Significance of Comprehensive Analysis of Preoperative Sarcopenia Based on Muscle Mass, Muscle Strength, and Physical Function for the Prognosis of Patients with Esophageal Cancer.

BACKGROUND: The assessment of muscle mass loss, muscle strength, and physical function has been recommended in diagnosing sarcopenia. However, only muscle mass has been assessed in previous studies. Therefore, this study investigated the effect of comprehensively diagnosed preoperative sarcopenia on the prognosis of patients with esophageal cancer. METHODS: The study analyzed 115 patients with esophageal cancer (age ≥ 65 years) who underwent curative esophagectomy. Preoperative sarcopenia was analyzed using the skeletal mass index (SMI), handgrip strength, and gait speed based on the Asian Working Group for Sarcopenia 2019 criteria. Clinicopathologic factors, incidence of postoperative complications, and overall survival (OS) were compared between the sarcopenia and non-sarcopenia groups. The significance of the three individual parameters also was evaluated. RESULTS: The evaluation identified 47 (40.9%) patients with low SMI, 31 (27.0%) patients with low handgrip strength, and 6 (5.2%) patients with slow gait speed. Sarcopenia was diagnosed in 23 patients (20%) and associated with older age and advanced pT stage. The incidence of postoperative complications did not differ significantly between the two groups. Among the three parameters, only slow gait speed was associated with Clavien-Dindo grade 2 or greater complications. The sarcopenia group showed significantly worse OS than the non-sarcopenia group. Those with low handgrip strength tended to have worse OS, and those with slow gait speed had significantly worse OS than their counterparts. CONCLUSIONS: Preoperative sarcopenia diagnosed using skeletal muscle mass, muscle strength, and physical function may have an impact on the survival of patients with esophageal cancer.

Clinical Impact of Conversion Surgery After Induction Therapy for Esophageal Cancer with Synchronous Distant Metastasis: A Multi-institutional Retrospective Study.

BACKGROUND: The standard treatment for advanced esophageal cancer with synchronous distant metastasis is systemic chemotherapy or immunotherapy. Conversion surgery is not established for esophageal cancer with synchronous distant metastasis. This study aimed to investigate the clinical impact of conversion surgery for esophageal cancer with synchronous distant metastasis after induction therapy. METHODS: This multi-institutional retrospective study enrolled 66 patients with advanced esophageal cancer, including synchronous distant metastasis, who underwent induction chemotherapy or chemoradiotherapy followed by conversion surgery between 2005 and 2021. Short- and long-term outcomes were investigated. RESULTS: Distant lymph node (LN) metastasis occurred in 51 patients (77%). Distant organ metastasis occurred in 15 (23%) patients. There were 41 patients with metastatic para-aortic LNs, and 10 patients with other metastatic LNs. Organs with distant metastasis included the lung in seven patients, liver in seven patients, and liver and lung in one patient. For 61 patients (92%), R0 resection was achieved. The postoperative complication rate was 47%. The in-hospital mortality rate was 1%, and the 3- and 5-year overall survival (OS) rates for all the patients were 32.4% and 24.4%, respectively. The OS rates were similar between the patients with distant LN metastasis and the patients with distant organ metastasis (3-year OS: 34.9% vs. 26.7%; P = 0.435). Multivariate analysis showed that pathologic nodal status is independently associated with a poor prognosis (hazard ratio, 2.43; P = 0.005). CONCLUSIONS: Conversion surgery after chemotherapy or chemoradiotherapy for esophageal cancer with synchronous distant metastasis is feasible and promising. It might be effective for improving the long-term prognosis for patients with controlled nodal status.

Prognostic impact of nodal status and lymphovascular invasion in patients undergoing neoadjuvant chemotherapy for esophageal squamous cell carcinoma.

Nodal status is well known to be the most important prognostic factor for esophageal cancer patients, even if they are treated with neoadjuvant therapy. To establish an optimal postoperative adjuvant strategy for patients, we aimed to more accurately predict the prognosis of patients and systemic recurrence by using clinicopathological factors, including nodal status, in patients with esophageal cancer who received neoadjuvant chemotherapy. The clinicopathological factors associated with survival and systemic recurrence were investigated in 488 patients with esophageal squamous cell carcinoma who received neoadjuvant chemotherapy. Overall survival differed according to tumor depth, nodal status, tumor regression, and lymphovascular (LV) invasion. In the multivariate analysis, nodal status and LV invasion were identified as independent prognostic factors (P < 0.0001, P = 0.0008). Nodal status was also identified as an independent factor associated with systemic recurrence, although LV invasion was a borderline factor (P = 0.066). In each pN stage, patients with LV invasion showed significantly worse overall survival than those without LV invasion (pN0: P = 0.036, pN1: P = 0.0044, pN2: P = 0.0194, pN3: P = 0.0054). Patients with LV invasion were also more likely to have systemic, and any recurrence than those without LV invasion in each pN stage. Pathological nodal status and LV invasion were the most important predictors of survival and systemic recurrence in patients with esophageal cancer who underwent neoadjuvant chemotherapy followed by surgery. This finding could provide useful information about selecting candidates for adjuvant therapy among these patients. Our analysis showed that LV invasion was an independent prognostic factor in patients with esophageal cancer who underwent neoadjuvant chemotherapy and that combining LV invasion with pathological nodal status makes it possible to stratify the prognosis in those patients.

Density and maturity of peritumoral tertiary lymphoid structures in oesophageal squamous cell carcinoma predicts patient survival and response to immune checkpoint inhibitors.

BACKGROUND: Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates in non-lymphoid tissues, which are associated with improved prognosis in some cancer types. This study aimed to investigate the clinical significance of TLSs in oesophageal cancer (EC). METHODS: In a series of 316 EC surgical specimens from two different institutes, we evaluated the density and maturity of peritumoral TLSs using haematoxylin/eosin, immunohistochemistry, and multiplex immunofluorescence staining. We analysed the association between TLSs and clinicopathological parameters. The clinical significance of TLSs was further evaluated in a different cohort of 34 patients with recurrent EC treated with anti-PD-1 antibody. RESULTS: Tumours with high TLS density predominantly consisted of matured TLSs. High TLS density was significantly associated with less advanced tumour stage, absence of lymphatic/vascular invasion, better serum nutrition parameters (neutrophils count, albumin, neutrophil-to-lymphocyte ratio, and prognostic nutritional index), and prolonged survival. This survival trend was more remarkable in cases with matured TLSs, which represented an increased population of CD138+ plasma cells. In the second EC cohort, TLS density predicted the clinical response to anti-PD-1 antibody and patient survival. CONCLUSION: The density and maturity of peritumoral TLSs are useful parameters for predicting long-term survival and response to anti-PD-1 antibody treatment in EC patients.

Clinical Impact of Metastatic Lymph Node Size on Therapeutic Effect and Prognosis in Patients with Esophageal Squamous Cell Carcinoma Who Underwent Preoperative Chemotherapy Followed by Esophagectomy.

BACKGROUND: Pretreatment metastatic lymph node (LN) size has been reported to be associated with prognosis in esophageal squamous cell carcinoma (ESCC). However, its relationship with response to preoperative chemotherapy or prognosis has not been clarified. We investigated the relationship between metastatic LN size and response to preoperative treatment, and prognosis in patients with metastatic esophageal cancer who underwent surgery. PATIENTS AND METHODS: A total of 212 clinically node-positive patients who underwent preoperative chemotherapy followed by esophagectomy for ESCC were enrolled. Patients were stratified into three groups on the basis of the length of the short axis of the largest LN in pretreatment computed tomography images: < 10 mm (group A), 10-19 mm (group B), and ≥ 20 mm (group C). RESULTS: Group A had 90 patients (42%), group B had 103 patients (49%), and group C had 19 patients (9%). Group C had significantly lower percent reduction in total metastatic LN size than groups A and B (22.5% versus 35.7%, P = 0.037). Group C had significantly more metastatic LNs based on histological examination than groups A and B (10.1 versus 2.4, P < 0.001). Group C patients whose LNs responded had significantly fewer metastatic LNs than nonresponders (5.1 versus 11.9, P = 0.042). Group C had significantly poorer overall survival than groups A and B (3-year survival, 25.4% versus 67.3%, P < 0.001). However, group C patients whose LNs responded had better survival than nonresponders (3-year survival, 57.1% versus 0%, P = 0.008). CONCLUSIONS: Patients with large metastatic LNs have poor response and poor prognosis. However, if a response is obtained, long-term survival can be expected.

Clinical Impact of Early Tumour Shrinkage in Metastatic or Unresectable Oesophageal Cancer Treated with Pembrolizumab plus Chemotherapy.

INTRODUCTION: Metastatic or unresectable locally advanced oesophageal cancer remains a disease with high mortality. More recently, pembrolizumab plus chemotherapy has been indicated as the first-line treatment for those patients, but the predictive factors for treatment efficacy remain controversial. This study investigated the clinical utility of early tumour shrinkage (ETS) and depth of response (DpR) in metastatic or unresectable oesophageal cancer treated with pembrolizumab plus CF therapy. METHODS: ETS and DpR, defined as the percent decreases at the second evaluation and the percentage of the maximal tumour shrinkage during treatment, were measured in 53 eligible patients. The ETS and DpR cut-off values were 20% and 30%, respectively, based on survival outcomes. RESULTS: Twenty-seven patients (51%) were treatment-naïve, while 26 (49%) had received any treatment before initiating pembrolizumab plus CF therapy. The median progression-free survival (PFS) and overall survival (OS) for ETS ≥20% and <20% were 12.7 and 5.5 months and 14.4 and 8.2 months, and 12.7 and 4.9 months and 14.4 and 8.0 months for DpR ≥30% and <30%, respectively. ETS <20% showed early tumour growth, whereas ETS ≥20% had a good response rate with sufficient longer response duration. In addition, an ETS cut-off of 20% predicted the best overall response and was not associated with prior treatment. In multivariable analysis, ETS ≥20% and DpR ≥30% were independent factors of longer PFS. CONCLUSION: Our findings suggest that an ETS is a promising on-treatment marker for early prediction of further sensitivity to pembrolizumab plus CF therapy.

Clinicopathological characteristics and survival outcomes in patients with advanced esophageal squamous cell carcinoma who were intraoperatively diagnosed non-curative.

INTRODUCTION: Curative esophagectomy is not always possible in patients with locally advanced esophageal cancer. However, few studies have investigated patients who underwent non-curative surgery with intraoperative judgment. This study aimed to investigate patient characteristics and clinical outcomes for patients undergoing non-curative surgery and compare them between non-resectional and non-radical surgery. METHODS: Among 989 consecutive patients with thoracic esophageal squamous cell carcinoma (ESCC) who were preoperatively expected for curative esophagectomy, 66 who were eligible for non-curative surgery were included in this study. RESULTS: Intraoperative diagnosis of T4b accounted for 93% of the reasons for the failure of curative surgery. In those patients, esophageal cancer locally invaded into the aortobronchial constriction (70%), trachea (25%), or pulmonary vein (5%). LN metastasis mainly invaded into the trachea (50%), or bronchus (28%).The overall survival of patients with non-curative surgery was 51.5%, 25.7%, and 10.4% at 6, 12, and 24 months after surgery, respectively. Although there were no differences in preoperative patient characteristics between non-resectional and non-radical surgery, distant metastasis, especially pleural dissemination, was significantly observed in T4b patients due to esophageal cancer with non-radical surgery than those with non-resectional surgery (35% vs. 15%, P=0.002). Even in patients with non-curative surgery, R1 resection and postoperative CRT were identified as independent factors for survival 1 year after surgery (P=0.047, and 0.019). CONCLUSIONS: T4b tumor located in aortobronchial constriction or trachea/bronchus makes it difficult to diagnose whether it is resectable or unresectable. Moreover, surgical procedures and perioperative treatment were deeply associated with the clinical outcomes.

Prognostic Value of a Novel Index Combining the Prognostic Nutritional Index and D-Dimer Levels for Gastric Cancer after Gastrectomy.

INTRODUCTION: The prognostic nutritional index (PNI) and D-dimer level are two useful measures for gastric cancer prognosis. As they each comprise different factors, it is possible to employ a more useful combined indicator. This study therefore aimed to establish a PNI-D score - which combines the PNI and D-dimer level - and validate its usefulness as a prognostic marker. METHODS: We collected data from 1,218 patients with gastric cancer who had undergone radical gastrectomy (R0) between January 2004 and December 2015. Patients were divided into three PNI-D score groups based on the following criteria: score 2, low-PNI (≤46) and high D-dimer levels (>1.0 µg/mL); score 1, either low-PNI or high D-dimer levels; and score 0, no abnormality. We defined the PNI-D score as low (score 0 or 1) and high (score 2), respectively. RESULTS: The PNI-D score was significantly associated with overall, recurrence-free, and disease-specific survival (all log-rank p < 0.0001). The 5-year overall survival rates of patients with PNI-D scores of low and high were 88.1% and 64.7%, respectively; their 5-year recurrence-free survival rates were 86.7% and 61.3%, respectively; and their 5-year disease-specific survival rates were 99.3% and 76.5%, respectively. Cox multivariate analysis revealed that a high-PNI-D score was an independent, statistically significant prognostic factor for poor overall (p = 0.01) survival in patients with gastric cancer. CONCLUSIONS: The PNI-D is an independent prognostic factor for patients with gastric cancer.

DUPAN-II normalisation as a biological indicator during preoperative chemoradiation therapy for resectable and borderline resectable pancreatic cancer.

BACKGROUND: Duke pancreatic mono-clonal antigen type 2 (DUPAN-II) is a famous tumour maker for pancreatic cancer (PC) as well as carbohydrate antigen 19-9 (CA19-9). We evaluated the clinical implications of DUPAN-II levels as a biological indicator for PC during preoperative chemoradiation therapy (CRT). METHODS: This retrospective analysis included data from 221 consecutive patients with resectable and borderline resectable PC at diagnosis who underwent preoperative CRT between 2008 and 2017. We focused on 73 patients with elevated pre-CRT DUPAN-II levels (> 230 U/mL; more than 1.5 times the cut-off value for the normal range). Pre- and post-CRT DUPAN-II levels and the changes in DUPAN-II ratio were measured. RESULTS: Univariate analysis identified normalisation of DUPAN-II levels after CRT as a significant prognostic factor (hazard ratio [HR] = 2.06, confidence interval [CI] = 1.03-4.24, p = 0.042). Total normalisation ratio was 49% (n = 36). Overall survival (OS) in patients with normalised DUPAN-II levels was significantly longer than that in 73 patients with elevated levels (5-year survival, 55% vs. 21%, p = 0.032) and in 60 patients who underwent tumour resection (5-year survival, 59% vs. 26%, p = 0.039). CONCLUSION: Normalisation of DUPAN-II levels during preoperative CRT was a significant prognostic factor and could be an indicator to monitor treatment efficacy and predict patient prognosis.

Modified Collard technique is more effective than circular stapled for cervical esophagogastric anastomosis in prevention of anastomotic stricture: a propensity score-matched study.

The anastomotic technique after esophagectomy is of great interest in the prevention of anastomotic complications that adversely affect postoperative recovery. This study aimed to compare the clinical outcomes of modified Collard (MC) and circular stapled (CS) anastomoses after esophagectomy. A total of 504 consecutive patients with thoracic esophageal cancer who underwent esophagectomy and cervical esophagogastric CS or MC anastomosis from January 2013 to December 2019 were enrolled. Out of 504 patients, 134 and 370 underwent CS and MC anastomoses. The frequency of anastomotic leakage and stricture was significantly lesser in the MC group than in the CS group (3.0 vs. 10.5%, P = 0.0014 and 11.1 vs. 34.3%, P < 0.001, respectively). CS anastomosis was an independent risk factor for anastomotic stricture (odds ratio, 4.89; P < 0.001). Oral intake was significantly higher in the group without anastomotic stricture than in the group with anastomotic stricture at 2, 3, and 6 months postoperatively (P < 0.001, P = 0.013, and P < 0.001, respectively). The percentage body weight loss (%BWL) was -12.2% in the group with anastomotic stricture and -7.5% in the group without anastomotic stricture at 3 months postoperatively (P = 0.0012). Anastomotic stricture was an independent factor associated with %BWL (odds ratio, 4.86; P = 0.010). Propensity score-matched analysis, which included 88 pairs of patients, confirmed a significantly lower anastomotic stricture rate in the MC group than in the CS group (10.2 vs. 35.2%, P < 0.001). MC anastomosis is better than CS anastomosis for reducing the frequency of anastomotic stricture, which may be useful for maintaining early postoperative nutritional status.

Significance of dissection in each regional lymph-node station of esophageal cancer based on efficacy index and recurrence patterns after curative esophagectomy.

BACKGROUND: The optimal extent of lymph-node (LN) dissection in esophageal cancer has not been established. Although the frequency and patterns of recurrence in each regional LN station after radical dissection are important in determining the regional LNs of thoracic esophageal cancer to be routinely dissected, this information has not been investigated sufficiently. We studied the significance of dissection at each LN station based on their recurrence patterns. METHODS: Six hundred and twelve patients with esophageal cancer who underwent curative esophagectomy were studied. The incidence and pattern of recurrence (systemic or non-systemic) at each regional LN station were analyzed. To compare the significance of dissection among regional LNs, the efficacy index (EI) was also calculated. RESULTS: Regional LN recurrence was diagnosed in 101 (16.5%) patients. Among the regional LNs, recurrent laryngeal nerve, paraesophageal, and perigastric LNs showed higher EIs (3.1-6.7). Pretracheal and posterior thoracic para-aortic LNs showed low EIs (0-0.2). Supraclavicular LNs had moderate EIs (1.7-2.0). The recurrence rate was highest in the pretracheal LN, followed by the supraclavicular LNs. The majority (81.8%) of the pretracheal LN had a systemic recurrence, while about half (right: 60.0%, left: 43.8%) of the supraclavicular LNs had a systemic recurrence. CONCLUSION: Due to the high incidence of systemic recurrence or low EI for pretracheal and posterior thoracic para-aortic LNs, we suggest that these LN stations be regarded as non-regional LNs and be excluded from routine dissection. Supraclavicular LNs may also be excluded from routinely dissected stations.

Salvage Surgery for Recurrent Disease after Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Outcomes of salvage surgery after failed definitive chemoradiation (CRT) for esophageal cancer have been well defined. However, only a few studies have focused on salvage esophagectomy for recurrent disease after CRT. METHODS: In 227 patients with esophageal cancer who underwent salvage esophagectomy after definitive CRT, consisting of 116 patients who underwent esophagectomy for persistent disease (the persistent group) and 111 patients who underwent esophagectomy for recurrent disease (the recurrent group), the short- and long-term outcomes were investigated. RESULTS: The rates of any postoperative complication were similar between the groups (49.1% in the persistent group vs. 49.5% in the recurrent group, p = 0.951), although there was a higher rate of anastomotic leakage in the recurrent group (p = 0.027). Thirty-day mortality was also similar between the groups (1.7% in the persistent group vs. 0.9% in the recurrent group, p = 0.587). The 3-year and 5-year overall survival rates were 33.7% and 28.0% in the persistent group and 48.7% and 41.7% in the recurrent group, respectively (p = 0.0175). In the recurrent group, clinically nodal status before CRT as well as pathologically nodal status and time to relapse were identified as independent prognostic factors. In the persistent group, pT and resection margin were identified as independent factors associated with survival. CONCLUSIONS: The present study showed that salvage surgery for recurrent disease can provide acceptable short- and long-term outcomes. Considering clinically and pathologically nodal status and time to relapse, adjuvant therapy might be offered for patients who underwent salvage esophagectomy for recurrent disease after definitive CRT.

Recurrence Pattern Comparing Preoperative Chemoradiotherapy and Preoperative Chemotherapy with Docetaxel plus 5-Fluorouracil and Cisplatin for Advanced Esophageal Cancer.

BACKGROUND: Preoperative chemoradiation therapy (CRT) or chemotherapy (CT) followed by surgery is currently being administered for advanced esophageal cancer. However, few studies have directly compared CRT and CT for treating locally advanced esophageal carcinoma. This study aimed to assess postoperative recurrence patterns and post-recurrence outcomes in patients with radical esophagectomy after CRT or triplet CT regimen with docetaxel, cisplatin, and 5-fluorouracil (DCF). METHODS: This study included 325 consecutive patients with thoracic esophageal cancer who received preoperative CRT or DCF followed by curative esophagectomy between January 2010 and December 2019. We compared recurrence patterns after surgery and post-recurrence treatments between CRT and DCF. Locoregional recurrence was defined as recurrences at the primary tumor site or regional lymph nodes. Distant recurrence was defined as non-regional lymph node recurrences, systemic metastases, malignant pleural effusions, or peritoneal metastases. RESULTS: Among 325 patients, 74 received preoperative CF + RT and 251 received preoperative DCF. A propensity score-matched cohort of 53 with CRT and 53 with DCF was included. CRT patients had tumors located in the upper esophagus and had more advanced cancer than DCF patients; however, no differences in patient characteristics were observed in the matched cohort. CRT patients had better histopathological responses and control of locoregional recurrence than DCF patients. On the other hand, distant recurrence, especially in the non-regional lymph node, lung, and pleural dissemination, significantly developed more frequently in CRT patients. Furthermore, CRT patients may have received insufficient post-recurrence treatment, owing to fewer treatment options. Therefore, although there was no difference in recurrence rate in the two groups, CRT patients had significantly poorer post-recurrence survival than DCF patients. CONCLUSIONS: Preoperative DCF could reduce distant recurrence after surgery compared to preoperative CRT. The differences in recurrence patterns can be related to the selection of post-recurrence treatment and their prognosis after recurrence.

Comparison of robotic gastrectomy and laparoscopic gastrectomy for gastric cancer: a propensity score-matched analysis.

BACKGROUND: The benefits of robotic gastrectomy (RG) over laparoscopic gastrectomy (LG) remain controversial. This single-center, propensity score-matched study aimed to compare the outcomes of RG with those of LG for treating gastric cancer. METHODS: We searched the prospective gastric cancer database of our institute for patients with gastric cancer who underwent RG or LG between January 2014 and December 2019, excluding patients with remnant stomach cancer and those who underwent concurrent surgery for comorbid malignancies. One-to-one propensity score matching was performed to reduce bias from confounding patient-related variables, and short- and long-term outcomes were compared between the groups. RESULTS: We identified 1189 patients who underwent LG (n = 979) or RG (n = 210). After propensity score matching, we selected 210 pairs of patients who underwent LG (distal gastrectomy, 138; total or proximal gastrectomy, 72) or RG (distal gastrectomy, 143; total or proximal gastrectomy, 67). RG was associated with a significantly shorter operative time (RG = 201 min vs. LG = 231 min, p = 0.0051), less blood loss (RG = 13 mL vs. LG = 42 mL, p < 0.0001), lower postoperative morbidity (RG = 1.0% vs. LG = 4.8%, p = 0.0066), and a shorter postoperative hospital stay (p = 0.0002) than LG. Drain amylase levels on postoperative Days 1 and 3 in the RG group were significantly lower than those in the LG group (p < 0.0001). CONCLUSIONS: RG is a safe and feasible treatment for gastric cancer, with a shorter operative time, less blood loss, and lower postoperative morbidity than LG. The application of robotics in minimally invasive gastric cancer surgery may offer an alternative to conventional surgery. Multicenter, prospective, randomized controlled trials comparing RG with conventional LG are needed to establish the feasibility and efficacy of minimally invasive gastric cancer surgery.

Clinical importance of carcinoembryonic antigen messenger RNA level in peritoneal lavage fluids measured by transcription-reverse transcription concerted reaction for advanced gastric cancer in laparoscopic surgery.

BACKGROUND: Transcription-reverse transcription concerted reaction (TRC) is recognized as a useful method for detecting free cancer cells in the peritoneal cavity and predicting peritoneal recurrence in patients with gastric cancer. Nonetheless, the clinical significance of TRC in laparoscopic surgery remains unclear. This study aimed to evaluate the clinical importance of carcinoembryonic antigen (CEA) messenger RNA (mRNA) level in peritoneal lavage fluids measured by TRC in laparoscopic surgery for locally advanced gastric cancer. METHODS: We enrolled patients with locally advanced gastric cancer who underwent laparoscopic gastrectomy. Peritoneal lavage fluids were collected prior to gastrectomy, and the TRC method was employed to quantify CEA mRNA in peritoneal washes. Overall survival (OS), recurrence-free survival (RFS), and peritoneal recurrence-free survival (PRFS) were analyzed using the Kaplan-Meier method and compared using the log-rank test. Adjusted Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) for CEA mRNA positivity. RESULTS: A total of 100 patients were analyzed in this study. Overall, 22 patients (22%) exhibited CEA mRNA positivity in peritoneal lavage fluids, as measured by TRC. No significant association between CEA mRNA levels and clinicopathological characteristics was observed. Patients who were CEA mRNA-positive in peritoneal lavage fluids had significantly worse OS, RFS, and PRFS than those who were CEA mRNA-negative (p = 0.0059, p < 0.0001, and p = 0.0022, respectively). In the univariate Cox model, the HR for all-cause mortality in CEA mRNA-positive versus CEA mRNA-negative patients was 3.60 (95% CI, 1.33-9.55; p = 0.0129). Multivariate analysis revealed that CEA mRNA positivity was a significant independent factor for recurrence. CONCLUSIONS: TRC enables the detection of free cancer cells in the peritoneal cavity and CEA mRNA levels can help predict the prognosis, even in laparoscopic gastrectomy.

Safety and efficacy of preoperative indocyanine green fluorescence marking in laparoscopic gastrectomy for proximal gastric and esophagogastric junction adenocarcinoma (ICG MAP study).

PURPOSE: The incidence of adenocarcinoma of the esophagogastric junction (AEG) and proximal gastric cancer (PGC) is rising worldwide. Recently, the use of indocyanine green (ICG) tracer-guided surgery has been reported; however, its efficacy for total/proximal gastrectomy has not been clarified. We evaluated the feasibility and safety of ICG fluorescent marking for tumor localization in AEG/PGC treatment by laparoscopic surgery. METHODS: We enrolled patients with AEG/PGC from October 2016 to March 2019 from a prospectively registered database. On the day before surgery, ICG markings were made at four locations just at the edge of the tumor by gastrointestinal fiberscope examination. Surgery was performed while viewing the fluorescence image of ICG, and the proximal portions of the esophagus and the distal portion of the stomach were resected at the edge of the area where ICG had spread. RESULTS: We enrolled 130 patients with AEG/PGC. Overall, 107 patients were eventually included in the study: AEG n = 64 (60%) and PGC n = 43 (40%). ICG markings were detected intraoperatively in all cases, and cancer invasion into the resection lines of the esophagus and stomach, performed based on ICG fluorescence images, was negative in all cases. The median visible range of ICG fluorescence was 22.5 mm. ICG diffusion expanded 20 mm proximal for AEG. There were no adverse events associated with endoscopic ICG injection. CONCLUSION: ICG fluorescence imaging is feasible and safe and can potentially be used as a tumor-marking agent for determining the surgical resection line for total/proximal gastrectomy in AEG and PGC treatment.

The DOLFIN method: a novel laparoscopic Billroth-I gastroduodenostomy for gastric cancer with duodenal invasion.

BACKGROUND: Laparoscopic Billroth-I gastroduodenostomy using a delta-shaped anastomosis is safe and feasible. However, it is often difficult to perform in patients who have a short posterior wall of the duodenum. Thus, we have developed a new method named duodenal overlap functional anastomosis with linear stapler (DOLFIN). We hereby report the technical details of the new method and our preliminary experience performing it. METHODS: After the completion of lymphadenectomy, the duodenum was transected craniocaudally with an endoscopic linear stapler. The hepatoduodenal mesentery was dissected approximately 4 cm along the duodenal bulb, and the anastomosis between the posterior wall of the stomach and the lesser curvature of the duodenum was created. The common entry hole was then transected using an endoscopic linear stapler, and the anastomosis was finally completed. RESULTS: There were 36 patients with gastric cancer who underwent laparoscopic distal gastrectomy (LDG) or robotic distal gastrectomy (RDG) with B-I reconstruction using DOLFIN. There were no postoperative complications classified as C-D grade 3 or more and complications related to anastomosis, such as anastomotic leak or stenosis. CONCLUSIONS: Our DOLFIN gastroduodenostomy can be performed safely. In addition, it results in good postoperative outcomes. A long-term comparative study is required to further evaluate the clinical usefulness of this method.

Postoperative aggressive diuresis prevents postoperative tissue edema and complications in patients undergoing distal pancreatectomy.

PURPOSE: Intraoperative fluid restriction is reported to be associated with reduced postoperative tissue edema and decreased incidence of postoperative pancreatic fistula (POPF) in pancreatic surgery. However, there is limited information regarding the postoperative approach to prevent postoperative tissue edema and reduce POPF. METHODS: Patients undergoing distal pancreatectomy from 2013 to 2018 in our institute were retrospectively enrolled (n = 128). The patients were classified into the two groups: an early diuresis group (ED group: patients administered diuretic agents on postoperative day 2 or earlier between 2016 and 2018, n = 69) and a conventional diuresis group (CD group: patients administered diuretic agents on postoperative day 3 or later between 2013 and 2015, n = 59). Postoperative tissue edema assessed by CT imaging and the incidence of clinically relevant POPF (CR-PF; grade B or C) were compared. RESULTS: Postoperative tissue edema was significantly reduced in the ED group (p < 0.0001). The incidence of CR-PF was lower in the ED group (19% vs. 32%, p = 0.082), especially in patients with postoperative diuresis on POD 1 (12%, p = 0.044). CONCLUSION: Early and aggressive postoperative diuresis potentially reduced postoperative visceral tissue edema. This postoperative approach to prevent tissue edema may reduce the incidence of CR-PF in pancreatic surgery.

Robotic total gastrectomy with thrombectomy and portal vein reconstruction for gastric cancer and portal vein tumor thrombus.

BACKGROUND: Gastric cancer with portal vein tumor thrombus (PVTT) is poor prognosis, and the treatment remains challenging. Regarding surgery, there are only reports of highly invasive laparotomy. We report some techniques of the completely robotic total gastrectomy with thrombectomy and portal vein reconstruction for the patient with gastric cancer and PVTT for the first time. CASE PRESENTATION: A 79-year-old man was diagnosed with a 5-cm gastric cancer on the side of the lesser curvature from the middle of the gastric body to the cardia. Computed tomography revealed a massive PVTT extending from the left gastric vein to the portal trunk (28 x 16 mm). There were no other distant metastases. After 3 cycles of the chemotherapy, the PVTT shrank to 19 x 12 mm. After obtaining informed consent from the patient, robotic total gastrectomy with regional lymphadenectomy and thrombectomy were performed. We used the da Vinci Xi Surgical System. A 3-cm incision was made at the umbilicus, and a wound retractor was placed. Five additional ports were placed. The right side suprapancreatic lymph nodes were performed at the time of the thrombectomy. It was important to identify the precise extent of the PVTT with intraoperative ultrasonography before the thrombectomy. After PVTT identification, the portal trunk was clamped above and below the tumor thrombus with vascular clips. The membrane on the anterior wall of the portal trunk around the PVTT was carefully incised with da Vinci Scissors. The tumor thrombus was completely enucleated without separation. The incised part of the portal trunk was reconstructed with continuous 5-0 synthetic monofilament nonabsorbable polypropylene sutures. After removing the vascular clamps, we made sure there was no leakage from the portal vein and no tumor thrombus remnants with intraoperative ultrasonography. Robotic total gastrectomy with lymphadenectomy and Roux-en-Y reconstruction were performed. The patient was discharged without complications. The patient has remained alive for 30 months after surgery. CONCLUSIONS: Robotic total gastrectomy with thrombectomy and portal vein reconstruction is a safe, minimally invasive, and precise surgery. It may contribute to improved prognosis of gastric cancer with PVTT when combined with chemotherapy.

[Three Cases Who Underwent Laparoscopic Radical Resection after Preoperative Therapy for Massive Rectal GIST].

The gastrointestinal stromal tumor(GIST)guidelines state that the use of neoadjuvant chemotherapy(NAC)for curable GIST is not apparent. However, NAC is performed for massive rectal GIST at our hospital to reduce surgical invasion and improve surgical results. The cases were a 39-year-old man, a 48-year-old man, and a 78-year-old man. The site was Rb in all cases, and the maximum diameters at the rectal GIST diagnosis were respectively 70 mm, 75 mm, and 60 mm, which were massive tumors. Imatinib mesylate(imatinib)was started as NAC. The duration of NAC was respectively 6, 11, and 12 months. The maximum tumor diameter on preoperative CT was smaller than before NAC, and the average reduction rate was 23%. Two cases underwent laparoscopic abdominal perineal resection, and 1 underwent laparoscopic ultra-low anterior resection and ileostomy. No perioperative complications of Clavien-Dindo classification Grade Ⅱ or higher were unsettled. All patients were in the high risk group and received imatinib as postoperative adjuvant chemotherapy. Currently, respectively 2 years and 3 months, 1 year and 2 months, and 1 year after surgery, all are alive without recurrence. NAC with imatinib has contributed to minimally invasive and radical surgery for giant rectal GIST.