[Evaluation of Bridge to Surgery(BTS) after Stenting for Malignant Colorectal Stenosis].

OBJECTIVE: To evaluate the current status and postoperative course of nutritional management in bridge to surgery(BTS) after colorectal stenting for malignant colorectal stenosis. SUBJECTS AND METHODS: The study included 242 colorectal cancer cases, 27 cases with malignant colorectal stenosis who underwent BTS group, 24 cases with malignant colorectal stenosis who fasted until the day of surgery and consumed drinking water and Elenthal®(no oral intake group), and 191 cases with non-stenotic colorectal cancer (diet group). The study items selected were nutritional management methods before colorectal cancer resection, nutritional assessment, surgical factors, and postoperative course. RESULTS: The BTS, no oral intake, and diet groups were compared in 27, 0, and 191 patients, respectively. In contrast, the intake of Elenthal® was compared in 4, 20, and 5 patients and total parenteral nutrition in 3, 15, and 1 patients, respectively. There were no differences in nutritional sufficiency during hospitalization. The Onodera Nutritional Index(PNI)was significantly lower in the BTS and no oral intake groups than the diet group at the first outpatient visit before surgery. The PNI was significantly lower in the no oral intake group than in the diet group immediately before surgery. Blood loss was higher in the BTS and no oral intake groups than in the diet group, but there was no difference in operative time. The postoperative course was poorer in the no oral intake group than in the diet group. However, there was no difference between the diet and BTS groups. CONCLUSION: In patients with obstructive colorectal cancer in whom BTS could be performed, the results suggest that preoperative nutritional management with a high sufficiency rate using the intestinal tract may lead to a postoperative course comparable to that in non-stenotic cases.

[A Case of Resected Diffuse Large B-Cell Lymphoma Diagnosed with Liver Metastasis and Peritoneal Dissemination after Surgery for Sigmoid Colon Cancer].

We experienced a case of diffuse large B-cell lymphoma(DLBCL)that developed around the kidney about 1 year after surgery for sigmoid colon cancer. In this case, imaging findings suggestive of liver metastasis were also observed at the same time of diagnosis, therefore, diagnosis was difficult because the possibility of peritoneal dissemination could not be ruled out. The lesion was excised by surgery and a definitive diagnosis was obtained by tissue diagnosis, leading to appropriate treatment. However, one wrong step could lead to the wrong treatment policy. Therefore, when there is any doubt about the diagnosis, it is considered important to proactively perform tissue diagnosis.

Feasibility of augmented rectangle technique in laparoscopic distal gastrectomy: comparison with hemi-double stapling technique in a single-center retrospective cohort study.

PURPOSE: Augmented rectangle technique (ART) anastomosis is a totally intracorporeal anastomosis of laparoscopic distal gastrectomy (LDG), Billroth I (B1) reconstruction for gastric cancer, which secures a wide anastomotic stoma. Since the conventional extracorporeal hemi-double stapling technique (HD) may have a narrow anastomotic stoma, our aim of this study was to evaluate the feasibility and usefulness of ART anastomosis by comparing the surgical outcomes with HD anastomosis. METHODS: Clinical data of 89 patients undergoing LDG with B1 reconstruction were retrospectively collected. Patients were divided into ART group (n = 40) and HD group (n = 49). Surgical outcomes including short-term outcomes, postoperative endoscopic findings, and nutritional factors 1 year after surgery were compared between the groups. RESULTS: Baseline characteristics were similar between the groups. In terms of short-term outcomes, blood loss was less (11.5 mL vs 40 mL, P = 0.011) and postoperative hospital stay was shorter (10 days vs 12 days, P = 0.022) in the ART group. In terms of endoscopic findings, residual food was less (P = 0.032) in the ART group. In terms of nutritional factors, percent decrease of visceral fat area (- 27.6% vs - 40.5%, P = 0.049) and subcutaneous fat area (- 25.7% vs - 39.3%, P = 0.050) 1 year after surgery attenuated in the ART group. CONCLUSIONS: ART anastomosis is superior in perioperative course such as postoperative hospital stay. Moreover, a better nutritional recovery is expected by securing a wide anastomotic stoma leading to a favorable food passage.

Expression of ASC splice variant found in Japanese patients with palindromic rheumatism is regulated by rs8056505 single nucleotide polymorphism and interleukin-1 beta.

BACKGROUND: Palindromic rheumatism (PR) is an infrequent form of periodic arthritis. Based on the similarity of the pathogenesis of PR to autoinflammatory syndromes, we previously found that the dominant-active splice variant of the inflammasome adaptor protein, apoptosis-associated speck-like protein containing a CARD (ASC), which lacks exon 2 (Δexon2), is expressed in Japanese patients with PR. OBJECTIVE: Elucidation of the mechanism of Δexon2 ASC production and the effect of IL-1ß on splicing. METHODS: The genomic DNA of Japanese patients with PR was sequenced. The effect of the observed single nucleotide polymorphisms (SNPs) on ASC splicing was determined via exon trapping using THP-1 cells stimulated with interleukin-1 beta (IL-1ß) or ceramide. To investigate the genes that affect alternative splicing via IL-1ß, we analyzed the transcriptome of IL-1ß-treated THP-1 cells using RNA sequencing. RESULTS: We found the rs8056505 A->G SNP located in the 5'-untranslated region of the genomic ASC gene in patients and that Δexon2 expression was induced by this SNP, whereas it was suppressed by IL-1ß or ceramide. We detected 131,426 transcripts and identified 52 differentially expressed genes (DEGs) consisting of 41 downregulated genes and 11 upregulated genes in IL-1ß-stimulated THP-1 cells. The splicing-related gene MASCRNA was the most significantly induced gene by IL-1ß. CONCLUSIONS: We propose a cyclic expression model in which ASC alternates between wild-type and Δexon2 expression regulated by the rs8056505 G allele and splicing factors induced by IL-1ß. This cycle may be correlated with the formation of periodic PR pathologies.

Expression of a PYCARD/ASC variant lacking exon 2 in Japanese patients with palindromic rheumatism increases interleukin-1ß secretion.

BACKGROUND: Palindromic rheumatism (PR) is a rare periodic arthritis characterized by relapsing short episodes of arthritis. Although the pathogenesis of PR is still unclear, the clinical condition is similar to that of autoinflammatory diseases caused by dysregulation of inflammasome-related genes. OBJECTIVE: We analyzed the inflammasome adapter PYD and CARD domain-containing protein/apoptosis-associated speck-like protein containing a CARD (PYCARD/ASC) in Japanese patients with PR. METHODS: Serum interleukin (IL)-1ß concentrations in three Japanese patients with PR were measured. We also cloned PYCARD/ASC cDNA variants and expressed them in THP-1 cells to determine their effects on inflammasome activity following stimulation with phorbol 12-myristate 13-acetate and monosodium urate. Lysates of recombinant THP-1 cells were subjected to co-immunoprecipitation assays. RESULTS: Serum IL-1ß concentrations were significantly elevated in patients with PR, and a splice variant of PYCARD/ ASC mRNA lacking exon 2 (Δexon2) was dominantly expressed compared with that in controls. Moreover, IL-1ß secretion was significantly increased in THP-1 cells expressing Δexon2PYCARD/ASC compared with that in cells expressing the wild-type protein. The amount of NLRP3 bound to Δexon2PYCARD/ASC was increased after stimulation, whereas that bound to the wild-type protein was decreased. There were no differences in caspase-1 binding. CONCLUSIONS: Δexon2 PYCARD/ASC was associated with the pathogenesis of PR.

[A Case of Serous Retinal Detachment after Encorafenib, Binimetinib, and Cetuximab Treatment for BRAF V600E Mutant Colorectal Cancer].

The patient was a 72-year-old man with a chief complaint of abdominal pain. We performed laparoscopic left hemicolectomy of the colon after descending colon cancer ileus stenting, and postoperative pathology was pT4aN0M0, pStage Ⅱb. In 1.5 years postoperatively, 2 liver metastases and 1 lymph node metastasis were found, and each was resected. Chemotherapy was initiated for multiple lung metastases. Genetic testing was positive for BRAF V600E mutation, and the patient received 8 mFOLFOXIRI plus bevacizumab therapy courses. After 15 5-FU plus LV plus bevacizumab courses, the patient had a brain infarction and lung metastasis reincreased. Chemotherapy was changed to encorafenib plus binimetinib plus cetuximab. On day 2, visual impairment was observed, and serous retinal detachment CTCAE Grade 2 was diagnosed. On day 7, the symptoms improved and one-step dose reduction was resumed. On day 2 of re-treatment, serous retinal detachment recurred and treatment was discontinued. On day 4 of re-treatment, the symptoms improved, another dose reduction was performed, and treatment was resumed. Since subjective MEK inhibitor-induced ocular symptoms are often minor, conducting an interview and early ophthalmologic diagnosis is recommended.

[A Case of Multiple Lung Metastases of Pancreatic Cancer with 50 Months Survival by Sequential Chemotherapy].

We hereby report a case in which a patient with multiple lung metastases of pancreatic cancer continued chemotherapy and maintained good performance status(PS)for 48 months after recurrence. But her disease progressed rapidly after withdrawal of chemotherapy, resulting in her death in a short period of time. The patient was a 66-year-old woman who underwent a substomach preserving pancreaticoduodenectomy for pancreatic head cancer at the age of 60 years. She was diagnosed as fT3N1M0, fStage ⅡB. During postoperative adjuvant chemotherapy S-1, multiple lung metastases were noted on CT scan 2 years after surgery. Thereafter, she was treated with gemcitabine(GEM)alone, GEM plus nab-paclitaxel(GnP), nal-CPT-11 plus 5-FU plus Leucovorin, and FOLFIRINOX for 48 months sequentially. Each of which achieved a best overall response SD or better. However, Trousseau syndrome developed following community-acquired pneumonia during chemotherapy withdrawal due to myelosuppression. The disease progressed rapidly and resulted in her death 50 months after relapse. The results suggest that chemotherapy may have contributed significantly to disease control in this case.

[Adjuvant Capecitabine for Residual Disease after Standard Neoadjuvant Chemotherapy Among Patients with Triple-Negative Breast Cancer].

CREATE-X trial demonstrated the effectiveness of additional capecitabine therapy in prolonging disease-free survival among patients who are HER2 negative, especially those with triple-negative breast cancer who had residual invasive disease after standard neoadjuvant chemotherapy. We investigated our data regarding adjuvant capecitabine for residual disease. Ten patients were enrolled, and the average age of the patients was 54.2 years. All patients completed 8 courses of treatment; all adverse events were Grade 2 or lower. Five-year disease-free survival rate was 70.0% in an average observation period of 40.9 months. Three patients recurred within 2 years, and all patients had brain metastasis. In the CREATE-X trial, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group; our results were same as those of CREATE-X. Brain metastasis may be detected by the early phase of enhanced brain MRI.

[A Case of Rectal Cancer Diagnosed Based on Brain Metastasis and Had a Long-Term Prognosis by Radical Resections].

The patient was a 57-year-old man who visited the department of neurosurgery for headache and lightheadedness. He was admitted with a diagnosis of brain tumor based on imaging findings. Severe brain dysfunction and mild ataxia were observed, and craniotomy tumor resection was performed 5 days after admission. He was diagnosed with brain metastasis of colorectal cancer based on histopathological examination and endoscopic findings, and was therefore referred to our department. No extracranial metastases were observed, laparoscopic-assisted low anterior resection was performed 1 month after the craniotomy. The final diagnosis was rectal cancer(Ra), pT3N0M1a(BRA), Stage Ⅳa. Three months after the craniotomy, subsequent MRI examination revealed a new metastatic lesion inferior to the tumor excision cavity, and gamma knife radiosurgery was performed. However, because an increasing tendency was noted, craniotomy was performed again 7 months after the first craniotomy. Following operative treatment, follow up has been performed without adjuvant chemotherapy or prophylactic irradiation, the patient has survived without recurrence at 34 months postoperatively. Here, we report a valuable rare case of solitary brain metastasis of colorectal cancer in which prognosis could be expected by radical resections.

[The Effects of Bridge to Surgery(BTS)for Malignant Colorectal Stenosis on the Nutritional and Immunological Status].

OBJECTIVE: This study aimed to clarify the effects of bridge to surgery(BTS)for malignant colorectal stenosis on the nutritional and immunological status. SUBJECTS AND METHODS: A total of 19 patients with colorectal cancer who underwent BTS were included. We examined the technical success of stenting, clinical improvement, treatment progress after BTS, and nutritional and immunological status changes before and after BTS. RESULTS: There were 19 technically successful cases and 18 clinically improved cases. One patient(Score 0)had an obstruction after BTS, which improved after stent repositioning. The CROSS Score before and after stenting improved in all patients. Scores 0 to 4 improved in 12 patients, Scores 0 to 3 in 5 patients, and Scores 3 to 4 in 2 patients. The median time to resume eating was 3 days, and the median surgery time was 25 days. The final diet before operation for colorectal consisted of a rokubugayu(rice gruel: polished rice content 12%)in 1 case, zengayu(rice gruel: polished rice content 20%)in 8 cases, soft diet in 5 cases, and regular diet in 5 cases. Before and after BTS, the nutritional and immunological status decreased significantly(p<0.05)with albumin levels ranging from 3.9- 3.5 g/dL, BUN/Cr from 24.8-12.5, and neutrophil-to-lymphocyte ratio from 3.8-2.5; however, no significant fluctuations in the prognostic nutritional index were observed. CONCLUSION: BTS enabled the nutritional management using the intestinal tract and improved the patient's immune status.

[A Case of Pathological Complete Response after Neoadjuvant Therapy for Resectable Pancreatic Cancer].

We report a case of resectable pancreas tail cancer treated with 2 courses of neoadjuvant therapy which is gemcitabine and S-1 therapy, and pathological diagnosis of the resected specimen revealed pathological complete response. A 56-year- old woman was referred to our hospital because she had back pain after eating for 5 months and her previous abdominal ultrasonography revealed an enlarged pancreatic tail. The tumor size was reduced from 30 mm to 12 mm, and the chemotherapy response was judged to be partial response. The patient underwent distal pancreatectomy, splenectomy, and D2 lymph node dissection. Intraoperative findings showed a pancreatic tail with a depression and surface erythema, thus we also diagnosed the patient as having pancreatic capsular invasion(S1). Postoperative histopathological examination revealed a 10×10 mm area of pancreatic parenchyma, which was replaced by fibrous tissue, with no evidence of active cancer cells. The patient was discharged from the hospital on the 14th after surgery.

Conditional Upregulation of IFN-α Alone Is Sufficient to Induce Systemic Lupus Erythematosus.

The cause of systemic lupus erythematosus (SLE) is unknown. IFN-α has been suggested as a causative agent of SLE; however, it was not proven, and to what extent and how IFN-α contributes to the disease is unknown. We studied the contribution of IFN-α to SLE by generating inducible IFN-α transgenic mice and directly show that conditional upregulation of IFN-α alone induces a typical manifestation of SLE in the mice not prone to autoimmunity, such as serum immune complex, autoantibody against dsDNA (anti-dsDNA Ab), and the organ manifestations classical to SLE, such as immune complex-deposited glomerulonephritis, classical splenic onion-skin lesion, alopecia, epidermal liquefaction, and positive lupus band test of the skin. In the spleen of mice, activated effector CD4 T cells, IFN-γ-producing CD8 T cells, B220+CD86+ cells, and CD11c+CD86+ cells were increased, and the T cells produced increased amounts of IL-4, IL-6, IL-17, and IFN-γ and decreased IL-2. In particular, activated CD3+CD4-CD8- double-negative T cells positive for TCRαß, B220, CD1d-teteramer, PD-1, and Helios (that produced increased amounts of IFN-γ, IL-4, IL-17, and TNF-α) were significantly expanded. They infiltrated into kidney and induced de novo glomerulonephritis and alopecia when transferred into naive recipients. Thus, sole upregulation of IFN-α is sufficient to induce SLE, and the double-negative T cells expanded by IFN-α are directly responsible for the organ manifestations, such as lupus skin disease or nephritis.

[A Case of Long-Term Survival after Administration of Regorafenib for Stage â £ Colorectal Cancer].

The patient was a 65-year-old man for whom a right hemicolectomy was performed for transverse colon cancer and multiple lymph node metastases. Peritoneal dissemination was observed throughout the abdominal cavity, and curative resection was not possible. Postoperative diagnosis: pT4bN2M1c(P3), Stage Ⅳc, and mutant RAS status. Therapy consisting of mFOLFOX6 plus bevacizumab was started 1 month after surgery, and up to 25 courses were completed. FOLFIRI plus bevacizumab therapy was performed up to 13 courses as the second-line therapy. Regorafenib 80 mg/day was started as the third-line therapy and the dose was gradually increased. It was performed up to 14 courses for about 13 months, without major adverse events, to keep the disease stable or slow its progression. Although up to 5 courses of FTD/TPI plus bevacizumab therapy were delivered as the fourth-line therapy, he died of disease progression. Regorafenib, which has been approved as a salvage line for metastatic colorectal cancer, features many adverse events, and there are few cases in which the approved dose can be administered. In our case, starting at a low dose resulted in fewer adverse events, adequate disease control, and long-term administration.

[A Case of Rectosigmoid T1b Cancer Which Had Been Under Control by Combination of Loco-Regional Therapies].

According to the Japanese Colorectal ESD/EMR guidelines, radical surgery should be recommended for additional treatment of T1 colorectal cancer(CRC)if pathological findings of the lesion after endoscopic resection show unfavorable factors to be evaluated as curative resection, considering the probability of lymph node metastasis and general condition of patients. We report a case of a 74-year-old man with T1b rectosigmoid(RS)cancer, whose pulmonary metastasis(PM) was curatively resected during the postoperative period of ESD for primary lesions. The patient underwent ESD in November 2018 for Type 0-Isp CRC in the RS junction, revealed using colonoscopy, which was performed for the examination of blood stool in September 2018. The patient had suffered from pulmonary tuberculosis in his thirties and regularly visited our hospital for COPD. He was under close observation after ESD because the depth of the lesion, which was pathologically diagnosed as T1b, was the only factor evaluated as non-curative. In April 2020, chest CT and FDG-PET/CT findings revealed the occurrence of PM. Subsequently, video-assisted wedge resection of the lung was performed for the treatment of PM, which was pathologically confirmed with a size of 10 mm. The patient has survived relapse-free to date, for 30 months after the resection of the primary lesion.

[Relationship between Degree of Obstruction of Colorectal Cancer and Nutritional and Immune Status].

This study examined the impact of the degree of occlusion in colorectal cancer during the perioperative period. The subjects included 207 patients who underwent elective colorectal cancer resection. The degree of obstruction at the first medical examination was evaluated using the ColoRectal Obstruction Scoring System(CROSS). We classified the subjects into two groups(CROSS score 0-2, CROSS score 3-4)and assessed their associations with clinicopathological factors, nutritional immune status, and postoperative course. Compared to the CROSS score 3-4 group, the CROSS score 0-2 group(42 subjects [20.3%])had a higher proportion of subjects with ≥2 lesions, T4, Stage classification Ⅳ, CEA >5.0 ng/mL, prognostic nutritional index( PNI)≤40, controlling nutritional status( CONUT) score ≥2, modified Glasgow prognostic score (mGPS)2, weight loss rate>2.3, mini nutritional assessment-short form(MNA®-SF)score <12, neutrophil lymphocyte ratio(NLR) ≥4.0, postoperative complications, and postoperative hospital stay >16 days( p<0.05). Our findings suggest that the degree of occlusion in colorectal cancer is associated with clinicopathological and nutritional/immune factors and is reflected by the postoperative course.

[Significance of Transitions in Neutrophil-to-Lymphocyte Ratio before and after Transcatheter Arterial Chemoembolizaton for Hepatocellular Carcinoma].

We investigated the significance of transitions in the neutrophil-to-lymphocyte ratio(NLR)before and after TACE for HCC could be a predictor of prognosis. The subjects were 108 patients with the first TACE performed from January 2010 to December 2019. NLR was calculated before and 1 month after TACE, and the relationship with therapeutic effect and prognosis was examined. When the transition of NLR before and after TACE was classified into 3 groups with a cut-off value of 5.0, group A(less than 5.0 after TACE): 52 cases(48.1%), group B(5.0 or more after TACE): 33 cases(30.6%)and C group(5.0 or more before and after TACE): 23 cases(21.3%). Median survival time were 25.0 months in group A, 18.5 months in group B, and 12.7 months in group C(p=0.0005). In multivariate analysis, treatment effect, NLR transition, AFP value, and serum albumin level were prognostic factors for HCC after TACE. Changes in NLR before and after TACE may help predict more detailed prognosis.

[Four Cases of Liver Resection for Liver Metastases from Renal Cell Carcinoma].

We report 4 cases of liver metastasis from renal cell carcinoma(RCC). Case 1: 72 years old, female. Pancreatic metastasis was resected 7 years after resection of left RCC, and hepatic posterior sectionectomy was performed for multiple liver metastases 2 years later. After that, multi-organ metastasis appeared and she died of the primary disease. Case 2: 72 years old, male. Liver metastasis and right RCC appeared 16 years after resection of left RCC, and hepatic posterior sectionectomy and partial resection of right kidney were performed. Nine months later, liver metastasis recurred and hepatic partial resection was performed. Case 3: 55 years old, male. After surgery for right RCC with tumor thrombus in the right atrium, multiple lung and liver metastases appeared, and hepatic central bisectionectomy was performed after chemotherapy. Case 4: 60 years old, male. Multiple pancreatic and lung metastases appeared 10 years after resection of left RCC, and most of them shrank or disappeared with chemotherapy. But increasing metastases appeared in the tail of pancreas and the right lobe of liver 16 months later, and hepatic subsegmentectomy and distal pancreatectomy were performed. Multidisciplinary treatment such as aggressive chemotherapy and excision is expected to improve the prognosis for liver metastasis from RCC.

[A Case of Advanced and Recurrent Colon Cancer with Long-Term Survival after Seven Repeated Surgical Resections].

We hereby report a case of advanced and recurrent colon cancer with long-term survival after 7 repeated surgical resections. A 73-year-old woman initially underwent right hemicolectomy and partial hepatectomy for an ascending colon cancer with synchronous liver metastasis. Pathological diagnosis of the tumors were moderately differentiated adenocarcinoma and metastasis to the liver compatibly. Final clinical stage was diagnosed as fT3N2M1(H1), fStage Ⅳ. But she was interrupted oxaliplatin-based adjuvant chemotherapy after 6 courses of CAPOX because of adverse drug reaction. One year after first operation, partial resection of right lung was performed for lung metastasis. Two years after first operation, 2nd resection of liver was performed for 2 liver metastatic lesions. Three years after first operation, 3rd partial liver resection, 2nd and 3rd partial lung resections were performed for metachronous metastases during 1 year. After 3 years recurrence free period, she complained of an induration of right neck and diagnosed as neck and supra clavicular lymph nodes metastases. Lymph nodes resection was performed. After the last operation, she has no sign of cancer recurrence for 1 year and 7 months, eventually she has been alive for 7 years and 7 months after the initial operation.

[Assessment of Curative Resection in Patients with Multiple Relapses of Colorectal Cancer].

We assessed the therapeutic effect of curative resection in patients with multiple relapses of colorectal cancer using the time to surgical failure(TSF)as an index. We included 24 patients who experienced recurrence after curative resection of primary colorectal cancer at our department between 1993 and 2015. Curative resection for multiple relapses was possible in these patients. The sites of recurrence included the liver, lungs, peritoneum, lymph nodes, localized, and brain in 9, 8, 3, 3, 2, and 1 patients, respectively. The relapse occurred in 2 organs in 2 patients. The TSF after curative resection of recurrent lesions was 25.6 months, with a 5-year TSF-free rate of 40.2%. The clinicopathological factors associated with poor prognosis were age B65 years at the time of recurrence, absence of distal metastasis at primary onset, and only 2 curative resections for relapses. However, there was no difference in prognosis because of the number of twice recurrent lesions. Therefore, curative resection should be proactively performed as long as feasible in colorectal cancer patients with multiple lesions or multiple relapses.

[A Case of Unresectable Ascending Colon Cancer Treated with a Newly Devised Bypass Method].

A 74-year-old man underwent a medical examination for anemia and had a positive fecal occult blood test. Ascending colon cancer was detected by colonoscopy. Since it was unresectable, a bypass operation was performed to prevent digestive symptoms prior to chemotherapy. The bypass was performed by cutting the ileum and attaching the oral side to the transverse colon with side to side anastomosis. The other end of the terminal ileum was anastomosed to the transverse colon on the oral side of the prior anastomosis, making a pretzel shaped bypass. There were no postoperative complications and the patient was treated with chemotherapy from postoperative day 23.