Background Proximal gastrectomy is a widely performed procedure that has become more common with an increasing number of proximal gastric cancer cases. Several types of reconstructive procedures after proximal gastrectomy have been developed, and it remains controversial which procedure is the most advantageous with regard to the preservation of postoperative gastric stump function and nutritional status. In the present study, we retrospectively analyzed reconstructive procedures in a consecutive case series for proximal gastrectomy, primarily focusing on postoperative body weight maintenance, nutritional status, and gastric remnant functional preservation. Methods We enrolled 69 patients who had undergone proximal gastrectomy for gastric cancer in our institute between 2005 and 2020. Short-term complications, preservation of gastric remnant functions, nutritional status, and post-operative weight changes were compared. Results After proximal gastrectomy, the numbers of patients who underwent direct esophago-gastrostomy, jejunal interposition, double tract reconstruction, and the double flap technique were 9, 10, 14, and 36, respectively. The patients in whom the double flap technique was performed suffered no reflux esophagitis after surgery. Prevalence of gastric residual at 12 months after surgery was lowest in the double flap technique group. Moreover, the double flap technique group had a better tendency regarding post-operative changes of serum albumin ratios. Furthermore, the post-operative body weight change ratio of the double flap technique group was smallest among all groups and was significantly better than that of the double tract group. Conclusions The double flap technique after proximal gastrectomy was considered the most effective technique for reconstruction which leads to better bodyweight maintenance, and results in less reflux esophagitis.

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The tumor microenvironment (TME) plays a key role in the efficacy of neoadjuvant chemotherapy (NAC) in solid tumors including esophageal squamous cell carcinoma (ESCC). However, the TME profile of ESCC treated with NAC is not fully understood. In this study, we investigated the effect of NAC on the TME especially tumor-associated macrophages (TAM), the important immunosuppressive components of the TME, in ESCC. We quantified the expression of CD163, a crucial marker of TAM, in pretherapeutic biopsy and surgically resected ESCC specimens from patients who received NAC (n = 33) or did not receive NAC (n = 12). We found that NAC dramatically increased the expression of CD163 on TAMs in ESCC. Colony-stimulating factor 1 (CSF-1) and IL34 are crucial cytokines that recruit monocytes into tumor sites and differentiate them into TAMs. Interestingly, NAC significantly upregulated the expression of IL34 but not CSF-1 on tumor cells, and the frequencies of CD163+ TAMs were significantly correlated with IL34 expression in ESCC after NAC. The expression of IL34 in NAC-nonresponsive patients was significantly higher than that in NAC-responsive patients, and patients with IL34-high ESCC exhibited worse prognosis as compared with patients with IL34-low ESCC. We also demonstrated that 5-fluorouracil (5-FU)/cisplatin preferentially increased mRNA expression of IL34 on human ESCC cell lines. Human peripheral blood monocytes co-cultured with ESCC cells treated with 5-FU/cisplatin increased the expression of CD163, which was attenuated by the treatment with CSF-1R inhibitors. These data suggest that IL34 expression by NAC shifts the TME toward CD163+ TAM-rich immunosuppressive and chemo-insensitive microenvironment in ESCC. Implications: The blockade of IL34 signaling may offer a novel therapeutic strategy against chemoresistance in ESCC by inhibiting M2-TAM polarization.

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