High hand grip strength is a significant risk factor and a useful predictor of postoperative pancreatic fistula following pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most critical complications of pancreaticoduodenectomy (PD). Studies on predictive factors for POPF that can be identified preoperatively are limited. Recent reports have highlighted the association between the preoperative nutritional status, including sarcopenia, and postoperative complications. We examined preoperative risk factors for POPF after PD, focusing on nutritional indicators. METHODS: A total of 153 consecutive patients who underwent PD at our institution were enrolled in this study. Preoperative nutritional parameters, including hand grip strength (HGS) and skeletal muscle mass as components of sarcopenia, were incorporated into the analysis. POPFs were categorized according to the International Study Group of Pancreatic Fistula (ISGPF) definition as biochemical (grade A) or clinically relevant (CR-POPF; grades B and C). RESULTS: Thirty-seven of the 153 patients (24.1%) fulfilled the ISGPF definition of CR-POPF postoperatively. In the univariate analysis, the incidence of CR-POPF was associated with male sex, non-pancreatic tumor diseases, a high body mass index, a high HGS and a high skeletal muscle mass index. In the multivariate analysis, non-pancreatic tumor diseases and an HGS ≥23.0 kg were selected as independent risk factors for CR-POPF (P <0.05). CONCLUSIONS: A high HGS, a screening tool for sarcopenia, was a risk factor for CR-POPF. It can accurately serve as a useful predictor of POPF risk in patients undergoing PD. These results highlight the potential of sarcopenia to reduce the incidence of POPF and highlight the need to clarify the mechanism of POPF occurrence.

Machine learning approach to predict postpancreatectomy hemorrhage following pancreaticoduodenectomy: a retrospective study.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is a rare yet dreaded complication following pancreaticoduodenectomy (PD). This retrospective study aimed to explore a machine learning (ML) model for predicting PPH in PD patients. METHODS: A total of 284 patients who underwent open PD at our institute were included in the analysis. To address the issue of imbalanced data, the adaptive synthetic sampling (ADASYN) technique was employed. The best-performing ML model was selected using the PyCaret library in Python and evaluated based on recall, precision, and F1 score metrics. In addition to assessing the model's performance on the test data, bootstrap validation (n = 1000) with the original dataset was conducted. RESULTS: PPH occurred in 11 patients (3.9%), with a median onset time of 22 days postoperatively. These minority cases were oversampled to 85 using ADASYN. The extra trees classifier demonstrated superior performance with recall, precision, and F1 score of 0.967, 0.914, and 0.937, respectively. Both validation using the test data and bootstrap resampling consistently demonstrated recall, precision, and F1 score exceeding 0.9. The model identified the peak value of C-reactive protein during the first 7 postoperative days as the most significant feature, followed by the preoperative neutrophil-to-lymphocyte ratio. CONCLUSIONS: This study highlights the potential of the ML approach to predict PPH occurrence following PD. Vigilance and early interventions guided by such model predictions could positively impact outcomes for high-risk patients.

A Liver-First Approach Using Ablation for Oligometastatic Pancreatic Cancer: A Report of a Successful Case.

Pancreatic cancer (PC) is a highly aggressive malignancy, often accompanied by liver metastases as a common manifestation. While palliative chemotherapy remains the mainstay treatment for liver metastatic PC, local treatment approaches have gained attention, especially for patients with oligometastasis who exhibit a positive response to chemotherapy. This case report illustrates the successful application of a liver-first strategy in a 79-year-old male diagnosed with liver oligometastatic PC, originating in the pancreatic tail. The strategy encompassed percutaneous microwave ablation for liver metastases, followed by FOLFIRINOX (5-fluorouracil, folic acid, irinotecan, and oxaliplatin) chemotherapy, and subsequent primary tumor resection. The patient has remained disease-free for over a year post-surgery. This multidisciplinary approach may hold promise for selected patients with liver oligometastatic PC, although further research and case studies are needed for comprehensive evaluation.

Prognostic value of geriatric nutritional risk index for patients with biliary tract cancer undergoing surgical resection - a single-institution retrospective cohort study.

Introduction: The geriatric nutritional risk index (GNRI) is an index of nutritional status associated with clinical outcomes in various cancers; however, its prognostic value in biliary tract cancer (BTC) remains to be elucidated. This retrospective study aimed to investigate the association between preoperative GNRI and long-term prognosis of patients with BTC undergoing surgical resection. Material and methods: A total of 213 patients were included. The relationships between GNRI and clinicopathological variables, including inflammatory markers such as C-reactive protein (CRP) and neutrophil-to-lympho-cyte ratio, were analysed. The impact of GNRI on overall survival (OS) and relapse-free survival (RFS) was investigated by Kaplan-Meier curves and Cox proportional hazards models. Results: Applying a GNRI cut-off of 98, the low-GNRI group comprised 135 patients (63%). The low-GNRI group had elevated carbohydrate antigen 19-9 and CRP levels, high rates of preoperative biliary stenting, lymph node metastases, and perineural invasion, and a lower rate of R0 resection than the high-GNRI group. Both OS and RFS in the low-GNRI group were significantly lower. In multivariate analysis, low GNRI was a significant predictor of poor OS (hazard ratio [HR], 1.731; 95% CI: 1.111-2.696; p = 0.015) and RFS (HR, 1.900; 95% CI: 1.231-2.931; p = 0.004), independently of inflammatory and tumour markers, as well as of pathological features. Conclusions: Preoperative GNRI may be an easily accessible predictor of poor prognosis in patients with BTC undergoing surgical resection.

Perioperative Fluid Balance and the Risk of Postoperative Pancreatic Fistula After Pancreaticoduodenectomy: A Propensity Score-adjusted Analysis.

BACKGROUND/AIM: The impact of perioperative fluid management on postoperative morbidity after pancreaticoduodenectomy (PD) remains uncertain. This study aimed to investigate the independent association between perioperative fluid balance (FB) and clinically relevant postoperative pancreatic fistula (POPF) in PD patients. PATIENTS AND METHODS: A total of 243 consecutive open PD patients were included. Intra- and postoperative FB until postoperative day 3 were calculated, and their predictive performance for POPF was assessed using receiver operating characteristic (ROC) analysis. Propensity score (PS) was estimated as the probability of having higher FB, and factors associated with POPF were identified using crude and PS-adjusted logistic regression models. RESULTS: POPF occurred in 60 patients (24.7%). ROC analysis showed the highest predictive value for total FB on postoperative days 1 and 2, with a cut-off value of 1,585 ml (area under the ROC curve=0.74). Patients with FB ≥1,585 ml had a significantly higher POPF rate (48.3%) compared to those with lower FB (11.0%, PS-adjusted p<0.001). Male sex, body mass index ≥25 kg/m2, non-pancreatic ductal adenocarcinoma, biliary drainage, main pancreatic duct diameter <3 mm, and higher FB showed significant associations with POPF in crude univariate analysis. Higher FB remained a significant factor in both crude multivariate and PS-adjusted analysis [crude multivariate: odds ratio (OR)=8.0; PS-adjusted univariate: OR=4.2; PS-adjusted multivariate: OR=6.1, all p<0.001]. CONCLUSION: Higher early postoperative FB, a potentially modifiable factor, may be independently associated with increased risk of POPF in PD patients.

S100A8/A9 Induced by Interaction with Macrophages in Esophageal Squamous Cell Carcinoma Promotes the Migration and Invasion of Cancer Cells via Akt and p38 MAPK Pathways.

Tumor-associated macrophages are associated with more malignant phenotypes of esophageal squamous cell carcinoma (ESCC) cells. Previously, an indirect co-culture assay of ESCC cells and macrophages was used to identify several factors associated with ESCC progression. Herein, a direct co-culture assay of ESCC cells and macrophages was established, which more closely simulated the actual cancer microenvironment. Direct co-cultured ESCC cells had significantly increased migration and invasion abilities, and phosphorylation levels of Akt and p38 mitogen-activated protein kinase (MAPK) compared with monocultured ESCC cells. According to a cDNA microarray analysis between monocultured and co-cultured ESCC cells, both the expression and release of S100 calcium binding protein A8 and A9 (S100A8 and S100A9), which commonly exist and function as a heterodimer (herein, S100A8/A9), were significantly enhanced in co-cultured ESCC cells. The addition of recombinant human S100A8/A9 protein induced migration and invasion of ESCC cells via Akt and p38 MAPK signaling. Both S100A8 and S100A9 silencing suppressed migration, invasion, and phosphorylation of Akt and p38 MAPK in co-cultured ESCC cells. Moreover, ESCC patients with high S100A8/A9 expression exhibited significantly shorter disease-free survival (P = 0.005) and cause-specific survival (P = 0.038). These results suggest that S100A8/A9 expression and release in ESCC cells are enhanced by direct co-culture with macrophages and that S100A8/A9 promotes ESCC progression via Akt and p38 MAPK signaling pathways.

[Two Cases of Elderly Patients with Giant Intrahepatic Cholangiocarcinoma Treated with Multidisciplinary Therapy including Ablation Therapy].

Case 1 consisted of an 86-year-old male diagnosed with intrahepatic cholangiocarcinoma(ICC), approximately 11 cm in diameter, at segment S7/8 of the liver. A total of 4 percutaneous radiofrequency ablations(PRFA)and 3 hepatic arterial infusion chemotherapies(HAIC)of 5-FU were performed. He died after developing lung metastases 27 months after the initial treatment. Case 2 was an 85-year-old female diagnosed with ICC, 8 cm in diameter, at the posterior segment of the liver, with lymph node metastasis. She underwent HAIC of 5-FU and S-1 as well as gemcitabine-based systemic chemotherapy. The main tumor developed 10 months after the initial treatment, and PRFAs were subsequently performed twice for the main lesion. Although the tumor markers gradually decreased, she died of jaundice 33 months after the initial treatment. As one of the multidisciplinary therapies for the giant ICC, ablation therapy may be safe and effective in elderly patients.

[Clinical Study of Peritoneovenous Shunt for Patients with Refractory Ascites Accompanied with Hepatocellular Carcinoma].

BACKGROUND: Hepatic ascites may cause a variety of symptoms and may progress deterioration of quality of life. Peritoneovenous shunt(PV shunt)is technically feasible and useful for the treating of refractory ascites, but sometimes it can be associated with fatal complications. This retrospective study aimed to investigate the effect of PV shunt for patients with refractory ascites, including hepatocellular carcinoma(HCC)patients. SUBJECTS: Between January 2010 and December 2021, we retrospectively analyzed 54 consecutive patients(including 35 HCC patients)with refractory ascites who underwent PV shunt at our institute. RESULTS: Body weight loss after surgery was observed in 39 of the 54 cases, and eGFR improved in 34 cases. There were 17(31.5%)in-hospital deaths. Cases with present of portal vein tumor thrombus, Child-Pugh classification C, ALBI score≥-1.12, or serum total bilirubin≥1.7 mg/dL were significantly higher in hospital-death group than in the discharged from the hospital group. CONCLUSIONS: PV shunt for HCC patients with refractory ascites may be effective for improvement of renal function and symptoms. However, indications for PV shunt should be carefully considered for high-risk patients with adequate preoperative evaluation.

[A Case of Long-Term Survival with S-1/Cisplatin for Liver Hilum Lymph Node Metastasis of Anal Canal Squamous Cell Carcinoma after Chemoradiotherapy].

A 70-year-old woman was admitted to a local hospital because of anal pain during defecation. Anoscopy revealed an anal mass lesion, and the patient was referred to our hospital. Colonoscopy revealed an anal canal tumor with ulceration, and biopsy showed squamous cell carcinoma. The patient was treated with chemoradiotherapy(chemotherapy with capecitabine plus mitomycin C and 54 Gy radiation in the anal region)and achieved complete response. However, metastatic recurrence was detected in a lymph node in the hepatic hilar region. We administered an S-1/CDDP combination chemotherapy (5 courses). For 3 years and 5 months since the initial treatment, the patient survived with no signs of recurrence. We report a rare case of long-term survival with S-1/CDDP for distant metastasis of anal canal squamous cell carcinoma after chemoradiotherapy.

[Clinical Efficacy of Recombinant Human Thrombomodulin for Surgical Patients with Disseminated Intravascular Coagulation Associated with Oncologic Emergency].

AIM: We evaluated the clinical efficacy of recombinant human thrombomodulin(rTM)for surgical patients with disseminated intravascular coagulation syndrome(DIC)associated with an oncologic emergency(OE). SUBJECTS AND METHODS: Thirteen patients who underwent surgery for OE complicated with DIC and were treated with rTM in our institution were evaluated. We retrospectively analyzed the clinical changes of parameters in white blood cell count(WBC), platelet count, CRP, PT-INR and DIC scores after the rTM treatment. RESULTS: The average length of the days using rTM was 4.7 for 12 patients, excluding one who died within 30 days after surgery. Nine of 12 patients(75%)had DIC scores of less than 3 after the rTM treatment. WBC tended to decrease after the rTM treatment, without statistical difference. However, CRP, platelet count, PT-INR and DIC scores were significantly improved after the rTM treatment(p<0.05). CONCLUSIONS: rTM may be useful in the treatment of DIC for surgical OE patients.

[A Rapid Clinical Course of Pulmonary Embolism Associated with Gallbladder Mucinous Carcinoma].

A 51-year-old woman with edema of the lower extremities and exertional dyspnea was admitted to our hospital. Enhanced CT revealed thrombi of the pulmonary artery and a gallbladder tumor. After anticoagulation therapy was started on her, anemia and jaundice progressed; thus, endoscopic retrograde cholangiopancreatography(ERCP)was performed on suspicion of bleeding from a gallbladder tumor. We performed cholecystectomy in emergency to control the anemia due to hemorrhage. Oxygenation suddenly worsened intraoperatively, maintaining her blood pressure became difficult, and the patient decompensated. The histopathological diagnosis was gallbladder mucinous carcinoma with severe lymphatic invasion. Although an autopsy was not performed, pulmonary artery embolism derived from a tumor embolus was the suspected cause of the sudden change of the clinical course.

Chemokine (C-C Motif) Ligand 1 Derived from Tumor-Associated Macrophages Contributes to Esophageal Squamous Cell Carcinoma Progression via CCR8-Mediated Akt/Proline-Rich Akt Substrate of 40 kDa/Mammalian Target of Rapamycin Pathway.

Tumor-associated macrophages (TAMs) promote tumor progression. The number of infiltrating TAMs is associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) patients; however, the mechanism underlying this phenomenon is unclear. cDNA microarray analysis indicates that the expression of chemokine (C-C motif) ligand 1 (CCL1) is up-regulated in peripheral blood monocyte-derived macrophages stimulated using conditioned media from ESCC cells (TAM-like macrophages). Here, we evaluated the role of CCL1 in ESCC progression. CCL1 was overexpressed in TAM-like macrophages, and CCR8, a CCL1 receptor, was expressed on ESCC cell surface. TAM-like macrophages significantly enhanced the motility of ESCC cells, and neutralizing antibodies against CCL1 or CCR8 suppressed this increased motility. Recombinant human CCL1 promoted ESCC cell motility via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway. Phosphatidylinositol 3-kinase or Akt inhibitors, CCR8 silencing, and neutralizing antibody against CCR8 could significantly suppress these effects. The overexpression of CCL1 in stromal cells or CCR8 in ESCC cells was significantly associated with poor overall survival (P = 0.002 or P = 0.009, respectively) and disease-free survival (P = 0.009 or P = 0.047, respectively) in patients with ESCC. These results indicate that the interaction between stromal CCL1 and CCR8 on cancer cells promotes ESCC progression via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway, thereby providing novel therapeutic targets.

PAI-1 derived from cancer-associated fibroblasts in esophageal squamous cell carcinoma promotes the invasion of cancer cells and the migration of macrophages.

Cancer-associated fibroblasts (CAFs) contribute to the progression of various cancers. Previously, we reported the significance of CAFs in esophageal squamous cell carcinoma (ESCC); however, the functions of CAFs in the ESCC microenvironment remain unknown. To investigate CAFs' function, we established an indirect coculture assay between human bone marrow-derived mesenchymal stem cells (MSCs) and ESCC cells. Cocultured MSCs expressed more fibroblast activation protein, one of the markers of CAFs, compared with monocultured MSCs. Therefore, we defined cocultured MSCs as CAF-like cells. To identify molecules associated with the ESCC progression in CAFs, we conducted a cDNA microarray analysis on monocultured MSCs and CAF-like cells to compare their gene expression profiles. We found that SERPINE1, which encodes plasminogen activator inhibitor-1 (PAI-1), was more abundant in CAF-like cells than in monocultured MSCs, and the PAI-1 derived from CAF-like cells induced the abilities of migration and invasion in both ESCC cells and macrophages by the Akt and Erk1/2 signaling pathways via the low-density lipoprotein receptor-related protein 1 (LRP1), which is a PAI-1 receptor. Based on immunohistochemistry assays of ESCC tissues, higher expression levels of PAI-1 and LRP1 were correlated with poor prognosis in ESCC patients. These results suggest that the PAI-1/LRP1 axis contributes to the progression of ESCC, making it a potential target for ESCC therapy.

Clinical outcomes of transanal total mesorectal excision using a lateral-first approach for low rectal cancer: a propensity score matching analysis.

BACKGROUND: Although transanal total mesorectal excision (ta-TME) is adopted for rectal cancer surgery by an increasing number of surgeons, it is still technically challenging. We have employed a lateral-first approach for ta-TME to overcome technical difficulties. However, its outcomes and advantage over conventional laparoscopic TME remain unclear. METHODS: Thirty-five consecutive patients who underwent ta-TME using a lateral-first approach (the ta-TME group) and 53 consecutive patients who underwent conventional laparoscopic TME (the lap-TME group) for low rectal cancer were included. Propensity score matching (PSM) was used to create balanced cohorts of ta-TME (n = 28) and lap-TME (n = 28). Their clinical outcomes were compared after PSM. RESULTS: The operative time and intraoperative blood loss were significantly lower in the ta-TME group than in the lap-TME group (P = 0.042 and P < 0.001, respectively). Postoperative complications ≥ Clavien-Dindo grade II were significantly less and postoperative hospital stay was significantly shorter in the ta-TME group (35.7% vs. 78.6%, P = 0.003, and 18 days vs. 32 days, P < 0.001, respectively). The distal margin was significantly larger in the ta-TME when excluding the abdominoperineal resection cases (20 mm vs. 10 mm, P = 0.032). The positive radial margin was observed in 2 of 28 patients (7.1%) in the ta-TME group. CONCLUSIONS: Ta-TME using a lateral-first approach is feasible and may offer several advantages over lap-TME in terms of short-term outcomes. It might be an alternative safe approach for ta-TME. To confirm the oncological superiority of this surgery, further study in a larger population and for a longer follow-up period is warranted.

Outcomes of Laparoscopic Surgery in Colorectal Cancer Patients With Dialysis.

BACKGROUND/AIM: To investigate the outcomes of laparoscopic surgery in colorectal cancer patients with dialysis. PATIENTS AND METHODS: Fourteen dialysis (dialysis group) and 567 non-dialysis (non-dialysis group) patients who underwent laparoscopic and open surgery for colorectal cancer between April 2008 and December 2015 were included. Short-term and long-term outcomes were compared between the groups. A 1:2 propensity score matching was performed to compare long-term outcomes. RESULTS: All the dialysis patients underwent laparoscopic surgery. There were no significant differences in operative outcomes and postoperative short-term outcomes between the two groups. In the whole cohort, overall survival of dialysis patients was shorter than that in the non-dialysis ones (p=0.020), while disease-free survival did not differ between the two groups. After matching, there was no significant difference between the groups in overall or disease-free survival. CONCLUSION: Laparoscopic colorectal cancer surgery for dialysis patients seems safe and feasible and associates with comparable short-term outcome and recurrence rate to non-dialysis patients.

[A Case of Recurrent Colorectal Cancer with Bilateral Ovarian Metastases That Were Reduced with Regorafenib Therapy].

A 63-year-old woman had recurrences of metastatic rectal cancer in the lung, peritoneum, and ovary. Regorafenib was administered at 160mg/day as third-line chemotherapy. The patient developed Grade(Gr)3 hand-foot syndrome(HFS) and Gr 2 rash, but the abdominal distension and pain were relieved by the 1st course. Analgesics could be reduced and regorafenib was administrated at reduced dosage. The patient received keishi-bukuryo-gan(EK-25)and sai-rei-tou(TJ-114) for HFS. At the beginning of therapy, ovarian metastases were not reduced and showed poor contrast enhancement on CT. Serum levels of lactate dehydrogenase(LDH)and tumor markers were increased. During the 4th course of therapy, ovarian metastases tended to shrink and serum levels of LDH and tumor markers were decreased. Ovarian metastases showed a partial response(PR)after the 6th course. Lung metastases showed a progressive disease during the 2nd course, but a PR after the 3rd course, and were not apparent after the 6th course. Reduction of metastases was maintained at 16 months after the start of therapy, and HFS was assessed at Gr 2 or lower. Physical, laboratory, and imaging findings should be carefully evaluated prior to long-term administration of regorafenib.

[Surgical Dissection for an Abdominal Para-Aortic Lymph Node Recurrence after Curative Resection for Early Gastric Cancer - Report of a Case].

A 72-year-old man underwent endoscopic submucosal dissection for early gastric cancer at antrum in July 2015. The histopathological examination revealed an adenocarcinoma invading the deep submucosal layer(SM2)with lymphatic invasion, consistent with the diagnosis of non-curative resection. Additional surgery was recommended, and he underwent laparoscopic distal gastrectomy in August 2015. The histopathological examination of resected specimen revealed there were no lymph node metastases, and postoperative diagnosis was Stage I A. However, 8 months after the surgery, abdominal enhanced computed tomography(CT)revealed an enlargement of para-aortic lymph node. Positron emission tomography-CT showed high accumulation at the enlarged lymph node. A para-aortic lymph node metastasis was suspected, and laparoscopic lymph node dissection was performed in July 2016. The histopathological examination revealed lymph node metastasis of gastric cancer. He was given systematic chemotherapy using S-1 plus cisplatin after the surgery, and has been followed-up without recurrences for 21 months after the first operation. Although recurrence of the para-aortic lymph nodes was assumed as part of a systemic metastasis, some population certainly benefit from multidisciplinary treatment including surgical approach.

[A case with multiple liver metastases from rectal cancer responding completely to FOLFOX for a long duration without exacerbation of peripheral neuropathy].

A 61-year-old man had undergone five courses of modified FOLFOX6(mFOLFOX6)chemotherapy with calcium-magnesium(Ca/Mg)infusion for a rectal cancer with multiple liver metastases from October 2008. After this treatment, the primary rectal tumor and metastatic tumors were considered as a partial response(PR), and lower anterior resection was carried out in February 2009. After the operation, mFOLFOX6 chemotherapy with bevacizumab was started in March 2009. After 15 courses of chemotherapy, the patient received 7. 5 g of gosha-jinki-gan(TJ-107)daily from August 2009, and the drug compliance was 69%. From the 18th course of chemotherapy in October 2009, glutathione(GSH)was given at a dose of 200 mg before each oxaliplatin administration. From the 35th course of chemotherapy in November 2010, the patient received 1. 5 g of powdered processed aconite root(TJ-3027)daily. TJ-3027 administration was escalated to 4. 5 g daily, and drug compliance was 73%. Grade 4 neutropenia was observed in December 2010, and we reduced oxaliplatin to 65 mg/m(2) from the 37th course. Fifty chemotherapy courses were administered until October 2011. The patient received a total 3, 970 mg/m(2) of oxaliplatin, however, the neurotoxicity level of the patient remained at grade 2. Ca/Mg infusion and TJ-107 administration have been reported not to reduce the activity of FOLFOX individually, and severe side effects are rare. So one must consider the combination treatment of Ca/Mg and TJ-107 for prevention of oxaliplatin-related neurotoxicity.