The response of pancreatic acinar cell carcinoma to platinum and olaparib therapy in a germline BRCA2 variant carrier: case report and literature review.

A 73-year-old Japanese man with a history of distal biliary cancer treated by pancreatoduodenectomy developed pancreatic acinar cell carcinoma (PACC) treated by remnant pancreatectomy and adjuvant chemotherapy. Thirteen months after surgery, multiple liver metastases developed and FOLFOX chemotherapy was initiated. Based on the PACC diagnosis and a positive family history for breast and ovarian cancer genetic testing was performed which revealed a pathogenic germline BRCA2 variant (c.8629G > T, p.Glu2877Ter). Olaparib therapy was initiated and the metastases responded well (partial response). PACC is a BRCA2-associated cancer which may respond well to PARP inhibitors.

A Japanese Family Meeting the Clinical Diagnostic Criteria for MEN1 with a MEN1 Variant of Uncertain Significance.

Multiple gastroenteric, pancreatic, and pituitary neuroendocrine neoplasms (NENs) were diagnosed in a 74-year-old man with a history of primary hyperparathyroidism (PHPT). Germline testing demonstrated a variant of MEN1 (c.1694T>A, p.L565Q), whose pathogenicity was classified as a variant of uncertain significance (VUS) according to the ACMG/AMP guidelines. The same germline variant was detected in the patient's son and daughter, who also showed PHPT or hypercalcemia and met the clinical diagnostic criteria for multiple endocrine neoplasia type 1 (MEN1). During surveillance of the son, multiple pancreatic tumors suggestive of NENs were detected. The pathogenicity of the current MEN1 variant was re-evaluated as likely pathogenic, based on additional family data.

A Japanese case of ovarian mucinous adenocarcinoma with germline double variants of MSH2 and BRCA2.

Germline double heterozygosity (GDH) is rarely reported in cases of inherited cancer syndromes, and GDH of a mismatch repair gene and BRCA has never been reported in Japan. Nonetheless, the current report demonstrates a case of ovarian mucinous adenocarcinoma with initiated Lynch syndrome (LS)-related surveillance because of a known germline MSH2 variant. Six and a half years after oophorectomy, multiple tumors developed in the patient's lungs, bones, and lymph nodes, and histology results confirmed mucinous adenocarcinoma. Systemic chemotherapy including an anti-PD-L1 antibody was effective for >1 year, but brain metastases developed. Pathology of the brain tumors showed mucinous adenocarcinoma without expression of MSH2 and MSH6, while multi-gene panel testing demonstrated not only high microsatellite instability and a high tumor mutation burden, but also germline BRCA2 variants. Further, germline testing in relatives confirmed both variants were from the paternal line, from which many LS-related cancers develop, but not BRCA-related cancer.

A Japanese case of familial malignant melanoma with germline CDK4 variant incidentally diagnosed by cancer genome profiling.

Familial malignant melanoma (FMM) is a hereditary tumor that is quite rare in Japan; to date, the germline CDK4 variant has scarcely been reported around the world. Thus, we report on a woman with FMM who developed salivary gland cancer, for which a germline pathogenic variant of CDK4 was incidentally identified through comprehensive genomic profiling. She had a history of multiple atypical nevi and a facial melanoma since her 30 s and multiple family histories of melanoma; however, none of her relatives were aware of its heredity. Genetic counseling and skin surveillance were performed. Precision medicine for cancer can discover this rare genetic syndrome and provides us with the opportunity to manage the health of patients and their relatives.

Discordance of microsatellite instability and mismatch repair immunochemistry occurs depending on the cancer type.

Microsatellite instability (MSI) and deficiency of mismatch repair (dMMR) are key markers for predicting the response of immune checkpoint inhibitors (ICIs) and screening for Lynch syndrome (LS). This study examined the incidences of and factors associated with the concordance of MSI and MMR in human cancers. A total of 518 formalin-fixed cancer tissues were analyzed for MSI and MMR immunohistochemistry (IHC). MSI was analyzed by a PCR-based method using Promega markers. Concordance with MMR expression and factors associated with concordance were analyzed. In 2 colorectal cancer samples, MMR IHC failed due to inadequate staining conditions. In the remaining 516 cancers, a high level of MSI (MSI-H) was identified in 113 cases, and dMMR was identified in 112. The concordance of MSI and MMR IHC was 98.3%. Only 9 cases (4 pancreatobiliary, 3 colorectal, and 2 endometrial cancers) were discordant. Of the 113 MSI-H cases, 4 (3.5%) were proficient MMR (pMMR); of the 403 microsatellite stability (MSS) cases, 5 (1.2%) were dMMR. The independent factors associated with MSI-H/dMMR included meeting Amsterdam II criteria, assay purpose, and sampling method. Multivariate analysis revealed that cancer type (gastrointestinal cancers or others) was associated with concordance of MSI and MMR IHC. Three LS cases with pancreatic or endometrial cancer demonstrated MSS and dMMR, and one biliary cancer showed MSI-H and pMMR. Discordance between MSI and MMR IHC occasionally occurs in pancreaticobiliary and endometrial cancers. When suspected, both MSI and MMR IHC should be done to judge the ICI indication and screen for LS.

Genetic medicine in companion diagnostics of germline BRCA testing of Japanese pancreatic cancer patients.

In 2021, Japan's national health insurance made germline BRCA (g.BRCA) testing available to unresectable pancreatic cancer (PC) patients as a companion diagnostic (CD) of the PARP inhibitor. This study investigated the incidence of the g.BRCA variant (g.BRCAv.) and the status of the genetic medicine associated with its testing. A total of 110 PC patients underwent the testing, five of whom (4.5%) had a deleterious g.BRCA2v. (all truncations) but no g.BRCA1v. The turnaround time (TAT) to the doctors was 13 days, and to the patients, 17 days. A higher incidence of a BRCA-related family history and a shorter TAT were seen in the g.BRCAv. patients, but they were insignificant (p = 0.085 and p = 0.059, respectively). Genetic counseling was not performed for three g.BRCA2v. patients because two of them had no accessible relatives and one died of the cancer before the genetic report was completed. Two families underwent generic counseling and testing based on the patient's genetic data. g.BRCAv. is recognized in a small fraction of PC cases, and the following genetic counseling is done more for the relatives than for the patients. TAT was constant and did not affect much on the genetic counseling, but the earlier testing is expected for patients with a deadly cancer.

Learning curve for the surgical time of laparoscopic cholecystectomy performed by surgical trainees using the three-port method: how many cases are needed for stabilization?

BACKGROUND: The assessment of laparoscopic cholecystectomy (LC) skills using operating times has not been well reported. We examined the total and partial operating times for LC procedures performed by surgical trainees to determine the required number of surgeries until the surgical time stabilizes. METHODS: We reviewed the video records of 514 consecutive LCs using the three-port method, performed by 16 surgical trainees. The total and partial surgical times were calculated and correlated to the surgeons' experience. RESULTS: The median total surgical time for a trainee's first LC was 112 (range 71-226) minutes. It reduced rapidly after the first 20 LCs and plateaued to its minimum after approximately 60 cases. A statistically significant time decrease was observed between the first 10 (median, range 112, 46-252 min) and the next 50-59 cases (64, 34-198 min), but not between the 50-59 and the subsequent 100-109 cases (71, 33-127 min). The total times taken by trainees who had performed > 50 operations were not significantly different from those taken by instructors during the study period. Surgery for 125 patients with acute cholecystitis took a significantly longer time (median 99 vs. 74 min with non-acute cholecystitis); however, the abovementioned time reduction findings showed similar results regardless of the patient's acute inflammation status. The partial operating times around the cervical/cystic duct and gallbladder bed reduced uniformly between the first 10 and the following 50-59 cases. Although time variations in total and cervical/cystic duct operating times were not correlated to the surgical experience, time fluctuation of gallbladder bed procedures reduced after 60 cases. CONCLUSION: The time required to perform an LC was inversely correlated with the experience of surgical trainees and halved after the first 60 cases. The surgical experience required for LC time stabilization is approximately 60 cases.

Comparison of surgical smoke between open surgery and laparoscopic surgery for colorectal disease in the COVID-19 era.

BACKGROUND: Surgical smoke during operation is a well-known health hazard for medical staff. This study aimed to investigate the dynamics of surgical smoke during open surgery or laparoscopic surgery for colorectal disease. METHODS: This study quantitated particulate matter (PM) counts as part of surgical smoke in 31 consecutive patients who underwent colectomy at the Niigata City General Hospital using a laser particle counter. Particles were graded by size as ≤ 2.5 µm PM (PM2.5) or > 2.5 µm PM (large PM). Operative procedures were categorized as either open surgery (n = 14) or laparoscopic surgery (n = 17). RESULTS: The median patient age was 72 (range 41-89) years and 58.1% were male. The total PM2.5, PM2.5 per hour, and maximum PM2.5 per minute counts during operation were significantly higher in open surgery than in laparoscopic surgery (P = 0.001, P < 0.001, and P = 0.029, respectively). Large PM counts (total, per hour, and maximum per minute) were also higher in the open surgery group than in the laparoscopic surgery group. The maximum PM2.5 concentration recorded was 38.6 µm/m3, which is considered "unhealthy for sensitive groups" according to the U.S. Environment Protection Agency air quality index standards, if it was a 24-h period mean value. CONCLUSION: Exposure to surgical smoke is lower during laparoscopic surgery than during open surgery for colorectal diseases.

Is radiological psoas muscle area measurement a predictor of postoperative complications after rectal resection for rectal cancer? A retrospective study.

PURPOSE: Previous studies have reported that sarcopenia increases the risk of postoperative complications following colorectal resection. This retrospective study assessed the postoperative complications of rectal resection associated with sarcopenia. METHODS: We retrospectively analyzed 262 patients who underwent curative low anterior resection for primary rectal cancer from January 2008 to May 2020 at our institution. The patients were divided into a sarcopenia group (normalized total psoas muscle area < 6.36 cm2/m2 in males and < 3.92 cm2/m2 in females; N = 49) and a non-sarcopenia group (N = 213). RESULTS: The overall rate of postoperative complications within 30 days of surgery was higher in the sarcopenia group than in the non-sarcopenia group (46.9 vs. 29.6%; P = 0.028). The rate of postoperative remote infections was higher in the sarcopenia group than in the non-sarcopenia group (12.2 vs. 2.8%; P = 0.012). Sarcopenia was found to be a predictor of remote infection by a multivariate analysis (odds ratio, 4.08; 95% confidence interval, 1.12-14.80; P = 0.033). CONCLUSION: Sarcopenia diagnosed using the psoas muscle index was found to be an independent predictive factor for postoperative remote infection after curative low anterior resection for rectal cancer.

Ileo-right colonic reconstruction preserving all four colonic vessels after esophagectomy for cancer.

When colonic graft is used as an esophageal substitute after esophagectomy, one or two feeding vessels of the colon are cut to obtain sufficient length, the graft is passed via the subcutaneous route, and microvascular anastomosis is often used to avoid fatal complications. Sixteen consecutive ileo-right colonic reconstructions via the posterior mediastinal or retrosternal route with preservation of all four colonic vessels were performed in the past eight years. We presented the surgical technique and evaluation of this surgical method. In 15 out of 16 consecutive cases, the graft could be pulled up to the neck through the posterior mediastinal or retrosternal route while preserving all four colonic vessels. Reconstruction was not possible in one patient because of ileocolic vessel injury during colonic mobilization. Anastomotic leakage occurred in three patients, but all were minor and were treated conservatively. There were no patients with graft necrosis resulting from insufficient blood supply. Ileo-right colonic reconstruction with preservation of all four colonic vessels through the posterior mediastinal or retrosternal route is a safe and feasible procedure and is considered the first choice for colonic reconstruction as an esophageal substitute.