Incidence of pancreatic injury and pancreatitis in patients treated with immune checkpoint inhibitors.

OBJECTIVES: Immune checkpoint inhibitors (ICIs) are being increasingly used to treat advanced malignancies. ICI-induced pancreatic injury (ICI-PI), which is an immune-related adverse event that may be a risk factor for ICI-associated pancreatitis, is not well documented in the literature. METHODS: Consecutive patients who received ICIs for advanced malignancies from August 2015 through October 2022 were analyzed with regard to the incidence of ICI-PI based on the Common Terminology Criteria for Adverse Events and ICI-associated pancreatitis. The imaging, clinical, and pathological findings of ICI-associated pancreatitis were also assessed. RESULTS: This study enrolled 843 patients. In multivariable analyses, dual or simultaneous immunotherapy and ≥10 cycles of ICI administration were significant predictive factors for all grades of pancreatic injury, including grade ≥ 3. Notably, patients who received simultaneous immunotherapy exhibited a higher incidence of grade ≥ 3 pancreatic injuries compared to those receiving asynchronous immunotherapy in univariable analysis (p = 0.032). One-fifth of the patients (16/70) with grade ≥ 3 pancreatic injuries had imaging evidence of pancreatitis similar to mild acute pancreatitis. ICI-associated pancreatitis was observed in 5.7% (48/843) of patients, including 1.8% (15/843) with moderate-to-severe pancreatitis (grade ≥ 2). Symptomatic cases (0.36%, 3/843) were treated with steroids with favorable outcomes. Immunohistochemistry for CD4 and CD8 revealed greater infiltration of CD8+ than CD4+ lymphocytes. CONCLUSION: Simultaneous immunotherapy and dual immunotherapy are risk factors for ICI-PI. Although most patients diagnosed with ICI-PI and ICI-associated pancreatitis were asymptomatic and had a low mortality likelihood, long-term outcomes, including endocrine and exocrine function should be carefully monitored.

[A Case of Medullary Carcinoma of the Colon].

The patient is a 79-year-old woman who visited her local doctor with a chief complaint of abdominal pain. A lower gastrointestinal endoscopy revealed a circumferential type 3 mass in the transverse colon. The patient was diagnosed with transverse colon cancer (cT3N0M0, cStage Ⅱa)and underwent laparoscopic transverse colectomy(D3). The postoperative course was good, and she was discharged on POD 9. Pathological results showed a diagnosis of medullary carcinoma(pT3N0M0, pStage Ⅱa)with MSI-high. The patient was treated with UFT/UZEL for 6 months as postoperative adjuvant chemotherapy. The patient has been recurrence-free for 1 year and 6 months postoperatively and is under outpatient follow-up. Medullary carcinoma is a rare histologic type that is estimated to account for 2-3% of all colorectal cancers. Medullary carcinoma of the colon is more common in elderly patients, women, and the right side of the colon, with a relatively favorable prognosis. We report a case of medullary carcinoma of the transverse colon in which the patient had a relatively long survival, with some discussion of the literature.

[A Case of Resection of Primary Hepatic Neuroendocrine Tumor].

Neuroendocrine tumors(NET)often occur in the digestive tract, pancreas, and lungs. Primary hepatic neuroendocrine tumor(PHNET)is extremely rare and has a high malignancy and poor prognosis. Diagnosis is extremely difficult only by imaging findings, and in majority of the cases, definitive diagnosis is produced by an excisional biopsy. We report a case of PHNET diagnosed by preoperative liver tumor biopsy and underwent surgical resection. A 60's man was admitted with the main complaint of weight loss. Image examination(abdominal echo, CT, MRI)revealed continuous tumors of 6 cm and 5 cm in the liver S4 to S8 area, respectively, and a tumor of <1 cm in the S5 and S7 areas. When liver biopsy was performed, immunostaining revealed that it was chromogranin A-positive. Therefore, it was diagnosed as NET. No other lesions were observed in PET-CT, and the patient was diagnosed with PHNET. Extended left hepatectomy and partial S5/S7 liver resections were performed. The pathological diagnosis was NET and Ki-67 index was 7%, which was equivalent to NET G2 in the WHO classification.

[A Case on the Long‒Term Effect of Imatinib on GIST of Unknown Primary Origin with Multiple Liver Metastases, Peritoneal Dissemination, and Bone Metastasis].

A 61‒year‒old woman observed that she had a lower limb edema approximately 1 month ago and began to feel a general malaise. The symptom was caused by multiple liver metastases, and the primary lesion was suspected to be an ovarian cancer. Peritoneal disseminations throughout the abdominal cavity were found in the exploratory laparotomy. No obvious primary lesion could be found in the searchable gastrointestinal tract. The patient was diagnosed with a gastrointestinal stromal tumor(GIST)based on the biopsy results of the peritoneal dissemination. Treatment with imatinib mesylate(imatinib) was initiated 13 days after surgery. The severe lower extremity edema disappeared within 2 months. Computed tomography (CT)scan showed a reduction of the multiple liver metastases and peritoneal dissemination, and the appearance and increase of calcifications in the tumor and cystic degeneration inside the liver metastasis. The abnormal accumulation observed by bone scintigraphy also disappeared. Imatinib has a long‒term effect on GIST of unknown primary origin with multiple liver metastases, peritoneal dissemination, and bone metastasis. Five years after the initiation of the treatment, the patient is still alive, and new lesions have not developed.

[A Case of Thyroid and Endotracheal Metastasis from Rectal Cancer].

A 75-year-old woman previously underwent low anterior resection for rectal cancer(pT3N0M1a[PUL1], Stage Ⅳa)in October 2012. We administered 7 courses of mFOLFOX6 plus bevacizumab(BV)followed by oral UFT/LV for 6 months. In November 2014, we performed partial lung resection for relapsing metastatic lung tumor. In April 2017, we performed right lower lobectomy for recurrence at the site of partial resection. In October 2018, since serum CEA was gradually elevated, FDG-PET was performed for metastasis. FDG-PET indicated FDG accumulation in the left neck and the trachea. Enhanced CT revealed the thyroid tumor, an enlarged cervical lymph node and a small nodule in the trachea. Needle aspiration cytology of the thyroid tumor and the lymph node showed Class Ⅴ(adenocarcinoma). Bronchoscopy indicated a polypoid tumor Class Ⅴ(adenocarcinoma). After 18 courses of FOLFIRI plus BV, all metastases were reduced significantly. We conclude that FOLFIRI plus BV seems to be effective for patients with thyroid and endotracheal metastasis from rectal cancer.

[A Case of Local Recurrence in the Reconstructed Breast Three Years after Reconstructive Surgery and Seven Years after Breast Cancer Surgery].

In recent years, breast reconstruction has been increasingly performed in breast cancer surgery with improving the appearance of the breast. We report a case of local breast cancer recurrence after artificial breast reconstruction. The patient was a 52-year-old woman. She had undergone total mastectomy for left breast cancer 11 years ago, and reconstruction with breast implant 3 years ago. She presented to our hospital with the chief complaint of skin redness and induration of the reconstructed breast. A core needle biopsy was performed, and its results showed in the invasive ductal carcinoma. She had an operation of resection of tumor and reconstruction implant. As a result of histopathological diagnosis, it was a local recurrence of breast cancer 11 years ago. After the surgery, she underwent endocrine therapy and there is no recurrence. As the increase in the number of cases of breast reconstruction, the number of recurrences in the reconstructed breast is expected to increase the future. The treatment strategy for cases of local recurrence after breast reconstruction is currently under review, the accumulation of evidence is necessary.

[A Case of Metaplastic Squamous Cell Carcinoma of the Breast Successfully Treated with S-1].

Metaplastic squamous cell carcinoma(MSCC)of the breast is very unusual and is histologically characterized by rapid progression. Conventionalchemotherapy for ductalcarcinoma of the breast is ineffective against MSCC. Here, we report a case of MSCC of the breast successfully treated with S-1. A 57-year-old woman was admitted to our hospital because of a left breast tumor. A tumor approximately 10 cm in diameter was palpable in the lower-outer quadrant(D region)of the left breast. Core needle biopsy indicated estrogen receptor(ER)-negative, progesterone receptor(PR)-negative, and human epidermalgrowth factor receptor 2(HER2)-negative MSCC of the breast. Computed tomography(CT)showed left axillary lymph node metastases but did not indicate distant metastasis. A diagnosis of T4N3cM0, Stage ⅢC, MSCC of the left breast was made. Each treatment course consisted of the administration of S-1(120mg/body/day)for 4weeks, followed by 2 drugfree weeks. After the second course, significant tumor and lymph node reduction was observed. We concluded that S-1 chemotherapy seems to be effective for patients with MSCC of the breast.

Hybrid method with explorative laparoscopy and anterior open approach for re-recurrent inguinal hernia.

The new guidelines of the HerniaSurge group recommend that only an expert hernia surgeon should repair a re-recurrent inguinal hernia. We report the efficacy of the hybrid method with explorative laparoscopy and anterior open approach for re-recurrent inguinal hernia repair. A 61-year-old man underwent anterior open preperitoneal mesh repair for right inguinal direct hernia and laparoscopic transabdominal preperitoneal repair for recurrence. Two years after the second surgery, re-recurrent inguinal hernia was confirmed. We carried out explorative laparoscopy for the re-recurrent inguinal hernia, which revealed a re-recurrent hernia orifice. We performed the anterior open approach while observing from the abdominal cavity. Explorative laparoscopy can help in accurately determining the orifice of the re-recurrent inguinal hernia. Based on that information, the hernia sac can be reached through the shortest route using the anterior open approach.

Combined therapy using interventional radiology and surgical management for a ruptured pseudoaneurysm of the iliac artery: A case report.

INTRODUCTION: An optimal treatment strategy for a ruptured pseudoaneurysm of the iliac artery must necessarily control bleeding and prevent ischemia in the ipsilateral lower extremity. PRESENTATION OF CASE: A 69-year-old man underwent resection of a metastatic lymph node from rectal cancer, which had invaded the sigmoid colon, the left internal iliac artery and vein, and his left ureter. The metastatic lymph node and the organs it invaded were resected together. Owing to postoperative complications, the patient was required to undergo a 2nd and 3rd operation after the initial surgery. During his 3rd surgery, sudden intraoperative bleeding was identified, which was diagnosed as a ruptured pseudoaneurysm of the internal iliac artery. After achieving temporary surgical hemostasis, the lesion was successfully treated using combined therapy comprising catheter embolization and an axillofemoral bypass. DISCUSSION: Even after temporary surgical hemostasis has been achieved, it is perhaps safer to block the arterial flow prophylactically to avoid recurrence of a pseudoaneurysm owing to infection. CONCLUSION: Combined therapy using catheter embolization and surgical revascularization is a minimally invasive and effective treatment option for a ruptured pseudoaneurysm of the iliac artery.

[A Case of Advanced Breast Cancer with Improvement in the Quality of Life by Local Treatment Using Mohs Paste and Systemic Pharmacotherapy].

Locally advanced breast cancer with skin invasion often causes malodor, bleeding, and massive exudates, which degrades patients' quality of life(QOL). A 61-year-old woman presented with locally advanced breast cancer with malodor and massive exudates, which had carcinomatous pleurisy causing dyspnea. We administered endocrine therapy and chemotherapy and used Mohs paste for local therapy. The exposed part of the tumor was fixed using Mohs paste. After continuing to apply Vaseline over the fixed part, the lesion spontaneously detached without surgical removal and completely epithelized, and malodor and exudates disappeared. Cancerous pleurisy also improved, and dyspnea disappeared. Local treatment using Mohs paste and systemic pharmacotherapy dramatically improved her QOL.

[A Case of Chest Wall Metastasis after Surgery for Lower Bile Duct Carcinoma].

A 76-year-old woman with lower bile duct carcinoma underwent subtotal stomach-preserving pancreaticoduodenectomy (SSPPD)after percutaneous transhepatic biliary drainages(PTBD). Nine months after the operation, chest computed tomography revealed a mass in the subcutis of the right chest wall, which was a different lesion from that in the PTBD site. The aspiration biopsy cytology and needle biopsy indicated no malignant findings. However, the mass was growing and was suspected to be a metastasis of bile duct cancer. We resected the mass, including portions of the sixth and seventh ribs. The pathological diagnosis was metastasis of bile duct carcinoma. The postoperative course was uneventful. Now, 2 years have passed since the resection of the primary lesion and 9 months since the resection of the chest wall metastasis. Thus far, no manifestations of recurrence have been observed, and the patient has been in a favorable condition. We report this case with a literature review.

[Three Cases of Remnant Pancreatic Cancer after Surgery for Invasive Ductal Carcinoma of Pancreas].

We report here 3 cases of remnant pancreatic cancer after surgery for invasive ductal carcinoma. Case 1 was a 73-year-old male who underwent distal pancreatectomy(pap, pT3, pN0, M0): fStage II A(JPS 7th). He developed a remnant pancreatic cancer 39 months later, and total remnant pancreatectomy was performed. He died from sepsis 9 months after surgery. Case 2 was a 72-year-old female who underwent subtotal stomach-preserving pancreatoduodenectomy(SSPPD)(tub2, pT1c, pN1a, M0): fStage II B. She developed a remnant pancreatic cancer 82 months later. This lesion seemed to be resectable. But she hoped to take a best supportive care, and died 13 months after diagnosis. Case 3 was a 68-year-old female who underwent SSPPD(tub1, pT3, pN1a, M0): fStage II B. She developed a remnant pancreatic cancer 20 months later and was successfully treated by chemotherapy and carbon-ion radiotherapy.

[A Case of Bladder Metastasis Occurring after Rectosigmoid Cancer Operation].

A 55-year-old man was admitted to our hospital for rectosigmoid(RS)cancer. We performed high anterior resection in the patient. Pathological findings showed mucinous adenocarcinoma, pT3(SS), pN1, sM0, sP0, pCy0, fStage III a. Two years and 3 months after the first operation, the patient visited our hospital due to lumbago, and we conducted a detailed abdominal examination. CT images showed the bladder tumor expanding into the vesical trigon and invading the prostate and mesorectum. Cystoscopy revealed the tumor, and tumor biopsy indicated poorly differentiated adenocarcinoma. These findings were consistent with metastasis of RS cancer; therefore, we performed total cystectomy, prostatectomy, and partial resection of the rectum. We performed a change of the ileum conduit to the urinary tract. Pathological findings showed many poorly differentiated adenocarcinomas in the lymph ducts ofthe bladder and prostate. Therefore, we diagnosed the condition as bladder cancer lymphogenous metastasis. The patient continues to do well without signs ofrecurrence 6 months later.

[A Case of Remnant Pancreatic Cancer after Pancreatoduodenectomy Successfully Treated Using Chemotherapy and Carbon-Ion Radiotherapy].

We report a case of remnant pancreatic cancer after pancreatoduodenectomy that was successfully treated using chemotherapy and carbon-ion radiotherapy. A 68-year-old woman received SSPPD for pancreatic head cancer. Gemcitabine(GEM) was administered for a year as postoperative chemotherapy. One year 8 months after surgery, abdominal CT showed a 20 mm solid mass in the stump of the remnant pancreas and dilation of the distal pancreatic duct. FDG-PET revealed a solitary tumor without any recurrence. We diagnosed the patient with a solitary recurrence of pancreatic cancer. Chemotherapy (GEM)and carbon-ion radiotherapy were performed. After treatment, the lesion was not detected on CT or FDG-PET. Chemotherapy(GEM)and carbon-ion radiotherapy for locally advanced pancreatic cancer seems to be effective and there might result in a survival benefit.

[A Case of Male Hereditary Breast Cancer Involving a Sentinel Lymph Node Biopsy].

We report a rare case of male hereditary breast cancer in which a sentinel lymph node biopsy was performed. A 62-yearold man was admitted to our hospital because of a palpable tumor in his right breast. Both his younger sister and daughter had had breast cancer. Genetic testing revealed a morbid mutation in the BRCA2 gene. The tumor was palpated to an elastic hard mass and had a clear border in the right DCE area. We performed a core needle biopsy and diagnosed invasive ductal carcinoma, specifically, cT1cN0cM0, cStage I hereditary breast cancer. The patient underwent mastectomy and a sentinel lymph node biopsy. Nine days later, tamoxifen therapy was initiated. There has been no sign of recurrence during the 9 months after the operation.

[A Case of Esophageal Carcinoma with an Aberrant Right Subclavian Artery].

We report a rare case of esophageal carcinoma with an aberrant right subclavian artery. A 67-year-old woman was admitted to our hospital because of a sense of discomfort during swallowing. A detailed gastrointestinal examination revealed advanced carcinoma of the middle thoracic esophagus. Preoperative CT also revealed an aberrant right subclavian artery (AR SA). After the second course of neoadjuvant chemotherapy (FP therapy), we conducted a transthoracic esophagectomy with a 3-field lymphadenectomy. The right recurrent nerve was not identified at the right subclavian artery during mediastinal dissection, but the non-recurrent inferior laryngeal nerve (NRILN) was identified as going directly from the vagal nerve to the larynx during the neck lymphadenectomy. The thoracic duct ran between the esophagus and the azygos vein, terminating at the right venous angle. We were able to perform a #106recL lymphadenectomy as usual. She continues to do well without signs of recurrence 1 year later. Though ARSA is a relatively rare congenital anomaly, it must be identified preoperatively, and anatomical anomalies such as NRILN must be taken into consideration, in order that the operation can be performed safely.

[A case of reduced port surgery after laparoscopic-assisted colectomy].

A 52-year-old woman was admitted to our hospital because of melena and right abdominal pain. Detailed gastrointestinal examination revealed ascending colon cancer. She underwent laparoscopic-assisted right hemicolectomy and D3 lymphadenectomy using 5 ports. After surgery, the patient refused adjuvant chemotherapy. Outpatient follow-up was periodically performed and included blood examination and imaging studies, but she refused colonoscopy. Four and a half years after the initial operation, stool was positive for occult blood. Following colon examination, descending colon cancer was diagnosed. Therefore, the patient underwent colectomy and D3 lymphadenectomy by double incision laparoscopic surgery (DILS) using the glove method. There were no adhesions in the operation field; therefore, laparoscopic surgery was effortless. Because there were almost no adhesions following the first laparoscopic surgery, the second laparoscopic surgery for metachronous colon cancer was possible.

[A case of esophageal cancer with lung metastases successfully resected after chemotherapy].

Herein, we report a case of esophageal cancer with lung metastases that was successfully resected after chemotherapy. A 61-year-old man was diagnosed with a middle thoracic esophageal squamous cell carcinoma showing lung metastases. The clinical Stage diagnosis was T4NxM1, Stage IVb. After systemic chemotherapy with 1 course of cisplatin/5-fluorouracil (CDDP/5-FU)and 3 courses of nedaplatin/5-FU (CDGP/5-FU), lung metastases could not be detected by using computed tomography (CT). We added 2 courses of CDGP/5-FU, followed by 3 courses of docetaxel. The patient underwent esophagectomy and was alive without recurrence for 6 months after surgery.

[A case report of laparoscopy-assisted low anterior resection after hepatectomy].

A 72-year-old man was admitted to our hospital because of anal discomfort. A detailed gastrointestinal examination revealed both left cholangiocellular carcinoma and rectal cancer. We performed endoscopic mucosal resection (EMR) for the rectal cancer. Pathological findings suggested the possibility of residual cancer after EMR. The cholangiocellular carcinoma was thought to be of greater influence on the patient's prognosis than the rectal cancer. We performed left hepatectomy and caudate lobectomy. Two months after the initial surgery, we performed laparoscopy-assisted low anterior resection and D2 lymphadenectomy. Laparoscopic surgery could proceed since no adhesions were observed. Two-stage surgery can be an effective strategy for avoiding excessive surgical stress when removing 2 cancer types.

UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism-directed phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer.

AIM: We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism. PATIENTS AND METHODS: A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS). RESULTS: In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively). CONCLUSION: This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.