle was developed by modifying the surface of doxorubicin-containing liposomes with rBC2LCN lectin. The efficiency and specificity of this formulation, termed Lec-Doxosome, were examined in vitro and in vivo in human pancreatic cancer models. METHODS: Lec-Doxosome was prepared by a post-insertion method based on the insertion of rBC2LCN lectin into the liposomal surface via a lipid linker. The in vitro cellular binding, uptake, and cytotoxicity of Lec-Doxosome were compared with the corresponding parameters in the unmodified liposomes by applying to human pancreatic cancer cell line (Capan-1) with affinity for rBC2LCN lectin. For the in vivo assay, Lec-Doxosome was intravenously injected once per week for a total of 3 weeks into mice bearing subcutaneous tumors. RESULTS: The in vitro application of Lec-Doxosome resulted in a 1.2- to 1.6-fold higher intracellular doxorubicin accumulation and a 1.5-fold stronger cytotoxicity compared with the respective rates of accumulation and cytotoxicity in the unmodified liposomes. In vivo, Lec-Doxosome reduced the mean tumor weight (368 mg) compared with that in mice treated with unmodified liposomes (456 mg), without causing any additional adverse events. CONCLUSION: It was demonstrated from the results obtained herein that rBC2LCN lectin is a potent modifier, as a means for boosting the efficiency of nanoparticles in the targeting of cancer cell surface glycans.

Exploring optimal examination to detect occult anastomotic leakage after rectal resection in patients with diverting stoma.

BACKGROUND: When considering "early stoma closure", both standardized inclusion/exclusion criteria and standardized methods to assess anastomosis are necessary to reduce the risk of occult anastomotic leakage (AL). However, in the immediate postoperative period, neither have the incidence and risk factors of occult AL in patients with diverting stoma (DS) been clarified nor have methods to assess anastomosis been standardized. The aim of this study was to elucidate the incidence and risk factors of occult AL in patients who had undergone rectal resection with DS and to evaluate the significance of computed tomography (CT) following water-soluble contrast enema (CE) to detect occult anastomotic leakage. METHODS: This was a single institutional prospective observational study of patients who had undergone rectal resection with the selective use of DS between May and October 2019. Fifteen patients had undergone CE and CT to assess for AL on postoperative day (POD) 7, and CT was performed just after CE. Univariate analysis was performed to assess the relationship between preoperative variables and the incidence of occult AL on POD 7. RESULTS: The incidence of occult AL on postoperative day 7 was 6 of 15 (40%). Hand-sewn anastomosis, compared with stapled anastomosis, was a significant risk factor. Five more cases with occult AL that could not be detected with CE could be detected on CT following CE; CE alone had a 33% false-negative radiological result rate. CONCLUSIONS: Hand-sewn anastomosis appeared to be a risk factor for occult AL, and CE alone had a high false-negative radiological result rate. When considering the introduction of early stoma closure, stapled anastomosis and CT following CE could be an appropriate inclusion criterion and preoperative examination, respectively.

Surgical resection of hepatic and rectal metastases of pancreatic acinar cell carcinoma (PACC): a case report.

BACKGROUND: Pancreatic acinar cell carcinoma (PACC), a rare variant of pancreatic malignancy, is generally managed the same way as pancreatic ductal adenocarcinoma (PDAC). Surgical resection is the gateway to curing it; however, once it metastasizes (usually to the liver, lungs, lymph nodes, or peritoneal cavity), systemic chemotherapy has been the only option, but with unfavorable results. CASE PRESENTATION: A 67-year-old man with symptoms of loss of appetite and weight underwent surgery for malignancy of the pancreatic tail extending into the entire pancreas. The pathological diagnosis was PACC following total pancreatectomy. Twenty-four months after the pancreatectomy, a solitary liver metastasis was treated by partial hepatectomy, and, subsequently, 4 months later, he presented with melena. Further examination revealed a type-2 rectal tumor. Histological examination following biopsy revealed it to be rectal metastasis of PACC, and it was treated by abdominoperineal resection. Subsequently, the patient did not have tumor recurrence as of 40 months after pancreatectomy. CONCLUSIONS: This is a rare case of PACC presenting with metachronal metastases in the liver and rectum, and we successfully treated them by surgical resections. Since the malignant behavior of PACC is usually less than that of PDAC, surgical resection could be an option even for metastatic lesions when the number and extent of metastases are limited.

Cetuximab delivery and antitumor effects are enhanced by mild hyperthermia in a xenograft mouse model of pancreatic cancer.

Even with current promising antitumor antibodies, their antitumor effects on stroma-rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa-2; moderate, BxPC-3; and abundant, Capan-1 and Ope-xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra-abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa-2 model, moderate (1063) in the BxPC-3 model, and negative in the Capan-1 and Ope-xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8-fold (2980, 3015) in the BxPC-3 model, 2.5- or 4.8-fold (1881, 3615) in the Capan-1 model, and 3.2- or 4.2-fold (1469, 1922) in the Ope-xeno model, respectively. Cetuximab was effective in treating even stroma-rich and k-ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia.

The Tight Adaptation at Pancreatic Anastomosis Without Parenchymal Laceration: An Institutional Experience in Introducing and Modifying the New Procedure.

BACKGROUND: Among the types of pancreatic anastomosis used after pancreatoduodenectomy (PD), Blumgart type reconstruction has rapidly been distributed for its theoretical reasonableness, including secure tight adaptation of jejunal wall and pancreatic parenchyma without cause of parenchymal laceration. The clinical appropriateness of our modified Blumgart method was demonstrated by comparing to that of Kakita method. METHODS: Retrospective analysis of 156 patients underwent elective open PD, reconstructed former 78 patients with the Kakita method, utilizing a full-thickness penetrating suture for tight stump adhesion. The later 78 patients were treated with the modified Blumgart method, which involved clamping the pancreatic parenchymal stump by the jejunal seromuscular layers with horizontal mattress-type penetration sutures. Evaluated variables were the rate of pancreatic fistula (PF) and the length of postoperative hospital stay (POHS). RESULTS: The rate of ISGPF grade B+C PF was 29/78 (37.2%) in the Kakita group and 16/78 (20.5%) in the Blumgart group (P=0.033). The median POHS for the Kakita group was 23 days, whereas that for the Blumgart group was 16 days (P<0.001), one of the shortest value among Japanese high-volume centers. There was no perioperative intensive hemorrhage or deaths in either group. CONCLUSION: A unique concept of Blumgart pancreatic anastomosis, i.e., utilizing the jejunum as an interstitial cushion to prevent pancreatic laceration at the knot site, has become realistic through a simple "one step" modification. This technique, also providing flexible handling space at main pancreatic duct anastomosis, should contribute to the improved PF prevention and shortening the POHS.

Laparoscopic extraction of a symptomatic upper abdominal pedunculated parietal peritoneal lipoma arising intermittent abdominal pain: a case report.

INTRODUCTION: Lipomas arising in the parietal peritoneum are rare, and some of them cause abdominal pain due to torsion of the pedunculated peritoneum. We encountered a case of parietal peritoneal lipoma arising upper peritoneum. In this report, we describe the detail of clinical presentation and discuss its potential pathogenesis and treatment strategy. CASE PRESENTATION: 45 year-old Japanese female patient presented with long-lasting intermittent pain in the left upper abdominal region. Abdominal imaging showed a well-defined fatty mass measuring 40 mm in size, suggesting a parietal peritoneal lipoma. Laparoscopy revealed a tumor with a twisted peduncle; however, no adhesion of the surrounding tissues and ischemic changes were visible. The tumor was easily removed by dissection of the tumor pedicle. CONCLUSION: Parietal peritoneal lipoma often shows pedunculated form and it causes abdominal pain by the torsion of tumor pedicle. Therefore, this type of lipoma should be considered a more aggressive surgery.