First-line systemic therapy for unresectable advanced or metastatic esophageal squamous cell carcinoma (ESCC) has been reshaped by PD-1 blockade, but treatment selection remains complex because the pivotal trials differ in chemotherapy backbone and PD-L1 scoring methodology. KEYNOTE-590 enrolled both ESCC and adenocarcinoma and established pembrolizumab plus chemotherapy as a durable chemoimmunotherapy standard across histologic subtypes. CheckMate 648, focused on ESCC, showed that nivolumab plus chemotherapy and nivolumab plus ipilimumab both improve overall survival (OS), although the patterns of benefit are distinct: progression-free survival (PFS) benefit was observed with nivolumab plus chemotherapy but not with nivolumab plus ipilimumab. RATIONALE-306 subsequently added tislelizumab plus chemotherapy as another evidence-based first-line option in ESCC. Accordingly, clinically relevant treatment selection is better framed by the need for rapid disease control, tolerance for chemotherapy, toxicity profile, histology, and biomarker context than by a simple comparison of individual antibodies. Interpretation of PD-L1 also requires caution because KEYNOTE-590 used combined positive score (CPS), CheckMate 648 used tumor-cell PD-L1 expression, and RATIONALE-306 used Tumor Area Positivity (TAP). This review summarizes the evidence supporting current first-line treatment selection and its implications for daily clinical practice. Key issues addressed include practical distinctions between chemoimmunotherapy and dual immune checkpoint blockade, harmonization of PD-L1 assessment, platinum-backbone selection, and the optimization of treatment sequencing after first-line immunotherapy.
Obtaining adequate tissue for histologic diagnoses and genomic testing can be challenging in metastatic lung cancer, particularly when conventional biopsy approaches are nondiagnostic. The study reports an effective salvage strategy using endoscopic ultrasound (EUS)-guided adrenal tissue acquisition in two cases. A 66-year-old woman (case 1) developed recurrent lung adenocarcinoma with progressive metastases to the left adrenal, liver, and lungs following multiple lines of systemic therapy. A percutaneous biopsy of a suspected liver metastasis proved nondiagnostic. Subsequently, transgastric EUS-guided biopsy was performed, which confirmed metastatic adenocarcinoma originating in the lung. Oncomine-based genomic testing detected a human epidermal growth factor receptor 2 exon 20 insertion. Trastuzumab deruxtecan was subsequently introduced, resulting in disease stabilization for 6 months. A 75-year-old man (case 2) developed bilateral pulmonary nodules and a right adrenal mass detected on positron emission tomography. Bronchoscopy failed to yield diagnostic tissue. Following careful review of cross-sectional anatomy, EUS-guided biopsy of the right adrenal gland was safely performed via the duodenal bulb, confirming metastatic squamous cell carcinoma and yielding adequate tissue for genomic testing. EUS-guided adrenal biopsy, including transduodenal sampling of the right adrenal gland, may provide tissue for histopathologic and precision oncology testing, facilitating definitive diagnoses.
Eosinophilic pancreatitis (EP) is a rare disorder characterized by prominent pancreatic eosinophilic infiltration and often associated with peripheral eosinophilia and elevated IgE. IgG4-related disease (IgG4-RD) may involve the pancreas as type 1 autoimmune pancreatitis, with lymphoplasmacytic infiltration, storiform fibrosis, and increased IgG4-positive plasma cells. Both can mimic pancreatic malignancy. We report a 43-year-old man who underwent distal pancreatectomy in 2016 for suspected cancer and later experienced three episodes of acute pancreatitis. In 2024, modest serum IgG4 elevation (304 mg/dL; reference range, 3–201 mg/dL) and persistent monocytosis prompted re-evaluation of the surgical specimen. Histology showed dense, patchy eosinophilic infiltration with microabscesses and non-storiform fibrosis, while IgG4-positive plasma cells were sparse. These findings favored EP over type 1 autoimmune pancreatitis. This case highlights that EP may occur without peripheral eosinophilia, mimic malignancy and IgG4-RD, and require re-examination of archival tissue. Careful clinicopathological correlation is therefore essential to avoid diagnostic delay and misclassification.
Adenocarcinoma of the minor duodenal papilla is rare, and most previously reported cases have been treated by pancreaticoduodenectomy. An 82-year-old woman underwent endoscopy for anemia, which revealed a granular, flat-elevated lesion in the descending duodenum, 2 cm proximal to the major papilla. Endoscopic retrograde pancreatography showed leakage of contrast medium from the orifice of the accessory pancreatic duct at the lesion, confirming a tumor of the minor papilla. The initial biopsy showed adenoma, and the lesion was followed. Six months later it had enlarged and become friable, and repeat biopsy was suspicious for adenocarcinoma. Because pancreaticoduodenectomy was considered too invasive given her age and comorbidities, and because the minor papilla—unlike the major papilla—can be lifted by submucosal injection, en-bloc endoscopic mucosal resection was performed for both diagnostic and therapeutic purposes. Histology showed well-differentiated adenocarcinoma arising in adenoma, confined to the mucosa, with tumor-free margins and no lymphovascular invasion. No adverse events occurred, and no recurrence was observed during approximately 5 years of follow-up (endoscopic surveillance up to 2 years); the patient later died of an unrelated cause. Endoscopic mucosal resection may be a minimally invasive option achieving histologically complete resection in selected intramucosal carcinomas of the minor duodenal papilla.
Flucytosine-induced colitis is exceedingly rare with very few cases reported in the literature. We present a case of a 56-year-old male with history of ulcerative colitis and seronegative spondyloarthropathy who developed abdominal pain, diarrhoea and rectal bleeding following commencement of flucytosine and amphotericin B for cryptococcal empyema. The clinical features and biochemistry initially raised concern for an ulcerative colitis flare. Histopathology demonstrated features of an acute colitis. Subsequent cessation of flucytosine without alteration to management of his underlying ulcerative colitis led to a rapid and complete resolution of symptoms, supporting a diagnosis of flucytosine-induced colitis. This case highlights the importance of considering a drug-induced colitis in patients with inflammatory bowel disease presenting with new or worsening gastrointestinal symptoms. Accurate differentiation from disease flare is essential to avoid unnecessary changes or escalation in immunosuppressive therapy.
We report a case of gallbladder adenosquamous carcinoma with characteristic imaging findings. A 78-year-old man was suspected of having gangrenous cholecystitis and liver abscess based on abdominal ultrasonography performed at another hospital. Contrast-enhanced computed tomography revealed a 10-cm hepatic mass contiguous with the gallbladder, with marked internal necrosis and persistent peripheral enhancement. These imaging findings suggested gallbladder adenosquamous or squamous cell carcinoma with hepatic invasion, and needle biopsy revealed both adenocarcinoma and squamous cell carcinoma components, supporting the diagnosis. This case highlights the importance of recognizing marked internal necrosis and aggressive infiltrative growth on imaging in gallbladder adenosquamous carcinoma presenting with imaging features mimicking gangrenous cholecystitis and liver abscess.
Gastrointestinal amyloidosis is a rare condition with diverse clinical and endoscopic manifestations. Among these subtypes, localized gastric AL amyloidosis is rare and associated with lymphoproliferative disorders. Here, we report a case of gastric mucosa-associated lymphoid tissue (MALT) lymphoma diagnosed during follow-up of localized gastric AL (κ) amyloidosis. A 65-year-old woman who underwent periodic endoscopic screening was found to have a localized erythematous lesion with erosion in the lower gastric body. Histopathological examination revealed amyloid deposits. Although potassium permanganate treatment suggested AA amyloidosis, immunohistochemical analysis confirmed AL (κ)-type amyloid. Systemic evaluation revealed no evidence of plasma cell dyscrasia, and localized gastric AL amyloidosis was diagnosed. After six months, the lesion regressed, but a newly identified discolored lesion was diagnosed as MALT lymphoma with plasmacytic differentiation. This case highlights the limitations of potassium permanganate-based amyloid typing and raises the possibility of an association between localized AL amyloidosis and lymphoproliferative disorders. These cases require careful endoscopic surveillance.
We describe two older patients with repeated bleeding due to gastric ulcers despite achieving endoscopic hemostasis. In both cases, laboratory tests suggested chronic disseminated intravascular coagulation, with an underlying aortic aneurysm identified as the cause of this bleeding. Both patients achieved successful hemostasis after supplementation with fresh frozen plasma, while surgical treatment of the underlying aneurysm was not feasible. Recurrent gastrointestinal bleeding warrants evaluation of coagulation abnormalities and screening for aortic pathology.
Atezolizumab plus bevacizumab (ATZ/BEV) is an established first-line therapy for advanced hepatocellular carcinoma (HCC); however, complete response (CR) is rare. A man in his 70s was diagnosed with unresectable, multifocal HCC (maximum diameter, 190 mm) with vascular invasion. Liver function was preserved (Child–Pugh A, ALBI grade 1). ATZ/BEV was initiated, but the second cycle was postponed due to adverse events and intratumoral hemorrhage. Eight weeks later, selective transcatheter arterial embolization (TAE) was performed. Follow-up imaging showed disappearance of arterial enhancement in both embolized and non-embolized lesions. The patient has maintained CR for three years without additional treatment following sequential ATZ/BEV and selective TAE.
Percutaneous left atrial appendage occlusion prevents cardiogenic embolism caused by atrial fibrillation. It involves sealing the left atrial appendage using a specific closing device to avoid long-term anticoagulation. Here, we report an 88-year-old patient with colorectal cancer scheduled for endoscopic submucosal dissection (ESD) who had tumor surface bleeding and a high procedural hemorrhagic risk. During dual therapy with an antiplatelet agent and a direct oral anticoagulant (DOAC), left atrial appendage occlusion permitted DOAC discontinuation and reduced tumor bleeding. ESD was subsequently performed successfully and without complications under antiplatelet monotherapy.
Colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare and aggressive tumors in which accurate preoperative diagnosis remains difficult because of marked intratumoral heterogeneity. A 75-year-old man presented with locally advanced rectal cancer with inguinal lymph node metastasis. Routine biopsy demonstrated moderately to poorly differentiated adenocarcinoma, while retrospective immunohistochemical analysis revealed focal neuroendocrine differentiation insufficient for a diagnosis of MiNEN. Initial systemic chemotherapy with FOLFOXIRI plus bevacizumab was administered for metastatic rectal adenocarcinoma, followed by chemoradiotherapy, and radical surgery was performed after a partial response. Histopathological examination of the resected specimen revealed composite-type MiNEN composed of poorly differentiated adenocarcinoma and large-cell neuroendocrine carcinoma (NEC). The NEC component showed marked lymphovascular invasion and a Ki-67 index exceeding 90
Herein, we report a rare case of pancreatic metastasis originating from a malignant phyllodes tumor of the breast. A 45-year-old woman initially underwent a partial mastectomy for malignant phyllodes tumor of the left breast, followed by a total mastectomy for local recurrence. Six years later, the patient presented with abdominal pain. Computed tomography revealed a heterogeneous mass with cystic degeneration in the pancreatic tail, morphologically resembling the previously resected breast lesions. Based on the patient's history and imaging findings, pancreatic metastasis from malignant phyllodes tumor was suspected. Endoscopic ultrasound-guided fine-needle aspiration of the solid component was performed, and histopathological examination revealed a sheet-like proliferation of atypical cells with spindle-shaped enlarged nuclei within an eosinophilic stroma. Immunohistochemical staining for AE1/3 cytokeratin was negative, consistent with metastatic malignant phyllodes tumor. The patient declined further treatment and died approximately two months after diagnosis.
Glecaprevir/Pibrentasvir (GLE/PIB) is an interferon-free direct-acting antiviral (DAA) regimen indicated for the treatment of chronic hepatitis C virus (HCV) infection. However, data on the pharmacokinetics and stability of crushed or split tablets are lacking, complicating administration in patients with dysphagia requiring percutaneous endoscopic gastrostomy (PEG). Additionally, no published studies have evaluated the safety and efficacy of DAAs in combination with Risdiplam, the first oral therapy developed for spinal muscular atrophy (SMA). We report a case of a 14-year-old dysphagic patient with SMA, receiving Risdiplam, who was successfully treated with crushed GLE/PIB administrated via PEG. The patient achieved a sustained virologic response (SVR) 12 weeks after the end of therapy, without significant adverse effects, and no drug interactions were observed during the course of treatment.
Ball-valve syndrome (BVS) is a rare condition characterized by intermittent gastric outlet obstruction caused by a mobile gastric lesion. Large gastric lipomas associated with BVS have traditionally been managed surgically; however, minimally invasive endoscopic treatment may be feasible in selected cases. We report a case of a 52-year-old woman presenting with a 1-month history of postprandial epigastric discomfort and nausea. Contrast-enhanced computed tomography revealed a well-defined, low-attenuation mass extending from the gastric antrum to the duodenal bulb. Esophagogastroduodenoscopy demonstrated a broad-based subepithelial lesion exceeding 50 mm in diameter that repeatedly prolapsed through the pylorus, consistent with BVS. Endoscopic ultrasound showed a homogeneous hyperechoic lesion arising from the submucosa. Based on these imaging findings, a lipoma was strongly suspected, although liposarcoma could not be completely excluded. Therefore, endoscopic submucosal dissection (ESD) was performed as a diagnostic and therapeutic approach. Using a clip-with-line traction method, en bloc resection was successfully achieved without adverse events. The resected specimen measured 103 × 41 × 20 mm, and histopathological examination confirmed a gastric lipoma. The patient’s symptoms resolved completely after the procedure, with no recurrence at 1-year follow-up. In conclusion, ESD can be a safe and effective minimally invasive treatment for large gastric lipomas causing BVS, particularly when a confident preoperative diagnosis can be established.
Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare and aggressive histological subtype of colorectal adenocarcinoma characterized by the expression of enteroblastic markers, including alpha-fetoprotein (AFP), glypican-3, and spalt-like transcription factor 4 (SALL4). CAED typically affects older adults and is often diagnosed at an advanced stage. We report a rare case of AFP-producing CAED in a 29-year-old asymptomatic man whose markedly elevated serum AFP level served as a diagnostic clue. After elevated serum AFP was incidentally detected during a routine medical examination at a local clinic, markedly elevated serum AFP was confirmed at his initial visit to our hospital. Hepatocellular carcinoma and germ cell tumors were excluded by laboratory and imaging studies. Colonoscopy identified a transverse colon tumor, and the patient underwent curative resection. Histopathological examination demonstrated CAED with clear cytoplasm and positivity for AFP, SALL4, and glypican-3, confirming expression of all three enteroblastic markers. The pathological stage was pT3N2b, Stage IIIC. Serum AFP normalized after surgery, before the initiation of adjuvant chemotherapy, and the patient remains free of recurrence 12 months after surgery. This case highlights markedly elevated serum AFP as a potential diagnostic clue that may facilitate the early recognition of CAED, even in asymptomatic young adults.
Verrucous carcinoma is an extremely rare subtype of esophageal cancer, with only approximately 60 previously reported cases. Its marked surface keratinization often makes a definitive endoscopic diagnosis challenging. We present a case of esophageal verrucous carcinoma that had been managed as refractory esophageal candidiasis for 12 years, with no definitive diagnosis despite repeated antifungal therapy and multiple biopsies. The lesion was ultimately treated by surgical resection, and the diagnosis of verrucous carcinoma was confirmed based on examination of the resected specimen. This case highlights the need to consider verrucous carcinoma as a differential diagnosis in patients with long-standing esophageal candidiasis.
A 66-year-old man underwent right hemicolectomy for ascending colon cancer with direct invasion of gallbladder. Numerous aberrant proliferative vessels from the duodenum were noted. The pathological diagnosis was T4bN0M0, Stage IIC, with a KRAS G12D mutation. He received four cycles of adjuvant chemotherapy. Four months later, a mass approximately 3 cm in diameter involving the duodenum and ileum was identified and diagnosed as localized recurrence with no evidence of distant metastasis. After administration of two cycles of chemotherapy, contrast-enhanced computed tomography demonstrated tumor shrinkage. A pancreaticoduodenectomy was performed, including resection of the involved ileum, and the short segment of transverse colon. Pathological examination revealed adenocarcinoma proliferation extending across the adhesion plane between the duodenum and ileum, infiltrating the muscularis propria of both intestinal walls without intraluminal exposure. These findings suggested that the tumor originated from residual cancer cells at the dissection plane of the initial surgery. No postoperative adjuvant chemotherapy was administered, in accordance with the patient’s wishes. The patient has remained disease-free for more than 7 years after the pancreaticoduodenectomy.
Hydatid disease is a zoonotic parasitic disease caused by Echinococcus larvae, with hepatic echinococcosis sometimes exhibiting malignant-like behavior including vascular invasion. Portal vein invasion is a rare complication, and no prior report has described gastrointestinal hemorrhage due to portal hypertension from hydatid-induced portal vein invasion and cavernous transformation successfully treated by transjugular intrahepatic portosystemic shunt (TIPS). A 44-year-old female with recurrent gastrointestinal bleeding and a history of right hepatectomy for hepatic alveolar echinococcosis was admitted. CT and ultrasound revealed portal vein invasion and cavernous transformation. TIPS was successfully performed, reducing the portosystemic pressure gradient from 22 mmHg to 9 mmHg. Hepatic echinococcosis may cause portal vein invasion and cavernous transformation. Medical therapy is poorly effective for severe complications like gastrointestinal hemorrhage. TIPS plays an important role in managing such patients. Portal hypertension-related complications are rare but challenging in echinococcosis treatment. TIPS is an effective option for patients with gastrointestinal bleeding, even in the setting of portal vein invasion and cavernous transformation.
Distant metastasis in distal cholangiocarcinoma (DCC) generally precludes curative treatment. However, chemo-immunotherapy may enable multidisciplinary treatment with curative intent in selected patients. We report a rare case of metastatic DCC with liver metastasis that achieved radiological complete response after gemcitabine, cisplatin, and durvalumab (GCD) therapy, followed by resection of the residual primary lesion. A 73-year-old woman with a history of total gastrectomy presented with DCC and a solitary liver metastasis. Following endoscopic ultrasound-guided hepaticojejunostomy and eight cycles of gemcitabine, cisplatin, and durvalumab (GCD) therapy, the liver metastasis achieved a radiological complete response. After 16 cycles of durvalumab maintenance therapy, conversion pancreaticoduodenectomy without hepatectomy was performed because disease remained controlled despite residual primary disease. Pathological examination revealed residual viable tumor (ypT2N2M0). Immunohistochemistry suggested differences in the immune microenvironment between the primary tumor and liver metastasis. The patient remained recurrence-free 15 months after surgery. This rare case highlights the heterogeneous response between the primary tumor and liver metastasis after GCD therapy and demonstrates the potential role of conversion surgery in selected patients with metastatic DCC. It provides important insight into treatment decision-making in this clinical setting.
Esophageal perforation is most commonly caused by foreign body ingestion, medical procedures, or spontaneous rupture. In contrast, perforation secondary to bacterial infection is extremely rare, particularly in immunocompetent individuals. A previously healthy 60-year-old man developed pharyngotonsillitis followed by progressive right-sided chest pain. Initial chest radiography showed no abnormalities; however, subsequent computed tomography performed after clinical deterioration revealed right-sided empyema and an intramural abscess of the esophageal wall. Despite chest drainage and broad-spectrum antibiotics, the patient’s respiratory status worsened, necessitating transfer to our hospital. Upper gastrointestinal endoscopy demonstrated extensive circumferential esophageal ulceration with purulent discharge. Streptococcus constellatus, a member of the Streptococcus anginosus group, was isolated from pleural fluid cultures. Because of severe infection, extensive empyema, and marked fragility of the esophageal wall, thoracoscopic total thoracic esophagectomy with a two-stage reconstruction strategy was performed. The postoperative course was favorable, and delayed reconstruction using a gastric conduit was successfully completed. This case suggests that streptococcal pharyngotonsillitis may be associated with life-threatening esophageal perforation and empyema even in immunocompetent patients. Early recognition of disease progression and timely surgical intervention are essential in severe infectious cases.
