Efficacy and survival of nivolumab treatment for recurrent/unresectable esophageal squamous-cell carcinoma: real-world clinical data from a large multi-institutional cohort.

BACKGROUND: Real-world clinical outcomes of and prognostic factors for nivolumab treatment for esophageal squamous-cell carcinoma (ESCC) remain unclear. This study aimed to evaluate real-world outcomes of nivolumab monotherapy in association with relevant clinical parameters in recurrent/unresectable advanced ESCC patients. METHODS: This population-based multicenter cohort study included a total of 282 patients from 15 institutions with recurrent/unresectable advanced ESCC who received nivolumab as a second-line or later therapy between 2014 and 2022. Data, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively collected from these patients. RESULTS: Objective response and disease control rates were 17.0% and 47.9%, respectively. The clinical response to nivolumab treatment significantly correlated with development of overall immune-related adverse events (P < .0001), including rash (P < .0001), hypothyroidism (P = .03), and interstitial pneumonia (P = .004). Organ-specific best response rates were 20.6% in lymph nodes, 17.4% in lungs, 15.4% in pleural dissemination, and 13.6% in primary lesions. In terms of patient survival, the median OS and PFS was 10.9 and 2.4 months, respectively. Univariate analysis of OS revealed that performance status (PS; P < .0001), number of metastatic organs (P = .019), C-reactive protein-to-albumin ratio (CAR; P < .0001), neutrophil-lymphocyte ratio (P = .001), and PMI (P = .024) were significant. Multivariate analysis further identified CAR [hazard ratio (HR) = 1.61, 95% confidence interval (CI) 1.15-2.25, P = .0053)] in addition to PS (HR = 1.65, 95% CI 1.23-2.22, P = .0008) as independent prognostic parameters. CONCLUSIONS: CAR and PS before nivolumab treatment are useful in predicting long-term survival in recurrent/unresectable advanced ESCC patients with second-line or later nivolumab treatment. TRIAL REGISTRATION: UMIN000040462.

Intra-abdominal desmoid-type fibromatosis successfully resected using laparoscopic fluorescence imaging with indocyanine green after intersphincteric resection for rectal cancer.

Successful resection of intra-abdominal tumors using indocyanine green (ICG) fluorescence imaging has not been reported. Here, we report a rare case of an intra-abdominal desmoid-type fibromatosis successfully resected using this technique after intersphincteric resection (ISR) for rectal cancer. One year after ISR for rectal cancer in a 47-year-old man, computed tomography showed a 50-mm intra-abdominal tumor near the left common iliac vein. Surgical resection was performed. The tumor was located in the mesentery of the remnant rectum after ISR. ICG fluorescence imaging confirmed the blood supply to the mesentery of the distal remnant rectum after tumor excision. The anal canal was successfully preserved without creating a permanent colostomy. The tumor was safely resected with resection margins, diagnosed as desmoid-type fibromatosis. No tumor recurrence was observed 6 months post-resection. This was the first case report to demonstrate the utility of this technique for an intra-abdominal tumor resection.

[A Case of Intestinal Obstruction Caused by Peritoneal Metastatic Recurrence One Year after Radical Operation for Pancreatic Cancer].

In December 20XX-1, abdominal enhanced CT of a 73-year-old female patient showed a 28mm-in-diameter pancreatic tail cancer with splenic venous invasion. She underwent neoadjuvant GEM/TS-1 combination chemotherapy but abandoned this chemotherapy due to melena and exanthema. She underwent a distal pancreatectomy with lymph node dissemination. In these pathological findings, the tumor was diagnosed as a pancreatic tail cancer with splenic venous invasion(T3, N0, M0, Stage ⅡA). She underwent adjuvant GEM chemotherapy, but she abandoned this chemotherapy due to exanthema and was managed with observation. In September 20XX, she had a postoperative bowel obstruction and was treated with natural light. However, she had a postoperative bowel obstruction again in July, 20XX+1. Fluoroscopic images revealed stenosis in the intestine located 170 cm from the nasal cavity. She underwent open surgery to manage the bowel obstruction. There was a peritoneal tumor with adhesion to each intestine serosa in 3 areas located 80 cm, 100 cm, and 150 cm from the Treitz ligament. Therefore, she underwent a small intestine resection and anastomosis 70 cm to 110 cm from the Treitz ligament. Pathological findings showed that there was a 3mm-in-diameter adenocarcinoma in this peritoneal tumor. In these findings, this final diagnosis was an adhesive intestinal obstruction caused by peritoneal metastasis. Curative resection for single peritoneal recurrent metastasis might be useful for prognosis prolongation.

[A Case of Laparoscopic Assisted Resection for Small Intestinal Cancer Diagnosed Preoperatively].

A 50-year-old woman was admitted to our hospital due to intermittent epigastric pain and vomiting for 2 months. Contrast enhanced CT scan showed stenosis in the upper jejunum. She was diagnosed with small intestinal ileus. A small enteroscopy revealed a peripheral type 2 lesion in the upper jejunum, approximately 10 cm from the Treitz's ligament. Upon biopsy, she was diagnosed with a well-differentiated adenocarcinoma. A laparoscope-assisted extracorporeal operation was performed due to the ease of raising the umbilical wound. Swollen lymph nodes were found in the mesentery. A surgical margin of 5 cm on the oral side and 20 cm on the anal side was secured. We performed partial resection of the small intestine, including the mesentery with the enlarged lymph nodes. The histopathological diagnosis was a Type 2, 3×2 cm, tub2, pT4aN1aM0, pStage Ⅲb small intestinal cancer. Due to the development of small intestinal ileus, the small bowel cancer was diagnosed preoperatively. Hence, it was slightly we will report including the literature consideration of.

[Bilateral Multiple Liver Metastases after Pancreatoduodenectomy for a Duodenal Neuroendocrine Tumor-A Case Report].

The patient was a 79-year-old woman. In January 20XX, upper gastrointestinal endoscopy revealed a duodenal tumor with bleeding and ulceration. This tumor was diagnosed as a duodenal neuroendocrine tumor(NET)based on biopsy findings. In March 20XX, the patient underwent pancreatoduodenectomy with lymph node dissemination. Based on these pathological findings, the tumor was diagnosed as a duodenal NET(G2)with a lymph node metastasis(T2, N1, M0, Stage Ⅲ). Twenty months after the operation, abdominal CT revealed multiple liver metastases(S4, S7, and S8). After this recurrence, she underwent the subcutaneous somatostatin analogue injection therapy every 28 days, and transarterial chemoembolization( TACE)when these recurrent tumors showed remarkable regrowth, once a year, accounting for her age. She has maintained good disease control for 5 years.

[A Case of Appendix Torsion with Low-Grade Appendiceal Mucinous Neoplasm].

An 84-year-old woman with a chief complaint of right lower abdominal pain was admitted to our hospital in November 20XX. Abdominal CT scan revealed a 9.6×4.1 cm diameter low density area proximal to the 13 mm diameter appendix, which led to perforated appendicitis with a huge abscess. The patient underwent an open appendectomy with partial cecum resection. The appendix was found to be twisted by 540°. The pathological diagnosis was low-grade appendiceal mucinous neoplasm(LAMN). Recent research has found that the use of laparoscopic surgery for the treatment of LAMN has been increasing. Appropriate surgical intervention should be considered for LAMN because it is a borderline malignancy. Careful treatment with laparoscopic surgery might be considered as one of the treatment options for LAMN. We hope to accumulate more cases of LAMN to confirm our results.

[A Case of Unresectable Advanced Esophageal Cancer Treated with Chemoradiotherapy Resulting in Complete Response].

A70s man was admitted to our hospital complaining of chest discomfort. Endoscopic examination showed mucosal erythema and irregularity and an area unstained by iodine in the middle esophagus 21 to 41 cm from the incisors. The biopsy specimen showed moderately differentiated squamous cell carcinoma. An abdominal computed tomographic(CT)scan revealed swelling of the lymph nodes along the celiac artery and abdominal aorta. The patient was diagnosed with unresectable advanced esophageal cancer(cT2N4M0, cStage Ⅳa). Systemic chemotherapy was initiated using a regimen of 5-FU and cisplatin(FP). After 2 courses of chemotherapy, an abdominal CT scan showed reduction of the lymph node swelling along the abdominal aorta, but the lymph node swelling remained along the celiac artery. Therefore, chemoradiotherapy(CRT; FP plus RT 60 Gy/30 Fr at the main tumor and the swelling of lymph nodes along the celiac artery)was administered. An abdominal CT scan showed reduced swelling of the lymph nodes along the abdominal aorta and the celiac artery after CRT. In addition, FP chemotherapy was also administered. APET -CT scan showed no increased FDG up take in the main tumor and swollen lymph nodes after 2 courses of chemotherapy. The complete response(CR)has been maintained for 30 months without therapy.

[XELIRI plus Bmab Therapy as a Secondary Treatment for Recurrent Colorectal Cancer with Long-Term Survival].

A 71-year-old woman complained of melena, and laparoscopic right hemicolectomy was performed for advanced colorec- tal cancer. Pathological examination revealed pStage Ⅲa(RAS-positive)disease. After the operation, UFT/LV was administered. However, peritoneal recurrence was confirmed. We changed the chemotherapeutic regimen to CapeOX plus Bmab and capecitabine plus Bmab. After 5 years and 9 months, pulmonary metastasis was observed. Therefore, we again changed the chemotherapeutic regimen to biweekly XELIRI plus Bmab. After 43 courses, the patient had stable disease. During biweekly XELIRI plus Bmab therapy, Grade 4 neutropenia occurred, so we reduced the CPT-11 dose by 20%. After dose reduction the patient experienced no more Grade 3/4 adverse events. We experienced a case of colorectal cancer wherein biweekly XELIRI plus Bmab therapy contributed to disease control as second-line treatment.

[Long-Term Survival after Palliative Surgery for Advanced Gastric Cancer with Bone Marrow Metastasis-A Case Report].

A 57-year-old woman was diagnosed with advanced gastric cancer with bone marrow metastasis(cT4aN1pM1[MAR], pStage Ⅳ). After 18 courses of S-1 and cisplatin and 18 courses of ramucirumab and paclitaxel, the chemotherapy was stopped because of stenosis. We performed endoscopic metallic stent placement, but stenosis reappeared after a month. Subsequently, distal gastrectomy was performed as a palliative surgery. She had no complications and improved appetite, therefore, she resumed chemotherapy after 3 postoperative months and continued for 4 years and 9 months from the first visit. In general, gastric cancer with bone marrow metastasis has a poor prognosis, however, in this case, long-term survival was achieved with palliative surgery.

[A Case of Chemotherapy with FOLFOXIRI plus Cetuximab for Liver Metastasis of Sigmoid Colon Cancer].

We report a case of chemotherapy with FOLFOXIRI plus cetuximab for liver metastasis of sigmoid colon cancer. The patient was a 40's man who was diagnosed with sigmoid colon cancer with liver metastasis. Colonoscopy revealed a type 2 tumor with stenosis in the sigmoid colon. He underwent sigmoidectomy under laparotomy, and after the operation, received 7 courses of chemotherapy with FOLFOXIRI plus cetuximab. The liver tumor was sufficiently reduced, and laparotomy and liver right lobectomy were performed. Histopathology revealed a modified, Grade 2 tumor regression. He has been followed for 1 year 4months after the operation.

[A Case of Primary Duodenal Cancer with Duodenocolic Fistula Treated with Pancreatoduodenectomy and Right Hemicolectomy].

A patient was 59-year-old female. She presented our hospital with weight loss, anorexia and lower abdominal bloating. Abdominal computed tomography(CT), gastrointestinal endoscopy, colonoscopy and duodenal fistulagram showed duodenal cancer or colon cancer with duodenocolic fistula and ovary metastasis. She underwent subtotal stomach preserving pancreatoduodenectomy and right hemicolectomy. In these pathological findings, tumor was diagnosed as a duodenal cancer with duodenocolic fistula. She was surviving 12 months after the last surgery. In cases of cancer with duodenocolic fistula, pancreatoduodenectomy with right hemicolectomy would be necessary for nutrition improvement and cancer treatment.

[Continued Chemotherapy for Advanced Gastric Cancer and Seven Year Survival after Operation].

The patient was a 66-year-old man. Total abdominal gastrectomy and D2 dissection were performed for gastric cancer (cT3N0M0P0CYXH0, cStage II A). Pathological examination confirmed a diagnosis of Stage III C mucinous adenocarcinoma (pT4pN3pM0, pStage III C). He underwent adjuvant chemotherapy with TS-1(120mg/body). One year after adjuvant chemotherapy, anastomotic stricture was caused. Although it was not possible to point out recurrent lesions on the CT image, we strongly suspected that extrinsic compression around the anastomotic portion was due to peritoneal dissemination recurrence because of symptoms and marked tumor elevation. Therefore, TS-1(120mg/body)plus cisplatin(CDDP 60mg/m2)were administered as first-line therapy for advanced gastric cancer. TS-1 plus CDDP(SP)chemotherapy resulted in marked tumor reduction and improved symptoms. However, after 33 courses of SP chemotherapy, renal function was worse due to cisplatin; thus, docetaxel(DTX 70mg/m2)was administered as second line therapy. After 8 courses of DTX, peritoneal dissemination recurrence was diagnosed, and the patient was treated with irinotecan(CPT-11 150mg/m / 2), ramucirumab(RAM 8 mg/kg) plus paclitaxel(PTX 80mg/m2 day 1, 8, 15). However, the disease worsened. The side effect of SP therapy was renal dysfunction. Nonetheless, we experienced that long-term disease control could be achieved by administering chemotherapy under strict follow-up.

Stable polyphosphate accumulation by a pseudo-revertant of an Escherichia coli phoU mutant.

phoU mutants of bacteria are potentially useful for the removal of inorganic phosphate (Pi) from sewage because they can accumulate a large amounts of polyphosphate (polyP). However, the growth of phoU mutants is severely defective and is easily outgrown by revertant(s) that have lost the ability to accumulate polyP during growth in a nutrient-rich medium. We found that a pseudo-revertant, designated LAP[+], that appeared in a culture of an Escherichia coli phoU mutant that could accumulate polyP even after ten serial passages. Reduction in the expression of the Pi-specific transporter Pst in LAP[+] may contribute to relieving stresses such as excess Pi incorporation that could stimulate reversions. The discovery of a LAP[+] provides a clue to generate phoU mutants that accumulate polyP in a stable manner.