Surgical and Perioperative Treatments for Esophagogastric Junction Cancer.

Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.

Single-incision Laparoscopic Colonic Surgery: A Systemic Review, Meta-analysis, and Future Prospect.

Although single-incision laparoscopic surgery (SILS) has gained some attention as a feasible alternative to conventional multiport laparoscopic surgery (MPLS) in colonic surgery, it became less prevalent than expected. Hence, we conducted this systematic review to evaluate the feasibility, safety, and oncological outcomes of single-incision laparoscopic colectomy (SILC) with meta-analysis and discussion of the future prospect of SILS. The search was conducted from September to October 2023 using PubMed and the Cochrane Central Register of Controlled Trials. Articles on colorectal cancer comparing SILC with multiport laparoscopic colectomy (MPLC) from all randomized controlled trials and comparative studies with 50 patients or more per arm were examined. The primary outcomes were the intra- and postoperative complication rates, and the secondary outcomes were the perioperative and oncological outcomes. The trends of the SILS number in Japan and the trends of the number of articles on SILS in PubMed were also reviewed. There were no significant differences in perioperative complication rates, operative factors, and oncological outcomes between SILC and MPLC, although heterogeneity was observed mainly in operative factors and the total length of the skin incision was significantly shorter in SILC. Therefore, SILC is technically and oncologically feasible and safe when performed by experienced laparoscopic surgeons. The case number of SILS was gradually increasing but the rate of SILS was decreasing in Japan. The number of articles on SILS was also decreasing. SILS has gained foothold to some extent but has plateaued. The emerging new robotic platform may reappraise the concept of SILS.

[Questionnaire Survey on Oral Care and Oral Troubles for Patients with Gastric Cancer Received Chemotherapy].

BACKGROUND: The actual situation of oral care and oral troubles for patients with gastric cancer received chemotherapy is not clear. METHODS: Questionnaire survey in the form of oral questions was performed for patients with gastric cancer who received chemotherapy from December 2021 to February 2022. The relevance between the survey results and background factors was examined using the χ2 test. RESULTS: We performed the questionnaire survey for 36 patients. Of the 36 patients, 29 patients received dental check-up before starting chemotherapy. Fourteen of the 29 patients(48%)continued the dental check-up. Of 14 patients who continued the dental check-up, 9 patients were 65 years or older, while 14 of 15 patients who discontinued the dental check-up were 65 years or older. Continuity of dental check-up was low among the elderly patients. The rate of dysgeusia were 78 vs 30% in the patients who adopted and who did not adopt oral care other than toothbrushing(p=0.01). The frequency of oral troubles was dysgeusia(47%), stomatitis(42%), and dry mouth(36%). The severity of the oral troubles was, in order, dysgeusia, dry mouth, and pain. The most common side effect due to chemotherapy causing decreased food intake was dysgeusia. CONCLUSIONS: Dysgeusia was the most frequent and severe oral trouble.

[Regimen Selection by Narrative Approach in Patients with Advanced Gastric Cancer-Paclitaxel or Nab-Paclitaxel?]

BACKGROUND: According to the sixth Gastric Cancer Treatment Guideline, the regimen included nab-paclitaxel(nab-PTX) is a conditional recommendation as second-line treatment for advanced gastric cancer. However, the selection criteria of nab-PTX is not clear. METHOD: Questionnaire survey as narrative approach on the problems of paclitaxel premedication, the symptoms due to paclitaxel containing alcohol, and infusion time was conducted for patients who had been treated with paclitaxel. RESULTS: Thirty-six patients answered the questionnaire. Nonelderly patients(<65 years)or patients without comorbid medications complained of dissatisfaction with the inconvenience due to premedication significantly more than elderly patients(≥65 years)or patients with comorbid medications. Females or nonelderly patients were significantly more troubled by sleepiness due to premedication than males or elderly patients. Eight out of 11 patients who had visited hospital by driving a car for first-line treatment were troubled by prohibition of driving on the day of treatment. Thirty out of 36 patients answered that they would feel benefits from 30-minutes shortening of infusion time. CONCLUSION: Questionnaire survey suggests that we may select the patients for nab-PTX properly by clarifying the inconvenience of daily life associated with premedication, the way of transportation for visiting hospital, and the benefits by shortening of infusion time.

[A Case of 30s Female with Advanced Anal Canal Adenocarcinoma Managed with Adolescent-And-Young-Adult Team].

A 30s female complaining of anal pain and melena was referred to our hospital. The support by adolescent-and-young- adult(AYA)team was initiated after the first encounter. Colonoscopic examination revealed an ulcerated tumor on the anterior wall of anal canal with its anal margin on anal verge and the tumor was diagnosed as an adenocarcinoma. Contrast- enhanced CT and MRI revealed adjacency of tumor and vagina, enlarged lymph nodes and multiple pulmonary nodules. 18F-fluorodeoxyglucose(FDG)-positron emission tomography(PET)additionally revealed tracer accumulation in left sciatica, which led us to the diagnosis of advanced anal cancer. We planned and safely performed concomitant partial vaginal resection in robot-assisted laparoscopic abdominoperineal resection for the palliative purpose after discussion on physical and psychosocial issues including stoma and fertility with the patient, her family and AYA members. The pathological diagnosis was pT4b(vagina)N1aM1b, pStage ⅣB, and the local margin was pathologically negative. The postoperative course was smooth and she was discharged on postoperative day 16. Fifty one days after operation, she started systemic chemotherapy after decision on not to take ovarian samples and continues systemic chemotherapy as of writing. Support by AYA team was effective to facilitate the patient's decision-making and the communication between the patient and the medical team.

[A Case of Diffuse Large B-Cell Lymphoma Which Was Diagnosed during the Best Supportive Care of Recurrent Ascending Colon Cancer].

A 70s male, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N3M0, Stage Ⅲc(without adjuvant chemotherapy), had enhanced-computed tomography(CT)for 3-month follow-up and a hepatic low-density area, an newly emergent nodule behind inferior vena cava and distal ileal tumor were found. Three months later, enhanced CT showed that the distal ileal tumor got exponentially larger and the diagnosis of"malignant lymphoma"was suspected. The patient became sepsis, so we planned and safely performed partial resection of the tumor. The pathological diagnosis was diffuse large B-cell lymphoma. Postoperative course was smooth except for the Clostridium difficile colitis and he was discharged on postoperative day 19. Although the regrowth of the remnant tumor was observed soon after surgery, partial response was confirmed after introduction of systemic chemotherapy. When we cope with malignant lymphoma of small intestine, we need to keep it in mind that surgery is an option for the prevention of perforation and bacterial translocation.

[A Case of Fibromatosis-Like Tumor Which Was Difficult to Differentiate from Local Recurrence of Ascending Colon Cancer].

A 60s female, who had undergone single-incision laparoscopic ileocecal resection for ascending colon cancer with pathological diagnosis of T3N1bM0, Stage Ⅲb, followed by adjuvant therapy with 8 courses CAPOX 2 years ago, had enhanced- computed tomography(CT)for follow-up and a 15-mm nodule near anastomotic site was found. 18F-fluorodeoxyglucose (FDG)-positron emission tomography(PET)CT revealed abnormal accumulation of 18F-FDG only to the lesion and diagnosis of"anastomotic recurrence"was made. We planned and safely performed resection of the anastomotic site and the nodule. The pathological diagnosis was fibromatosis-like tumor without evidence of recurrence, and margin was negative. Postoperative course was smooth and she was discharged on postoperative day 9. When we diagnose local recurrence, we need to keep it in mind that fibromatosis is one of the differential diagnoses, although its incidence rate is low.

Protocol digest of a randomized controlled adaptive Phase II/III trial of neoadjuvant chemotherapy for Japanese patients with oesophagogastric junction adenocarcinoma: Japan Clinical Oncology Group Study JCOG2203 (NEO-JPEG).

Treatment strategies for oesophagogastric junction adenocarcinoma have not been standardized despite its poor prognosis due to differences in the incidence rates between Western countries and Asia. This randomized Phase II/III trial was initiated in June 2023 to determine which neoadjuvant chemotherapy regimen, docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel, is a more promising treatment in Phase II and confirm the superiority of neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel followed by surgery and postoperative chemotherapy over upfront surgery and postoperative chemotherapy in terms of overall survival in patients with Clinical Stage III or IVA oesophagogastric junction adenocarcinoma in Phase III. A total of 460 patients, including 150 patients in Phase II and 310 patients in Phase III, are planned to be enrolled from 85 hospitals in Japan over 5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230182 (https://jrct.niph.go.jp/latest-detail/jRCTs031230182).

Association between methicillin-resistant Staphylococcus aureus nasal carriage and infection after pancreatic surgery.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections after pancreatectomy are relatively rare; however, they can be fatal when associated with pseudoaneurysms. For the past 12 years, we have been investigating nasal MRSA carriage by polymerase chain reaction testing, postoperatively in patients admitted to the intensive care units, to prevent nosocomial infections. Here, we investigated the relationship between MRSA nasal carriage and postoperative MRSA infection at the surgical site, following pancreatectomy. METHODS: This single-center retrospective study analyzed 313 pancreatectomies (220 pancreaticoduodenectomies and 93 distal pancreatectomies), performed at our hospital between January 2011 and June 2022. The incidence of surgical site infection (SSI) and postoperative MRSA infection were compared between the nasal MRSA-positive and nasal MRSA-negative groups. RESULTS: MRSA nasal carriage was identified in 24 cases (7.6%), and the frequency of SSIs in the nasal MRSA-positive and MRSA-negative groups were 50% and 36.7%, respectively, with no significant difference (p = .273). However, the frequency of MRSA infection among the SSI cases was significantly higher in the nasal MRSA-positive group (16.7%) than in the nasal MRSA-negative group (1.7%) (p = .003). CONCLUSION: It should be noted that MRSA carriers have a significantly higher frequency of MRSA-positive SSIs.

Randomized controlled phase III trial to investigate superiority of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer patients (JCOG1907, MONA LISA study): a study protocol.

BACKGROUND: Laparoscopic gastrectomy (LG) is considered a standard treatment for clinical stage I gastric cancer. Nevertheless, LG has some drawbacks, such as motion restriction and difficulties in spatial perception. Robot-assisted gastrectomy (RG) overcomes these drawbacks by using articulated forceps, tremor-filtering capability, and high-resolution three-dimensional imaging, and it is expected to enable more precise and safer procedures than LG for gastric cancer. However, robust evidence based on a large-scale randomized study is lacking. METHODS: We are performing a randomized controlled phase III study to investigate the superiority of RG over LG for clinical T1-2N0-2 gastric cancer in terms of safety. In total, 1,040 patients are planned to be enrolled from 46 Japanese institutions over 5 years. The primary endpoint is the incidence of postoperative intra-abdominal infectious complications, including anastomotic leakage, pancreatic fistula, and intra-abdominal abscess of Clavien-Dindo (CD) grade ≥ II. The secondary endpoints are the incidence of all CD grade ≥ II and ≥ IIIA postoperative complications, the incidence of CD grade ≥ IIIA postoperative intra-abdominal infectious complications, relapse-free survival, overall survival, the proportion of RG completion, the proportion of LG completion, the proportion of conversion to open surgery, the proportion of operation-related death, and short-term surgical outcomes. The Japan Clinical Oncology Group Protocol Review Committee approved this study protocol in January 2020. Approval from the institutional review board was obtained before starting patient enrollment in each institution. Patient enrollment began in March 2020. We revised the protocol to expand the eligibility criteria to T1-4aN0-3 in July 2022 based on the results of randomized trials of LG demonstrating non-inferiority of LG to open surgery for survival outcomes in advanced gastric cancer. DISCUSSION: This is the first multicenter randomized controlled trial to confirm the superiority of RG over LG in terms of safety. This study will demonstrate whether RG is superior for gastric cancer. TRIAL REGISTRATION: The protocol of JCOG1907 was registered in the UMIN Clinical Trials Registry as UMIN000039825 ( http://www.umin.ac.jp/ctr/index.htm ). Date of Registration: March 16, 2020. Date of First Participant Enrollment: April 1, 2020.

Essential updates 2021/2022: Perioperative and surgical treatments for gastric and esophagogastric junction cancer.

In recent years, important clinical trials for gastric cancer (GC) and esophagogastric junction cancer (EGJC) have been reported, changing the strategies of surgical and perioperative treatment. Although laparoscopic gastrectomy has already been shown to be effective for early-stage cancer, recent evidence from both Asia (JLSSG0901, CLASS-01 and KLASS-02) and Europe (LOGICA and STOMACH trials) has demonstrated that it is useful for advanced GC. Robotic surgery has been rapidly gaining popularity in recent years, and randomized controlled trials are ongoing to evaluate its efficacy. A prospective nationwide multicenter study mapped sites with frequent metastasis and revealed lymphatic flow specific to EGJC, thus establishing the optimal lymph node dissection area and surgical approach based on esophageal involvement. Perioperative chemotherapy, the mainstay of treatment in Europe, also has been established in Asia by the PRODIGY and RESOLVE studies. New clinical trials have been conducted to evaluate the efficacy of combining immunotherapy or molecular-targeted therapy with perioperative chemotherapy or chemoradiotherapy. In this review, we present important recent clinical trials regarding the treatment of GC and EGJC published in 2021 or 2022.

The effect of specimen processing time on HER2 expression in gastric cancer and esophagogastric junction cancer: a single-center retrospective observational study.

BACKGROUND: Recent developments in the field of companion diagnosis and molecular-targeting therapeutic agents have helped in developing treatments targeting human epidermal growth factor receptor 2 (HER2) in gastric cancer (GC) and esophagogastric junction cancer (EGJC), and the importance of accurate diagnosis of HER2 expression is increasing. However, the HER2-positivity rate significantly differs among reports in GC and EGJC, and factors that affect HER2-positivity require elucidation. METHODS: The present study retrospectively examined factors related to HER2-positivity in a single institution, including age, sex, body mass index, the American Society of Anesthesiologists physical status, tumor information, and surgery information, including time to specimen processing. RESULTS: Our study included 165 patients tested for HER2 using GC and EGJC surgery specimens among the 1,320 patients who underwent gastrectomy from January 2007 to June 2022. In total, 35 (21.2%) and 130 (78.8%) patients were HER2-positive and -negative, respectively. Multivariate analysis revealed that intestinal type (odds ratio [OR]: 3.41, 95% confidence interval [CI]: 1.44-8.09, p = 0.005), pM1 (OR: 3.99, 95% CI: 1.51-10.55, p = 0.005), and time to specimen processing of < 120 min (OR: 2.65, 95% CI: 1.01-6.98, p = 0.049) were independent factors that affected HER2-positivity. CONCLUSIONS: The outcomes of the present study indicated that intestinal type, pM, and time to specimen processing are important factors affecting HER2-positive rates in GC and EGJC. Therefore, the risk of false-negative HER2 results may be reduced by decreasing the time required to process the resected specimen. Additionally, accurate diagnosis of HER2 expression may increase the opportunity to administer molecular-targeted drugs that can expect therapeutic effects to patients appropriately. TRAIL REGISTRATION: Retrospectively registered.

Robot-assisted laparoscopic surgery with a fluorescent near-infrared ray ureteral catheter for a rectal cancer patient with pelvic kidney: A case report.

An 85-year-old woman presented with a stomachache after a meal and was admitted to the previous clinic. Multi-detector computed tomography (CT) of the abdomen showed wall thickening in the rectum and right ectopic pelvic kidney. Colonoscopy revealed a mass at the rectum, and a biopsy showed adenocarcinoma. CT showed no lymphadenopathy or distant metastasis. Hartmann's procedure with fluorescent near-infrared ray ureteral catheters was used to avoid causing urinary injury. Robotic surgery was performed while checking the route of the ureter in near-infrared mode. The patient was discharged on postoperative day 14 without specific complications. This case appears to be the first of robot-assisted laparoscopic surgery for a rectal cancer patient with pelvic kidney.

[Conversion Surgery Performed after SOX plus Nivolumab Therapy for Advanced Gastric Cancer with Para-Aortic Lymph Node Metastasis].

The patient was a 78-year-old woman. She presented with anemia and a positive fecal occult blood test. Endoscopic findings revealed type 3 advanced gastric cancer. As it had metastasized to the para-aortic lymph node(PALN: No. 16a2 lat), it was diagnosed as gastric cancer at cardia cT4aN1(No.1)M1(No.16a2 lat), cStage Ⅳ. She was administered S-1, oxaliplatin, and nivolumab(SOX plus Nivo)therapy as a first-line treatment. SOX plus Nivo resulted in a remarkable reduction of the lymph nodes, which were PR. After 3 courses of chemotherapy, a laparoscopic proximal gastrectomy was performed, with D2 plus No. 16a2 int/lat lymph nodes dissection as conversion surgery. Histopathological examination was pT3N0M0, and R0 resection was pStage ⅡA. She was discharged at POD21 and started S-1 from POD69. The patient is alive with no signs of recurrence 10 months postoperatively.

[Tolerability and Outcome of Neoadjuvant GS Therapy for Resectable Pancreatic Cancer].

INTRODUCTION: Neoadjuvant chemotherapy with gemcitabine plus S-1(NAC GS)has been reported to prolong the prognosis of resectable pancreatic cancer, and is now being used in daily practice. In this study, we investigated the tolerability and outcome of neoadjuvant GS therapy for resectable pancreatic cancer in our hospital. PATIENTS: Fifty-two patients who underwent NAC GS for resectable pancreatic cancer between November 2019 and March 2023 were included in this study. RESULTS: The mean age of all 52 patients was 75 years, 28 were male and 24 were female. Tumor site was pancreatic head cancer in 32 patients, pancreatic body cancer in 13 patients, and pancreatic tail cancer in 8 patients. Only 2 patients of the 52 patients completed 2 cycles of GS therapy with full dose, and dose reduction and treatment deferral were performed in remaining 50 patients. The dose intensity was 78.4% for gemcitabine and 66.7% for S-1. Grade 3 or higher adverse events included neutropenia in 21 patients(40.4%), biliary tract infection in 6 patients(11.5%), fatigue, anorexia, hepatic dysfunction, and constipation in 1 patient each(1.9%). 47 patients(90.4%)underwent R0 resection. 4 patients had pancreatic fistula, which was classified as Grade Ⅲ by Clavien-Dindo, and one of them died in the hospital due to bleeding from a pseudoaneurysm. CONCLUSION: NAC GS therapy for resectable pancreatic cancer was considered feasible with appropriate management of adverse events.

[A Case of Preoperative Chemotherapy for Advanced Gastric Cancer, Laparoscopic Total Gastrectomy, Pancreaticoduodenectomy, and Para-Aortic Lymph Node Dissection].

Bulky N+ gastric cancer has a poor prognosis. The results of JCOG0405 showed the efficacy of neoadjuvant chemotherapy with S-1 plus cisplatin combination therapy for Bulky N+ gastric cancer. JLSSG0901 demonstrated the safety and efficacy of laparoscopic surgery for advanced gastric cancer. But the safety of laparoscopic surgery for locally advanced and extensive nodal metastasis cancer(T4b, para-aortic lymph node metastasis)is not apparent. After DOS therapy, we performed total laparoscopic gastrectomy, DP(distal pancreatectomy), D2+ #16a2/b1 lat, and Roux-en-Y reconstruction, and histopathological results showed that the aortic lymph node metastasis disappeared. We controlled extensive lymph node metastasis using preoperative triplet chemotherapy. Laparoscopic surgery after preoperative chemotherapy for Bulky N+ gastric cancer can be a treatment option because we performed laparoscopic resection and para-aortic lymph node dissection with no complications, including pancreatic complications.

[Our Experience with Atezolizumab plus Bevacizumab for Unresectable Hepatocellular Carcinoma].

We report our experience with atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma. METHODS: Fourteen patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab at our department were retrospectively evaluated for antitumor efficacy and adverse events. RESULTS: Age ranged from 66-91 years(median 77.5 years), 11 males and 3 females, number of doses ranged from 2-26(median 13), and observation period ranged from 31-790 days (median 427 days). Antitumor efficacy was CR in 3 patients, PR in 3, SD in 6, and PD in 2. One patient with PD died 650 days after the start of treatment, but the others are still alive. Adverse events included proteinuria in 9 patients who discontinued bevacizumab, hypothyroidism requiring levothyroxine sodium hydrate in 7 patients, dermatitis in 2 patients, and colitis requiring hospitalization in 2 patients. DISCUSSION: Despite the small number of cases, a high antitumor effect was observed with a CR rate of 21%. Although proteinuria and hypothyroidism were observed relatively frequently as adverse events, they were easily controlled and did not pose a major clinical problem.

[Clinical Outcome of Five Patients with Perforated Colorectal Cancer].

We studied the clinicopathological findings of 5 patients with perforated colorectal cancer. Three patients were male, and the primary cancer site was left side colon in 4 patents. Two patients had endoscopy-related perforation. The chief complaint was abdominal pain in all cases. All patients underwent emergency surgery. Two patients had Stage Ⅱ cancer, 3 had Stage Ⅳ. The mean ICU stay was 2.8 days. The average postoperative hospital stay was 71.8 days. Three patients were discharged home and 2 were transferred to other hospitals. The 3 patients who were discharged home received chemotherapy. Perforation of the cancer site is a risk factor for recurrence, and early recovery and additional treatment should be considered.

[A Case Report of the Ascending Colon Cancer with Bullous Pemphigoid].

The patient was a 70-year-old man. The patient had progressive anemia while taking 10 mg/day of prednisolone and 100 mg/day of mizoribine orally for bullous pemphigoid, a colonoscopy diagnosed ascending colon cancer. Adenocarcinoma, Group 5 was detected on biopsy. Abdominal computed tomography showed no metastases. The tumor was diagnosed as ascending colon cancer, cT4aN0M0, cStage Ⅱb. We performed laparoscopic right hemicolectomy and D3 dissection. Histopathological examination revealed pT3N0M0, pStage Ⅱa. In the present report, we describe a case of the ascending colon cancer with bullous pemphigoid, and discuss the case with a review of the literature.