An 82-year-old, male. He visited his local doctor with a chief complaint of dyspnea on exertion. Anemia was noted, and upper gastrointestinal endoscopy was performed, which revealed an ulcerative lesion in the gastric antrum. A biopsy revealed Group 5, tub2, and HER2 negative, with PD-L1≥5%. cT3N1H1(M1 HEP), cStage ⅣB was diagnosed based on CT scan showing enlarged #8 lymph node and a single liver metastasis in the 2 cm range in S6 of the liver. The patient was deemed unresectable and was started on SOX plus nivolumab therapy. On day 11 after initiation, the patient had Grade 3 diarrhea by CTCAE v5.0, and S-1 was withdrawn for 3 days, but was administered for 2 courses. CT and MRI after chemotherapy showed shrinkage of both the primary tumor and liver metastases; R0 resection was deemed possible, and pyloric gastrectomy, D2 lymph node dissection, and partial hepatic S6 resection were performed. The histological evaluation of response to treatment was Grade 1b, and the patient was in ypStage ⅠA. The patient has been alive without recurrence for 6 months postoperatively while receiving S-1 monotherapy on an outpatient basis.

The case was a 70-year-old man of highly advanced gastric cancer with 2 liver metastases(S3, S8)and pancreatic invasion. Three courses of S-1 plus L-OHP(SOX therapy)were performed, and total gastrectomy and combined resection of the spleen and body and tail of the pancreas and partial resection of the liver S3 and S8 were performed after reduction of primary tumor and liver metastasis. S-1 therapy was continued for 1 year as postoperative adjuvant chemotherapy. Left adrenal metastasis was detected by CT, 1 year and 6 months after the operation. PET-CT revealed no other areas suspected of recurrence, so left adrenalectomy was performed through the retroperitoneal space. Radical resection was not achieved because adhesions and scarring from the previous surgery were severe. Paclitaxel plus Ramucirumab was started and after 10 courses, the disappearance of the tumor shadow was observed on enhanced CT, and PET-CT. Three years and 3 months after the initial surgery and 1 year and 8 months after resection of adrenal metastasis, the patient is alive without recurrence.

A 77-year-old man presented to our hospital with diarrhea and weight loss. Upper gastrointestinal endoscopy revealed advanced Type 3 gastric cancer measuring 40 mm in the lower greater curvature of the stomach. Biopsy from a gastric tumor revealed moderately differentiated tubular adenocarcinoma overexpressing HER2. Abdominal contrast-enhanced computed tomography(CT)showed multiple liver metastases in S3 and S5. We diagnosed HER2-positive gastric cancer with liver metastasis. Systemic chemotherapy was administrated, with a total of 13 courses of combination therapy with S-1, oxaliplatin and trastuzumab. After chemotherapy, the primary tumor was significantly reduced and liver metastases were almost undetectable. Laparoscopic distal gastrectomy and partial hepatectomy were performed as conversion surgery. The patient was discharged on the 9th day without any postoperative complications. Postoperative pathological findings showed no residual tumor in either gastric and hepatic specimens, and the therapeutic effect of chemotherapy was diagnosed as pathological complete response. We report a case of HER2-positive advanced gastric cancer with multiple liver metastases that achieved a pathologically complete response to chemotherapy followed by conversion surgery. Laparoscopic surgery would be one of an effective option for conversion surgery.

Laparoscopic and endoscopic cooperative surgery(LECS)for gastric gastrointestinal stromal tumor(GIST)has become a popular surgery with both curability and functional preservation. In this study, we examined the outcomes of 14 patients who underwent classical LECS or CLEAN-NET in our hospital. Until March 2022, classical LECS was performed in patients with intraluminal growth tumors or tumors close to the gastroesophageal junction. After April 2022, classical LECS was performed in patients with intraluminal growth tumors without ulceration, and CLEAN-NET was performed in patients with ulceration or intramural growth tumors. There were 10 males and 4 females with a median age of 80.5 years. Intraluminal growth tumor were 8 patients, close to the gastroesophageal junction tumor were 3, and intramural growth tumor were 4, respectively. Five of these patients had tumors with ulceration. Classical LECS was performed in 10 patients and CLEAN-NET in 4 patients, and the median operative time was 165.5 minutes. All patients underwent R0 resection, and no postoperative complications or recurrences were observed. LECS was performed safely, and it is important to select the surgical procedure according to the tumor site and growth type.

All three patients were female, one in her 50s, and the other two in their 60s. The one in her 50s had liver metastasis and the other two had unresectable advanced cholecystic carcinomas with peritoneal dissemination. All three received 8-12 courses of gemcitabine plus CDDP(GC). After GC, all three were deemed to be candidates for R0 resection and underwent resection of two central liver segments. In addition, the second patient required an extrahepatic cholangiectomy; an extended cholecystectomy, plus an extrahepatic cholangiectomy, plus a complete omental resection; and the third needed an extended cholecystectomy, plus an extrahepatic cholangiectomy with a partial transverse colon resection, plus a partial duodenectomy. The pathologic response to chemotherapy was moderate in the patient with liver metastases, mild in the one who underwent the omental resection, and moderate in the patient who had the partial resection of the digestive tract. All three patients continued with postoperative chemotherapy. The patient with liver metastases and the one with the partial gastrointestinal tract resection have survived without recurrence for 52 months and 43 months, respectively, after the initial treatment. The patient with the omental resection has survived 44 months after the initial treatment with recurrent peritoneal dissemination and is continuing chemotherapy as an outpatient. Although further study is needed to accumulate more cases, the results suggest the usefulness of multidisciplinary treatment including conversion surgery in cases such as these.

A 50s female was diagnosed as rectal cancer with multiple liver metastases after fecal occult blood scrutiny. Liver metastases were multiple in both lobes and involved the right Glisson's capsule. We determined that the liver metastases were unresectable and initiated FOLFOXIRI plus panitumumab treatment. After 6 courses of chemotherapy, rectal cancer resection was performed. After 12 courses of chemotherapy, the liver metastases which had extensively involved the right Glisson on imaging, shrank until the P7 root was visible. If S7 Glisson could be preserved, the radical resection was planned. If not, associated liver partition and portal vein ligation for staged hepatectomy(ALPPS)was planned. Intraoperatively, it was determined that preservation of S7 Glisson was possible and blood flow preservation in the S7 region was feasible, and an anterior segment hepatic resection(S5-6-8)and lateral segment hepatic partial resection(S2/3)were performed. She was discharged on the 18th day and has been under outpatient observation 12 months after hepatectomy.

Immune checkpoint inhibitor(ICI)combination therapy is the first-line of treatment for unresectable or recurrent esophageal cancer. The frequency and mechanism of immune-related adverse events(irAEs)associated with ICI are still unclear and may require differentiation from other diseases. The present study examined a patient with unresectable, advanced esophageal cancer treated with cisplatin plus 5-fluorouracil(CF)plus nivolumab as the first-line treatment. CF therapy was discontinued after 1 course owing to adverse events. Nivolumab was continued, but progressive anemia stemming from pure red cell aplasia(PRCA), an irAE of nivolumab administration, was observed. Nivolumab was discontinued, but later, interstitial pneumonia also developed, and pulse steroid therapy was begun. After steroid tapering, both the PRCA and interstitial pneumonia improved. At present, about 6 months have elapsed since the last nivolumab administration without any PRCA recurrence or evidence of tumor progression.

We experienced a case of multiple endocrine neoplasia type 2A(MEN2A)diagnosed with medullary thyroid carcinoma. The patient was a 50s woman who was referred for a thyroid nodule detected in the right lobe during a carotid ultrasound examination. After undergoing a hemithyroidectomy, it was determined that the tumor was medullary carcinoma. RET gene test was performed, confirming a mutation at codon768, leading to the diagnosis of MEN2A. A completion thyroidectomy was performed to remove the remaining thyroid tissue. Postoperatively, the patient is undergoing systemic surveillance.

A 73-year-old woman underwent left nephrectomy for renal cell carcinoma(RCC). The computed tomography(CT)and magnetic resonance imaging(MRI)revealed a 20-mm tumor in the pancreatic tale showing early enhancement in the arterial phase 16 years after surgery. Fluorodeoxyglucose positron emission tomography(FDG-PET)showed slightly uptake (maximum standard uptake value: SUVmax 2.3)and EUS-FNA showed a hyper-vascularized tumor in the pancreatic tail. A single pancreatic metastasis from RCC was diagnosed, and we performed distal pancreatectomy. The histopathological diagnosis was a metastatic pancreatic tumor from RCC. The postoperative course was uneventful and 1 month after surgery, she is alive with no recurrence.

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.

An 80-year-old woman presented with epigastric discomfort and dysphagia, underwent upper gastrointestinal endoscopy, and was diagnosed with type 2 advanced lower esophageal adenocarcinoma. Computed tomography data revealed that there was the lower esophageal tumor is T3, but a large carina lymph node invading the left bronchus. We diagnosed this patient unresectable cT4bN1M0, cStage ⅣA advanced esophageal adenocarcinoma, and we administered nivolumab plus S-1 plus oxaliplatin(SOX)therapy. After 3 courses of the therapy, imaging showed marked reduction in the size of primary tumor and carina lymph node. We diagnosed partial response(PR)and attempted conversion surgery. Video-assisted thoracoscopic esophagectomy with 2 fields lymphadenectomy was performed. The pathological examination demonstrated no residual tumors and no lymph node metastases, and the histological response of primary tumor was determined to be Grade 3, with a pathological complete response(pCR). Currently, the patient is alive without recurrence for 1 year after surgery.

A woman in her 70s underwent mastectomy plus axillary lymph node excision(Bt plus Ax)in December 2011 for left breast cancer classified as pT2N1M0, pStage ⅡB. The tumor was identified as an invasive ductal carcinoma(IDC), neural/ glial antigen 2(NG2), pT2(35 mm), INF γ, ly2, v0, g+, f+, s+, extensive intraductal component(EIC)-negative, ICT- positive, NCAT-positive, n(4/18), estrogen receptor(ER)-negative, progesterone receptor(PgR)-negative, human epidermal growth factor receptor 2(HER2)-negative, Ki-67 30-40%. Postoperative adjuvant fluorouracil plus epirubicin HCl plus cyclophosphamide(FEC)plus paclitaxel(PTX)therapy was administered. The patient refused to undergo postoperative radiation therapy. Two years after the surgery, she was diagnosed as having a lung metastasis and local disease recurrence. Biopsy of the local recurrent lesion revealed the same histopathological diagnosis as before. Capecitabine was selected for treatment of the recurrent lesion. After 2 years of capecitabine treatment, the response was rated as progressive disease (PD). At this time, eribulin mesylate was selected, along with intensity-modulated radiation therapy(IMRT). This resulted in disappearance of the tumor on imaging. However, considering that the histological findings did not suggest complete response(CR)and that the tumor was triple-negative(TN), we adopted a strategy of continuing the drug therapy at reduced dose level. With this strategy, the disease activity could be successfully controlled for 6.5 years. Subsequently, liver metastasis was detected, and the drug was switched to vinorelbine ditartrate(a drug with less non-hematological toxicity). Meanwhile, a breast cancer susceptibility gene(BRCA)analysis was performed in January 2021, which was negative. Subsequently, in September 2021, we obtained a positive result for PDL1-SP142 and negative result for 22C3. About half a year later, ie, in October 2021(11 years after the surgery), we detected an increase in the size of the liver metastasis and selected atezolizumab and nab-PTX for treatment. Applicable regimens of drug therapy are still available at present and drug therapy has been continued based on a discussion and mutual understanding of the adverse reactions, etc. with the patient. Few reports have been published concerning long-term survivors among TN breast cancer cases.

The patient, a man in his 60s, first noticed an elevated lesion around the anus 3 years ago. The lesion failed to subside with the topical drug preparations prescribed at a local clinic, and the patient was referred to the Department of Dermatology of our hospital for further workup and treatment. The findings of biopsy from the lesion suggested skin infiltration of anal canal carcinoma, and the patient was referred to the Department of Surgery. Examination here revealed only induration of the anal canal, with no abnormality of the rectal mucosa even when the endoscope was reversed to visualize the rectum. Examination by various imaging modalities failed to reveal any metastases to the lymph nodes or distant organs, and the primary lesion remained unidentified. Laparoscopic abdominoperineal excision of the rectum was performed, beginning with anal manipulation. First, a 15-mm margin was set on the skin from the tumor edge, and the skin stump was divided into 4 equal portions. After confirming by rapid intraoperative frozen-section examination that the margin was negative along the full circumference, anal manipulation was performed, leaving a distance in the vertical direction immediately below the tumor. Upon completion of the anal manipulation, intraperitoneal manipulation was performed in a routine manner. The anal skin was relaxed subcutaneously, as done during mastectomy, and the subsequent suture closure could be done smoothly. The tumor was classified as pT1bN0M0, pStage Ⅰ. The experience with this case indicates that biopsy should be proactively employed for the diagnosis in such cases, and that proactive skin biopsy is useful when dealing with intractable anal skin lesions.

A 66-year-old man was referred to our hospital with fever and abdominal pain. CT showed a mass in the intrapancreatic bile duct but no wall thickness in the perihilar bile ducts. Neither regional lymphadenopathy nor distant metastasis was observed. Biliary cytology showed adenocarcinoma. The diagnosis was distal cholangiocarcinoma, and pancreatoduodenectomy was performed. Intraoperative frozen section examination of the ductal resection margins at the right and left hepatic ducts was positive for carcinoma in situ, and the operation ultimately completed with R1 resection. Histological examination confirmed a diagnosis of cholangiocarcinoma with superficial spread and a single positive lymph node. Adjuvant chemotherapy with S-1 was administered for 1 year. Anastomotic recurrence at the hepaticojejunostomy was found 5 years after resection; biopsy specimens revealed adenocarcinoma. Thereafter, S-1 chemotherapy was resumed, and the patient remains alive and well 9 years and 1 month after resection.

A 56-year-old woman. She was underwent a lower gastrointestinal endoscopy for bloody stool, and type 2 advanced rectal cancer was found. In CT scan, although distant metastasis is not found, the tumor has been expanded to the dorsal side. So, infiltration into the sacrum was suspected. For the risk of bleeding and residual tumor in circumferential resection surface, it was decided to perform pre-operative adjuvant chemotherapy. Because RAS gene has no mutation, the regimen chose CAPOX plus cetuximab. Although skin damage and cytopenia were observed, there was no appearance of adverse events that were intolerant, and 4 courses were performed. Although scar stenosis was observed in the endoscope after 4 courses, tumor size decreased. Even in CT, the wall thickening was significantly reduced, and progress to the tumor dorsal side was also reduced, so laparoscopic lower anterior resection was performed. During surgery, the tumor dorsal side sacral infiltration was suspected, although observed a sclerotic change, it is relatively easily peelable, it was possible to safely complete the laparoscopic operation. Even after the operation, the course was good, and it was discharged from the hospital lightly on the 12th day after the operation. In pathological diagnosis, medium-differentiated adenocarcinoma, T3, N0, histological therapeutic effect of chemotherapy was grade 2. Cetuximab combination regimen was considered to be an effective option.

A 36-year-old woman was diagnosed with acute appendicitis after a close examination of her abdominal pain and nausea. Laparoscopic appendectomy was performed, and pathological examination revealed a NET G1. They were localized lesions on the tips and body of the appendix, with no additional resection because the tumor size was less than 2 cm and no risk factors for recurrence and metastasis(vascular invasion, NET G2 or higher, or invasion of the mesentery). The patient was followed up with contrast-enhanced CT every 6 months and has been recurrence-free for 2 years postoperatively.

The patient underwent sigmoidectomy with D3 lymph node dissection and partial bladder resection for sigmoid colon cancer(cT4bN1M0, cStage Ⅲa), after preoperative chemotherapy with mFOLFOX plus panitumumab, and FOLFOXIRI plus bevacizumab. Postoperative adjuvant chemotherapy was performed by 8 courses of CAPOX. He relapsed hilar lymph nodes and peritoneal dissemination after 13 months after surgery, he underwent resection of the recurrent lesions. Four months after, he developed recurrence in liver and peritoneum. Although he was treated with FOLFIRI plus ramucirumab or aflibercept, resulted in progression of disease, then he received trifluridine tipiracil hydrochloride plus bevacizumab. At this point, the Japanese health insulance had started to cover pembrolizumab, this therapy was started as the fourth chemotherapy after the diagnosis of high frequency microsatellite instability(MSI), and then tumor markers rapidly declined. He underwent 38 courses of pembrolizumab, the recurrent lesions both liver and peritoneum disappeared. He had stoma closure, peritoneal dissemination disappeared not only intraoperatively but also in histologically from the peritoneal scar. He has received pembrolizumab for 4 years without another recurrence. Here, we report a case of MSI-high sigmoid colon cancer in which long-term survival was achieved by pembrolizumab for recurrent lesions resistant to conventional chemotherapy.

49-year-old woman, who diagnosed advanced breast cancer with, ER-positive, HER2-positive, T4bN1M1, Stage Ⅳ. At the time of initial diagnosis, liver damage equivalent to Child-Pugh classification C due to diffuse liver metastasis was observed, but trastuzumab/pertuzumab(HP)and paclitaxel(PTX)adjusted according to liver function were administered every 3 weeks, resulting in rapid improvement of liver function, PR of the primary tumor(90% reduction), PR of the liver metastases(70% reduction), and improvement of tumor markers. Currently, chemotherapy has been switched to docetaxel (DTX)due to peripheral neuropathy caused by PTX, and treatment is continuing. In the case of HER2-positive breast cancer, good disease control may be achieved with aggressive treatment and intervention under dose adjustment and careful systemic management, even in the setting of liver injury.

Case 1: A 48-year-old woman, had right breast cancer with multiple liver metastases. Seven courses of paclitaxel plus bevacizumab were administered, but due to disease progression, 12 courses of FEC 75(total epirubicin 900 mg/m2)were administered. 2 months after the last FEC administration, the patient developed heart failure and died about 3 months later. Case 2: A 58-year-old woman, was on endocrine therapy after surgery for left breast cancer. Recurrence of lung and bone metastases were appeared 5 years after surgery, 10 courses of FEC 75(total epirubicin 750 mg/m2)were administered due to disease progression. Eight months after the last administration of FEC, the patient developed heart failure and died about 8 months later. Anthracycline induced cardiotoxicity is irreversible and has a severe course. Therefore, anthracycline should be administered with caution.

A 94-year-old woman presented with anorexia, persisting for several months, and marked anemia. An upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer in the antrum. CT imaging indicated a large esophageal hiatus hernia and the elevation of the gastric fornix to the level of the bronchus. Wall thickening in the antrum, surrounded by increased fat tissue density, and swollen lymph nodes along the common hepatic artery, were detected. She was diagnosed with advanced gastric cancer(cT3N1M0, cStage Ⅲ)and a large hiatal hernia. A laparoscopic hiatal hernia repair and distal gastrectomy were performed. The cancer was exposed outside the serosa in the antrum, yet there was no indication of ascites, liver metastasis or peritoneal dissemination. The esophageal hiatus was sutured, and a distal gastrectomy(Billroth-Ⅱ reconstruction)was conducted. To avert hernia recurrence, sutures were applied to the posterior wall of the abdominal esophagus and the crus of the diaphragm, as well as the fornix of the remnant stomach and the diaphragm. Her postoperative course was uneventful, and she was discharged on POD13. There were no instances of gastric cancer recurrence or hiatal hernia 7 months post-operation.