Long-term outcomes of robot-assisted versus minimally invasive esophagectomy in patients with thoracic esophageal cancer: a propensity score-matched study.

BACKGROUND: Recently, robot-assisted minimally invasive esophagectomy (RAMIE) has gained popularity worldwide. Some studies have compared the long-term results of RAMIE and minimally invasive esophagectomy (MIE). However, there are no reports on the long-term outcomes of RAMIE in Japan. This study compared the long-term outcomes of RAMIE and MIE. METHODS: This retrospective study included 86 patients with thoracic esophageal cancer who underwent RAMIE or MIE at our hospital from June 2010 to December 2016. Propensity score matching (PSM) was employed, incorporating co-variables such as confounders or risk factors derived from the literature and clinical practice. These variables included age, sex, body mass index, alcohol consumption, smoking history, American Society of Anesthesiologists stage, comorbidities, tumor location, histology, clinical TNM stage, and preoperative therapy. The primary endpoint was 5-year overall survival (OS), and the secondary endpoints were 5-year disease-free survival (DFS) and recurrence rates. RESULTS: Before PSM, the RAMIE group had a longer operation time (min) than the MIE group (P = 0.019). RAMIE also exhibited significantly lower blood loss volume (mL) (P < 0.001) and fewer three-field lymph node dissections (P = 0.028). Postoperative complications (Clavien-Dindo: CD ≥ 2) were significantly lower in the RAMIE group (P = 0.04), and postoperative hospital stay was significantly shorter than the MIE group (P < 0.001). After PSM, the RAMIE and MIE groups consisted of 26 patients each. Blood loss volume was significantly smaller (P = 0.012), postoperative complications (Clavien-Dindo ≥ 2) were significantly lower (P = 0.021), and postoperative hospital stay was significantly shorter (P < 0.001) in the RAMIE group than those in the MIE group. The median observation period was 63 months. The 5-year OS rates were 73.1% and 80.8% in the RAMIE and MIE groups, respectively (P = 0.360); the 5-year DFS rates were 76.9% and 76.9% in the RAMIE and MIE groups, respectively (P = 0.749). Six of 26 patients (23.1%) in each group experienced recurrence, with a median recurrence period of 41.5 months in the RAMIE group and 22.5 months in the MIE group. CONCLUSIONS: Compared with MIE, RAMIE led to no differences in long-term results, suggesting that RAMIE is a comparable technique.

Malignant Melanoma Arising from Esophageal Melanosis and Synchronous with Esophageal Squamous Cell Carcinoma.

BACKGROUND Primary malignant melanoma of the esophagus is a rare disease. However, its exact etiology and progression from melanosis to malignant melanoma have not been elucidated due to its rarity. CASE REPORT We report a case of esophageal melanosis that progressed to malignant melanoma and was synchronous with esophageal squamous cell carcinoma. A male patient in his 60s was diagnosed with right hypopharyngeal cancer. Cervical dissection and chemoradiation therapy were performed. Esophageal melanosis was discovered using gastrointestinal endoscopy during a pre-treatment screening 2 years later and revealed a 0-Ia tumor in the middle thoracic esophagus, coinciding with the esophageal melanosis site. A biopsy revealed malignant melanoma. We performed thoracoscopic total thoracic esophagectomy. The resected specimen showed a 0-Ia lesion, and the invasion depth of the esophageal malignant melanoma was submucosal (pT1b-SM3), N0, Stage I. A 0-IIc lesion was found in the resected specimen [squamous cell carcinoma in situ, intraepithelial mucosal (pTis/T1a-EP), N0, Stage 0]. The patient has been recurrence-free for 18 months post-surgery without postoperative adjuvant chemotherapy and is still receiving outpatient followup. CONCLUSIONS The close relationship between esophageal melanosis and primary malignant melanoma of the esophagus has implicated the melanosis as the origin of the malignant melanoma. The coexistence of esophageal melanosis and esophageal cancer warrants improved patient followup, including biopsy and multiple endoscopic examinations after esophageal melanosis diagnosis.

Functional evaluation of non-oxidative glycolysis in Escherichia coli in the stationary phase under microaerobic conditions.

In microbial bioproduction, CO2 emissions via pyruvate dehydrogenase in the Embden-Meyerhof pathway, which converts glucose to acetyl-CoA, is one of the challenges for enhancing carbon yield. The synthetic non-oxidative glycolysis (NOG) pathway transforms glucose into three acetyl-CoA molecules without CO2 emission, making it an attractive module for metabolic engineering. Because the NOG pathway generates no ATP and NADH, it is expected to use a resting cell reaction. Therefore, it is important to characterize the feasibility of the NOG pathway during stationary phase. Here, we experimentally evaluated the in vivo metabolic flow of the NOG pathway in Escherichia coli. An engineered strain was constructed by introducing phosphoketolase from Bifidobacterium adolescentis into E. coli and by deleting competitive reactions. When the strain was cultured in magnesium-starved medium under microaerobic conditions, the carbon yield of acetate, an end-product of the NOG pathway, was six times higher than that of the control strain harboring an empty vector. Based on the mass balance constraints, the NOG flux was estimated to be between 2.89 and 4.64 mmol g-1 h-1, suggesting that the engineered cells can convert glucose through the NOG pathway with enough activity for bioconversion. Furthermore, to expand the application potential of NOG pathway-implemented strains, the theoretical maximum yields of various useful compounds were calculated using flux balance analysis. This suggests that the theoretical maximum yields of not only acetate but also lactam compounds can be increased by introducing the NOG pathway. This information will help in future applications of the NOG pathway.

Clinicopathological Features of Remnant Gastric Cancer After Gastrectomy.

BACKGROUND: Remnant gastric cancer (RGC) encompasses all cancers arising from the remnant stomach. Various studies have reported on RGC and its prognosis, but no consensus on its surgical treatment and postoperative management has been reached. Moreover, the correlation between the clinicopathological characteristics and long-term outcomes of RGC remains unclear. This study investigated the clinicopathological factors associated with the long-term survival of RGC patients. METHODS: The medical records (March 1993-September 2020) of 104 RGC patients from Tokyo Medical University Hospital database were analyzed. Of these 104 patients, the medical records of 63 patients who underwent surgical curative resection were analyzed using R. Kaplan-Meier plots of cumulative incidence of RGC were made. Differences in survival rates were compared using the log-rank test. Prognostic factors were analyzed using multivariate Cox regression analysis (P < .05). RESULTS: Of the 104 RGC patients, 63 underwent total remnant stomach excision. The median time from the first surgery to the total excision was 10 years. The 5-year survival rate of the 63 RGC patients was .55 ((95% CI); .417-.671). The clinicopathological factors that were significantly associated with the long-term outcome of the RGC patients were tumor diameter (≥3.5 cm), presence or absence of combined resection of multiple organs, tumor invasion (deeper than T2), TNM stage, and postoperative morbidity. The multivariate Cox regression analysis showed that tumor invasion depth was the only independent prognostic factor for RGC patients [HR (95% CI): 5.49 (2.629-11.5), P ≤ .005]. CONCLUSIONS: Among prognostic factors, tumor invasion depth was the only independent factor affecting RGC's long-term outcome.

Direct observation of Mn distribution/speciation within and surrounding a basidiomycete fungus in the production of Mn-oxides important in toxic element containment.

Biogenic manganese (Mn) oxides occur ubiquitously in the environment including the uranium (U) mill tailings at the Ningyo-toge U mine in Okayama, Japan, being important in the sequestration of radioactive radium. To understand the nanoscale processes in Mn oxides formation at the U mill tailings site, Mn2+ absorption by a basidiomycete fungus, Coprinopsis urticicola, isolated from Ningyo-toge mine water samples, was investigated in the laboratory under controlled conditions utilizing electron microscopy, synchrotron-based X-ray analysis, and fluorescence microscopy with a molecular pH probe. The fungus' growth was first investigated in an agar-solidified medium supplemented with 1.0 mmol/L Mn2+, and Cu2+ (0-200 µM), Zn2+ (0-200 µM), or diphenyleneiodonium (DPI) chloride (0-100 µM) at 25 °C. The results revealed that Zn2+ has no significant effects on Mn oxide formation, whereas Cu2+ and DPI significantly inhibit both fungal growth and Mn oxidation, indicating superoxide-mediated Mn oxidation. Indeed, nitroblue tetrazolium and diaminobenzidine assays on the growing fungus revealed the production of superoxide and peroxide. During the interaction of Mn2+ with the fungus in solution medium at the initial pH of 5.67, a small fraction of Mn2+ infiltrated the fungal hyphae within 8 h, forming a few tens of nm-sized concentrates of soluble Mn2+ in the intracellular pH of ∼6.5. After 1 day of incubation, Mn oxides began to precipitate on the hyphae, which were characterized as fibrous nanocrystals with a hexagonal birnessite-structure, these forming spherical aggregates with a diameter of ∼1.5 µm. These nanoscale processes associated with the fungal species derived from the Ningyo-toge mine area provide additional insights into the existing mechanisms of Mn oxidation by filamentous fungi at other U mill tailings sites under circumneutral pH conditions. Such processes add to the class of reactions important to the sequestration of toxic elements.

Use of Polyglycolic Acid Sheets for the Prevention of Pancreatic Fistula after Laparoscopic Gastrectomy: A Single-Center Retrospective Study.

BACKGROUND: Laparoscopic gastrectomy (LG) indications have been extended to advanced gastric cancer requiring expansive lymph node dissection. Despite the huge benefits of this minimally invasive surgery, major complications such as postoperative pancreatic fistula (POPF) remain a concern. With technical advances in surgical procedures, the treatment outcomes of gastric cancer surgery have improved. However, effective methods for preventing POPF have not yet been established. Herein, we examined the usefulness of polyglycolic acid (PGA) sheets for preventing POPF after LG. METHODS: We retrospectively assessed 142 patients who underwent curative LG at our institution between January 2017 and August 2022. The 142 patients were divided into 2 groups; PGA group (n = 61): the site of lymph node dissection at the superior margin of the pancreas and pancreatic head was covered with PGA sheets, and nPGA group (n = 81): the site was not covered. We retrospectively compared the short-term surgical outcomes including POPF incidence. RESULTS: There was no significant difference in the background factors between the 2 groups and in the incidence of Grade II or higher postoperative complications according to the Clavien-Dindo (CD) classification. However, the incidence of CD Grade II or higher POPF was significantly lower in the PGA group than in the nPGA group (.0% vs 2.3%, respectively, P = .007). CONCLUSIONS: There was no POPF in any of the 61 patients in the PGA group. This outcome suggests that POPF incidence may be reduced by covering the lymph node dissection site with PGA sheets after LG.

Long-term surgical outcomes of gastric neuroendocrine carcinoma and mixed neuroendocrine-non-neuroendocrine neoplasms.

BACKGROUND: Neuroendocrine carcinoma (NEC) and mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) are extremely rare subtypes of gastric cancer. MiNEN is a mix of carcinomatous components and neuroendocrine neoplasm in the same lesion. NEC and MiNEN have a poor prognosis, are difficult to diagnose, and have no established treatment. Herein, we assessed the clinicopathological characteristics and long-term surgical outcomes of gastric NEC and MiNEN patients in our hospital. METHODS: We retrospectively assessed 1538 patients pathologically diagnosed with gastric cancer and who underwent curative surgical resection at our institution between January 1999 and October 2021. Of these patients, 25 (1.6%) were pathologically diagnosed with neuroendocrine neoplasms. From these 25 patients, we retrospectively analyzed the clinicopathological characteristics and surgical outcomes of 13 (0.8%) patients pathologically diagnosed with NEC or MiNEN. RESULTS: The NEC and MiNEN patients consisted of 11 men and 2 women [mean age, 74 (62-84) years]. The preoperative histological diagnoses were NEC (n = 4) and adenocarcinoma (n = 9). The final pathological diagnoses were large cell neuroendocrine carcinoma (LCNEC; n = 7) and MiNEN (n = 6). Total gastrectomy was the most common surgical procedure (9/13, 69.2%), followed by distal gastrectomy (3/13, 23.1%) and proximal gastrectomy (1/13, 7.7%). Immunohistochemical staining showed 8 CD56-positive patients. All 13 patients were positive for chromogranin A and synaptophysin. The mean Ki-67 value was 64.8 (0-95)%, and the mean mitotic score was 107.9 (0-400). Nine patients survived without recurrence postresection. The median postresection overall survival time was 68.7 (8.0-129) months. The 5-year survival rate was 0.75 ([95% CI] 0.408-0.912). CONCLUSION: The surgical treatment outcomes of NEC and MiNEN patients were relatively favorable. Although evidence concerning the effectiveness of surgery alone is meager, radical resection as part of multidisciplinary treatment including chemotherapy can potentially improve prognosis.

[A Case of Combined Modality Therapy for Progressive Esophagus Cancer with Perforation Due to Preoperative Chemotherapy].

A nearby doctor sensed incongruity in deglutition as a chief complaint from a 56-year-old man. A middle intrathoracic esophagus cancer was subsequently diagnosed and referred to our department. We started FP therapy based on the preoperative chemotherapy guidelines, but perforation of esophageal cancer developed. We conducted chest drainage, and attempted to improve the patient's overall status with antibiotic medical treatment and hyperalimentation; single-stage operations were performed. As tumor invaded the left pleura, surgery occurred for R2 resection of the left lung. Subsequently, we started nivolumab therapy because we give DCF therapy and detected a liver metastasis and we continue it now and survive.

[Combined Modality Therapy for HER2-Positive Progressive Stomach Cancer Metastasis Achieving Treatment Response-A Case Report].

The patient was a 73-year-old man whose chief complaint was a 1-month history of anorexia and weight loss. Pyloric stenosis due to a circumferential type 2 lesion was detected on the pylorus ring from the gastric angle. Close inspection revealed a diagnosis of progressive stomach cancer cT3N+M0, stage Ⅲ. We judged that perioperative radical excision would be impossible and performed gastrojejunal bypass surgery. Postoperatively, the patient was treated with 2 courses of SOX plus trastuzumab and 7 courses of S-1. PR was identified, and a distal-side gastrectomy plus D2 lymph node dissection were performed as conversion surgery. The patient was discharged on postoperative day 9. For 1 year postoperative, no recurrence was noted. The prognosis of the unresectable gastric cancer is poor, but chemotherapy and conversion surgery in this case resulted in a favorable prognosis.

[A Case of Esophageal Malignant Melanoma during Follow-Up of Esophageal Melanosis Metastasis].

Man 62-years-old as for the case. In 2019, he was diagnosed with right hypopharyngeal cancer, and esophageal melanosis was noted on upper gastrointestinal endoscopy before treatment. We did a follow-up upper gastrointestinal endoscopy every year. At a follow-up upper gastrointestinal endoscopy performed in February 2021, he was histologically diagnosed with an esophageal primary malignant melanoma. Computed tomography showed no metastatic lesions. He underwent esophagectomy. He is currently being followed on an outpatient basis and has had no recurrence. Careful follow-up for esophageal melanocytosis is important for early diagnosis of esophageal primary malignant melanoma.

[Duodenal Stent Placement against Anastomotic Stenosis after Esophageal Cancer Resection-A Case Report].

A 53-year-old man was diagnosed as esophageal cancer, and esophagectomy was performed. Anastomotic stenosis was caused due to lymphorrhea and anastomotic leakage after surgery. Dilation was performed, though stenosis did not improved, we placed esophageal stent across the stenotic lesion. Pharyngitis occurred after indwelling esophageal stent, we hence removed the stent. Passage disorder was developed, we placed duodeneal stent which is more flexible. Stenosis is now palliated after placing duodeneal stent. Duodeneal stent could be an option for the tratment of anastomotic stenosis after esophageal surgery.

CD15+ Bone Marrow-derived Cells Are Regulators of Immune Response in ARG1-producing Colorectal Cancer Cells.

BACKGROUND/AIM: Bone marrow-derived cells regulate the antitumor functions of tumor infiltrating lymphocytes (TILs) through arginase 1 (ARG1)-dependent metabolism. This study examines which ARG1-producing lineage is responsible for the inhibitory function of TILs. MATERIALS AND METHODS: Multiplexed immunohistochemistry was performed for CD11b, CD163, CD68, and CD15, together with ARG1 expression and CD3+ TIL infiltration estimation in human colorectal cancer specimens. RESULTS: Stratified survival analyses demonstrated that a large number of CD3+ TILs is a favorable prognostic factor in subgroups with a high level of ARG1+ infiltration and in the subgroup with a low level of ARG1- CD15+ infiltration. Calculation of the ARG1+/ARG1- ratio demonstrated that CD3+ TIL infiltration was prognostic in the subgroup with a low ARG1+/ARG1- ratio for CD15+ cells, contrary to other lineages. CONCLUSION: Tumor infiltrating CD15+ cells, the majority of which show polymorphonuclear features, are responsible for the ARG1-dependent T-cell dysfunction in human colorectal cancer.

Acceleration of target production in co-culture by enhancing intermediate consumption through adaptive laboratory evolution.

Co-culture is a promising way to alleviate metabolic burden by dividing the metabolic pathways into several modules and sharing the conversion processes with multiple strains. Since an intermediate is passed from the donor to the recipient via the extracellular environment, it is inevitably diluted. Therefore, enhancing the intermediate consumption rate is important for increasing target productivity. In the present study, we demonstrated the enhancement of mevalonate consumption in Escherichia coli by adaptive laboratory evolution and applied the evolved strain to isoprenol production in an E. coli (upstream: glucose to mevalonate)-E. coli (downstream: mevalonate to isoprenol) co-culture. An engineered mevalonate auxotroph strain was repeatedly sub-cultured in a synthetic medium supplemented with mevalonate, where the mevalonate concentration was decreased stepwise from 100 to 20 µM. In five parallel evolution experiments, all growth rates gradually increased, resulting in five evolved strains. Whole-genome re-sequencing and reverse engineering identified three mutations involved in enhancing mevalonate consumption. After introducing nudF gene for producing isoprenol, the isoprenol-producing parental and evolved strains were respectively co-cultured with a mevalonate-producing strain. At an inoculation ratio of 1:3 (upstream:downstream), isoprenol production using the evolved strain was 3.3 times higher than that using the parental strain.

Urinary titin N-terminal fragment concentration is an indicator of preoperative sarcopenia and nutritional status in patients with gastrointestinal tract and hepatobiliary pancreatic malignancies.

OBJECTIVES: Recent reports indicate that preoperative patients with gastrointestinal malignancies often have sarcopenia. The diagnosis of sarcopenia is generally done by evaluation of walking speed, grip strength, and skeletal muscle volume of the limbs on computed tomography (CT). However, these parameters are objective indices, and new indicators for diagnosis, such as molecular biomarkers, have been anticipated. The aim of this study was to investigate whether titin, a muscular contractile protein present in sarcomeres, is an indicator of sarcopenia. METHODS: We analyzed 39 patients with gastrointestinal tract and hepatobiliary pancreatic malignancies who underwent surgery. We compared urinary titin n-terminal fragment concentration (UTF) with clinical factors, subcutaneous fat volume, and skeletal muscle volume index, and also compared UTF levels between patients with and without sarcopenia. RESULTS: The patients comprised 24 men and 15 women, with a mean age of 72 y (range: 35-85 y). Cancer locations were the pancreas (n = 17), liver (n = 9), stomach (n = 5), colorectum (n = 5), and esophagus (n = 3). UTF was significantly higher in patients with sarcopenia (P = 0.04), and showed statistically significant negative correlations with albumin (r = -2.61, P = 0.001), pre-albumin (r = -2.14, P = 0.02), body mass index (r = -0.49, P = 0.007), cholinesterase (r = -0.02, P = 0.01, skeletal muscle volume index (r = -0.16, P = 0.04), and subcutaneous fat volume (r = -0.03, P = 0.007). CONCLUSION: UTF may be a new index for preoperative nutritional assessment in patients with gastrointestinal malignancies.

[A Case of Left Transverse Colon Cancer Safely Resected Using Three-Dimensional CT Angiography and Indocyanine Green Fluorography].

A 77-year-old man was admitted to our hospital because of a positive occult blood test result and diagnosed as having left transverse colon cancer(cT2N0M0)on detailed examination. The patient underwent a sigmoidectomy for colon cancer 24 years previously. Three-dimensional(3D)-CT angiography was performed before the present operation. The left branch of the middle colic artery, which was independently branched, and the marginal artery of the colon were found to be supplying blood from the left side of the transverse colon to the anastomosis of the sigmoid colon. In addition, the root of the left branch of the middle colic artery arose from the caudal side of the first jejunal vein. Therefore, a left hemicolectomy was performed. In accordance with the preoperative simulation, we safely resected the left branch of the middle colic artery at the root. Intraoperative blood flow evaluation using indocyanine green(ICG)fluorography clearly displayed the demarcation of the oral blood flow and the point of anastomosis. No notable complications occurred after the surgery. The results of the pathological analyses indicated a pT1bN0M0 tumor stage. Therefore, we conclude that 3D-CT angiography and ICG fluorography are useful for performing safer operations for left transverse colon cancers.

Number of positive lymph nodes and lymphatic invasion are significant prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma.

Background: Early recurrence of distal cholangiocarcinoma (DCC) may result in a poorer prognosis. This study aimed to evaluate the clinicopathological factors that predict survival and recurrence in patients with DCC. Methods: Fifty-five patients with DCC who underwent pancreaticoduodenectomy between 2005 and 2015 were studied retrospectively. The following clinicopathological parameters were analyzed as predictors of disease-free survival (DFS) and overall survival (OS): sex, age, body mass index, presence of biliary tract decompression, macroscopic type, histological type, tumor size, TNM classification, lymph node metastasis ratio, number of positive lymph nodes (PLNs), lymphatic invasion, venous invasion, perineural invasion, proximal bile duct margin, dissected margin, portal system invasion, arterial system invasion, stage, and residual tumor. Results: Univariate analysis showed that contiguous extension of the primary tumor, PLN, lymphatic invasion, venous invasion, perineural invasion, and stage were significant prognostic factors for DFS and OS. Multivariate analysis revealed that PLN and lymphatic invasion were prognostic for DFS and OS (P<0.001). Significant differences in OS and DFS were found in analyses stratified by PLN (0, 1, 2 vs ≥3) and lymphatic invasion (0 vs 1, 2, 3). Conclusion: Among the clinicopathological parameters analyzed, PLN and lymphatic invasion were confirmed as prognostic factors for DCC.

[A Case of Early Rectal Cancer Recurring as Liver Metastasis Nine Months after ESD].

A 70-year-oldwoman underwent colonoscopy as a follow-up examination for colon polyps, during which early-stage rectosigmoid cancer was detected. Endoscopic submucosal dissection(ESD)was performed to remove this lesion. Additional radical anterior resection was recommended according to the histological findings but the patient chose to undergo observation. Nine months after the ESD, the patient decided to undergo additional surgical resection: a CT scan revealed liver metastasis in S6. Laparoscopic anterior resection andpartial resection of S6 of the liver was performed. Histological analysis showed no residual cancer in the rectosigmoid, no lymph node metastasis, and liver metastasis in S6. Carcinoma cells were exposed on the radial margin of the liver. After surgery, oral UFT/LV chemotherapy was administered for 6 months. The patient remains free of recurrence 4 years and6 months after the surgery.

[A Case Where Function Preservation Was Possible for Quadruple Cancer Metastasis].

The patient was a 69-year-old man visited our hospital because of fecal occlt blood test at medical checkup and diagnosed with rectal cancer and gastric cancer. The patient underwent super low anterior resection for rectal cancer cStage III b and underwent endoscopic submucosal dissection(ESD)for early gastric cancer. In 1 year after surgery the patient had recurrence of gastric cancer after ESD and recurrent gastric cancer was additionally resected. In 1 year and 4 months after surgery pulmonary metastasis was recognized and the patient underwent pulmonary segmentectomy. In 5 years after surgery renal cell carcinoma was recognized and the patient underwent partical renal excision. In 8 years after surgery esophagus cancer was recognized and the patient underwent radical chemoradiationtherapy and completed local complete remission. Current the patient is alive without relapse. We report a case where function preservation was possible for quadruple cancer by appropriate preoperative and postoperative examination and appropriate treatment.