Scoring system to predict positive peritoneal cytology in patients with resectable and borderline resectable pancreatic cancer.

BACKGROUND: The aim of this study was to evaluate factors to predict positive peritoneal cytology, whcih would determine the indication for staging laparoscopy in pancreatic cancer. METHODS: A total of 430 patients that underwent pancreatectomy for resectable and borderline resectable pancreatic cancer were retrospectively reviewed. RESULTS: Among 430 patients, 36 had positive cytology (8.4%). Median survival time in negative cytology was 24.7 months, compared with 15.1 months in positive cytology (p = .004). Factors to predict positive cytology in pancreatic cancer according to multivariate analysis were tumor location (body, tail; OR 2.66; 95% CI: 1.21-5.85; p = .015), tumor size ≥30 mm (OR 2.95; 95% CI: 1.35-6.47; p = .007) and radiographic other-organ invasion (HR 2.79; 95% CI: 1.01-7.67; p = .047). Patients were scored 0 to 3 corresponding with these factors. Rates of positive cytology increases in each score were: score 0: 2.9%, score 1: 6.7%, score 2: 18.3%, score 3: 36.8%. CONCLUSIONS: Tumor location (body or tail), tumor size ≥30 mm, and radiographic other-organ invasions were risk factors for positive cytology in pancreatic cancer. This scoring system might be a useful indicator to perform staging laparoscopy to diagnose positive cytology.

Laparoscopic Radical Total Gastrectomy and Pancreatosplenectomy for Synchronous Cancer of the Stomach and Pancreas.

The safety of laparoscopic surgery for advanced gastric and pancreatic cancers has been established individually, but there is little evidence for synchronous cancers. In this case, a 59-year-old man with a history of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) treatment for diffuse large B-cell lymphoma underwent laparoscopic surgery for a suspected pancreatic invasion of advanced gastric cancer. Pathology revealed double cancer of the stomach and pancreas. Laparoscopic total gastrectomy and distal pancreatectomy were successfully performed. The patient had a pancreatic leak on postoperative day seven but was discharged from the hospital on postoperative day 21. This case suggests the possibility of expanding the indications for laparoscopic surgery for similar cancers in the future. Additionally, the anatomical reticulum can be resected as a single mass using laparoscopy alone.

Successful Robot-Assisted Surgery for Advanced Metachronous Cancer in a Gastric Conduit after Esophagectomy: A Case Report.

The incidence of gastric tube cancers has increased due to improved survival rates in patients after esophagectomy. However, the optimal surgical approach for gastric tube cancer remains controversial. Here, we report the case of a 70-year-old man with advanced gastric cancer arising from a retrosternally placed gastric conduit, 12 years after thoracic esophagectomy for esophageal cancer. Total resection of the gastric conduit was performed with robotic assistance. Although the working space was limited, secure resection was possible. Continuous en bloc mobilization was achieved with neck dissection, and reconstruction was performed via the same retrosternal route using the ileocolon. The patient was discharged on the 14th postoperative day without any adverse events. Robot-assisted surgery can overcome the technical limitations of laparoscopic mediastinal surgery and has advantages such as improved ergonomics, comfort, and elimination of hand tremors, and therefore may be an option for future minimally invasive surgeries.

Internal Hernia Through a Mesenteric Defect Following Esophagectomy and Reconstruction With a Stomach-Preserved Ileocolic Interposition.

Esophagectomy is the standard treatment for esophageal cancer and often involves the stomach as a substitute organ for esophageal reconstruction. However, we actively perform stomach-preserved ileocolic interposition because of its advantages in gastrointestinal function and the prevention of reflux esophagitis. Despite its benefits, few facilities perform esophageal reconstruction with ileocolic interposition; hence, postoperative complications following this procedure have rarely been reported. We present the first case of internal hernia through a mesenteric defect following esophagectomy and reconstruction with a stomach-preserved ileocolic interposition. This type of internal hernia after esophageal cancer surgery is a rare complication following a common gastric pull-up reconstruction. A 66-year-old Japanese female underwent esophagectomy and reconstruction with stomach-preserved ileocolic interposition for stage I esophageal cancer. One month after surgery, the patient experienced abdominal pain and vomiting. CT showed a dilated small bowel and a suspected postoperative adhesive bowel obstruction. Despite conservative management, the patient experienced recurrent episodes that required hospitalization. Although an exact preoperative diagnosis was not made, we decided on a surgical exploration six months after the first symptoms appeared. Laparotomy revealed an internal herniation through a mesenteric defect between the transverse mesocolon and the ileum mesentery following ileocolic interposition. We then repositioned the fitted small intestine and closed the mesenteric defects. The patient recovered uneventfully without a hernia recurrence. Minimally invasive techniques for treating esophageal cancer are becoming more common. As survival rates improve, the number of internal hernia cases, such as those described in this report, will likely increase. Therefore, more cases are needed to determine whether closing mesenteric defects can effectively prevent herniation. However, immediate surgical treatment should be considered based on the symptoms, even when a preoperative diagnosis is difficult.

Explainable artificial intelligence prediction-based model in laparoscopic liver surgery for segments 7 and 8: an international multicenter study.

BACKGROUND: Artificial intelligence (AI) is becoming more useful as a decision-making and outcomes predictor tool. We have developed AI models to predict surgical complexity and the postoperative course in laparoscopic liver surgery for segments 7 and 8. METHODS: We included patients with lesions located in segments 7 and 8 operated by minimally invasive liver surgery from an international multi-institutional database. We have employed AI models to predict surgical complexity and postoperative outcomes. Furthermore, we have applied SHapley Additive exPlanations (SHAP) to make the AI models interpretable. Finally, we analyzed the surgeries not converted to open versus those converted to open. RESULTS: Overall, 585 patients and 22 variables were included. Multi-layer Perceptron (MLP) showed the highest performance for predicting surgery complexity and Random Forest (RF) for predicting postoperative outcomes. SHAP detected that MLP and RF gave the highest relevance to the variables "resection type" and "largest tumor size" for predicting surgery complexity and postoperative outcomes. In addition, we explored between surgeries converted to open and non-converted, finding statistically significant differences in the variables "tumor location," "blood loss," "complications," and "operation time." CONCLUSION: We have observed how the application of SHAP allows us to understand the predictions of AI models in surgical complexity and the postoperative outcomes of laparoscopic liver surgery in segments 7 and 8.

Short-term serial circulating tumor DNA assessment predicts therapeutic efficacy for patients with advanced pancreatic cancer.

PURPOSE: We investigated the potential clinical utility of short-term serial KRAS-mutated circulating cell-free tumor DNA (ctDNA) assessment for predicting therapeutic response in patients undergoing first-line chemotherapy for advanced pancreatic cancer. METHODS: We collected 144 blood samples from 18 patients with locally advanced or metastatic cancer that were undergoing initial first-line chemotherapy of gemcitabine plus nab-paclitaxel (GEM plus nab-PTX). Analysis of KRAS-mutated ctDNA was quantified by digital droplet polymerase chain reaction (ddPCR) as mutant allele frequency (MAF). This study investigated pretreatment KRAS-mutated ctDNA status and ctDNA kinetics every few days (days 1, 3, 5 and 7) after initiation of chemotherapy and their potential as predictive indicators. RESULTS: Of the 18 enrolled patients, an increase in KRAS-mutated ctDNA MAF values from day 0-7 after initiation of chemotherapy was significantly associated with disease progression (P < 0.001). Meanwhile, positive pretreatment ctDNA status (MAF ≥ 0.02%) (P = 0.585) and carbohydrate antigen 19-9 (CA19-9) values above the median (P = 0.266) were not associated with disease progression. In univariate analysis, this short-term increase in ctDNA MAF values (day 0-7) was found to be associated with significantly shorter progression free survival (PFS) (hazard ration [HR], 24.234; range, (2.761-212.686); P = 0.0002). CONCLUSION: This short-term ctDNA kinetics assessment may provide predictive information to reflect real-time therapeutic response and lead to effective refinement of regimen in patients with advanced pancreatic cancer undergoing systemic chemotherapy.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Histone methyltransferase SUV420H1/KMT5B contributes to poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high rate of recurrence and poor prognosis, even after curative surgery. Multikinase inhibitors have been applied for HCC patients, but their effect has been restricted. This study aims to clarify the clinical impact of SUV420H1/KMT5B, one of the methyltransferases for histone H4 at lysine 20, and elucidate the novel mechanisms of HCC progression. We retrospectively investigated SUV420H1 expression using HCC clinical tissue samples employing immunohistochemical analysis (n = 350). We then performed loss-of-function analysis of SUV420H1 with cell cycle analysis, migration assay, invasion assay and RNA sequence for Gene Ontology (GO) pathway analysis in vitro, and animal experiments with xenograft mice in vivo. The SUV420H1-high-score group (n = 154) had significantly poorer prognosis for both 5-year overall and 2-year/5-year disease-free survival than the SUV420H1-low-score group (n = 196) (p < 0.001 and p < 0.05, respectively). The SUV420H1-high-score group had pathologically larger tumor size, more tumors, poorer differentiation, and more positive vascular invasion than the SUV420H1-low-score group. Multivariate analysis demonstrated that SUV420H1 high score was the poorest independent factor for overall survival. SUV420H1 knockdown could suppress cell cycle from G1 to S phase and cell invasion. GO pathway analysis showed that SUV420H1 contributed to cell proliferation, cell invasion, and/or metastasis. Overexpression of SUV420H1 clinically contributed to poor prognosis in HCC, and the inhibition of SUV420H1 could repress tumor progression and invasion both in vitro and in vivo; thus, further analyses of SUV420H1 are necessary for the discovery of future molecularly targeted drugs.

Laparoscopic anatomical resection of segment II: left lateral section-flip up method to safely and effectively encircle the Glissonean branch and expose the left hepatic vein (with video).

Laparoscopic anatomical resection of liver segment II (S2 segmentectomy) using left lateral section-flip up method is introduced to safely and effectively encircle the Glissonean branch of segment II (G2) and to expose the left hepatic vein (LHV). The left lateral section is completely mobilized and then flipped up. After encircling and clamping the G2 root, indocyanine green is intravenously injected and the demarcation line is clearly confirmed by near infrared fluorescence imaging. After exposure of the LHV from the root to this intersegmental plane between segments II/III, residual parenchymal resection is performed using the clamp crushing method. There are two difficulties concerning S2 segmentectomy. The first is encirclement of the G2 root without interfering with the G3. Compared with the conventional front view of the umbilical portion, the view behind the left lateral section contribute to easy confirmation and direct encircle of the G2 root without dividing the G3 and injuring LHV on the same plane. The second difficulty is that the boundary of the visible liver surface between segments II/III does not match the direction of the LHV. This can cause confusion to the operator aiming to perform precise inner parenchymal resection. Our procedure allows easy access to the LHV root and exposure of the peripheral directing hepatic vein. Hepatic vein-guided approaches will likely be helpful in precise performance of inner parts of liver resection.

Laparoscopic and open minor liver resection for hepatocellular carcinoma with clinically significant portal hypertension: a multicenter study using inverse probability weighting approach.

BACKGROUND: Liver resection offers substantial advantages over open liver resection (OLR) for patients with hepatocellular carcinoma (HCC) in terms of reduced intraoperative blood loss and morbidity. However, there is limited evidence comparing the indications and perioperative outcomes with the open versus laparoscopic approach for resection. This study aimed to compare postoperative outcomes between patients undergoing laparoscopic liver resection (LLR) and OLR for HCC with clinically significant portal hypertension (CSPH). METHODS: A total of 316 HCC patients with CSPH (the presence of gastroesophageal varices or platelet count < 100,000/ml and spleen diameter > 12 cm) undergoing minor liver resection at eight centers were included in this study. To adjust for confounding factors between the LLR and OLR groups, an inverse probability weighting method analysis was performed. RESULTS: Overall, 193 patients underwent LLR and 123 underwent OLR. After weighting, LLR was associated with a lower volume of intraoperative blood loss and the incidence of postoperative complications (including pulmonary complications, incisional surgical site infection, and paralytic ileus) compared to the OLR group. The 3-, 5-, and 7-year postoperative recurrence-free survival rates were 39%, 26%, and 22% in the LLR group and 49%, 18%, and 18% in the OLR group, respectively (p = 0.18). And, the 3-, 5-, and 7-year postoperative overall survival rates were 71%, 56%, and 44% in the LLR group and 76%, 51%, 44% in the OLR group, respectively (p = 0.87). CONCLUSIONS: LLR for HCC patients with CSPH is clinically advantageous by lowering the volume of intraoperative blood loss and incidence of postoperative complications, thereby offering feasible long-term survival.

Clinical Outcomes of Preserving Bronchial Arteries During Radical Esophagectomy: A Propensity-Score Matched Analysis.

BACKGROUND: Postoperative pneumonia is a common and major cause of mortality after radical esophagectomy. Intraoperative preservation of the bronchial arteries is often aimed at avoiding tracheobronchial ischemia; however, it is unknown whether this contributes to a reduction in postoperative pneumonia. PATIENTS AND METHODS: We enrolled 348 consecutive patients who underwent radical esophagectomy for esophageal cancer at Toranomon Hospital from January 2011 to July 2018. We classified patients into a bronchial artery-resected (BA-R) group (n = 93) and a bronchial artery-preserved (BA-P) group (n = 255) and compared the incidence of postoperative pneumonia between the two groups. A propensity score-matching analysis for bronchial artery preservation versus resection was performed. RESULTS: Overall, 182 patients were matched. Univariate analysis of the propensity score-matched groups showed that Brinkman index ≥ 400, vital capacity (%VC) < 80%, and bronchial artery resection were associated with the development of postoperative pneumonia. Multivariate analysis revealed three significant factors associated with postoperative pneumonia: Brinkman index ≥ 400 [p = 0.006, odds ratio (HR) 3.302, 95% confidence interval (95% CI) 1.399-7.790], %VC < 80% (p = 0.034, HR 6.365, 95% CI 1.151-35.205), and bronchial artery resection (p = 0.034, HR 2.131, 95% CI 1.060-4.282). The incidence of postoperative complications (CD grade III) was higher in the BA-R group (BA-R 42.8% versus BA-P 27.5%, p = 0.030). There was no significant difference in overall survival between the two groups at 5 years (BA-R 63.1% versus BA-P 72.1%, p = 0.130). CONCLUSION: Preserving the bronchial artery is associated with a decreased incidence of postoperative pneumonia.

Impact of tumor shrinkage pattern with biweekly triplet gemcitabine+cisplatin+S-1 regimen for biliary tract cancers: Implications for neoadjuvant therapy from the data of KHBO1401 (KHBO1401-1A study).

BACKGROUND: The multicenter randomized phase III KHBO1401 study (gemcitabine+cisplatin+S-1 [GCS] versus GC in biliary tract cancers [BTC]) demonstrated that GCS not only prolonged patient survival but also achieved a high response rate and that it should be good for neoadjuvant therapy. Therefore, to explore the possibilities of neoadjuvant therapy, we investigated the tumor shrinkage pattern. METHODS: Among the total of 246 patients enrolled in the KHBO1401, the tumor shrinkage pattern and survival were investigated in patients with measurable BTC (n=183, 74%; GCS, n=91; GC, n=92). RESULTS: The tumor shrinkage pattern could be divided to 4 categories based on the response at 100 days after enrollment: category A (<-30% in size), B (-30% to 0%), C (0% to +20%), and D (>+20%). The GCS arm included more category A and B cases (61 [67%] vs. 33 [36%], P<0.0001). Each category predicted best response and overall survival (P<0.0001). Category A showed sustained tumor response compared with category B; in GCS, the time to maximum tumor response was 165 ± 76 days in category A and 139 ± 78 in category B. Categories C and D did not achieve tumor shrinkage. The maximum tumor shrinkage size in category A was -53% in the GCS arm and -65% in the GC arm (P=0.0892). Twenty percent of patients in the GCS showed tumor regrowth 154 ± 143 days later. CONCLUSION: GCS provided faster and greater tumor shrinkage with better survival in comparison to GC, although 20% of patients showed re-growth after 6 cycles.

Renin inhibition and the long-term renal function in patients with hypertensive emergency: a retrospective cohort study.

BACKGROUND: The rehospitalization rate in hypertensive emergency is high, indicating the necessity for optimizing its long-term management. The role of the renin-angiotensin system (RAS) blockade in this disorder remains uncertain. METHODS: We conducted a retrospective analysis involving 20 admitted patients who received aliskiren, a direct renin inhibitor (DRI), for the management of hypertensive emergency associated with elevated plasma renin activity (PRA). We analyzed the changes in blood pressure (BP), kidney function, and RAS activity in the subacute and chronic phases. RESULTS: The use of DRI was associated with a marked reduction in PRA (median, from 25.0 to 1.2 ng/mL/hr) and serum aldosterone levels (from 404 to 130 pg/mL) during the index admission. BP also decreased from 226/143 to 142/80 mmHg. A comparison of clinical characteristics according to the renal function indicated that dialysis-dependent patients had higher aldosterone levels than non-dialysis-dependent patients at admission, despite comparable BP levels. After a median follow-up of 567 days in non-dialysis-dependent patients with DRI, median eGFR levels were significantly increased from 14.3 to 23.1 mL/min/1.73 m2. PRA levels were consistently suppressed at 0.8 ng/mL/hr. We found a significant correlation between the degree of PRA suppression and changes in eGFR (r = -0.58), indicating that the effective blockade of RAS is associated with the preservation of eGFR in the study subjects. CONCLUSIONS: DRI can successfully suppress PRA in patients with high-renin hypertensive emergency in both subacute and chronic phases. An efficient RAS blockade is associated with preserved renal function in these patients.

Impact of Trinal Histological Glandular Differentiation Grade on the Prognosis of Patients with Intrahepatic Cholangiocarcinoma: a Multicenter Retrospective Study.

INTRODUCTION: It is unclear whether the histological glandular differentiation (HGD) score that evaluates the tumor grade of two dominant components is prognostic for survival in patients with intrahepatic cholangiocarcinoma (ICC). METHOD: We retrospectively analyzed the clinical and histopathologic data of 235 consecutive patients with histologically confirmed ICC following hepatectomy at 5 university hospitals in the Kansai region of Japan. RESULTS: Survival was statistically significantly stratified by trinal HGD grade (p < 0.05). Median disease-free survival (DFS) of patients with high HGD grade was significantly shorter compared with moderate HGD grade (13.0 vs 31.2 months, respectively; p = 0.004). By Cox proportional hazards regression analysis, HGD grade had the fifth-highest hazard ratio (HR = 1.77, p = 0.002) for DFS after vascular and/or biliary invasion, extrahepatic invasion, lymph node metastasis and multiple tumors. Multivariate logistic regression analysis revealed four predictors of early recurrence after hepatectomy (lymph node metastasis: odds ratio [OR] = 3.74, p = 0.001; tumor size > 50 mm: OR = 2.80, p = 0.002; HGD grade, high: OR = 2.11, p = 0.012; and vascular or biliary tract invasion: OR = 2.11, p = 0.048). CONCLUSION: Trinal HGD grade had a significant prognostic impact on the survival of patients with ICC after radical hepatectomy.

Slowly Progressive ANCA-associated Glomerulonephritis with Strong Mesangial MPO Deposits Following a Diagnosis of Interstitial Lung Disease: A Case Report.

An elderly woman showed positive conversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibodies (ANCAs) following the diagnosis of interstitial lung disease (ILD) and glomerular hematuria and subsequently experienced slowly progressive glomerulonephritis. A kidney biopsy revealed chronic damage and necrotizing crescentic glomerulonephritis with mesangial MPO deposits. After corticosteroid treatment, the patient's urinalysis results and MPO-ANCA titers almost normalized and her renal function stabilized. This case is similar to recently reported cases of slowly progressive ANCA-associated glomerulonephritis. ILD likely triggered the production of MPO-ANCAs, and the accumulation of MPO deposits in the glomeruli may have contributed to the progression of her renal disease.

TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by TDP-43 inclusions in the cortical and spinal motor neurons. It remains unknown whether and how pathogenic TDP-43 spreads across neural connections to progress degenerative processes in the cortico-spinal motor circuitry. Here we established novel mouse ALS models that initially induced mutant TDP-43 inclusions in specific neuronal or cell types in the motor circuits, and investigated whether TDP-43 and relevant pathological processes spread across neuronal or cellular connections. We first developed ALS models that primarily induced TDP-43 inclusions in the corticospinal neurons, spinal motor neurons, or forelimb skeletal muscle, by using adeno-associated virus (AAV) expressing mutant TDP-43. We found that TDP-43 induced in the corticospinal neurons was transported along the axons anterogradely and transferred to the oligodendrocytes along the corticospinal tract (CST), coinciding with mild axon degeneration. In contrast, TDP-43 introduced in the spinal motor neurons did not spread retrogradely to the cortical or spinal neurons; however, it induced an extreme loss of spinal motor neurons and subsequent degeneration of neighboring spinal neurons, suggesting a degenerative propagation in a retrograde manner in the spinal cord. The intraspinal degeneration further led to severe muscle atrophy. Finally, TDP-43 induced in the skeletal muscle did not propagate pathological events to spinal neurons retrogradely. Our data revealed that mutant TDP-43 spread across neuro-glial connections anterogradely in the corticospinal pathway, whereas it exhibited different retrograde degenerative properties in the spinal circuits. This suggests that pathogenic TDP-43 may induce distinct antero- and retrograde mechanisms of degeneration in the motor system in ALS.