[Analysis of Short-Term Results after Introduction of Robotic Gastrectomy for Gastric Cancer at Our Hospital].

BACKGROUND: Robotic gastrectomy(RG)for gastric cancer(GC)has been covered by health insurance since 2018. In this study, we examined the results of RG for GC at our hospital during the initial period of its introduction. MATERIALS AND METHOD: From August 2022 to May 2023, we retrospectively examined the surgical outcomes and short-term postoperative outcomes of the first 9 patients who underwent RG for GC at our hospital. RESULTS: The median patient age was 77(67-82) years, gender was 4 males and 5 females, and distal gastrectomy was performed in all patients. The median operative time was 410(323-486)min, blood loss was 5(1-140)mL, postoperative hospital stay was less than 9 days in all patients, and there was no conversion to laparoscopic or open surgery. There were no postoperative complications of Clavien-Dindo Grade Ⅱ or above. CONCLUSION: In this study, RG for GC was performed safely without intraoperative or postoperative complications.

Catalytic isoforms of AMP-activated protein kinase differentially regulate IMPDH activity and photoreceptor neuron function.

AMP-activated protein kinase (AMPK) plays a crucial role in maintaining ATP homeostasis in photoreceptor neurons. AMPK is a heterotrimeric protein consisting of α, ß, and γ subunits. The independent functions of the 2 isoforms of the catalytic α subunit, PRKAA1 and PRKAA2, are uncharacterized in specialized neurons, such as photoreceptors. Here, we demonstrate in mice that rod photoreceptors lacking PRKAA2, but not PRKAA1, showed altered levels of cGMP, GTP, and ATP, suggesting isoform-specific regulation of photoreceptor metabolism. Furthermore, PRKAA2-deficient mice displayed visual functional deficits on electroretinography and photoreceptor outer segment structural abnormalities on transmission electron microscopy consistent with neuronal dysfunction, but not neurodegeneration. Phosphoproteomics identified inosine monophosphate dehydrogenase (IMPDH) as a molecular driver of PRKAA2-specific photoreceptor dysfunction, and inhibition of IMPDH improved visual function in Prkaa2 rod photoreceptor-knockout mice. These findings highlight a therapeutically targetable PRKAA2 isoform-specific function of AMPK in regulating photoreceptor metabolism and function through a potentially previously uncharacterized mechanism affecting IMPDH activity.

[A Case of Hepatocellular Carcinoma with Haemobilia after Transcatheter Hepatic Arterial Embolization for Tumor Rupture].

A 79-year-old man was scheduled for surgery for hepatocellular carcinoma(HCC)after transcatheter hepatic arterial embolization for rupture. Two weeks before surgery, the patient came to our hospital with a chief complaint of back pain. First, we performed biliary drainage, under the diagnosis of HCC with obstructive jaundice due to haemobilia. Hepatectomy was performed when the patient's condition stabilized. It should be kept in mind that haemobilia may occur after TAE for HCC with bile duct tumor thrombus, and appropriate treatment should be performed when bleeding occurs.

[A Case of Colon Metastasis from Gastric Cancer Treated by Laparoscopic-Assisted Segmental Colectomy].

We report a case of colon metastasis from gastric cancer treated by laparoscopic-assisted segmental colectomy. An 81-year-old man was undergone distal gastrectomy, D2 dissection and Billroth Ⅰ reconstruction for gastric cancer 3 years previously, with a final diagnosis of gastric cancer L, Post, Type 2, sig/por2, pT4a(SE), pN3b(30/56), H0, P0, M0, pStage ⅢC. Three years after gastrectomy, CT scan showed an elevated lesion in the transverse colon, which was suspected to be metastatic colorectal cancer on closer examination. As no metastatic lesions were found other than the tumor of transverse colon, we performed laparoscopic-assisted segmental colon resection. A small incision was placed in the umbilical region, and the transverse colon was extracted from the umbilical region after dissection of the adhesions by single-incision laparoscopic surgery. The transverse colon containing the mass lesion was partially resected extracorporeally and reconstructed with a functional end-to-end anastomosis. The postoperative pathological findings revealed tumor cells predominantly below the submucosal layer and partly showing the signet ring cell carcinoma, and the transvers colon tumor was diagnosed as a metastasis from gastric cancer. The postoperative course was uneventful and the patient was discharged 8 days after surgery, and is alive for 10 months after the segmental colon resection followed by chemotherapy.

[A Case of Recurrent Esophageal Cancer with Long-Term Survival Treated by S-1 Monotherapy].

We report a case of recurrent esophageal cancer with long-term survival treated by S-1 monotherapy. A 66-year-old man underwent subtotal esophagectomy, two-field lymphadenectomy after 2 courses of DCF chemotherapy for esophageal cancer 1 year earlier. The final diagnosis was esophageal cancer, Lt, CT-Type 2, ypT3, ypN0(0/62), M0, ypStage Ⅲ. At 6 months after esophagectomy, CT scan revealed mediastinal lymph node metastasis and pleural dissemination, and paclitaxel monotherapy was performed, but lymph node re-enlargement was observed on CT at 12 months after esophagectomy. Chemotherapy with S-1 monotherapy was performed, and 3 months after initiation of S-1 monotherapy, CT showed reduced lymph node metastases and pleural dissemination remained reduced. Adverse events were CTCAE v5.0 Grade 2 thrombocytopenia and diarrhoea, but no Grade 3 or higher adverse events were observed. Long-term survival was achieved with no disease progression for more than 2.5 years after initiation of S-1 monotherapy.

[A Case of Sigmoid Rectal Cancer with a Vesicoconstrictor Fistula Curatively Resected after Neoadjuvant Chemotherapy].

A 50-year-old man presented with fecaluria and was diagnosed with sigmoid colon cancer with a colovesical fistula. Total bladder resection was determined to be necessary for curative resection at the time of diagnosis. In anticipation of bladder preservation, 6 courses of mFOLFOX6 plus panitumumab were administered after transverse colostomy, resulting in marked tumor regression and a decision to proceed with surgery. The patient underwent robotic-assisted low anterior resection of the rectum and partial cystectomy, which yielded pathological radical treatment. We report a case of sigmoid colon cancer with a colovesical fistula complicated by bladder invasion, in which preoperative chemotherapy was effective and total cystectomy was avoided, allowing bladder preservation.

[A Rare Case of Advanced Gastric Cancer with Duodenal Intramural Metastasis].

Here we report the case of a patient with advanced gastric cancer who presented with duodenal intramural metastasis based on the pathological results after surgery. The patient was 78-year-old female, who was referred to our department for further evaluation and treatment of upper abdominal pain. An upper gastrointestinal series demonstrated a tumor occupying the lesser curvature of the gastric body. Biopsy specimens from the tumor demonstrated moderately to poorly differentiated adenocarcinoma. A computed tomography scan showed thickening of the gastric wall and swelling of the regional lymph nodes. The patient underwent distal gastrectomy and D2 lymph node dissection for gastric cancer. A histopathological examination disclosed that the gastric tumor was poorly differentiated adenocarcinoma with severe lymphatic permeation and also demonstrated the other poorly differentiated adenocarcinoma occupying the part of the muscularis propria layer of the duodenum. The gastric tumor was not contiguous with the duodenal tumor, and the duodenal cancer cells had the same pathological characteristics as the primary gastric cancer cells; therefore, we diagnosed the duodenal tumor as an intramural metastasis from gastric cancer. The patient's disease was staged as pT4aN3bM1, Stage Ⅳ according to the TNM classification. We report this rare case along with a discussion of the literature.

Macrophage depletion blocks congenital SARM1-dependent neuropathy.

Axon loss contributes to many common neurodegenerative disorders. In healthy axons, the axon survival factor NMNAT2 inhibits SARM1, the central executioner of programmed axon degeneration. We identified 2 rare NMNAT2 missense variants in 2 brothers afflicted with a progressive neuropathy syndrome. The polymorphisms resulted in amino acid substitutions V98M and R232Q, which reduced NMNAT2 NAD+-synthetase activity. We generated a mouse model to mirror the human syndrome and found that Nmnat2V98M/R232Q compound-heterozygous CRISPR mice survived to adulthood but developed progressive motor dysfunction, peripheral axon loss, and macrophage infiltration. These disease phenotypes were all SARM1-dependent. Remarkably, macrophage depletion therapy blocked and reversed neuropathic phenotypes in Nmnat2V98M/R232Q mice, identifying a SARM1-dependent neuroimmune mechanism as a key driver of disease pathogenesis. These findings demonstrate that SARM1 induced inflammatory neuropathy and highlight the potential of immune therapy as a treatment for this rare syndrome and other neurodegenerative conditions associated with NMNAT2 loss and SARM1 activation.

[Analysis of Short-Term Outcomes and Nutritional Assessment of Elderly Gastric Cancer Surgery Cases].

BACKGROUND: We analyzed the short-term outcomes and nutritional assessment of gastric cancer surgery patients who underwent exercise intervention after gastrectomy. MATERIALS AND METHOD: Gastric cancer patients who underwent gastrectomy at our department from January 2021 were included in the study. Postoperative exercise intervention(lower limb training) was performed in gastric cancer patients aged 75 years or older(group H: 7 patients)and compared retrospectively with gastric cancer patients younger than 75 years(group L: 10 patients)who did not receive exercise intervention. The rate of decrease in each index after 1 week was compared between the 2 groups. RESULTS: Postoperative complications(yes/no) were 3/4(42.8%)in group H and 2/8(20.0%)in group L(p=0.59); postoperative hospital stay was 11.5(10.8-21.3) days in group H and 11.0(9.0-14.0)days in group L(p=0.37). The percentage decrease in each index was as follows: for BMI in groups H/L: 2.9/5.6%(p=0.17), grip strength in groups H/L: 2.4/－7.6%(p=0.07), skeletal muscle mass in groups H/L: －2.3/7.0%(p=1.00), PNI in groups H/L: 26.6/18.1%(p=0.12). CONCLUSION: In this study, no significant differences were noted in postoperative complication rates or postoperative hospital stay between groups H and L.

[Analysis of Chemotherapy-Induced Nausea and Vomiting during Chemotherapy for Gastric Cancer].

BACKGROUND: Chemotherapy-induced nausea and vomiting(CINV)are typical side effects caused by chemotherapy. We analyzed CINV during first-line chemotherapy for gastric cancer. MATERIALS AND METHOD: Thirty-one patients who received first-line chemotherapy for gastric cancer were retrospectively assessed for CINV. RESULTS: The median age was 70 years, and the gender(male/female)was 23/8 cases. NK1 receptor antagonist, 5-HT3 receptor antagonist, and dexamethasone were used as antiemetic agents in 29 patients(94%). Sixteen patients(52%)had Grade 1 or higher nausea, and 6 patients (19%)had Grade 1 or higher vomiting, and complete control of nausea and vomiting was achieved in 21 patients(68%). Nausea was significantly more frequent in patients with liver metastasis(p=0.0008), but there was no significant difference in vomiting(p=1.0000). There was no significant difference in the occurrence of CINV between chemotherapy regimens or combination of olanzapine. CONCLUSION: During first-line chemotherapy for gastric cancer, 3 antiemetic agents were used in 94% of cases, and the complete control rate of CINV was 67.8%.

[A Case of Early Gastric Cancer with Adachi Type â ¥ Vascular Anomaly Treated by Laparoscopic Distal Gastrectomy].

We report a case of early gastric cancer with Adachi Type Ⅵ vascular anomaly treated by laparoscopic distal gastrectomy. An 81-year-old woman was admitted because of anorexia, and was diagnosed with early gastric cancer. Preoperative MDCT revealed Adachi Type Ⅵ vascular anomaly, where the hepatic artery does not appear at the superior border of the pancreas. The patient was treated successfully with laparoscopic distal gastrectomy with D1+lymph node dissection. At surgery, we identified the portal vein, then, dissection of No. 8a lymph nodes was performed. The postoperative course was uneventful and the patient was discharged 10 days after surgery. The final pathology result showed gastric cancer, M, Less, Type 0-Ⅱc+Ⅲ, 58×50 mm, tub1>pap, pT1a(M), Ly0, V0, pN0(0/40), H0, P0, M0, pStage ⅠA. We understand the arterial running pattern before surgery by using MDCT, and performed laparoscopic surgery safely.

Products of gut microbial Toll/interleukin-1 receptor domain NADase activities in gnotobiotic mice and Bangladeshi children with malnutrition.

Perturbed gut microbiome development has been linked to childhood malnutrition. Here, we characterize bacterial Toll/interleukin-1 receptor (TIR) protein domains that metabolize nicotinamide adenine dinucleotide (NAD), a co-enzyme with far-reaching effects on human physiology. A consortium of 26 human gut bacterial strains, representing the diversity of TIRs observed in the microbiome and the NAD hydrolase (NADase) activities of a subset of 152 bacterial TIRs assayed in vitro, was introduced into germ-free mice. Integrating mass spectrometry and microbial RNA sequencing (RNA-seq) with consortium membership manipulation disclosed that a variant of cyclic-ADPR (v-cADPR-x) is a specific product of TIR NADase activity and a prominent, colonization-discriminatory, taxon-specific metabolite. Guided by bioinformatic analyses of biochemically validated TIRs, we find that acute malnutrition is associated with decreased fecal levels of genes encoding TIRs known or predicted to generate v-cADPR-x, as well as decreased levels of the metabolite itself. These results underscore the need to consider microbiome TIR NADases when evaluating NAD metabolism in the human holobiont.

[A Case of Sigmoid Colon Cancer with Bladder Fistula Treated by Laparoscopic Radical Resection].

The patient was a woman in her 70 s. Computed tomography(CT)showed a sigmoid colon tumor invading the uterus and ovaries, and a fistula to the bladder. The patient was scheduled to receive neoadjuvant chemotherapy(NAC), but while waiting for treatment, generalized peritonitis due to perforation of the tumor was observed, and a laparoscopic transverse colostomy was performed. After NAC with CAPOX and FOLFIRI plus panitumumab, the tumor was found to have shrunk, and a laparoscopic posterior pelvic exenteration was performed. The bladder including the fistula was partially resected, and the tumor, uterus, and right ovary were resected in combination as R0, besides the ureter and remaining bladder could be preserved. The postoperative course was uneventful, and the patient is alive without recurrence to date. In this article, we report a case of a patient with sigmoid colon cancer with a bladder fistula who underwent laparoscopic surgery after NAC, and bladder function could be preserved, with some discussion of the literature.

[A Case of Laparoscopic Resection Using the ICG Fluorescence for Peritoneal Disseminations of Hepatocellular Carcinoma].

A 71-year-old male had repeated resection and transcatheter arterial chemo-embolization(TACE)for hepatocellular carcinoma(HCC). Treatment with lenvatinib was started due to multiple liver recurrences and peritoneal disseminations. Since only the disseminated lesion had increased, it was decided to perform laparoscopic resection. Indocyanine green(ICG) was intravenously injected the day before surgery. Disseminated lesions could be easily detected with intraoperative fluorescence imaging, and we could completely resect disseminated lesions. The ICG fluorescence could be considered to be useful in laparoscopic resection for peritoneal dissemination of HCC.

[A Case of Recurrent Sigmoid Colon Cancer with Peritoneal Metastasis and Liver Metastasis Successfully Treated with Capecitabine plus Bevacizumab].

A 78-year-old man had undergone a laparoscopic sigmoid colon resection; left ureteral resection; and a ureteral reconstruction for sigmoid colon cancer with left ureteral invasion. The patient did not wish to undergo postoperative adjuvant chemotherapy, and he was followed up at fixed intervals. Six months after surgery, CT revealed peritoneal metastasis and liver metastasis(S6). Considering his advanced age and adverse events, the patient was started on capecitabine plus bevacizumab therapy. The patient was able to continue the treatment, even though he had to suspend and reduce the dose due to adverse events of hand-foot syndrome, and achieved CR by CT after 21 courses of treatment. Chemotherapy was discontinued after 24 courses, CR was maintained for 5 years, and the patient is still alive with no evidence of recurrence.

Live imaging reveals the cellular events downstream of SARM1 activation.

SARM1 is an inducible NAD+ hydrolase that triggers axon loss and neuronal cell death in the injured and diseased nervous system. While SARM1 activation and enzyme function are well defined, the cellular events downstream of SARM1 activity but prior to axonal demise are much less well understood. Defects in calcium, mitochondria, ATP, and membrane homeostasis occur in injured axons, but the relationships among these events have been difficult to disentangle because prior studies analyzed large collections of axons in which cellular events occur asynchronously. Here, we used live imaging of mouse sensory neurons with single axon resolution to investigate the cellular events downstream of SARM1 activity. Our studies support a model in which SARM1 NADase activity leads to an ordered sequence of events from loss of cellular ATP, to defects in mitochondrial movement and depolarization, followed by calcium influx, externalization of phosphatidylserine, and loss of membrane permeability prior to catastrophic axonal self-destruction.

[A Case of Advanced Gastric Cancer Successfully Treated with mFOLFOX6 Therapy].

We report a case of advanced gastric cancer that was successfully treated with mFOLFOX6 therapy. A 78-year-old man presented to our hospital with a chief complaint of weight loss. Esophagogastroduodenoscopy(EGD)and computed tomography( CT)revealed the presence of type 3 advanced gastric cancer with distant lymph node metastasis and peritoneal dissemination. Biopsy specimen examination revealed moderately differentiated adenocarcinoma with a HER2 score of 1. Chemotherapy comprising 5-fluorouracil, Leucovorin, and oxaliplatin(mFOLFOX6)was administered because of renal failure. Subsequently, the gastric lesion, distant lymph node metastasis, and peritoneal dissemination were seen to be reduced on EGD and CT. After 7 courses, the regimen was changed to 5-fluorouracil and Leucovorin(5-FU/l -LV)chemotherapy because of thrombocytopenia. For more than 10 months, he has continued to receive chemotherapy without the recurrence of metastasis.

Coexisting primary tumors from esophageal cancer and myelodysplastic syndromes: A case report.

This is the first report of the double primary cancer of esophageal cancer (EC) and myelodysplastic syndromes (MDS) treated without esophagectomy. Previously reported cases of the double cancer mostly describe secondary MDS arising after treatment for EC. The double primary cancer was manageable with close follow-ups for possible recurrence.

Arterial chemoembolisation with cisplatin versus epirubicin for hepatocellular carcinoma (ACE 500 study): A multicentre, randomised controlled phase 2/3 trial.

BACKGROUND: Transarterial chemoembolisation (TACE) is a treatment option for hepatocellular carcinoma (HCC), but the optimum agent for TACE remains unclear. We compared the efficacy of TACE with cisplatin versus with epirubicin in patients with unresectable HCC. METHODS: This multicentre, randomised, phase 2/3 trial was performed at 21 hospitals in Japan. Patients with liver-confined HCC, performance status 0-2, and Child-Pugh class A/B were randomised to receive TACE with cisplatin or epirubicin. Patients were stratified in accordance with the institution, Child-Pugh class, tumour size, tumour thrombosis, α-fetoprotein and prior treatment. The primary end-point was overall survival in the intention-to-treat population. Tumour response was evaluated in accordance with the Response evaluation criteria in solid tumours criteria. FINDINGS: Between 2008 and 2012, 455 patients were randomly assigned to undergo TACE with cisplatin (n = 228) or epirubicin (n = 227). Eleven patients were ineligible, and 444 patients were included in the full analysis. Twelve patients not receiving TACE were excluded, and 432 patients were included in the safety analysis set. In phase 2, disease control rates in cisplatin (91·7%) and epirubicin (91·8%) groups exceeded the predefined threshold of 70%, and the study proceeded to phase 3. After a median follow-up of 32·7 months (IQR = 15·3-49·3), median overall survival periods were 2·93 years (95% CI 2·60-3·79) and 2·74 years (95%CI 2·26-3·21), respectively (hazard ratio 0·90 [95% CI 0·71-1·15], p = 0·22). Median times to treatment failure were 1·38 and 1·46 years (hazard ratio 1·09 [95% CI 0·88-1·35], p = 0·88), response rates were 65·3% and 60·6% (p = 0·31), and serious adverse event rates were 49·8% and 48·3% (p = 0·56), respectively. No treatment-related deaths occurred in either group. INTERPRETATION: In our phase 2/3 randomised trial, cisplatin is not significantly superior to epirubicin in TACE for patients with HCC.

[Analysis of Delirium in Patients with Malignant Tumor in Palliative Care Unit].

BACKGROUND: Since delirium has various adverse effects in patients with malignant tumors, it is important to eliminate the cause. We investigated delirium in patients with malignant tumors. METHOD: Seventy seven malignant tumor patients who admitted to palliative care unit from May 2015 to March 2016 were subjected to a retrospective analysis of delirium. RESULTS: Delirium was present in 17 patients(22.1%)on admission, and in 38 patients(49.4%)before discharge. After hospitalization, delirium improved without relapse in 5 patients(29%)and the onset of delirium was avoided in 34 patients(57%). Factors of delirium at admission were nausea and day/night reversal, factors of delirium at discharge were dementia, pain, and day/night reversal. CONCLUSIONS: In the present study, we investigated the causes and course of delirium in patients with malignant tumors.