Successful multidisciplinary treatment for synchronous advanced esophageal and cecal cancers after total gastrectomy with reconstruction by jejunal interposition.

BACKGROUND: Esophageal squamous cell carcinoma is characterized by field cancerization, wherein multiple cancers occur in the esophagus, head and neck, and stomach. Synchronous esophageal and colorectal cancers are also encountered with a certain frequency. A good prognosis can be expected if the tumors in both locations can be safely and completely removed. For patients with multiple cancers that occur simultaneously with esophageal cancer, it is necessary to perform a staged operation, taking into consideration the associated surgical invasiveness. It is also necessary to select multidisciplinary treatment depending on the degree of progression of the multiple lesions. We report our rare experience with a staged operation for a patient with synchronous advanced cancers of the esophagus and cecum who had previously undergone total gastrectomy with reconstruction by jejunal interposition for gastric cancer. CASE PRESENTATION: A 71-year-old man with a history of reconstruction by jejunal interposition after total gastrectomy was diagnosed as having multiple synchronous esophageal and cecal cancers. After neoadjuvant chemotherapy, we performed a planned two-stage operation, with esophagectomy and jejunostomy in the first stage and ileocecal resection and jejunal reconstruction with vascular anastomosis in the second. Postoperatively, the patient was relieved without major complications, and both tumors were amenable to curative pathologic resection. CONCLUSIONS: Our procedure reported here may be recommended as an option for staged resection and reconstruction in patients with simultaneous advanced esophageal and cecal cancer after total gastrectomy.

IL13 and periostin in active fibrogenic areas of the extrahepatic bile ducts in biliary atresia patients.

BACKGROUND: The leading pathology of biliary atresia (BA) is inflammatory and fibrous obstruction of extrahepatic bile duct, but the pathogenesis remains unclear. IL13 is a cytokine associated with allergies and inflammatory fibrosis, and periostin induces fibrogenesis by stimulation with IL13. We analyzed the involvement of IL13 and periostin in inflammatory fibrosis in the extrahepatic bile duct of BA patients. MATERIALS AND METHODS: Surgically resected tissues from the hepatic hilar area of BA patients were immunostained with CD45, α-SMA, IL13 and periostin and statistically analyzed. Fibroblasts from the resected tissue were cultured with recombinant IL13, and periostin production was analyzed by quantitative polymerase chain reaction and Western blotting. RESULTS: IL13 was stained in 93% of large and micro bile ducts, and 92.1% matched with the CD45 location (p = 0.006) around the large bile ducts. Periostin staining correlated with the localization of IL13 and αSMA (p < 0.001) around the large bile ducts. Periostin mRNA and protein were upregulated by IL13 stimulation in cultured fibroblasts. CONCLUSION: IL13 was associated with induced periostin expression by fibroblasts, playing a vital role in the pathogenesis of fibrogenesis around the extrahepatic bile duct in BA.

The clinical impact of macrophage polarity after Kasai portoenterostomy in biliary atresia.

Introduction: Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called "macrophage polarity." The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course. Materials and methods: Thirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed. Results and discussion: The M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high (n = 19) and non-high (n = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0-2), the M2 non-high group had a significantly lower native liver survival rate than the high group (p = 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE. Conclusions: Non-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis.

Oligometastases of Esophageal Squamous Cell Carcinoma: A Review.

Patients with oligometastases show distant relapse in only a limited number of regions. Local therapy such as surgical resection, radiotherapy, chemoradiotherapy, and radiofrequency ablation for the relapsed sites may thus improve patient survival. Oligometastases are divided into oligo-recurrence and sync-oligometastases. Oligo-recurrence indicates a primary lesion that is controlled, and sync-oligometastases indicate a primary lesion that is not controlled. The management of oligo-recurrence and sync-oligometastases in esophageal squamous cell carcinoma has not been clearly established, and treatment outcomes remain equivocal. We reviewed 14 articles, including three phase II trials, that were limited to squamous cell carcinoma. Multimodal treatment combining surgical resection and chemoradiotherapy for oligo-recurrence of esophageal squamous cell carcinoma appears to be a promising treatment. With the development of more effective chemotherapy and regimens that combine immune checkpoint inhibitors, it will become more likely that sync-oligometastases that were unresectable at the initial diagnosis can be brought to conversion surgery. Currently, a randomized, controlled phase III trial is being conducted in Japan to compare a strategy for performing definitive chemoradiotherapy and, if necessary, salvage surgery with a strategy for conversion surgery in patients who can be resected by induction chemotherapy.

Oligometastasis of Gastric Cancer: A Review.

The concept of oligometastasis is not yet fully established in the field of gastric cancer. However, metastatic lesions that are localized, technically resectable at diagnosis, present a certain response to preoperative chemotherapy, and present favorable survival outcomes with local treatments, sometimes in combination with chemotherapy, are recognized as oligometastasis in the field of gastric cancer. Oligometastasis is noted in European Society for Medical Oncology guidelines and Japanese gastric cancer treatment guidelines, and local treatment is mentioned as one of the pivotal treatment options for oligometastasis. Solitary liver metastasis or a small number of liver metastases; retroperitoneal lymph node metastasis, especially localized para-aortic lymph node metastasis; localized peritoneal dissemination; and Krukenberg tumor are representative types of oligometastasis in gastric cancer. The AIO-FLOT3 trial prospectively evaluated the efficacy of multimodal treatments for gastric cancer with oligometastasis, including surgical resection of primary and metastatic lesions combined with chemotherapy, confirming favorable survival outcomes. Two phase 3 studies are ongoing to investigate the efficacy of surgical resection combined with perioperative chemotherapy compared with palliative chemotherapy. Thus far, the evidence suggests that multimodal treatment for oligometastasis of gastric cancer is promising.