Curative resection via right hemicolectomy and regional lymph node dissection for colonic adenomatous polyposis of unknown etiology with adenocarcinomas localized in the right side of the colon: a case report.

BACKGROUND: APC and MUTYH are both well-known colorectal polyposis causative genes. However, 30-50% of colorectal adenomatous polyposis cases are classified as colonic adenomatous polyposis of unknown etiology and lack identifiable pathogenic variants. Although guidelines recommend total proctocolectomy for colonic adenomatous polyposis of unknown etiology with over 100 adenomas, evidence is lacking. This study presents a unique case of localized colonic adenomatous polyposis of unknown etiology with multiple adenocarcinomas, treated with hemicolectomy and regional lymph node dissection. CASE PRESENTATION: The patient was a 72-year-old woman whose colonoscopy revealed numerous polyps and two adenocarcinomas localized in the right side of the colon, with no lesions in the left side. The patient had no family history of polyposis or colorectal cancer. No extracolonic lesions, enlarged lymph nodes, or distant metastases were found. Considering the patient's age and lesion localization, laparoscopic right hemicolectomy with regional lymph node dissection was performed. Histopathological diagnosis revealed three adenocarcinoma lesions with no lymph node metastasis. The most advanced pathological stage was T2N0M0 Stage I (UICC 8th edition). The patient was alive 5 years postoperatively, without recurrence of cancer or polyposis in the remaining colon and rectum. To diagnose hereditary colorectal cancer/polyposis, a germline multigene panel testing for APC, EPCAM, MBD4, MLH1, MLH3, MSH2, MSH3, MSH6, MUTYH, NTHL1, PMS2, POLD1, POLE, and TP53 was performed using DNA extracted from blood samples: however, no pathogenic variant was detected. Therefore, the patient was diagnosed with colonic adenomatous polyposis of unknown etiology. CONCLUSIONS: In this rare case, colonic adenomatous polyposis of unknown etiology, with numerous adenomatous polyps and multiple adenocarcinomas localized in the right side of the colon, was successfully treated with right hemicolectomy and regional lymph node dissection. Despite genetic analysis, no causative germline variants were identified. Segmental colectomy according to the distribution of polyps might be a curative approach.

Circulating tumor-associated antigen-specific IFNγ+4-1BB+ CD8+ T cells as peripheral biomarkers of treatment outcomes in patients with pancreatic cancer.

CD8+ T cells affect the outcomes of pancreatic ductal adenocarcinoma (PDAC). Using tissue samples at pre-treatment to monitor the immune response is challenging, while blood samples are beneficial in overcoming this limitation. In this study, we measured peripheral antigen-specific CD8+ T cell responses against four different tumor-associated antigens (TAAs) in PDAC using flow cytometry and investigated their relationships with clinical features. We analyzed the optimal timing within the treatment course for effective immune checkpoint inhibition in vitro. We demonstrated that the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells was correlated with a fold reduction in CA19-9 before and after neoadjuvant therapy. Moreover, patients with TAA-specific IFNγ+4-1BB+ CD8+ T cells after surgery exhibited a significantly improved disease-free survival. Anti-PD-1 treatment in vitro increased the frequency of TAA-specific IFNγ+4-1BB+ CD8+ T cells before neoadjuvant therapy in patients, suggesting the importance of the timing of anti-PD-1 inhibition during the treatment regimen. Our results indicate that peripheral immunophenotyping, combined with highly sensitive identification of TAA-specific responses in vitro as well as detailed CD8+ T cell subset profiling via ex vivo analysis, may serve as peripheral biomarkers to predict treatment outcomes and therapeutic efficacy of immunotherapy plus neoadjuvant chemotherapy.

Results of a Randomized Clinical Study of Gemcitabine Plus Nab-Paclitaxel Versus Gemcitabine Plus S-1 as Neoadjuvant Chemotherapy for Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (RCT, CSGO-HBP-015).

BACKGROUND: The optimal neoadjuvant chemotherapy (NAC) regimen for patients with localized pancreatic ductal adenocarcinoma (PDAC) remains uncertain. This trial aimed to evaluate the efficacy and safety of two neoadjuvant chemotherapy (NAC) regimens, gemcitabine plus nab-paclitaxel (GA) and gemcitabine plus S-1 (GS), in patients with resectable/borderline-resectable (R/BR) PDAC. PATIENTS AND METHODS: Treatment-naïve patients with R/BR-PDAC were enrolled and randomly allocated. They received two cycles (2 months) of each standard protocol, followed by radical surgery for those without tumor progression in general hospitals belonging to our intergroup. The primary endpoint was to determine the superior regimen on the basis of achieving a 10% increase in the rate of patients with progression-free survival (PFS) at 2 years from allocation. RESULTS: A total of 100 patients were enrolled, with 94 patients randomly assigned to the GS arm (N = 46) or GA arm (N = 48). The 2-year PFS rates did not show the stipulated difference [GA, 31% (24-38%)/GS, 26% (18-33%)], but the Kaplan-Myer analysis showed significance (median PFS, GA/GS 14 months/9 months, P = 0.048; HR 0.71). Secondary endpoint comparisons yielded the following results (GA/GS arm, P-value): rates of severe adverse events during NAC, 73%/78%, P = 0.55; completion rates of the stipulated NAC, 92%/83%, P = 0.71; resection rates, 85%/72%, P = 0.10; average tumor marker (CA19-9) reduction rates, -50%/-21%, P = 0.01; average numbers of lymph node metastasis, 1.7/3.2, P = 0.04; and median overall survival times, 42/22 months, P = 0.26. CONCLUSIONS: This study found that GA and GS are viable neoadjuvant treatment regimens in R/BR-PDAC. Although the GA group exhibited a favorable PFS outcome, the primary endpoint was not achieved.

Cardiac tamponade complicating esophagectomy and retrosternal gastric tube reconstitution in a patient with an abnormal ascending aorta position: a case report.

BACKGROUND: Cardiac tamponade is a rare postoperative complication of esophageal cancer surgery, which leads to rapid hemodynamic changes and can be fatal if not treated properly and promptly. Herein, we report a case of cardiac tamponade after thoracoscopic subtotal esophagectomy and retrosternal gastric tube reconstitution for esophageal cancer that was successfully treated with surgical drainage. CASE PRESENTATION: An 86-year-old man with lower thoracic esophageal cancer underwent thoracoscopic subtotal esophagectomy and retrosternal gastric tube reconstitution. No intra-operative complications were observed. On the first postoperative day, tachycardia and hypotension were observed, and pericardial effusion was identified on computed tomography images. The patient was diagnosed with obstructive shock secondary to cardiac tamponade. As percutaneous puncture drainage was not possible due to the presence of a retrosternal gastric tube, pericardiotomy with a small left anterior thoracotomy was performed, and a large amount of hematogenous fluid was drained, which instantly improved circulation. On the second postoperative day, the patient showed decreased pulse pressure, and computed tomography revealed a residual and enlarged hematoma around the right ventricle. The patient underwent surgical drainage and another pericardiotomy with a small right anterior thoracotomy was performed to drain the hematoma. At this time, multiple injuries to the fatty tissue, epicardium, and myocardium with active bleeding were observed on the anterior surface of the right ventricle near the root of the pulmonary artery. In this patient, the ascending aorta ran further to the right and dorsal sides than usual, causing the anterior wall of the right ventricle near the root of the pulmonary artery to be closer to the back of the sternum. This abnormality may have contributed to injury during the creation of the retrosternal pathway, leading to cardiac tamponade. CONCLUSIONS: Cardiac tamponade after esophagectomy can occur because of manipulation during creation of the retrosternal route, with an anomaly in the aortic position being present in this case. Gentle manipulation and selection of the reconstruction route according to the patient's condition are necessary in cases with such anatomical abnormalities.

Comparison of percutaneous ablation and hepatectomy for liver metastasis: A single center retrospective study.

AIM: To investigate the current treatment for liver metastasis and clarify the indications for percutaneous thermal ablation for liver metastasis. METHODS: Ninety-two patients were enrolled and retrospectively analyzed. The patients underwent hepatectomy and/or percutaneous thermal ablation for liver metastases between January 2012 and December 2018. Twenty-six patients who underwent ablation treatment and seven patients who underwent both ablation and hepatectomy were included in the ablation treatment group (group A). We compared these patients with 59 patients who underwent hepatectomy only (group H). Subgroup analyses were performed between ablation (group AC) for colorectal liver metastasis and hepatectomy (group HC) for colorectal liver metastasis in 17 and 53 patients, respectively. RESULTS: The percentage of liver metastases other than colorectal cancer in group A was higher than that in the group H. Maximum tumor size in group A was significantly smaller than that in group H. Similarly, the patients in group AC were significantly older and demonstrated higher total bilirubin, lower serum albumin, and lower platelet counts than those in group HC. Overall survival was poorer in the AC group than that in the HC group. However, no differences were observed at metastasis ≤2 cm in size. CONCLUSIONS: Percutaneous thermal ablation was performed for many cancer types than hepatectomy. It is performed in elderly patients. We suggested that ablation for colorectal liver metastasis sized ≤2 cm is a suitable indication.

Exploratory prospective, randomized phase II study of neoadjuvant transcatheter arterial chemoembolization plus surgery versus surgery alone for large hepatocellular carcinoma (CSGO-HBP-005): Clinical Study Group of Osaka University, Hepato-Biliary-Pancreatic Group.

AIM: Neoadjuvant transcatheter arterial chemoembolization (TACE) for large tumors is controversial, especially in the minimally invasive surgery era. The aim of this study was to compare features between groups treated with neoadjuvant TACE followed by surgery (TACE + surgery) or upfront surgery for hepatocellular carcinoma >5 cm. METHODS: In this exploratory, multicenter, randomized phase I study, the primary measure was 2-year disease-free survival (DFS). Secondary measures were resection rate, necrosis rate by TACE, 2-year overall survival, and site of recurrence. A total of 30 patients were randomly allocated to each arm. RESULTS: The two arms did not differ in patient characteristics. The median time to surgery from randomization was 48 days for TACE + surgery and 29 for surgery only (p < 0.001). Postoperative morbidities did not differ between arms. The 2-year DFS, overall survival, and resection rates were 56.7%, 80.0%, and 93.3%, respectively, in the TACE + surgery arm, and 56.1%, 89.9%, and 90.0% in the upfront surgery arm. Minimally invasive surgery was carried out in 35.7% in the TACE + surgery arm and in 29.6% in the upfront surgery arm. The median necrosis rate by TACE was 90.0%. In resected specimens, invasion to the hepatic vein was less with TACE + surgery (3.6% vs. 22.2%, p = 0.0380). In cases of 100% necrosis with TACE, 2-year DFS was 100%. Site of recurrence did not differ between groups. CONCLUSION: Neoadjuvant TACE did not improve 2-year DFS, and neoadjuvant TACE allowed delay of surgical treatment without increased morbidity and cancer progress. CLINICAL TRIAL REGISTRATION: UMIN: 000005241.

[A Case of Hepatic Encephalopathy Caused by Portal Vein Thrombosis after Surgery for Perihilar Cholangiocarcinoma].

A female in her 70s underwent right hepatectomy with resection of caudate lobe and extrahepatic bile duct for perihilar cholangiocarcinoma(T2aN0M0, Stage Ⅱ: Biliary Cancer Treatment Regulations, 7th edition). On the 4th postoperative day, the patient had impaired consciousness, which worsened to almost coma on the 5th postoperative day. On the same day, a blood test showed high ammonia level, thus the state was thought to be hepatic encephalopathy. Contrast -enhanced CT on the same day showed thrombus from the main trunk of the portal vein to the remnant left branch, narrowing of the lumen of the vessel. Simultaneously, enlarged portosystemic shunt in the pelvic floor due to portal hypertension induced by the thrombosis. Plasmapheresis was performed, and anticoagulation with sodium heparin and antithrombin Ⅲ were started. Then, the portal vein thrombus was reduced, and encephalopathy was improved. She was discharged from the hospital on postoperative day 48. She was treated with edoxaban as an outpatient, and anticoagulation therapy was terminated after a CT scan 6 months after surgery, which confirmed no recurrence of thrombus. She is now alive without recurrence of thrombus or tumor for about 2 years after the surgery.

[A Case of Single Hole Ileal Resection for Ascendiry Colon Cancer with Ureterocutaneous Fistula in the Right Lower Abdomen].

The patient is a 70s woman. She underwent cystectomy for bladder cancer 6 years ago and had a ureterocutaneous fistula in the right lower abdomen. After colonoscopy for positive fecal occult blood, a type 1 elevated lesion was found in the ascending colon, which was diagnosed as a well-differentiated adenocarcinoma on biopsy. Surgery was performed with a single hole. The approach from the right lower abdomen, where the ureterocutaneous fistula and ureter are located, was avoided, and the approach from the hepatic flexure of the transverse colon was used first. After the right colon was mobilized, the large mesh adhesions around the ureter were carefully dissected, and the right ureter was identified and preserved, extending from the lateral ascending colon to the abdominal wall. The ileal artery was dissected at the root and after dissection of the D3 lymph node, the intestine was dissected and anastomosed extracorporeally. The operative time was 246 minutes with small amount of blood loss. The patient was discharged on the 6th postoperative day without any postoperative complications. The pathology result was pT3N0M0, pStage Ⅱa, and radical resection had been performed. The patient is currently undergoing recurrence-free follow-up.

[A Case of Pathological Complete Response for MSI-High Locally Advanced Unresectable Transverse Colon Cancer Treated with Nivolumab plus Ipilimumab Combination Therapy].

74-year-old woman was diagnosed with locally advanced unresectable transverse colon cancer. She started CAPOX therapy as first-line therapy after ileostomy. After second course, MSI-high was detected, so nivolumab plus ipilimumab combination therapy was started as second-line therapy. After 4 courses of combination therapy, she was judged to be in partial response and surgery was performed. Histopathological diagnosis of the surgical specimen showed complete response, and she is still alive without recurrence 15 months after surgery.

[A Case of Response to Pembrolizmab in Unresectable MSI-High Transverse Colon Cancer].

A 80s man was diagnosed circulated type 2 colon cancer at the transverse colon, and pathological findings was adenocarcinoma( por1). Genomic findings were microsatellite instability-high(MSI-H), all RAS wild type and BRAFV600E mutated. Contrast-enhanced CT showed an enlarged lymph nodes(#221, #222, #223, #214)along the middle colic and superior mesenteric artery. Clinical diagnosis was a locally advanced unresectable transverse colon cancer, cT4aN3M1a(LYM), cStage Ⅳa. Drug therapy with pembrolizumab was prescribed. Six months later, contrast-enhanced CT and PET demonstrated remarkable shrinkage of the primary tumor and lymph nodes except 2 peri-colic enlarged lymph nodes. Primary lesion turned almost undetectable, however the biopsy demonstrated residual tumor. Two months later, CT showed that the residual lymph nodes had also disappeared.

[A Case of Conversion Surgery after Chemotherapy for Locally Advanced Unresectable Rectal Cancer].

We report a case of locally advanced rectal cancer that could not be curatively resected, in which the patient underwent conversion surgery after chemotherapy. The patient is a 70-year-old woman. She came to our hospital with a chief complaint of lower abdominal pain, and a close examination revealed rectal cancer with invasion of the external iliac artery and pelvic wall. She was treated with mFOLFOX6 plus cetuximab for locally advanced rectal cancer that was not amenable to surgical resection. After 11 courses of chemotherapy, significant shrinkage of the tumor was observed, and robot assisted laparoscopic high-anterior resection was performed. The patient didn't relapse at 12 months after surgery without adjuvant chemotherapy.