Non-interventional Management of Asymptomatic Diminutive Choledocholithiasis Versus Endoscopic Extraction in Consecutive Patients.

BACKGROUND: Current guidelines recommend treating choledocholithiasis, regardless of symptoms or stone size, with endoscopic retrograde cholangiopancreatography (ERCP). However, asymptomatic choledocholithiasis, discovered incidentally on imaging, may carry a higher risk of ERCP-related adverse events, and some asymptomatic and diminutive stones may not cause biliary adverse events during extended follow-up. Therefore, we aimed to clarify the best treatment strategies for asymptomatic choledocholithiasis based on stone size. METHODS: We retrospectively identified patients with incidental imaging-found asymptomatic diminutive (≤ 4 mm) or non-diminutive (> 4 mm) choledocholithiasis and divided them into two groups: those who did not undergo ERCP and were treated when complications arose (on-demand group) and those who underwent ERCP before being symptomatic (intervention group). Adverse events were defined as any biliary or pancreatic complication related to ERCP or arising during observation or after intervention. The primary outcome was the adjusted overall adverse event-free survival using the propensity score-based matching weights method comparing the two groups of stone size. RESULTS: Among 148 patients identified (median follow-up period, 969 days), 68 had diminutive stones and 80 had non-diminutive stones. Of the 68 patients with diminutive stones, 51 were in the on-demand group and 17 in the intervention group. The overall adjusted adverse event-free survival was significantly higher in the on-demand group for diminutive stones (97.4% and 70.1%, respectively, at 3 years; p = 0.01). DISCUSSION: Patients with incidental imaging-detected asymptomatic diminutive choledocholithiasis may benefit from clinical observation, pursuing ERCP when symptoms develop.

The ZIP Transporter Family Member OsZIP9 Contributes To Root Zinc Uptake in Rice under Zinc-Limited Conditions.

Zinc (Zn) is an important essential micronutrient for plants and humans; however, the exact transporter responsible for root zinc uptake from soil has not been identified. Here, we found that OsZIP9, a member of the ZRT-IRT-related protein, is involved in Zn uptake in rice (Oryza sativa) under Zn-limited conditions. OsZIP9 was mainly localized to the plasma membrane and showed transport activity for Zn in yeast (Saccharomyces cerevisiae). Expression pattern analysis showed that OsZIP9 was mainly expressed in the roots throughout all growth stages and its expression was upregulated by Zn-deficiency. Furthermore, OsZIP9 was expressed in the exodermis and endodermis of root mature regions. For plants grown in a hydroponic solution with low Zn concentration, knockout of OsZIP9 significantly reduced plant growth, which was accompanied by decreased Zn concentrations in both the root and shoot. However, plant growth and Zn accumulation did not differ between knockout lines and wild-type rice under Zn-sufficient conditions. When grown in soil, Zn concentrations in the shoots and grains of knockout lines were decreased to half of wild-type rice, whereas the concentrations of other mineral nutrients were not altered. A short-term kinetic experiment with stable isotope 67Zn showed that 67Zn uptake in knockout lines was much lower than that in wild-type rice. Combined, these results indicate that OsZIP9 localized at the root exodermis and endodermis functions as an influx transporter of Zn and contributes to Zn uptake under Zn-limited conditions in rice.

A case of neuroendocrine carcinoma in the hepatic hilar lymph nodes concomitant with an adenocarcinoma of the gallbladder.

BACKGROUND: Neuroendocrine tumors (NETs) are rare especially in the gallbladder. They have not been elucidated in the pathogenesis, clinicopathological characteristics, and treatment options. CASE PRESENTATION: We present a 76-year-old woman with a gallbladder tumor and hepatic hilar lymph node swelling. The lymph node biopsy demonstrated neuroendocrine carcinoma (NEC). We performed cholecystectomy, hepatic hilar lymphadenectomy, extrahepatic biliary duct resection, and hepaticojejunostomy prior to chemotherapy. Pathological examination revealed the gallbladder mass was an adenocarcinoma invading to the muscular layer without any NEC components, whereas the hepatic hilar lymph nodes were filled with high-grade NEC cells with negligible area of adenocarcinoma. The patient received general chemotherapy consisting of carboplatin and etoposide, but a recurrence in the para-aortic lymph nodes occurred 4 months after surgery. CONCLUSIONS: We report a rare case of NEC of the hepatic hilar lymph nodes that were concomitant with an adenocarcinoma of the gallbladder. High-grade NEC generally has an aggressive behavior and an optimal treatment strategy should be chosen for each patient.

The gut-liver axis in hepatobiliary diseases.

Recent advances in the analysis of intestinal bacteria have led to reports of variations in intestinal bacterial levels among hepatobiliary diseases. The mechanisms behind the changes in intestinal bacteria in various hepatobiliary diseases include the abnormal composition of intestinal bacteria, weakening of the intestinal barrier, and bacterial translocation outside the intestinal tract, along with their metabolites, but many aspects remain unresolved. Further research employing clinical studies and animal models is expected to clarify the direct relationship between intestinal bacteria and hepatobiliary diseases and to validate the utility of intestinal bacteria as a diagnostic biomarker and potential therapeutic target. This review summarizes the involvement of the microbiota in the pathogenesis of hepatobiliary diseases via the gut-liver axis.

Successful management of bile duct injury with duodenal perforation using endoscopic naso-pancreatic drainage and fully covered self-expandable metallic stent deployment.

Video 1A case of bile and pancreatic duct injury with duodenal perforation during endoscopic submucosal dissection for superficial duodenal epithelial neoplasia.

Vascular pseudoinvasion in a solitary Peutz-Jeghers polyp in the ileum.

A Peutz-Jeghers polyp (PJP) is a hamartomatous lesion characterized by arborescent smooth muscle bundles covered with mucosa native to the site of involvement. PJPs in the small intestine may represent misplacement of non-neoplastic epithelium into the submucosa, muscularis propria and subserosa. Although epithelial misplacement in PJPs is a well-documented phenomenon, pseudoinvasion even into the vascular space in PJPs has not previously been reported. We report a case of a 22-year-old Japanese woman with a solitary PJP in the ileum. The ileal PJP in this patient showed epithelial herniation even into the vascular space. All the herniated epithelium, including the epithelial components invaginated into the vascular space, demonstrated features of pseudoinvasion, that is, presence of normal small intestinal type mucosa accompanied by the lamina propria, absence of any stromal desmoplastic reaction, and retention of the basal-luminal gradient. Pathologists must be aware of the possibility of vascular pseudoinvasion in small intestinal PJPs to avoid overdiagnosis of carcinoma and resulting unnecessary major surgery.

Long-term remission of VEXAS syndrome achieved by a single course of CHOP therapy: A case report.

We herein describe the case of a 52-year-old male patient who presented with fever, arthritis, and neutrophilic dermatosis in 2013 and subsequently experienced macrophage activation syndrome treated with high-dose glucocorticoid therapy. Due to the persistent symptoms refractory to several immunomodulatory and immunosuppressive (IS) drug therapies with dapsone, methotrexate, tacrolimus, infliximab (IFX), and tocilizumab (TCZ), he received prednisolone (PSL) ≥20 mg/day to suppress disease activity. In 2017, Epstein-Barr virus (EBV)-associated haemophagocytic lymphohistiocytosis (HLH) was diagnosed and initially treated with immunochemotherapy consisting of dexamethasone, cyclosporine (CyA), and etoposide (ET). Because of the suboptimal response to the initial therapy, cytoreduction therapy consisting of CHOP (combination chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and PSL) was administered. This regimen improved the EBV-associated HLH. Later, the patient's condition stabilised with methylprednisolone 1 mg/day and CyA 100 mg/day. In 2022, ubiquitylation-initiating E1 enzyme (UBA1) variant analysis using Sanger sequencing of peripheral blood leukocytes detected a previously reported somatic variant (NM_003334.3: c.118-1G>C), confirming the diagnosis of vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. The clinical course in the present case suggested the possibility that CHOP could be a potential treatment option for VEXAS syndrome, in the pathophysiology of which the expansion of clones with UBA1 variant seems to play a pivotal role.

Two cases of colorectal liver metastasis with residual liver recurrence after a long recurrence-free survival period.

BACKGROUND: The rate of residual liver recurrence after the resection of colorectal liver metastases is high, and most cases recur within 5 years of the initial hepatectomy. Here, we report two cases of residual liver recurrence after radical resection of colorectal liver metastases after a long recurrence-free survival period. CASE PRESENTATION: Case 1 involved a 62-year-old woman treated for ascending colon cancer in April 2011 who underwent right hepatectomy for synchronous colorectal liver metastasis in April 2012. However, in September 2021, computed tomography revealed residual recurrence in the lateral segment of the liver, and a lateral segmentectomy of the liver was performed. In Case 2, a 52-year-old man treated for cecal cancer in July 2002 underwent lateral segmentectomy of the liver for metachronous colorectal liver metastasis in October 2006. Subsequently, there was no recurrence; however, computed tomography showed residual liver recurrence in the right lobe of the liver in October 2021, and an expanded posterior hepatic segmentectomy was performed. Histopathological findings in both cases were consistent with colorectal liver metastases. CONCLUSIONS: We encountered two cases in which residual liver recurrence was observed after a long period of recurrence-free survival. Although rare, there have been a few cases of late recurrence of liver metastases after radical resection of cancer liver metastases.

A case of acquired hemophilia A after pancreaticoduodenectomy for distal cholangiocarcinoma.

Acquired hemophilia A (AHA) is a rare disease that results from factor VIII inhibitors causing abnormal coagulation, and certain cases may develop after highly invasive surgery. The present case study reports on a 68-year-old male patient who developed AHA after undergoing a subtotal stomach-preserving pancreatoduodenectomy for distal cholangiocarcinoma. The patient experienced complications after surgery, requiring reoperation on postoperative day (PD) 5 due to rupture of the Braun's enterostomy. On PD 6, angiography was performed after bleeding was detected in the jejunal limb, but hemostasis occurred spontaneously during the examination. Bleeding was observed again on PD 8 and direct surgical ligation was performed. On PD 14, bleeding recurred in the jejunal limb and angiography was performed to embolize the periphery of the second jejunal artery. During the procedure, the prothrombin time was normal, but only the activated partial thromboplastin time was prolonged. A close examination of the coagulation system revealed a decrease in factor VIII levels and the presence of factor VIII inhibitors, resulting in the diagnosis of AHA. Administration of steroids was initiated on PD 15 and, in addition to daily blood transfusions, activated prothrombin complex concentrate was administered to achieve hemostasis. The patient was discharged from the intensive care unit on PD 36 but later developed an intractable labial fistula due to suture failure at the gastrojejunostomy site. As the use of factor VIII inhibitors continued despite the administration of steroids, cyclophosphamide (CPA) pulse therapy was added at PD 58. However, CPA was ineffective and the administration of rituximab was initiated on PD 98. After 12 courses of rituximab, the patient tested negative for factor VIII inhibitors on PD 219. On PD 289, labial fistula closure was performed with continuous replacement of factor VIII and the patient was discharged on PD 342.

Successful Management of Resuscitative Endovascular Balloon Occlusion of the Aorta for Hemorrhagic Shock Due to Ruptured Hepatocellular Carcinoma.

A 68-year-old man was transferred to our hospital because of sudden right costal pain with unmeasurable hypotension. Ultrasonography revealed possible hemorrhagic shock due to ruptured hepatocellular carcinoma (HCC). As the patient was not hemodynamically stable after primary treatment, resuscitative endovascular balloon occlusion of the aorta (REBOA) was performed, and hemodynamic stability was then achieved. Contrast-enhanced computed tomography confirmed the diagnosis. Transcatheter artery embolization with gelatin sponge particles and coils eliminated the extravasation. The patient was discharged on day 36 post-procedure. Our observations suggest that REBOA may help achieve hemodynamic stability in cases of ruptured HCC.

A Clinical Case of Insulinoma Presenting with Postprandial Hypoglycemia in a Patient with a History of Gastric Bypass Surgery.

A 61-year-old man with a history of total gastrectomy for cancer with Roux-en-Y reconstruction showed severe postprandial hypoglycemia accompanied by endogenous hyperinsulinemia. Abdominal ultrasonography and contrast-enhanced computed tomography showed no abnormal findings in the pancreas. A selective arterial secretagogue injection test showed the marked induction of serum immunoreactive insulin when calcium was injected into the splenic artery. A pathological analysis following distal pancreatectomy with splenectomy revealed a pancreatic neuroendocrine microadenoma containing insulin-producing cells in the resected pancreas. This case highlights the importance of carefully evaluating refractory and severe hypoglycemia in patients with a history of gastric surgery to exclude insulinoma.

Nivolumab and Ipilimumab Combination Immunotherapy for Patients with Metastatic Collecting Duct Carcinoma.

Collecting duct carcinoma (CDC) is a rare, extremely aggressive form of renal cancer. Recently, immune checkpoint inhibitors (ICI), anti-programmed death-1 (PD-1) antibody, and anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antibody were approved for use against metastatic renal cell carcinoma. We herein described two cases of metastatic renal collecting duct carcinoma treated with a combination immunotherapy consisting of nivolumab and ipilimumab. In the first case, which included a bone metastasis, the best response achieved was stable disease (SD) for one year. In the second case, which was accompanied by a lung metastasis, the best response achieved was a partial response. The outcome of these cases suggested that the combination of nivolumab and ipilimumab is effective against renal collecting duct carcinoma.

A case of laparoscopic partial hepatic S7 resection for postoperative liver metastasis of rectal malignant melanoma.

BACKGROUND: Anorectal malignant melanoma (ARMM) has an extremely poor prognosis, and there is no report of resection of liver metastases so far. We report herein a rare case of postoperative laparoscopic partial hepatic S7 resection for rectal malignant melanoma. CASE PRESENTATION: A 51-year-old female patient with a diagnosis of an ARMM underwent a laparoscopic rectal amputation. Eleven months later, computed tomography (CT) revealed a 14-mm nodule in liver segment 7 (S7), which was diagnosed as a hepatic recurrence of the ARMM. Because no other recurrences were found, a laparoscopic partial resection of S7 was performed. Pathological analysis found intracellular melanin deposition, and immunostaining was S-100 (+), HMB-45 (+), and SOX-10 (+). Based on these findings, a liver metastasis of malignant melanoma was diagnosed. The patient is alive 7 months after the second surgery and has so far experienced no recurrences. CONCLUSION: We reported an extremely rare case of a laparoscopic resection of a liver metastasis following surgery for ARMM.

Assessment of a self-assembling peptide gel, SPG-178, in providing a clear operative field for trabeculectomy surgery for glaucoma in an animal model.

The presence of blood during ophthalmic surgery is problematic, as it can obstruct a surgeon's view of the operative field. This is particularly true when performing trabeculectomy surgery to enhance ocular fluid outflow and reduce intraocular pressure as a treatment for glaucoma, one of the most common vision loss conditions worldwide. In this study, we investigated the performance of a transparent, self-assembling peptide gel (SPG-178) and its ability to maintain visibility during trabeculectomy surgery. Unlike the hyaluronic acid gel commonly used in ophthalmic surgery, SPG-178 did not permit the ingress of blood into the gel itself. Rather, it forced blood to flow peripherally to the gel. Moreover, if bleeding occurred under the SPG-178 gel, perfusion with saline was able to effectively flush the blood away along the interface between the SPG-178 and the ocular tissue (in this case scleral) to clear the surgical field of view. In experimental trabeculectomy surgeries with mitomycin C used as an adjuvant, there were no differences in the postoperative recovery of intraocular pressure or bleb morphology with or without the use of SPG-178. SPG-178, therefore, when used in a gel formulation, represents a new material for use in intraocular surgery to ensure a clear operative field with likely beneficial treatment outcomes.