Japanese Journal of Cancer and Chemotherapy最新文献

Cytotoxic anticancer drugs, including alkylating agents or platinum‒based compounds, have been central to cancer treatment since the 1980s and remain in use today. Recently, following the emergence of immune checkpoint inhibitors(ICI)across multiple cancer types, attention has shifted to the potential of cytotoxic anticancer drugs to enhance cancer immunotherapy efficacy through immunogenic cell death. Furthermore, it has been suggested that these drugs can positively or negatively influence the anticancer immune response by acting on cell populations within the tumor microenvironment, such as Tregs, MDSCs, and macrophages, or by affecting systemic physiological changes, including the gut microbiota. While the combination therapy with cytotoxic anticancer drugs with ICIs had broadened treatment options for cancers with limited response to ICI monotherapy, the significance of such combination therapy may differ in cancers that respond well to ICI alone, such as in non‒small cell lung cancer with PD‒L1 high. This review discusses the clinical significance of cytotoxic anticancer drugs in combination immunotherapy, based on preclinical evidence and clinical trial results.

A 72‒year‒old man was referred to our hospital with a chief complaint of abdominal pain. Computed tomography(CT)revealed a tumor approximately 17 mm in diameter in segment 7(S7)of the liver. The tumor demonstrated ring enhancement and was associated with vascular invasion(Vp2). He was diagnosed with intrahepatic cholangiocarcinoma and underwent a laparoscopic posterior segmentectomy. Intraoperative findings revealed the tumor as a hard white mass on the surface of the liver. The patient was discharged on postoperative day 9. Histopathological examination revealed a highly sclerotic lesion with extensive hyalinization and fibrosis, leading to a final diagnosis of sclerosed hemangioma. It is generally difficult to distinguish sclerosed hemangiomas from malignant tumors preoperatively. We report this case along with a review of the literature.

The patient was a 53‒year‒old man who presented to our hospital for evaluation of epigastric pain. Gastroscopy revealed a submucosal tumor with delle. Biopsy specimens showed spindle cell proliferation in a palisading pattern, and immunohistochemical staining(IHC)was positive for c‒kit, leading to a diagnosis of GIST. We underwent surgical resection after NAC and achieved a complete resection. The histopathological findings from the resected specimen differed markedly from the biopsy specimen, making the postoperative diagnosis difficult. There have been few reports on the IHC change in cases of GIST after NAC, so we report this case and provide a literature review.

Neoadjuvant chemotherapy followed by radical esophagectomy is the standard treatment for advanced esophageal cancer in Japanese treatment guideline. However, in elderly patients with dysphagia and impaired organ function, preoperative chemotherapy may worsen their condition. We report here a case of a 79‒year‒old malnourished man with advanced esophageal squamous cell carcinoma and EGJ adenocarcinoma presenting with severe dysphagia. Given his age, frailty, and high‒risk of systemic decline, initial mediastinoscopic esophagectomy was selected over neoadjuvant therapy. Pathology showed a positive radial margin and PD‒L1 expression, prompting postoperative local salvage radiotherapy(40 Gy/20 fr)with nivolumab(480 mg/4 weeks). After 4 cycles, nivolumab was discontinued due to immune‒related pneumonitis, and S‒1 chemotherapy was initiated. Nearly 2 years postoperatively, the patient remains recurrence‒free. This case demonstrates the feasibility of a personalized, minimally invasive treatment strategy with tailored adjuvant therapy in high‒risk elderly patients.

Background: Chronic inflammatory conditions, such as obstructive colitis and inflammatory bowel disease(IBD), are representative causes of colonic fibrosis. In addition, there have been reports that endoscopic interventions, including biopsies and local therapies, may induce submucosal fibrosis.

Case presentation: A 50‒year‒old woman presented to our hospital with abdominal pain and fever that had developed the day before presentation. She reported chronic constipation for several years and had not had a bowel movement for several days. Abdominal computed tomography revealed bowel wall thickening from the lower rectum(RS)to the upper rectum(Ra), along with enlargement of the regional lymph nodes. Colonoscopy revealed a lesion located approximately 12 cm from the anal verge in the rectum, presenting as a type 2 advanced carcinoma involving one‒third of the circumference. Histopathological examination of the biopsy specimen revealed well‒differentiated tubular adenocarcinoma(tub1), and positron emission tomography‒computed tomography(PET‒CT)showed no evidence of distant metastasis. Based on these findings, the clinical diagnosis was rectal cancer, cT3N2aM0, Stage Ⅲb. The patient underwent laparoscopic low anterior resection. Intraoperative findings revealed rectal distension with a tumor appearing to reach the subserosal layer, raising suspicion of subserosal invasion. D3 lymph node dissection was performed, and the rectum was resected with anastomosis using the double stapling technique. The postoperative course was uneventful: the patient resumed oral intake on postoperative day 6 and was discharged on day 11. Histopathological examination of the resected specimen revealed pT2N0M0, Stage Ⅰ disease. Notably, subserosal fibrosis accompanied by lymphoid follicular hyperplasia was observed, without any continuity between the tumor and the fibrotic area. The patient has remained recurrence‒free during the 3‒year follow‒up period after surgery.

Discussion: In this case, subserosal fibrosis was observed without histological evidence of tumor invasion into the subserosal layer. Moreover, no common causes of colonic fibrosis were identified. A possible mechanism for the fibrosis is chronic mechanical traction at the tumor base, resulting in reactive changes in the subserosa.

Conclusion: We report a rare case of colorectal carcinoma associated with subserosal fibrosis in the absence of tumor invasion. A brief review of the relevant literature is also presented.

Case 1: Urgent examination of a 72‒year‒old man with hematemesis revealed a gastroesophageal tumor. Biopsy revealed gastric cancer, and computed tomography(CT)revealed enlarged lymph nodes and multiple liver metastases. Laparoscopic gastrectomy led to the diagnosis of a pT3N2M1(HEP), pStage Ⅳ liver tumor. A CT scan performed 2 months postoperatively revealed enlargement of the liver tumor, suggesting hepatocellular carcinoma and prompting right liver lobectomy. Histopathological examination of the operative specimen revealed metastatic hepatocellular carcinoma. Adjuvant chemotherapy(S‒1)was administered postoperatively but was discontinued because of severe adverse effects. To date, the patient has been recurrence‒free for 3 years. Case 2: A 79‒year‒old man with black stools who had not sought treatment presented to the emergency department with nausea and dizziness. A CT scan revealed a gastric mass, enlarged lymph nodes, and a liver tumor. After a thorough investigation, gastric cancer(cT4aN2M1[HEP], cStage ⅣB)was diagnosed. As the liver metastasis was solitary, pylorus‒preserving gastrectomy and partial hepatic resection were performed. Adjuvant chemotherapy(S‒1)was administered for 1 year, during which the patient remained recurrence‒free. Given that resection of liver metastases from gastric cancer often achieves long‒term survival, we performed this procedure as a component of multidisciplinary treatment.

A woman in her 70s underwent left upper lobectomy with ND2a‒1 dissection for suspected lung cancer(cT1cN0M0, stage ⅠA3)and was discharged on postoperative day(POD)4. On POD 12, she developed watery diarrhea, nausea, vomiting, abdominal pain, mild lower back pain, and hematochezia. Stool cultures were negative. Gastroenteritis was diagnosed, and the symptoms resolved with fasting and intravenous hydration. She was discharged again on POD 21. However, that night, she returned to the emergency department with a fever of 38℃. Laboratory examinations showed elevated inflammatory markers and lactate dehydrogenase(LDH). Contrast‒enhanced computed tomography(CT)showed thrombi in the left pulmonary vein stump, distal left subclavian artery, and superior mesenteric artery, along with left renal infarction. Anticoagulation therapy was started, and follow‒up CT on POD 34 showed that the pulmonary vein stump thrombus was smaller, and contrast enhancement of the left kidney had improved. Anticoagulant therapy is currently ongoing. This case demonstrates that left upper lobectomy, a known risk factor for thromboembolism, can lead to atypical presentations such as gastrointestinal symptoms and fever. Mesenteric ischemia and renal infarction may mimic common postoperative conditions. Clinicians should maintain a high level of suspicion for thromboembolic complications, even when symptoms involve non‒thoracic organs.

A 52‒year‒old female with gastric cancer revealed by a medical examination. The patient was diagnosed with T4b(pancreas)N2M0, CY0P0, cStage ⅣA, and after 3 courses of docetaxel+oxaliplatin+S‒1(DOS)therapy as preoperative chemotherapy, laparoscopic distal gastrectomy with D2 lymph node dissection and Roux‒en‒Y reconstruction were performed. Pathological histological examination showed ypT3(SS)N2M1(CY+), Stage Ⅳ, HER2(-), and S‒1+oxaliplatin(SOX)therapy was initiated as first‒line treatment. Tumor markers elevated and CT scan showed ascites after 5 courses and the treatment was consequently changed to paclitaxel+ramucirumab(PTX+Ram)therapy as second‒line treatment. CT scan showed para‒aortic lymph node enlarged and increased ascites after 2 courses, MSI‒High was identified at the same time and the treatment was consequently changed to pembrolizumab(Pem)monotherapy(200 mg/body, q21 days)as third‒line treatment. CT scan showed partial response(PR)after 3 courses, and subsequently resulted in a complete response(CR). After 36 courses of Pem monotherapy, the chemotherapy was terminated at the patient's request. Four years after the initial onset, the patient is currently alive without recurrence. No serious adverse events have occurred since the start of Pem monotherapy.

A 49‒year‒old woman presented to our hospital with right lower abdominal pain that had been presenting for about 6 days without any improvement. An abdominal CT examination demonstrated an enlarged appendix and stercolith of appendix with inflamed surrounding adipose tissue. Antibiotic treatment was administered, but an abdominal CT examination taken 3 days later showed worsening inflammation around the appendix. An appendectomy was laparoscopically performed. Upon resection, the enlarged appendix was found. In immunohistochemical staining, the resected tissue was positive for neuroendocrine markers, including chromogranin A, synaptophysin, Ki‒67, and a definitive diagnosis of neuroendocrine tumor(NET)G1 was obtained. The patient has been followed up without additional resection or adjuvant chemotherapy, and no recurrence has been observed. Appendix NETs are often diagnosed incidentally, as in this case. In treating appendicitis, it is essential to perform pathological examination of the resected specimen.

An 88‒year‒old woman visited the gynecology department of our hospital with a chief complaint of frequent urination and abdominal mass. Contrast‒enhanced CT and MRI scans of the abdomen revealed an 8 cm‒sized irregularly shaped mass in widely contact with sigmoid colon and perforated to the bladder. Colonoscopy could not reach the tumor because of huge mass. The diagnosis was resectable pelvic tumor without distant metastasis, and surgery was performed. The tumor was resected en bloc with sigmoidectomy, hysterectomy and partial cystectomy. The majority of the tumor was in the bladder lumen and appeared to be of bladder origin, but final histopathology led to a diagnosis of mucous carcinoma from a diverticulum in the sigmoid colon. Eighteen months after surgery, the patient is alive without recurrence.