[A Case of Advanced Recurrent Rectal Cancer Successfully Treated by Rechallenge Therapy with an Anti-Epidermal Growth Factor Receptor(EGFR)Drug].

The patient was a 75-year-old man who had undergone potentially curative surgery for Stage Ⅲb rectal cancer followed by resection of liver metastases. Two years after the resection of liver metastases, lung and remnant liver metastases were found. He received chemotherapy for unresectable metastatic tumors. Based on the findings of molecular and pathological examinations(RAS: wild type; BRAF: wild type; MSI: negative; HER2: negative), the following chemotherapy regimens were administered: first-line, FOLFIRI plus panitumumab(PANI); second-line, mFOLFOX6; third-line, trifluridine/tipiracil; fourth- line, regorafenib. After fourth-line treatment, he was judged to have disease progression due to the increase in his lung and liver metastases and the elevation of tumor markers. All standard regimens were refractory, but the Eastern Cooperative Oncology Group performance status was zero and a liquid biopsy for RAS still showed wild type. Therefore, rechallenge therapy with anti-epidermal growth factor receptor(EGFR)drugs, cetuximab(CET)and irinotecan(IRI), was administered 13 months after the final course of FOLFIRI plus PANI treatment. After 4 courses of CET plus IRI, the size of the 2 metastatic tumors markedly decreased and his tumor marker levels normalized.

[Synchronous Double Primary Non-B, and Non-C Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma-A Case Report].

A 78-year-old man without hepatitis virus B or C underwent right hemi-hepatectomy and lymph node dissection for a tumor 5 cm in diameter located in the hepatic hilum of the posterior segment of the liver with portal vein thrombi extending into the main portal trunk and a tumor 1.5 cm in diameter in the peripheral side of segment 5 of the liver. Histopathologically, the former was diagnosed as intrahepatic cholangiocarcinoma and the latter as hepatocellular carcinoma(HCC). Five months after the surgery, intrahepatic and lymph node metastases were diagnosed based on computed tomography(CT); therefore, chemotherapy with S-1 for 3 months and gemcitabine and cisplatin(GC)for 5 months was administered, after which the metastatic lesions were not detected. Nineteen months after the surgery, partial resection of segment 2 of the liver was performed for a tumor 3 cm in diameter, which was diagnosed as HCC histopathologically. Two years after the second surgery, 2 recurrent nodules in the liver in segments 3 and 4 were detected on CT. Platinum-based hepatic arterial infusion chemotherapy(HAIC)and transcatheter arterial chemoembolization(TACE)were performed, and chemotherapy with GC was then administered for 7 months. For a new tumor detected in segment 1 in the liver, TACE was performed 17 months after initial HAIC. Seventy-four months after the initial surgery, 5 new nodules less than 1 cm in diameter were detected, and chemotherapy with sorafenib was administered for 5 months, after which the patient died of coronavirus disease 2019.

Development and evaluation of a colorectal cancer screening method using machine learning-based gut microbiota analysis.

Accumulating evidence indicates that alterations of gut microbiota are associated with colorectal cancer (CRC). Therefore, the use of gut microbiota for the diagnosis of CRC has received attention. Recently, several studies have been conducted to detect the differences in the gut microbiota between healthy individuals and CRC patients using machine learning-based gut bacterial DNA meta-sequencing analysis, and to use this information for the development of CRC diagnostic model. However, to date, most studies had small sample sizes and/or only cross-validated using the training dataset that was used to create the diagnostic model, rather than validated using an independent test dataset. Since machine learning-based diagnostic models cause overfitting if the sample size is small and/or an independent test dataset is not used for validation, the reliability of these diagnostic models needs to be interpreted with caution. To circumvent these problems, here we have established a new machine learning-based CRC diagnostic model using the gut microbiota as an indicator. Validation using independent test datasets showed that the true positive rate of our CRC diagnostic model increased substantially as CRC progressed from Stage I to more than 60% for CRC patients more advanced than Stage II when the false positive rate was set around 8%. Moreover, there was no statistically significant difference in the true positive rate between samples collected in different cities or in any part of the colorectum. These results reveal the possibility of the practical application of gut microbiota-based CRC screening tests.

[A Case of Neuroendocrine Carcinoma Originating from the Papilla of Vater].

A woman in her late 70s with fatigue, nausea, and epigastric discomfort was found to have a tumor at the papilla of Vater through endoscopy. We performed subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. The immunohistological analysis showed positive staining for chromogranin A, synaptophysin, and CD56. The definitive diagnosis was neuroendocrine carcinoma of the papilla of Vater. Although the patient declined adjuvant chemotherapy, she had to start chemotherapy with carboplatin and etoposide because multiple liver metastases, lymph node metastasis, and peritoneal dissemination occurred 6 months after surgery. We performed 6 courses of chemotherapy. However, progressive disease(PD)was assessed, and she died of cancer 13 months after the surgery. The prognosis of the disease is poor when surgery alone is performed. Adjuvant chemotherapy, in addition to surgery, may be necessary.

[A Case of Disturbance of Consciousness Due to Hyperammonemia during Chemotherapy for Metastasis of Sigmoid Colon Cancer].

A 76-year-old woman had underwent 5-fluorouracil(5-FU), oxaliplatin(L-OHP)combination therapy(mFOLFOX6)as first-line chemotherapy for peritoneal recurrence after resection of sigmoid colon cancer. She showed severe general fatigue and disturbance of consciousness on the second day of the 12th course of chemotherapy. Computed tomography of the head detected no abnormal findings in the central nervous system. The laboratory results revealed a marked hyperammonemia. She was diagnosed as a disturbance of consciousness due to hyperammonemia and treated her with branched- chain amino acid solution. Then the disturbance of consciousness resolved on the following day. After changing the regimen of chemotherapy, the disturbance of consciousness was not found. Recently, it has been reported that high-dose 5-FU regimen such as mFOLFOX6 causes hyperammonemia as a rare adverse event. We should take hyperammonemia into account when disturbance of consciousness occurs during high-dose 5-FU chemotherapy.

[Laparoscopic Liver Resection for Liver Metastasis from Unresectable Pancreatic Ductal Adenocarcinoma Well-Controlled by Chemotherapy-A Case Report].

A 45-year-old man with unresectable locally advanced pancreas head cancer with multiple synchronous liver metastases was treated with gemcitabine plus nab-paclitaxel therapy as a first-line chemotherapy. During 24 months of 30 courses of this therapy, the primary lesion remained stable and liver metastases were completely disappeared on CT. Three months later, however, solitary relapse of liver metastasis occurred in segment 2. Therefore, we changed the chemotherapy regimen to the second-line treatment, FOLFIRINOX. After 3 courses of FOLFIRINOX, the primary lesion was kept well-controlled, but the solitary metastatic liver lesion was enlarged. An interdisciplinary team suggested surgical resection of the liver metastasis to control disease progress. We performed laparoscopic lateral segmentectomy of the liver. The postoperative course was uneventful, and the patient was discharged on postoperative day 8. The patient underwent another round of gemcitabine therapy owing to the good response of the primary pancreatic lesion to this drug. Three years after starting the first-line chemotherapy, the patient is still alive with well-controlled PDAC without distant metastasis. Surgical intervention for liver metastases may be a promising treatment option when unresectable primary PDAC is well controlled by chemotherapy.

[Laparoscopic Resection of Solitary Lymph Node Metastasis of Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization and Percutaneous Locoregional Therapies].

A 75-year-old woman underwent transcatheter chemoembolization(TACE)for 2 small hepatocellular carcinoma(HCC) lesions associated with severe alcoholic liver cirrhosis that necessitated management for ascites. Over 5 years after the initial TACE, she received multidisciplinary therapies with TACE, transcatheter arterial infusion of anticancer agents, percutaneous ethanol injections, or percutaneous radiofrequency ablation performed on 5 occasions for small recurrent HCC lesions. Computed tomography performed after the last therapy for HCC revealed a solitary lymph node swelling(39 mm in diameter) around the common hepatic artery. Magnetic resonance imaging performed 3 months later revealed that the lymph node had enlarged to 45 mm, without recurrence of the primary HCC, and after 4 months, to 60 mm; she then underwent laparoscopic lymph node resection. Histopathological examination of the resected specimen showed HCC metastasis. A recurrent metastatic lymph node(30 mm in diameter)was detected around the common hepatic artery and was resected laparoscopically 17 months postoperatively. Pancreatic head cancer was diagnosed 22 months after the second surgery; however, the patient refused cancer therapy and died 16 months after this diagnosis. No recurrence of the primary HCC or lymph node metastasis was observed over the 38 months after the second surgery.

Stent-graft placement for delayed extrahepatic portal hemorrhage after surgical treatment for perihilar cholangiocarcinoma: A case report.

INTRODUCTION: Potential curative therapy for perihilar cholangiocarcinoma requires extensive surgical treatment, which can still be associated with significant morbidity and mortality. Postoperative hemorrhage from the portal vein is a rare but life-threatening complication. We herein report postoperative hemorrhage from an extrahepatic portal vein pseudoaneurysm successfully treated by stent graft placement late after surgical treatment for perihilar cholangiocarcinoma. PRESENTATION OF CASE: An 83-year-old man was referred to our hospital with a chief complaint of jaundice. Based on radiological findings, we diagnosed the patient with hilar cholangiocarcinoma. After endoscopic retrograde biliary drainage, resection of the extrahepatic bile duct combined with extended left hemi-hepatectomy, including the caudate lobe, lymphadenectomy of the hepatoduodenal ligament, partial resection and reconstruction of the portal vein, and right hepaticojejunostomy was performed. Fourteen days postoperatively, bleeding through the abdominal drain around the portal vein was observed. Twenty days postoperatively, abdominal computed tomography revealed a portal vein pseudoaneurysm that had formed at the portion of reconstruction. Therefore, 24 days postoperatively, a stent graft placement of the pseudoaneurysm through the ileocolic vein was performed. Subsequently, the portal vein hemorrhage ceased. DISCUSSION: Our present postoperative extrahepatic portal vein hemorrhage case was caused by an extrahepatic portal vein pseudoaneurysm that had formed at the reconstructed portion by erosion due to the chemical effect of the leaking bile and mechanical irritation of the surgical drain adjacent to the portal vein. CONCLUSION: Stent-graft placement is a minimally-invasive, safe, and effective treatment option for hemorrhage from postoperative portal vein pseudoaneurysm.

Concise synthesis of multisubstituted isoquinolines from pyridines by regioselective Diels-Alder reactions of 2-silyl-3,4-pyridynes.

A four-step regioselective synthesis of multisubstituted isoquinoline derivatives from 3-bromopyridines was developed by the Diels-Alder (DA) reactions of 2-silyl-3,4-pyridynes with furans, followed by functional-group transformations. In particular, the silyl group at the C2-position of the 3,4-pyridynes played two important roles: firstly, it functioned as the directing group for the DA reaction, and secondly, it served to introduce diverse substituents at the C1-position of the isoquinolines by electrophilic ipso-substitution.

Nucleophilic deoxyfluorination of catechols.

Nucleophilic deoxyfluorinaiton of one of the two hydroxyl groups of catechols has been developed via the Umpolung concept. This method was successively applied to naturally occurring catechols, such as catechins and dopamine, to produce novel fluorinated analogues.

A domino process for benzyne preparation: dual activation of o-(trimethylsilyl)phenols by nonafluorobutanesulfonyl fluoride.

Benzynes were generated from o-(trimethylsilyl)phenols using nonafluorobutanesulfonyl fluoride (NfF) by a domino process, i.e., the nonaflation of the phenolic hydroxyl group of o-(trimethylsilyl)phenols by NfF followed by the attack of the produced fluoride ion on the trimethylsilyl group. The generated benzyne immediately underwent various reactions to give polysubstituted benzenes.