Lysyl oxidase-like 2 as a predictor of hepatocellular carcinoma in patients with hepatitis C virus after sustained virological response.

Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.

REV7 is involved in outcomes of platinum-based chemotherapy in pancreatic cancer by controlling the DNA damage response.

REV7 is a multifunctional protein implicated in various biological processes, including DNA damage response. REV7 expression in human cancer cells affects their sensitivity to DNA-damaging agents. In the present study, we investigated the significance of REV7 in pancreatic ductal adenocarcinoma (PDAC). REV7 expression was immunohistochemically examined in 92 resected PDAC specimens and 60 endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) specimens of unresectable PDAC treated with platinum-based chemotherapy, and its association with clinicopathologic features was analyzed. Although REV7 expression was not significantly associated with the progression of primary tumors (T-factor and Stage) in either resected or unresectable PDAC, decreased levels of REV7 expression in EUS-FNAB specimens of unresectable PDAC were significantly associated with better outcomes of platinum-based chemotherapy and a favorable prognosis. REV7-deficient PDAC cell lines showed suppressed cell growth and enhanced sensitivity to cisplatin in vitro. Tumor-bearing mice generated using REV7-deficient PDAC cell lines also showed enhanced sensitivity to cisplatin in vivo. RNA sequencing analysis using WT and REV7-deficient PDAC cell lines revealed that REV7 inactivation promoted the downregulation of genes involved in the DNA repair and the upregulation of genes involved in apoptosis. Our results indicate that decreased expression of REV7 is associated with better outcomes of platinum-based chemotherapy in PDAC by suppressing the DNA damage response. It is also suggested that REV7 is a useful biomarker for predicting the outcome of platinum-based chemotherapy and the prognosis of unresectable PDAC and is a potential target for PDAC treatment.

Colloid Carcinoma Arising in an Intestinal-Type Intraductal Papillary Mucinous Neoplasm with High-Grade Dysplasia Appearing as Signet-Ring Cells of the Pancreas by Serial Pancreatic Juice Aspiration Cytology: A Case Report.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months after an explorative laparotomy. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. This case highlights the diagnostic utility of SPACE, with particular emphasis on the characteristic presence of signet-ring cells. Furthermore, it anticipates the potential use of anti-claudin-18.2- specific monoclonal antibody therapy in the management of IPMNHGD patients.

Recurrent Mural Thrombosis of the Ascending Aorta in a Patient with Antiphospholipid Syndrome.

A 38-year-old man presented with embolic occlusion of the brachial artery. As per his computed tomography results, a pedunculated mass in the proximal ascending aorta was detected. Since discrimination between a thrombus and a tumor was deemed difficult, the patient underwent replacement of the ascending aorta. Histopathology revealed the mass to be a thrombus. The diagnosis of antiphospholipid syndrome was then confirmed postoperatively. Six months post-surgery, a new thrombus was detected in the vascular prosthesis. The thrombus resolved after treatment with edoxaban and aspirin. To the best of our knowledge, this is the first report on graft thrombosis in antiphospholipid syndrome, highlighting the importance of seamless anticoagulation therapy.

Mac-2-binding protein glycan isomer predicts all malignancies after sustained virological response in chronic hepatitis C.

Despite reports of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection after achieving sustained virological response (SVR), only few studies have demonstrated the incidence of other (non-HCC) malignancies. This study aimed to clarify the incidence, survival probability, and factors associated with malignancy, especially non-HCC malignancies, in patients with chronic HCV infection after achieving SVR. In this retrospective study, records of 3580 patients with chronic HCV infection who achieved SVR following direct-acting antiviral (DAA) treatment were analyzed. The cumulative post-SVR incidence of non-HCC malignancies was 0.9%, 3.1%, and 6.8% at 1, 3, and 5 years, respectively. The survival probability for patients with non-HCC malignancies was 99.1%, 78.8%, and 60.2% at 1, 3, and 5 years, respectively, and the rate was significantly lower than that for patients with HCC. The Cox proportional hazards regression model identified Mac-2-binding protein glycan isomer (M2BPGi) cutoff index (COI) ≥ 1.90 at baseline and ≥ 1.50 at 12 weeks following DAA treatment as significant and independent factors associated with the post-SVR incidence of non-HCC malignancies. Furthermore, patients with either M2BPGi COI ≥ 1.90 at baseline or M2BPGi COI ≥ 1.50 at SVR12 had a significantly higher risk of post-SVR incidence of non-HCC malignancies than of HCC. Conclusion: M2BPGi measurements at baseline and SVR12 may help predict the post-SVR incidence of non-HCC malignancies in patients with chronic HCV infection who achieved SVR following DAA treatment. Early identification of these patients is critical to prolong patient survival.

Comparison of clinical outcomes, including the wound healing rate, between inframalleolar bypass to the pedal artery and that to the pedal branch artery in the modern endovascular era.

OBJECTIVE: Inframalleolar (IM) bypass has been reported to demonstrate acceptable patency and limb salvage in patients with chronic limb-threatening ischemia. However, wound healing after IM bypass and comparisons between pedal artery (PA) bypass and pedal branch artery (PBA) bypass are lacking. METHODS: We reviewed prospectively collected data from 208 consecutive patients after IM bypass performed over a period of 6 years. Patients were divided into two groups based on the distal anastomotic artery: the PA group (dorsal pedis artery or common plantar artery) and the PBA group (medial tarsal, lateral tarsal, medial plantar, and lateral plantar artery). The primary outcome was wound healing, and secondary outcomes included loss of patency and limb and life prognosis. RESULTS: Of the 208 patients, 174 (74%) had PA bypass, whereas 34 (16%) had PBA bypass. Patients in the PBA group were significantly younger than those in the PA group (69 ± 7 vs 73 ± 9; P = .03). Although early (30-day) graft failure was more common in the PBA group, late clinical outcomes, including the wound healing rate (79% in the PA group and 84% in the PBA group; P = .74), were similar between the two groups. The Global Limb Anatomic Staging System IM grade (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.58-0.93; P = .006); wound, ischemia, and foot infection wound grade (HR, 0.67; 95% CI, 0.51-0.89; P < .01); and wound, ischemia, and foot infection foot infection grade (HR, 0.79; 95% CI, 0.65-0.96; P = .02) were independent predictors of wound healing. CONCLUSIONS: The current study revealed that wound healing in patients after PBA bypass was acceptable and comparable with that after PA bypass. In the modern era, including a high prevalence of infrapopliteal angioplasty, our results could provide useful information to clinicians in actual clinical settings. Moreover, PBA bypass may be an alternative revascularization procedure to avoid major amputation when the PA is occluded, such as in the global vascular guideline IM P2 grade. Prospective multicenter larger studies are warranted to confirm the findings of this study and to compare PBA bypass and IM endovascular treatment in patients with anatomical no-option chronic limb-threatening ischemia.

A case of pancreatic neuroendocrine carcinoma with a favorable clinical response to pembrolizumab.

A 76-year-old man with epigastric pain developed 1 month earlier was referred to our department for additional screening and treatment after abdominal ultrasound revealed a mass shadow in the pancreatic head and liver. Blood biochemistry revealed signs of mild jaundice and hepatic dysfunction. Abdominal contrast-computed tomography revealed an irregular hypodense mass with poor enhancement in the pancreatic head and several hypodense nodules in the liver. Endoscopic examination revealed duodenal infiltration signs. The biopsied duodenal mucosa contained atypical cells with high nuclear-to-cytoplasmic ratios; the cells stained positive for CD56, chromogranin, and synaptophysin, and the Ki-67 index was 90%. Accordingly, pancreatic neuroendocrine carcinoma (PanNEC) was diagnosed. Platinum-based chemotherapy (6 courses) and streptozotocin (10 courses) were adopted as the first- and second-line regimens, respectively. However, the patient showed progressive disease (PD). Pembrolizumab was added as a third-line regimen (13 courses) after confirming PanNEC with high microsatellite instability (MSI-high). Despite a temporary partial response (PR), the patient showed PD by the end of the 13 courses and died 1 year and 7 months after diagnosis. Although there is no established PanNEC therapy, those with MSI-high may respond favorably to pembrolizumab. Therefore, we should ascertain the MSI status of any PanNEC in routine practice.

Colitis nucleomigrans: The third type of microscopic colitis (part 1).

Microscopic colitis (MC), encompassing collagenous colitis and lymphocytic colitis, is featured by chronic diarrhea, normal-looking endoscopic findings and unique microscopic appearance. After reviewing biopsied nonspecific colitis, we propose the third type of MC: colitis nucleomigrans (CN). Histopathological criteria of CN included: (i) chained nuclear migration to the middle part of the surface-lining columnar epithelium; (ii) apoptotic nuclear debris scattered below the nuclei; and (iii) mild/moderate chronic inflammation in the lamina propria. Thirty-three patients (M:F = 20:13; median age 63 years, range 17-88) fulfilled our criteria. Seven cases demonstrated MC-like clinical/endoscopic features. Mucosal reddening with or without erosion/aphtha was endoscopically observed in the remaining 26 cases with inflammatory bowel disease (IBD)-like features: occult/gross hematochezia seen in 19, abdominal pain in two and mucin secretion in two. Cleaved caspase-3-immunoreactive apoptotic debris appeared more frequently in IBD-like CN than in MC-like CN, while CD8-positive intraepithelial lymphocytes comparably appeared in both. Proton pump inhibitors (PPIs) were administered in five (71%) cases with MC-like features, and in three diarrhea improved after drug cessation. In IBD-like CN cases, eight (31%) received PPIs. Four patients received chemotherapy against malignancies. Four patients associated immune-related disorders. Microscopic appearance of CN also appeared in a remission state of ulcerative colitis (12/20 lesions).

A Ruptured Popliteal Artery Aneurysm Treated with Coil Embolization.

A popliteal artery aneurysm is one of the most common peripheral arterial aneurysms. These aneurysms can cause distal embolization and thrombosis, leading to limb loss. However, their rupture is unusual. Here we report a case in which a popliteal aneurysm with chronic occlusion at its outflow artery developed a nonfatal, painful rupture. We performed only coil embolization of the proximal artery, and the aneurysm was successfully excluded. After the procedure, collateral circulation was maintained. No ischemic symptoms such as intermittent claudication or pain at rest were observed. This approach may be useful in treating similar cases.

Clinical characteristics and risk factors for stent-stone complex formation following biliary plastic stent placement in patients with common bile duct stones.

BACKGROUND: Stent-stone complex (SSC) formation is one of the complications of endoscopic biliary stent placement. This study aimed to clarify the clinical characteristics and risk factors for SSC formation following plastic stent (PS) placement in patients with common bile duct (CBD) stones. METHODS: We retrospectively reviewed the charts of 78 patients with CBD stones who had undergone 107 biliary stent placements as palliative treatment. Demographic, historical, and stent-related data were collected and analyzed. RESULTS: At PS removal, SSC formations were observed in 18% of the 107 cases (SSC group) studied and not in the remaining 82% (non-SSC group). The duration of PS placement was significantly longer in the SSC group. The increase in CBD diameter during the stenting period as well as the incidence of cholangitis at PS removal was significantly greater in the SSC group. Multivariate analysis identified long-term (≥301 days) PS placement and the increase in CBD diameter during the stenting period as independent factors for SSC formation. CONCLUSIONS: Long-term PS placement induces a risk of SSC formation in patients with CBD stones. The increase in diameter of CBD during the period of PS placement is a predictive factor for SSC formation in this situation.

Management of symptomatic abdominal aortic aneurysms following emergency computed tomography.

PURPOSE: It is still difficult to determine the appropriate timing of surgery for a symptomatic abdominal aortic aneurysm (AAA). Since recent developments in computed tomography (CT) have made the procedure substantially less time-consuming, we used CT on patients with symptomatic AAA to determine the most appropriate management option. METHODS: CT was performed on 79 patients with symptomatic AAA. If rupture of the AAA was confirmed by CT, patients underwent emergency surgery. If there was no rupture, patients were observed in an intensive care unit, and surgery was scheduled according to the results of repeated CT (2.1 times on average) and physical examinations, as well as on their clinical signs and symptoms. RESULTS: By CT, we identified 42 ruptures, one contained rupture, one aortocaval fistula, five acute aortic dissections with AAAs, six inflammatory AAAs, six pseudoaneurysms and 18 non-ruptured AAAs. The mortality rate of the patients with ruptures was 33%. For the 37 patients without rupture, as determined by CT, three emergency, nine urgent, and 20 elective operations were performed. Two patients who refused surgery experienced late rupture and died. Among the other 35 patients, the mortality rate was 6%. CONCLUSION: CT was an effective modality to classify patients with symptomatic AAA into those who needed emergency surgery and those who did not. We could observe patients with symptomatic non-ruptured AAAs before urgent/elective operations by repeated CT and monitor the clinical findings.

Effect of irreversible electroporation on three-dimensional cell culture model.

Irreversible electroporation (IRE) is a new treatment to necrotize abnormal cells by high electric pulses. Electric potential difference over 1 V across the plasma membrane permanently permeabilizes the cell with keeping the extracellular matrix intact if the thermal damage due to the Joule heating effect is avoided. This is the largest advantage of the IRE compared to the other conventional treatment. However, since the IRE has just started to be used in clinical tests, it is important to predict the necrotized region that depends on pulse parameters and electrode arrangement. We therefore examined the numerical solution to the Laplace equation for the static electric field to predict the IRE-induced cell necrosis. Three-dimensionally (3-D) cultured cells in a tissue phantom were experimentally subjected to the electric pulses through a pair of puncture electrodes. The necrotized area was determined as a function of the pulse repetition and compared with the area that was estimated by the numerical analysis.

Solitary profunda femoris artery aneurysm.

Solitary profunda femoris artery aneurysm (PFAA) is extremely rare but presents with symptoms related to rupture, distal embolization, or local compression of veins and nerves. We report two surgically treated cases of solitary PFAA. In case 1, a 69-year-old man presented with sudden onset of pain in the left groin. Computed tomography scan showed a large aneurysm with extravasation of the contrast medium in the left mid-thigh, indicating ruptured aneurysm of the profunda femoris artery. Case 2 involved a 70-year-old man whose computed tomography scan revealed a large, nonruptured PFAA. Both aneurysms were successfully resected with vascular reconstruction using the great saphenous vein.

Novel technique of retrograde cerebral perfusion for descending aortic repair: direct cannulation into left internal jugular vein.

We performed descending thoracic aortic repair via posterolateral thoracotomy using retrograde cerebral perfusion with direct cannulation into the left internal jugular vein. No postoperative neurological dysfunction was observed. This patient was discharged without any adverse events.

Surgical experience of 13 infected infrarenal aortoiliac aneurysms: preoperative control of septic condition determines early outcome.

BACKGROUND: The surgical management of infected aneurysms remains challenging and controversial. We aimed to assess the results of our retrospective series of patients surgically treated for infected infrarenal aortoiliac aneurysms and to verify our strategy. METHODS: Retrospective case review of a single center. RESULTS: Between January 1994 and December 2008, 545 patients with infrarenal aortoiliac aneurysms underwent surgery at our institution. Among these cases, 13 (2.4%) were classified as primary infected aneurysms. Seven were located in the infrarenal aorta and 6 were located in the iliac artery. The identified pathogens were Salmonella species (n = 2), methicillin-resistant Staphylococcus aureus (n = 2), and others. Systemic antibiotics were administered preoperatively to control septic conditions. At the time of surgery, 4 (31%) aneurysms had ruptured already. All but 2 cases, which were treated with extra-anatomic bypass, were repaired in situ using a Dacron graft. Although no in-hospital deaths occurred among the 3 patients who underwent planned surgery after successful control of septic conditions, 4 of 8 patients who underwent emergency surgery under septic conditions died during the early postoperative period. No signs of persistent or recurrent infection have been observed in our surviving patients with a mean follow-up of 40 months. CONCLUSION: Timely surgical intervention after controlling sepsis provided excellent outcomes, whereas the mortality rate of patients with sepsis or rupture was still high. Debridement of periaortic-infected tissue and in situ prosthetic graft repair are feasible.

Hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma: an audit of 50 consecutive cases.

OBJECTIVE: To outline our experience with hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma, and to discuss the clinical significance of this challenging hepatectomy. SUMMARY BACKGROUND DATA: Only a few authors reported negative results for this surgery in a very limited number of patients. METHODS: We retrospectively reviewed medical records of 50 patients with advanced cholangiocarcinoma who underwent hepatectomy (left trisectionectomy in 26, left hepatectomy in 23, and right hepatectomy in 1) with simultaneous resection and reconstruction of the portal vein and hepatic artery, focusing on surgical outcome and survival. RESULTS: The operative time was 776 +/- 191 minutes, and blood loss was 2593 +/- 1890 mL. Time of vessel resection and reconstruction was 25 +/- 19 minutes for the portal vein and 119 +/- 56 minutes for the hepatic artery. A total of 27 (54.0%) patients developed several kinds of complications, including intra-abdominal abscess (n = 13), wound infection (n = 9), bile leakage from liver stump (n = 9), and liver failure (n = 7). Relaparotomy was necessary in 5 (10.0%) patients. One (2.0%) patient died of a postoperative complication. Microscopic cancer invasion of the resected portal vein was found in 44 (88.0%) patients, while that of the resected hepatic artery was found in 27 (54.0%). The distal bile duct margin, proximal bile duct margin, and radial margin were positive for cancer in 2 (4.0%), 4 (8.0%), and 17 (34.0%) patients, respectively. Consequently, R0 resection was achieved in 33 (66.0%) patients. The 1-, 3-, and 5-year survival rates were 78.9%, 36.3%, and 30.3%, respectively. Survival for 30 patients with pM0 disease who underwent R0 resection was better, being 40.7% at the 3- and 5-year time points. CONCLUSION: Major hepatectomy with simultaneous resection and reconstruction of the portal vein and hepatic artery is technically demanding. However, this surgery can be performed with acceptable mortality by an experienced surgeon and offers a better chance of long-term survival in selected patients.

Type I Endoleak-like Phenomenon Causing Rupture of the Replaced Aneurysm Sac 12 Years after Open Repair of Abdominal Aortic Aneurysm.

Only a few cases of endoleak following conventional abdominal aortic aneurysm repair have been reported. We treated a patient with a type I endoleak-like phenomenon occuring 12 years after conventional abdominal aortic aneurysm repair. Computed tomography demonstrated dilation of the surgically replaced, once-shrunken aneurysm sac to a diameter of 3.5 cm. Thrombus was identified between the graft and the sac. Four months later the sac ruptured, and emergency repair was performed. Dehiscence of the proximal anastomosis causing dilation and tearing of the sac was found. Dilation of a surgically replaced aneurysm sac after initial shrinkage may suggest an endoleak-like phenomenon requiring second repair.

Acute hemorrhagic colitis associated with oral administration of oseltamivir for the treatment of influenza A.

The importance of oseltamivir as a strategy for the treatment of influenza has been recognized; however, the risk of acute hemorrhagic colitis should be considered, although it is rare. This report describes a case of acute hemorrhagic colitis in a 61-year-old Japanese man after the oral administration of oseltamivir for influenza A. A definitive diagnosis of influenza A was made using a rapid diagnosis kit. Abdominal pain, diarrhea, and hematochezia occurred the day after the first administration of oseltamivir (The patient had taken two capsules of oseltamivir). Endoscopic examination revealed extensive acute hemorrhagic colitis. Histopathological examination of the colonic mucosa revealed small atrophic glands with partial deciduation of the epithelium and a decrease in the number of goblet cells. Hemorrhage and mild infiltration of inflammatory cells were observed as well. These changes were suggestive of an ischemic change. A culture test showed normal flora.

Comparison of Doppler and oscillometric ankle blood pressure measurement in patients with angiographically documented lower extremity arterial occlusive disease.

To assess the reliability of the oscillometric method in patients with peripheral vascular disease, ankle blood pressure measurement by Doppler and oscillometry was compared. This study represents a prospective, non-blinded examination of pressure measurements in 168 patients. Twenty-two patients were included who had abdominal aortic aneurysms (AAA) and 146 had peripheral arterial occlusive disease (PAOD). Patients with PAOD were divided into 2 groups according to angiography results: a crural artery occlusion group (CAO, n = 32), and a no crural artery occlusion group (NCAO, n = 114). All subjects underwent pressure measurement by both Doppler and oscillometry. The correlation coefficient was 0.928 in AAA patients and 0.922 in PAOD patients. In CAO patients, there were significantly fewer patients whose oscillometric pressure was equivalent to the Doppler pressure (DP), as compared to NCAO patients, because the oscillometric pressure (OP) was 10% higher than DP in 44% of CAO patients. A high correlation exists between Doppler and oscillometric ankle pressure measurements irrespective of the type of vascular disease. However, the oscillometric method could not be substituted for the Doppler method completely, because there were several patients whose OP was greater than DP especially in those with crural artery occlusive disease.

AH amyloidosis associated with lymphoplasmacytic lymphoma secreting a monoclonal gamma heavy chain carrying an unusual truncated D segment.

To date, the presence of amyloidosis associated with immunoglobulin heavy chain (AH amyloidosis) was reported in only 7 cases. Although AH amyloidosis is caused mainly by plasma cell dyscrasia, as in AL amyloidosis, we report a 61-year-old patient who presented with nephrotic syndrome caused by AH amyloidosis associated with lymphoplasmacytic lymphoma. Biochemical and molecular analyses of the deposited amyloid fibrils and heavy-chain genes of lymphocytes showed that proliferative lymphoma cells produced a gamma heavy chain, not a mu heavy chain, which carried an unusual truncated diversity (D) segment of the variable region. Our results indicate that production of the abnormal heavy chain caused by the partially deleted D segment gene is responsible for gamma heavy-chain-related amyloid fibril formation in this patient.