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Background: The significance of reinforcement of the duodenal stump with seromuscular sutures and the effectiveness of reinforced staplers in preventing duodenal stump leakage remain unclear. We aimed to explore the importance of duodenal stump reinforcement and determine the optimal reinforcement method for preventing duodenal stump leakage., Methods: This retrospective cohort study was conducted between January 1, 2012 and December 31, 2021, with data analyzed between December 1, 2022 and September 30, 2023. This multicenter study across 57 institutes in Japan included 16,475 patients with gastric cancer who underwent radical gastrectomies. Elective open or minimally invasive (laparoscopic or robotic) gastrectomy was performed in patients with gastric cancer., Results: Duodenal stump leakage occurred in 153 (0.93%) of 16,475 patients. The proportions of males, patients aged ≥ 75 years, and ≥ pN1 were higher in patients with duodenal stump leakage than in those without duodenal stump leakage. The incidence of duodenal stump leakage was significantly lower in the group treated with reinforcement by seromuscular sutures or using reinforced stapler than in the group without reinforcement (0.72% vs. 1.19%, p = 0.002). Duodenal stump leakage incidence was also significantly lower in high-volume institutions than in low-volume institutions (0.70% vs. 1.65%, p = 0.047). The rate of duodenal stump leakage-related mortality was 7.8% (12/153). In the multivariate analysis, preoperative asthma and duodenal invasion were identified as independent preoperative risk factors for duodenal stump leakage-related mortality., Conclusions: The duodenal stump should be reinforced to prevent duodenal stump leakage after radical gastrectomy in patients with gastric cancer., (© 2024. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Background: We investigated the prognostic role of preoperative chemotherapy in patients who underwent hepatectomy for liver-limited metastasis (LLM) from gastric cancer (GC)., Methods: A retrospective analysis was conducted for 52 consecutive patients who underwent macroscopically complete (R0 or R1) resection for synchronous or metachronous LLM from GC., Results: Of the 52 patients, 18 (35%) received preoperative chemotherapy (PC group), while 34 (65%) underwent upfront surgery (US group). The PC group had a significantly longer overall survival than the US group (cumulative 5-year OS rate: 47.6% vs. 24.8%, p = 0.041). Multivariate analysis of OS revealed that preoperative chemotherapy was an independent favorable prognostic factor (hazard ratio: 0.445, p = 0.036). Patients showing a partial response to preoperative chemotherapy on RECIST had an improved OS compared with those exhibiting stable or progressive disease after preoperative chemotherapy and with US (p = 0.025), even among those with solitary LLM (p = 0.062) and multiple LLM (p = 0.026). At recurrence after hepatectomy for LLM, the PC group had a significantly higher incidence of solitary tumors than the US group (p = 0.043) and had a higher chance to undergo surgical resection for recurrent sites (p = 0.006)., Conclusions: Preoperative chemotherapy can be recommended for patients with LLM from GC. The evaluation of the efficacy of preoperative chemotherapy offers additional information to determine the surgical indication for LLM., (© 2024. Society of Surgical Oncology.)

Introduction: Despite the increasing performance of laparoscopic proximal gastrectomy (LPG) for proximal gastric cancer and esophagogastric junction cancer, the benefit of LPG over laparoscopic total gastrectomy (LTG) remains to be established. Therefore, this study was conducted to compare postoperative outcomes between LPG and LTG., Methods: Data from 141 patients who underwent LPG or LTG for gastric neoplasm with curative intent between 2016 and 2022 were retrospectively reviewed. Clinicopathological findings, body weight changes, and serological nutritional markers during the postoperative course were evaluated., Results: LPG and LTG were performed in 78 patients and 63 patients, respectively. Patients' characteristics did not differ; however, tumor stages in patients who underwent LTG were more advanced than those who underwent LPG. The mean (± standard deviation) weight loss rate after 1 year was -13.5 (±6.9)% and -18.7 (±6.6)% for LPG and LTG, respectively (p < .01). LTG (OR: 3.326, p < .01), pT disease (OR: 3.000, p = .01), pN disease (OR: 2.708, p = .02), and postoperative chemotherapy (OR: 2.488, p = .05) were correlated with severe weight loss (16% or more) 1 year after surgery, then multivariate analysis identified LTG as an independent factor (p = .01). The mean (± standard deviation) serum total protein level of LPG was significantly higher than that of LTG at 3 months (6.8 ± 0.5 vs. 6.6 ± 0.4 g/dL, p = .02) and 1 year (6.9 ± 0.4 vs. 6.7 ± 0.5 g/dL, p = .01) postoperatively. No difference was observed in postoperative serum hemoglobin and albumin levels., Conclusion: LPG more improved postoperative weight loss than LTG., (© 2023 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Following the establishment of the anti-cancer effect of immune checkpoint inhibitors, lymphopenia has attracted attention as a parameter of preexisting cancer-related immune tolerance. Although the pretreatment absolute lymphocyte count (ALC) has been reported as a prognostic factor in gastric cancer patients, the impact of perioperative changes in the ALC remains unknown. The aim of the present study was to explore the relationship between surgery-induced lymphopenia and outcome., Methods: Database entries for 584 patients who underwent curative resections for pathological Stage IB-III gastric cancer were reviewed. We retrospectively compared clinicopathological factors including pretreatment ALC (pre-ALC) and ALC at first visit after discharge (post-ALC) with the survival. The low ALC was defined as < 1000/μL., Results: The ALC decreased significantly at 1 and 3 days after surgery and then recovered to the baseline value. A low pre-ALC (p < 0.001) and a low post-ALC (p < 0.001) were both correlated with a poor relapse-free survival (RFS). A multivariate analysis of RFS identified a low post-ALC (hazard ratio 1.875, 95% CI 1.156-3.402, p = 0.01), age, gender, BMI, T disease, N disease, severe vessel invasion, type of gastrectomy and postoperative morbidity as independent factors. The low post-ALC group had a poor RFS among patients with Stage II (p = 0.04) and Stage III (p = 0.04) disease, but not among patients with Stage IB disease (p = 0.13). Consistently, the overall survival (OS) rate was significantly lower among patients with a low post-ALC for all stage (p < 0.001), stage II (p = 0.02) and stage III (p = 0.01) disease, not for stage IB (p = 0.09). A low post-ALC was identified as an independent factor for predicting OS by multivariate analysis (hazard ratio: 2.275, 95% CI 1.373-3.769, p = 0.01)., Conclusions: A decrease in post-ALC was correlated with both of RFS and OS after curative resection in patients with locally advanced gastric cancer., Highlights: Postoperative lymphopenia was a poor prognostic factor for gastric cancer., (© 2023. The Author(s).)

Background: Recent improvements in systemic chemotherapy have provided an opportunity for patients with stage IV gastric cancer (GC) to undergo conversion surgery (CS). The aim of this study was to evaluate the long-term outcomes of patients who underwent CS and to elucidate the prognostic factors for CS in stage IV GC., Methods: A total of 79 patients who underwent CS with the aim of R0 resection for stage IV GC at six institutions from January 2008 to July 2019 were enrolled. We retrospectively reviewed the clinicopathological data and prognosis., Results: Of the 79 patients, 23 (31.1%) had initially resectable disease (IR) before chemotherapy, defined as positive for cancer on peritoneal cytology (CY1), resectable hepatic metastasis, or para-aortic lymph node No. 16a2/b1 metastasis. Of the 56 remaining patients with primary unresectable disease, 39 had peritoneal dissemination. R0 resection was accomplished in 63 patients (79.7%). The 3-year OS rates for patients with IR and unresectable disease were 78.3% and 44.5%, respectively. Multivariate analysis showed that IR (P = 0.014) and R0 (P = 0.014) were statistically significant independent prognostic factors for favorable OS. Among patients with peritoneal dissemination alone, OS was significantly better for patients with R0 resection than for patients with R1/2 resection, with the 3-year OS rates of 65.5% and 23.1%, respectively (P = 0.011)., Conclusions: CS is a treatment option for selected patients with stage IV GC. Patients with IR and patients who achieve R0 resection may obtain a survival benefit from CS., (© 2022. The Author(s).)

Purpose: While proximal gastrectomy is being performed increasingly frequently for the treatment of gastric cancer, a standard reconstruction method to obtain optimal postoperative quality of life (QOL) still remains to be established. We modified the original esophagogastrostomy technique by introducing an additional posterolateral fundoplication (PLF) technique to minimize the risk of reflux esophagitis in patients undergoing proximal gastrectomy. The aim of this study was to clarify the clinical benefit of PLF., Methods: A retrospective analysis of the database was conducted to evaluate the effects of PLF. The data were compared between 44 patients in whom PLF was performed (PLF group) and 17 patients in whom conventional esophagogastrostomy without PLF was performed (C group). A number of incidence of postoperative reflux esophagitis and symptoms were assessed by findings of endoscopic examination and the PGSAS-45 questionnaire, respectively., Results: The incidence of grade B or worse esophagitis after surgery was significantly lower in the PLF group than in the C group (0% vs. 58.8%, P < 0.01). The score for the esophageal reflux subscale, as the main outcome measure of PGSAS-45, was significantly better in the PLF group (PLF: 1.5 vs C: 2.4, P < 0.01). Cohen's d value was 1.75, which suggested a rather large effect size. Postoperative benign anastomotic stricture was encountered in 10 cases (22.7%) of the PLF group and 4 cases (23.5%) of the C group, all of whom were successfully treated by brief endoscopic mechanical dilatation., Conclusion: PLF is an expedient procedure for reconstruction after proximal gastrectomy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although several procedures for mechanical anastomosis have recently been reported, intracorporeal manually hand-sewn anastomosis for totally laparoscopic pylorus-preserving gastrectomy (TLPPG) is considered technically difficult. Here, we report a new technique for laparoscopic reconstruction using hand-sewn sutures., Methods: Together with a proper lymphadenectomy, the stomach was detached and resected using separate two-layer incisions, similar to the original laparotomy method. An approximately 5-cm antral cuff was left in place. The essential concept of this new method was to align the anastomotic site by rotating each clamped gastric stump. This allowed us to perform a secure, hand-sewn, two-layer anastomosis successfully. The short-term surgical outcome after TLPPG was retrospectively compared with that for patients who underwent a conventional laparoscopy-assisted procedure (LAPPG)., Results: Of the 20 consecutive patients who underwent pylorus-preserving gastrectomy in our department between 2014 and 2021, the first 8 patients and the subsequent 12 patients underwent LAPPG and TLPPG, respectively. The operation time was significantly longer in the TLPPG group (median, 302 vs. 269 min). The morbidity was comparable (8.3% in TLPPG vs. 12.5% in LAPPG). Postoperative delayed gastric emptying was only observed in one patient in the LAPPG group. TLPPG reduced the cost of the operation by reducing the number of linear stapler cartridges required., Conclusion: A purely hand-sewn gastrogastrostomy is safe, feasible, and cost-effective, and it omits the need for a mini-laparotomy in the upper abdomen., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ramucirumab (RAM) plus paclitaxel (PTX) therapy has shown promising results as a standard second-line treatment for advanced gastric cancer patients. Recently, combined docetaxel (DOC) plus S-1 (DS) therapy could be regarded as the new standard adjuvant chemotherapy for patients with curatively resected stage III gastric cancer. However, the efficacy and safety of RAM plus PTX therapy in patients treated previously with DOC-containing therapy remains unclear., Methods: This study assessed the clinical outcomes of RAM plus PTX therapy in advanced gastric cancer patients with or without a previous history of treatment with a DOC-containing regimen., Results: In a series of 107 consecutive patients enrolled for this study, the median PFS and OS were 4.2 and 6.2 months, respectively. Fifty-five patients had a history of prior therapy with DOC and 52 did not. There was no significant difference between with and without DOC groups in the ORR (22.2% vs. 23.5%), PFS (4.2 vs. 5.3 months), or OS (7.2 vs. 6.4 months). In a comparison taking into account the interval from the DOC-containing therapy to the RAM plus PTX therapy, the number of treatment courses was significantly smaller and the PFS significantly shorter in the patient group with an interval of ≤ 6 months (median, 2 vs 4.5 courses, P = 0.033; 3.4 months vs. 5.1 months, P = 0.043)., Conclusions: RAM plus PTX therapy in patients with advanced gastric cancer is effective even in patients who have previously received DOC-containing chemotherapy, especially if the interval is > 6 months.

Aim: Pylorus-preserving gastrectomy (PPG) is widely used for early gastric cancer located in the middle third of the stomach. The minimization of the extent of gastrectomy may increase the risk of metachronous multiple gastric cancer (MGC). We report the findings of a study that was conducted to evaluate the prevalence of MGC after PPG., Methods: The clinical data of 533 patients who underwent PPG for gastric cancer between 1993 and 2018 were reviewed. The clinicopathological characteristics at the time of the primary treatment that were predictive of the development of MGC were explored. The median (range) observation period was 112.4 (8.1-290.7) months., Results: Metachronous MGC was diagnosed in 33 of the 533 patients. The cumulative 5-year and 10-year event rates were 3.3% and 6.2%, respectively. The patient gender, presence/absence of synchronous MGC and the macroscopic type of the primary gastric cancer were significantly associated with the risk of development of metachronous MGC. Multivariate analysis identified the presence of synchronous MGC (hazard ratio [HR]: 4.828, 95% confidence interval [CI]; 1.611-12.30, p = 0.004) and Type 0-IIa primary gastric cancer (HR 2.810, 95% CI; 1.113-7.090, p = 0.029) as independent factors associated with the risk of development of MGC. All the patients could be treated by surgical or endoscopic resection for the metachronous MGC. Recurrence was observed in one patient., Conclusions: There was quite a few incidence of development of metachronous MGC after PPG. Nevertheless, PPG remains reasonable treatment option, if adequate postoperative surveillance can be ensured.

Background: We sought to determine the prognostic significance of intraoperative peritoneal lavage cytology (CY) at 3 different abdominal cavities and establish the optimal treatment for gastric cancer patients with positive peritoneal cytology (CY1)., Methods: A total of 1,039 patients with primary gastric adenocarcinoma who underwent CY at 3 cavities (Douglas' pouch, left subphrenic cavity, and right subhepatic cavity) were enrolled; 116 (11%) patients had at least one positive cavity. We retrospectively analyzed the clinicopathologic characteristics and survival of these 116 patients with CY1., Results: Seventeen (15%) of the patients had negative cytology at Douglas' pouch but positive cytology at one or both of the other cavities. The 116 patients' overall 2-year survival rate was 22.9%, with the median survival time of 11 months. The overall 2-year survival rates for the patients with positive cytology at 1, 2, and 3 cavities were 41.9%, 35.8%, and 15%, with median survival times of 17, 18, and 9 months, respectively (P < .01). A multivariate analysis revealed that macroscopic type 4 tumor, R2 resection, lymph node metastasis, and postoperative chemotherapy were independent prognostic factors. Among the CY1 patients with type 4 tumors, there was no substantial difference in survival between the patients who underwent R1 or R2 resection, although the statistical power of this subgroup analysis was low., Conclusion: CY at 3 cavities might be a useful method to decrease the false-negative rate. Palliative gastrectomy for CY1 patients with type 4 tumors is still controversial., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Recent improvement in the survival of patients after esophagectomy for esophageal cancer has led to increasing occurrence of second primary cancer in the pulled-up stomach as gastric tube cancer (GTC). However, a treatment strategy for GTC including surveillance has not been established. The aims of this study are to clarify the incidence and clinicopathological characteristics of GTC and to assess the treatment results of endoscopic resection., Methods: Twenty-five patients with 29 GTC lesions treated between 1989 and 2007 were analyzed retrospectively., Results: The median interval between esophagectomy and GTC detection was 86 months, and the 10-year cumulative incidence rate of GTC was 8.6%. Of 18 asymptomatic GTCs, 17 lesions (94.4%) were detected by periodic endoscopy and 15 (88.2%) of them were treated endoscopically. Of all 29 GTCs, endoscopic submucosal dissection (ESD) was performed in 10 GTCs with a completely curative resection rate of 90%, which was significantly higher than that of 7 GTCs treated with endoscopic mucosal resection (EMR) (14.3%, P = 0.004). In these 17 GTCs, no cancer recurrence developed during a median follow-up period of 24 months, and the 3-year survival rate was 80.8%., Conclusions: For patients after esophagectomy with gastric pull-up, long-term follow-up including periodic endoscopy is necessary to detect a potentially curable GTC. ESD is a feasible and safe procedure for GTC, with oncologically favorable features.

We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid. Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy. During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids, respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum. The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case, and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.

We examined safety and efficacy of hypotonic CDDP intraperitoneal administration followed by systemic chemotherapy using MTX/5-FU and UFT. Between 1998 and 2004, seven patients who had histologically proven gastric adenocarcinoma with peritoneal metastases underwent palliative gastrectomy at Niigata University Medical Hospital. For residual peritoneal tumors, 100 mg/body of CDDP diluted with distilled water was intraperitoneally administered to the patients before closure of abdominal wall and was drained 30 to 60 minutes after administration. During the postoperative period, a patient suffered from intraperitoneal abscess and another patient had a renal dysfunction with an increasing level of serum Cr (2.1 mg/dl). As adverse effects of the following systemic chemotherapy, three patients had grade 3 anemia and one had grade 3 leukopenia. The median time to progression was 109 days and the median survival time was 248 days. Although intraperitoneal CDDP administration is safe to be carried out intraoperatively, the effect on survival is not better than new anticancer drugs, such as TS-1 and paclitaxel.

Sequential changes of chromosomal copy number were analyzed retrospectively in five diffuse-type gastric cancer cell lines by comparative genomic hybridization (CGH), DNA cytometry, and fluorescence in situ hybridization (FISH) with centromeric and painting probes. By CGH, we found loss of 18q21 in all of the cell lines and gains of 7p11-q31, 20q, and 22 in four of the five cell lines. Actual copy numbers of chromosomes 7 and 18 were determined by FISH: disomy 18 with (partial) loss of 18q in the two DNA-diploid cell lines (AGS and MKN-45), trisomy 7 in MKN-45, disomy 18 and tetrasomy 7 with one-copy loss of 7p and one-copy gain of 7q tip in DNA-triploid HSC-39/40A, and trisomy 18 and hexasomy 7 with one-copy loss of 7q in DNA-tetraploid KATO-III. Because the DNA aneuploidy is thought to result through tetraploidization, and the duplicated chromosomal changes in DNA aneuploid tumors seem to precede tetraploidization, the duplicated gain of chromosome 7 and one-copy loss of 7q in KATO-III were inferred to have occurred before and after tetraploidization, respectively. Similarly, HSC-39/40A were inferred to be preceded by the DNA-diploid stage with disomy 7 and monosomy 18. As the loss of 18q21 and the gain of 7p11-q31 were inferred to have occurred already in the DNA diploid stage in at least four and two of the cell lines, respectively, the 18q21 loss may be more important than the 7q gain as an earlier event in the genesis of diffuse-type stomach cancer. The combined CGH, FISH, and ploidy analyses thus give us a clue to extract important earlier events from the chromosomal changes that were screened by CGH alone.

Alpha fetoprotein (AFP)-producing gastric cancer is relatively rare and meningitis carcinomatosa is similarly a rare manifestation among the neoplastic diseases. There have been no previous reports of meningitis carcinomatosa originating from AFP-producing gastric cancer. A 68-year-old man with AFP-producing gastric cancer was treated with cisplatin and doxifluridine because of multiple liver metastases. Although the liver lesion was reduced to 30% of pretreatment size after 6 courses of chemotherapy, meningitis carcinomatosa subsequently occurred. Immunostaining of AFP and magnetic resonance imaging (MRI) were useful in the diagnosis of meningitis caused by AFP producing cancer cells.

A 54-year-old man with primary gastric Burkitt's lymphoma is described. He was evaluated for appetite loss and intermittent midepigastric pain. Upper gastroduodenal endoscopy detected an ulcer in the lesser curvature of the body, and biopsy specimens revealed infiltration of medium-sized lymphoblasts with "starry sky" macrophages. The infiltrated cells were positive for a B-cell marker. Abdominal computed tomography scan demonstrated marked enlargement of the gastric wall, but no enlargement of lymph nodes. These findings led us to diagnose primary gastric Burkitt's lymphoma. The patient responded dramatically to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy, but 6 months after his initial admission, the disease recurred in the stomach and bone marrow. Lymphoblastic cells were positive for B-cell markers (CD 10, 19, 20, and human leukocyte antigen [HLA]-DR) and showed an abnormal karyotype, 47, XY, t(8;14)(q24;q32), +12. In these cells, the Epstein-Barr virus genome was detected by polymerase chain reaction. Southern blot analysis revealed rearrangement of Ig heavy and light chain genes. In addition, c-myc gene rearrangement was detected. Eight months after the beginning of chemotherapy, the patient died of central nervous system involvement. To our knowledge, this is the first description of a genetic analysis of primary gastric Burkitt's lymphoma.

Background: An important unanswered question concerning the histogenesis of superficial-type gastric carcinoma is whether it is monoclonal or multiclonal in origin. Therefore, the authors analyzed multiple areas of each cancer with a clonality assay based on trinucleotide repeat length polymorphism of the human androgen receptor gene (HUMARA) that was subject to random inactivation of X chromosomes., Methods: The HUMARA assay was applied to 15 gastric carcinomas, early and advanced stage, manifested in superficial, depressed lesions of various sizes and at least some signet ring cells. DNA was extracted from fresh frozen and formalin fixed tumor tissues that were microdissected from the mucosal lesions, and the HUMARA locus was amplified by polymerase chain reaction with and without prior digestion of nonmethylated DNA with Hpa II. The amplified DNA samples were loaded on polyacrylamide gels, electrophoresed, and visualized by a silver-staining method., Results: In the 15 cases examined, 9 cancers were informative (had features of the types sought in this study), and in these 9 cancers a total of 57 areas were analyzed. In 7 of the 9 cancers, the inactivated allele was common to all the informative areas of each tumor, irrespective of the macroscopic shape of the tumor or the degree of histologic heterogeneity within it. In one of the two remaining cancers, the inactivated allele of one of the areas examined was different from those in the other areas., Conclusions: Most of the superficial depressed-type gastric carcinomas in this study were demonstrated to be of monoclonal origin. This finding supports a notion expressed previously in the literature that superficial-type carcinoma has a long natural history, and it indicates that efforts to detect gastric carcinomas in early stages to improve patients' survival should be encouraged.