FBXW7 regulates the sensitivity of imatinib in gastrointestinal stromal tumors by targeting MCL1.

BACKGROUND: Imatinib contributes to improving prognosis of high-risk or unresectable gastrointestinal stromal tumors (GISTs). As therapeutic efficacy is limited by imatinib resistance and toxicity, the exploration of predictive markers of imatinib therapeutic efficacy that enables patients to utilize more effective therapeutic strategies remains urgent. METHODS: The correlation between FBXW7 and imatinib resistance via FBXW7-MCL1 axis was evaluated in vitro and in vivo experiments. The significance of FBXW7 as a predictor of imatinib treatment efficacy was examined in 140 high-risk patients with GISTs. RESULTS: The ability of FBXW7 to predict therapeutic efficacy of adjuvant imatinib in high-risk GIST patients was determined through 5-year recurrence-free survival (RFS) rates analysis and multivariate analysis. FBXW7 affects imatinib sensitivity by regulating apoptosis in GIST-T1 cells. FBXW7 targets MCL1 to regulate apoptosis. MCL1 involves in the regulation of imatinib sensitivity through inhibiting apoptosis in GIST-T1 cells. FBXW7 regulates imatinib sensitivity by down-regulating MCL1 to enhance imatinib-induced apoptosis in vitro. FBXW7 regulates imatinib sensitivity of GIST cells by targeting MCL1 to predict efficacy of imatinib treatment in vivo. CONCLUSIONS: FBXW7 regulates imatinib sensitivity by inhibiting MCL1 to enhance imatinib-induced apoptosis in GIST, and predicts efficacy of imatinib treatment in high-risk GIST patients treated with imatinib.

Para-aortic lymph node dissection following neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer with extensive lymph node metastasis.

BACKGROUND: D2 and para-aortic lymph node dissection (PAND) following neoadjuvant chemotherapy (NAC) are reportedly effective for gastric cancer (GC) with extensive lymph node metastasis (ELM), such as para-aortic nodal metastasis or bulky nodal metastasis, around the major perigastric arteries. However, type 4 and large type 3 tumors were excluded from previous studies, as they are considered special subtypes that easily spread to the peritoneum. Whether or not PAND contributes to the survival of type 4 or large type 3GC with ELM is thus unclear. METHODS: This study examined patients who underwent radical gastrectomy with D2 resection and PAND following NAC between 2002 and 2019. Patients were classified into the normal-type group and the type 4 or large type 3 group. The overall survival (OS) and prognostic factors were investigated. RESULTS: Forty-nine patients were examined and classified into the normal-type group (34 patients) and type 4 or large type 3 group (15 patients). The 5-year OS rates of the normal-type and type 4 or large type 3 groups were 55.5% and 26.7%, respectively. Type 4 or large type 3 tumors were an independent risk factor for a poor prognosis in the multivariate analysis (hazard ratio: 2.506, 95% confidence interval: 1.111-5.650, and p = 0.027). CONCLUSIONS: The prognosis of type 4 or large type 3 GC with ELM treated with radical gastrectomy with D2 and PAND after NAC was poor. Type 4 or large type 3 GC with ELM should be treated using a different strategy than the normal type with ELM.

Possible candidates for splenic hilar nodal dissection among patients with upper advanced gastric cancer without invasion of the greater curvature.

BACKGROUND: Spleen preserving D2 total gastrectomy without dissection of the splenic hilar nodes (#10) is a standard operation for upper advanced gastric cancer without invasion of the greater curvature (UGC-wGC). However, some patients with #10 metastasis have survived after splenectomy with dissection of #10. This study explored possible candidates for dissection of #10 among patients with UGC-wGC by examining the metastatic rate and the therapeutic index. METHODS: This study retrospectively reviewed data of patients treated in National Cancer Center Hospital (Japan) between 2000 and 2012. We applied the following inclusion criteria: (1) ≥ D2 total gastrectomy with splenectomy, (2) UGC-wGC, and (3) gastric adenocarcinoma histology. Univariate and multivariate analyses were performed to identify risk factors for #10 metastasis. RESULTS: A total of 366 patients were examined; #10 metastasis was observed in 4.4% (16/366). The multivariate analysis revealed that location (posterior vs. others, P = 0.025) and histology (undifferentiated vs. differentiated, P = 0.048) were significant factors for #10 metastasis among sex, age, tumor size, dominant circumferential location, macroscopic type, depth of invasion, and histology. The incidence of #10 metastasis was 14.9% (7/47) for tumors located on the posterior wall with undifferentiated type histology. The 5-year overall survival rate of these patients was 42.9%, and the therapeutic index was 6.38, which was the second highest value among the second-tier nodal stations. CONCLUSION: Even for upper advanced gastric cancer without invasion of the greater curvature, dissection of #10 could be justified for tumors located on the posterior wall with undifferentiated type histology.

Impact of D2 Gastrectomy for Locally Advanced Gastric Cancer in the Era of Effective Adjuvant Chemotherapy.

BACKGROUND: Gastrectomy with D2 dissection has been established as the standard procedure for locally advanced gastric cancer in the era of surgery alone. However, no consideration has been given to the efficacy of dissection in the era of effective adjuvant chemotherapy. METHODS: This study included 1298 advanced gastric cancer patients, consisting of 725 cases treated between January 2000 and December 2006 (Former group), and 573 cases treated between January 2007 and July 2015 (Latter group). Clinicopathological data were collected, survival and the therapeutic value index were determined. RESULTS: The background characteristics were well balanced, except for age, tumor location, and intraoperative blood loss. The Latter group showed the following characteristics: an older population (p < 0.001), a frequent upper location (p = 0.008), and less blood loss (p < 0.001). Adjuvant chemotherapy was administered to 75.2% of the Latter group and was 9.4% in the Former group. The 5-year overall survival rate of the Latter group was 75.7% (95% confidence interval: 71.7-79.1), significantly better than that of the Former group (70.0%, 95% confidence interval: 66.5-73.2) (p = 0.025). Improvement in the index from the Former group was observed in the Latter group at almost all stations. The ratio of the index between these two groups was 1.09 at the D1 station and 1.19 at the D2 station. CONCLUSION: The therapeutic value index was improved in all nodal stations by S-1 adjuvant chemotherapy, regardless of whether the D1 or D2 nodes were involved. D2 gastrectomy would be still important for locally advanced gastric cancer in the era of effective adjuvant chemotherapy.

Acceleration of sarcopenia in elderly patients who develop asymptomatic pneumonia shadow within one year after surgery for early gastric cancer.

BACKGROUND: Although early gastric cancer is curable with local treatment, the overall survival in elderly patients did not reach 80% at five years after surgery. The major cause of death in elderly patients with early gastric cancer is not cancer itself but is related to postoperative sarcopenia. Elderly patients frequently develop postoperative asymptomatic pneumonia shadow, which is associated with a poor prognosis. However, why asymptomatic pneumonia shadow worsens the prognosis remains unclear. We investigated whether sarcopenia is accelerated in patients who developed asymptomatic pneumonia shadow. METHODS: We retrospectively examined patients of > 75 years of age who underwent R0 gastrectomy for gastric cancer and were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. The diagnosis of asymptomatic pneumonia shadow was defined by diagnostic findings of pneumonia (consolidation type, reticular type, and nodular type) which were newly observed on chest computed tomography performed one year after surgery in comparison to preoperative computed tomography. Postoperative muscle loss was assessed by a computed tomography-based analysis using the L3 skeletal muscle index before and two years after surgery and the rate of decrease was calculated. Patients were classified into two groups according to the rate of decrease (cut-off value: 10%). RESULTS: Of the 3412 patients who underwent gastrectomy in our hospital during the study period, 142 were included in this study. Asymptomatic pneumonia shadow was found in 26 patients (18%). Patients who developed asymptomatic pneumonia shadow showed a significantly greater loss of muscle volume in comparison to patients who did not develop asymptomatic pneumonia shadow. In the multivariate analysis, total gastrectomy and asymptomatic pneumonia shadow were the independent risk factors for severe muscle loss. However, there was no significant difference in prognosis between the two groups. CONCLUSIONS: Sarcopenia was accelerated in elderly patients who developed asymptomatic pneumonia shadow after surgery for early gastric cancer. However, the poor prognosis in these patients may not be related to accelerated sarcopenia.

[Gentle Method to Elevate Left Liver Lobe in Robot Assisted Gastrectomy].

Robot-assisted gastrectomy with the Davinci XiTM has been performed in our department since August 2019. This technique requires elevation of the left liver lobe. In order to prevent perioperative liver injury and expansion of postoperative subcutaneous emphysema, we use a silicone disc(HAKKO MEDICAL Co., Ltd.)and thread to elevate the liver. After docking the Davinci system, we move the needle as follows:(ⅰ). left side peritoneum near the left triangular ligament, (ⅱ). silicone rubber(, ⅲ). center of crus(, ⅳ). silicone rubber(, ⅴ). hepatic cirrus, and(ⅵ). right side peritoneum. Both ends of the thread are guided out of the abdominal cavity from both hepatic circumflex by end-close, forming a V-shape with the center of crus at the bottom, which provides a stable and effective view of the liver. Fifty-three cases were performed after introduction of this elevation technique. Median AST and ALT on postoperative day 1 were 37(14-1,556)IU/L and 30(10- 1,676)IU/L, respectively, although small subcutaneous emphysema confined to the anterior chest and upper abdominal wall was observed in 2 patients(3.8%). No cases of extensive subcutaneous emphysema involving the neck or extremities were observed. This elevation technique protects the liver and may reduce the incidence of postoperative subcutaneous emphysema.

Feasibility and Safety of Oral Nutritional Supplementation with High-Density Liquid Diet After Total Gastrectomy for Gastric Cancer.

INTRODUCTION: Patients requiring total gastrectomy for gastric cancer experience a decrease in food intake leading to severe body weight loss after surgery. This loss may be prevented using a high-density liquid diet of high caloric content and minimal volume. This phase II study evaluated the feasibility and safety of a high-density liquid diet (UpLead®; Terumo Corporation, Tokyo, Japan) after total gastrectomy. METHODS: UpLead® (1 pack, 100 mL, 400 kcal/day) was administered after surgery for 28 days. The primary endpoint was the % relative dose intensity of 28 days of UpLead intake®. The secondary endpoint was % body weight loss at 1 and 3 months after surgery. The sample size was 35 considering expected and threshold values of 80 and 60%, respectively, with a one-sided alpha error of 10% and statistical power of 80%. RESULTS: Among 35 patients enrolled before surgery between April 2018 and December 2019, 29 patients who could initiate UpLead® after surgery were analyzed. Seven patients had interrupted UpLead® intake due to taste intolerance (n = 6) and due to a duodenal stump fistula (n = 1). The remaining 22 patients completed 28 days of UpLead® intake, including temporary interruption, with no associated adverse events. The median relative dose intensity was 25.8% (95% confidence interval: 20.6-42.0%). The median body weight loss at 1 and 3 months after surgery was 7.2% (range: 3.2-13.9%) and 13.1% (range: 2.5-20.4%), respectively. CONCLUSIONS: Oral nutritional supplementation with a high-density liquid diet (UpLead®) was safely administered but was not feasible after total gastrectomy for gastric cancer. Clinical trial registration number UMIN000032291.

Optimal surgery for esophagogastric junctional cancer.

Esophagogastric junctional cancer is classified into three categories according to the Siewert classification, which reflects the epidemiological and biological characteristics. Therapeutic strategies have been evaluated according to the three Siewert types. There is a consensus that types I and III should be treated as esophageal cancer and gastric cancer, respectively. On the other hand, type II is often described as true cardiac cancer, which has different clinicopathological features from the other types. Thus, there is no consensus on the surgical management of type II esophagogastric junctional cancer. The optimal surgical management should focus on the principles of cancer surgery, which take into consideration oncological curability, including an appropriate resection margin, adequate lymphadenectomy, and minimization of postoperative complications. In this review, we evaluate the current relevant literature and evidence, on the surgical treatment of esophagogastric junctional cancer, focusing on type II. Esophagectomy with a thoracic approach has the advantage of ensuring a sufficient proximal resection margin and adequate mediastinal lymphadenectomy. However, the oncological benefit is offset by a high incidence of postoperative complications. Minimally invasive esophagectomy could be a possible solution to reduce complications and improve long-term outcomes. Further development of surgical treatments for Siewert type II is required to improve the outcomes. Furthermore, the surgical team should have expertise in both gastric cancer and esophageal cancer treatment, or patients should be managed with close collaboration between thoracic surgeons and gastric cancer surgeons.

Long-term postoperative pneumonia in elderly patients with early gastric cancer.

BACKGROUND: Pneumonia is a major cause of death in the elderly population. Considering body weight loss, muscle loss, and reflux after gastrectomy, elderly patients are considered to be at very high risk for pneumonia, which could decrease overall survival because early gastric cancer is mostly curable only by surgery. We aimed to clarify the incidence of pneumonia in the long-term period after gastrectomy in elderly patients who were diagnosed with early gastric cancer and its risk factors. METHODS: We retrospectively examined patients of > 75 years of age who underwent R0 gastrectomy for gastric cancer and who were diagnosed with T1 disease at National Cancer Center Hospital between 2005 and 2012. Long-term postoperative pneumonia was diagnosed by chest computed tomography every year until 2 years after surgery. The presence of preoperative sarcopenia was assessed using preoperative L3 skeletal muscle index. RESULTS: 167 patients were included in this study. Long-term postoperative pneumonia was observed in 44 (26%) patients. Of the 44 people diagnosed with long-term postoperative pneumonia, 33 were diagnosed in the 1st year and 11 in the 2nd year. 117 patients (70%) were diagnosed with sarcopenia which was significantly frequently found in the patients who developed long-term postoperative pneumonia (91%) than those without (63%). Preoperative sarcopenia was the only independent risk factor in multivariate analysis. Type of gastrectomy was not a significant risk factor. CONCLUSIONS: Long-term postoperative pneumonia was frequently observed in the elderly patients. Preoperative sarcopenia was associated with long-term postoperative pneumonia in elderly patients who underwent curative surgery for gastric cancer. After gastrectomy, long-term special care would be required for elderly patients, especially with sarcopenia.

The prognostic impact of macroscopic serosal change on resectable advanced gastric cancer.

BACKGROUND: Advanced gastric cancer sometimes causes macroscopic serosal change (MSC) due to direct invasion or inflammation. However, the prognostic significance of MSC remains unclear. METHODS: A total of 1410 patients who had been diagnosed with deeper-than-pathological-T2 gastric cancer and undergone R0 gastrectomy with lymph node dissection at the National Cancer Center Hospital during January 2000 and December 2012 were restrospectively reviewed. RESULTS: MSC was not found in 108 of the 506 patients with pathological T4a (21.3%), whereas it was detected in 250 of the 904 patients with pathological T2-T3 (27.7%). The sensitivity, specificity and accuracy for diagnosing pathological serosa exposed (SE) by MSC were 78.7, 72.3 and 74.6%, respectively. The MSC-positive cases had a worse 5-year overall survival (OS) than the MSC-negative cases in pT3 (72.9% vs. 84.3%, p = 0.001), pT4a (56.2% vs. 73.4%, p = 0.001), pStageIIB (76.0% vs. 88.4%, p = 0.005), pStageIIIA (63.4% vs. 75.6%, p = 0.019), pStageIIIB (53.6% vs. 69.2%, p = 0.029) and pStage IIIC (27.6% vs. 50.0%, p = 0.062). A multivariate analysis showed that MSC was a significant independent predictor for the OS (hazard ratio [HR]: 1.587, 95%CI 1.209-2.083, p = 0.001) along with the tumor depth (HR: 7.742, 95%CI: 2.935-20.421, p < 0.001), nodal status (HR:5.783, 95% CI 3.985-8.391, p < 0.001) and age (HR:2.382, 95%CI: 1.918-2.957, p < 0.001). Peritoneal recurrence rates were higher in the MSC-positive cases than in the MSC-negative cases at each pT stage. CONCLUSIONS: In this study, the MSC was one of the independent prognostic factors in patients with resectable locally advanced gastric cancer.

Is splenectomy for dissecting splenic hilar lymph nodes justified for scirrhous gastric cancer?

BACKGROUND: Splenectomy for dissecting splenic hilar lymph nodes (#10) should be avoided for most gastric cancer, considering the high morbidity and lack of any survival benefit, but it is often selected for scirrhous gastric cancer because this type frequently invades the whole stomach and lymph nodes. Splenectomy is necessary for dissecting #10; however, the survival benefit of dissecting #10 is unclear. METHODS: Patients who had scirrhous gastric cancer and underwent D2 total gastrectomy with splenectomy at National Cancer Center Hospital, Japan, between 2000 and 2011 were retrospectively analyzed. The therapeutic value index was calculated by multiplying the metastatic rate of each nodal station and the 5-year survival of patients who had metastasis to each node. RESULTS: In total, 137 patients were eligible for the present study. The most frequent metastatic node was #3(58%), followed by #4d(46%), #1(35%), #4sb(23%), #6(22%), #7(21%), #4sa(18%), #10(15%), #2(14%), #11p(14%), #11d(13%), #9(13%), and #8a(11%). These lymph nodes had a metastatic rate of more than 10%. The node station with the highest index was #3(18.9), followed by #4d(14.1), #1(10.8), #4sa(6.11), #4sb(6.06), #10(5.09), #7(4.39), #11d(4.36), #11p(4.06), #2(2.93), #8a(2.18), and #9(1.45). The index of #10 exceeded that of #2, #7, #8a, and #9, which are the key nodes dissected in D2. CONCLUSION: The metastatic rate of the splenic hilar lymph nodes was relatively high, and the therapeutic index was the sixth highest among the 15 regional lymph nodes included in D2 dissection. Splenectomy for dissecting splenic hilar lymph nodes would be justified for scirrhous gastric cancer.

Feasibility and safety of laparoscopy-assisted distal gastrectomy performed by trainees supervised by an experienced qualified surgeon.

BACKGROUND: Laparoscopic gastrectomy is becoming more commonly performed, but acquisition of its technique remains challenging. We investigated whether laparoscopy-assisted distal gastrectomy (LDG) performed by trainees (TR) supervised by a technically qualified experienced surgeon (QS) is feasible and safe. METHODS: The short-term outcomes of LDG were assessed in patients with gastric cancer between 2008 and 2018. We compared patients who underwent LDG performed by qualified experienced surgeons (QS group) with patients who underwent LDG performed by the trainees (TR group). RESULTS: The operation time was longer in the TR group than in the QS group (median time: 270 min vs. 239 min, p < 0.001). The median duration of the postoperative hospital stay was 9 days in the QS group and 8 days in the TR group (p = 0.003). The incidence of postoperative complications did not differ significantly between the two groups. Grade 2 or higher postoperative complications occurred in 18 patients (12.9%) in the QS group and 47 patients (11.7%) in the TR group (p = 0.763). Grade 3 or higher postoperative complications occurred in 9 patients (6.4%) in the QS group and 17 patients (4.2%) in the TR group (p = 0.357). Multivariate analysis showed that the American Society of Anesthesiologist Physical Status was an independent predictor of grade 2 or higher postoperative complications and that gender was an independent predictor of grade 3 or higher postoperative complications. The main operator (TR/QS) was not an independent predictor of complications. CONCLUSIONS: Laparoscopy-assisted distal gastrectomy performed by trainees supervised by an experienced surgeon is a feasible and safe procedure similar to that performed by experienced surgeons.

Relationship Between the Waiting Times for Surgery and Survival in Patients with Gastric Cancer.

BACKGROUND: Surgery for gastric cancer should be performed as soon as possible after diagnosis. However, sometimes the waiting time for surgery tends to be longer. The relation between the waiting time for surgery and survival in patients with gastric cancer remains to be fully investigated. METHODS: This retrospective, single-center cohort study evaluated patients with gastric cancer who underwent curative surgery from 2006 through 2012 at Kanagawa Cancer Center in Japan. Patients who received neoadjuvant chemotherapy were excluded. The waiting time for surgery was defined as the time between the first visit and surgery. We investigated whether the waiting time for surgery has a linear negative impact on outcomes by using a Cox regression model with clinical prognostic factors. RESULTS: In total, 801 patients were eligible. The median waiting time was 45 days (range 10-269 days). The restricted cubic spline regression curve showed that the adjusted time-specific hazard ratios of waiting times did not indicate a linear negative trend on survival between 20 and 100 days (p = 0.759). In the Cox model with a quartile of waiting times, waiting times in the 32-44-day group, 43-62-day group, and ≥63 day groups were not associated with poorer overall survival as compared with the ≤31 day group (HR: 1.01, 95% CI 0.63-1.60, p = 0.984, HR: 1.17, 95% CI 0.70-1.94, p = 0.550, HR: 1.06, 95% CI 0.60-1.88, p = 0.831, respectively). CONCLUSIONS: There was no negative relation between the waiting time for surgery (within 100 days) and survival in patients with gastric cancer.

Postoperative D-dimer elevation affects tumor recurrence and the long-term survival in gastric cancer patients who undergo gastrectomy.

INTRODUCTION: We retrospectively evaluated the blood coagulation activity using the D-dimer level in the early period after gastrectomy and investigated whether postoperative hypercoagulation affects tumor recurrence and long-term survival in gastric cancer patients. METHODS: The study involved 650 patients who underwent curative resection for gastric cancer at Kanagawa Cancer Center between July 2009 and July 2013. They were divided into a low-D-dimer group (LD group) and high-D-dimer group (HD group) according to the median D-dimer level on postoperative day (POD) 7. The risk factors for overall survival (OS) and relapse-free survival (RFS) were identified. RESULTS: Of the 448 enrolled patients, 218 were classified into the LD group and 230 into the HD group. The 5-year OS rates after surgery were 90.8% and 81.3% in the LD and HD groups, respectively (p < 0.001). The 5-year RFS rates after surgery were 89.9% and 76.1% in the LD and HD groups, respectively (p < 0.001). A high D-dimer level on POD 7 (≥ 4.9 µg/ml) was identified as an independent predictive factor for both the OS (hazard ratio [HR] 1.955, 95% confidence interval [CI] 1.158-3.303, p = 0.012) and RFS (HR 2.182, 95% CI 1.327-3.589, p = 0.002). Furthermore, hematological recurrence was significantly more frequent in the HD group than in the LD group (p = 0.014). CONCLUSION: A high D-dimer level on POD 7 may predict tumor recurrence and the long-term survival in patients who undergo gastrectomy for locally advanced gastric cancer. Patients with an elevated postoperative D-dimer level need careful observation and diagnostic imaging to timely detect tumor recurrence.

Extra-gastrointestinal stromal tumor arising in the lesser omentum with a platelet-derived growth factor receptor alpha (PDGFRA) mutation: a case report and literature review.

BACKGROUND: Gastrointestinal stromal tumors (GIST) arising from sites other than the gastrointestinal (GI) tract, termed extra-gastrointestinal stromal tumors (EGIST), are rare. Among EGIST, those with platelet-derived growth factor receptor alpha (PDGFRA) mutations are even rarer, with only a few cases reported. About 80% of GIST has KIT mutations, and 10% of GIST have PDGFRA mutations, which commonly affect the TK2 domain (exon 18). Among the exon 18 mutations, the D842V substitution is limited to gastric GIST. In EGIST, the degree of KIT and PDGFRA mutations varies on where the location of the tumor is, and it is suggested that omental EGIST is similar to gastric GIST. Adjuvant imatinib therapy is recommended for high-risk GIST; however, it is known that imatinib is less effective against GIST with a PDGFRA D842V mutation. CASE PRESENTATION: A 75-year-old man was referred to our hospital with an extrinsic tumor of the lesser curvature of the gastric body. Intraoperative findings showed a tumor located outside of the lesser omentum with no connection between the tumor and the gastric wall. The tumor was subsequently resected. Pathological examination indicated a GIST arising in the lesser omentum measuring 70 mm in its longer dimension. Because the tumor had a PDGFRA mutation (D842V substitution), imatinib was suspected to lack efficacy to the tumor. Thus, although the tumor was considered clinically to have a high risk of recurrence, adjuvant imatinib therapy was not indicated. The patient has been free of recurrence for 29 months since the surgery. CONCLUSION: We described a case of EGIST with a PDGFRA mutation arising in the lesser omentum. And we reviewed 57 cases of omental EGIST and showed that the clinicopathological characteristics and mutation status in omental EGIST were very similar to gastric GIST. In particular, PDGFAR D842V mutation rate in omental EGIST seemed as high as that in gastric GIST. These results suggested that omental EGIST is strongly related to gastric GIST, so the behavior of omental EGIST might be akin to gastric GIST. However, further studies are required to determine the prognosis and the necessity of adjuvant therapy for EGIST with a PDGFRA mutation.

A nodal diagnosis by computed tomography is unreliable for patients who need additional gastrectomy after endoscopic submucosal dissection.

PURPOSE: T1 gastric cancer is treated by endoscopic submucosal dissection (ESD) or surgery, considering the risk of lymph node metastasis. Additional gastrectomy is necessary when the pathological specimens after ESD show some risk of lymph node metastasis. Preoperative computed tomography (CT) after ESD sometimes reveals enlarged lymph nodes, which should prompt surgeons to select D2 over D1/D1+. However, whether or not CT after ESD is reliable remains unclear. METHODS: Patients who underwent radical gastrectomy for clinical T1 between April 2015 and June 2019 were enrolled. The patients were classified into those who underwent CT after ESD (group A) and those who underwent CT before primary surgery or ESD (group B). The accuracy of the nodal diagnosis was compared between groups. RESULTS: A total of 650 patients (group A; 81, group B; 569) were examined. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (group A vs. group B) were 77.8% vs. 84.2%, 0.0% vs. 15.9%, 84.0% vs. 95.7%, 0.0% vs. 38.2%, and 91.3% vs. 87.1%, respectively. The false-positive rate was 100% in group A and 61.8% in group B (p = 0.011). CONCLUSIONS: A nodal diagnosis by CT is unreliable for patients who need additional gastrectomy after ESD.

Laparoscopic resection of a primary diaphragmatic schwannoma: a case report and literature review.

BACKGROUND: Schwannomas are nerve sheath tumors that commonly originate from the stomach and small intestine. A primary schwannoma of the diaphragm is rare and does not show any symptoms until it grows to a certain size. Hence, it is extremely rare that it was found at a size that allowed resection under videoscopic surgery. CASE PRESENTATION: A 77-year-old woman was referred to our department for surgical treatment of a tumor located near the gastric fornix. She underwent a routine esophagogastroduodenoscopy 2 years and 7 months prior to the referral. It was suspected that she had a submucosal tumor measuring 10 mm, located in the fornix, and was then referred to her previous physician. During her follow-up, endoscopic ultrasonography (EUS) revealed that the cystic structure had continued to grow toward the gastric wall, and she was then referred to the endoscopy division of our hospital. She continued to be followed-up, and it was noted that the tumor was gradually increasing in size. Therefore, she requested surgical resection, and was finally referred to our division. Since the tumor was rather small, we planned a laparoscopic surgery. An initial examination during the operation revealed that the tumor was located on the left diaphragm. Since the tumor was relatively small and visibility was good, we decided to continue with the laparoscopic surgery. Partial diaphragmectomy with complete inclusion of the tumor was performed, and the defect of the diaphragm was directly closed by a running suture. Pathological examination revealed a benign schwannoma that had originated from the diaphragm. To support our findings, we also reviewed the scientific literature on diaphragmatic schwannoma cases reported up to April 2020. CONCLUSIONS: In this extremely rare case, we successfully resected the diaphragmatic schwannoma using laparoscopic surgery.

Risk factors analysis and stratification for microscopically positive resection margin in gastric cancer patients.

BACKGROUND: Cancer cells are often found postoperatively at surgical resection margins (RM) in patients with gastric cancer because of submucosal infiltration or hesitation to secure adequate RM. This study was designed to evaluate risk factors for microscopic positive RM and to clarify which patients should undergo intraoperative frozen section diagnosis (IFSD). METHODS: Patients who underwent R0/1 gastrectomy for gastric adenocarcinoma between 2000 and 2018 in a single cancer center in Japan were studied. We divided the patients into a positive RM group and negative RM group according to the results of definitive histopathological examinations. We performed multivariate analysis to analyze risk factors for positive RM by and used the identified risk factors to risk stratify the patients. RESULTS: A total of 2757 patients were studied, including 49 (1.8%) in the positive RM group. The risk factors significantly associated with positive RM were remnant gastric cancer (odds ratio [OR] 4.7), esophageal invasion (OR 6.3), tumor size ≥80 mm (OR 3.9), and a histopathological diagnosis of undifferentiated type (OR 3.6), macroscopic type 4 (OR 3.7), or pT4 disease (OR 4.6). On risk stratification analysis, the incidence of positive RM was 0.1% without any risk factors, increasing to 0.4% with one risk factor, 3.1% with two risk factors, 5.3% with three risk factors, 21.3% with four risk factors, and 85.7% with five risk factors. CONCLUSIONS: The risk of macroscopically positive RM increased in patients who have risk factors. IFSD should be performed in patients who have four or more risk factors.

Equivalent feasibility and safety of perioperative care by ERAS in open and laparoscopy-assisted distal gastrectomy for gastric cancer: a single-institution ancillary study using the patient cohort enrolled in the JCOG0912 phase III trial.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) has an advantage of earlier recovery after surgery due to having lower invasiveness and wound pain than open distal gastrectomy (ODG). However, whether the same enhanced recovery after surgery (ERAS) program for LADG is equally feasible and safe for ODG remains unclear. METHODS: We retrospectively extracted the clinical data of the patients enrolled in JCOG0912 from the medical record system of our hospital and compared the treatment process and short-term surgical outcomes between LADG and ODG. Our ERAS program consisted of 13 elements (4 preoperative, 4 intraoperative, and 5 postoperative elements). The morbidity was defined as complications of grade 2 or more. RESULTS: One hundred and sixty-three patients were entered from our hospital and randomized to undergo ODG (82 patients) or LADG (81 patients). The patient's backgrounds, surgical outcomes, and pathological outcomes were similar between the ODG and LADG groups. The rate of completing the clinical pathway was 95.1% in both groups, and the rates of completing each ERAS element were similar. However, the additional use of acetaminophen was significantly more frequent in the ODG group than in the LADG group (18.3% vs. 6.2%, p = 0.03). The median hospital stay after surgery was 9 days in both groups. Morbidity, defined as Clavien-Dindo classification > grade 2, was observed in 6.1% of the ODG group and 11.1% of the LADG group. No mortality occurred in either group. CONCLUSION: This study showed that the regimen of perioperative care performed by the ERAS program for LADG was equally feasible and safe for ODG with additional pain control. Less pain observed in LADG was not so apparent advantage for completion and safety of ERAS care.

[Curative Resection of Pancreatic Head Cancer with Liver Metastasis after GEM plus Nab-PTX Therapy].

A 63-year-old man was admitted to our hospital for examination and treatment of a pancreatic head tumor detected at a nearby hospital. After CT, EUS-FNA, and PET-CT, he was diagnosed with unresectable pancreatic cancer with liver metastasis. After 9 courses of gemcitabine and nab-paclitaxel therapy, the primary tumor was dramatically reduced in size and the liver metastasis had disappeared. He underwent subtotal stomach-preserving pancreaticoduodenectomy. The postoperative diagnosis according to the General Rules of the Study of Pancreatic Cancer(7th edition)was Ph, TS1(15mm), adenosquamous carcinoma, ypT3, ypRP1, ypPL1, R0, ypN0(0/29), M0, CY0, ypStage ⅡA. The histological response was Grade 2. The patient remains alive without recurrence 5 months after surgical resection.