Feasibility of transperineal minimal invasive surgery when performing sacrectomy for advanced primary and recurrent pelvic malignancies.

BACKGROUND: This study aimed to clarify the efficacy and safety of minimally invasive transabdominal surgery (MIS) with transperineal minimal invasive surgery (tpMIS) for sacrectomy in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of MIS with tpMIS for sacrectomies. Surgery was performed between February 2019 and May 2023. The median follow-up period was 27 months (5-46 months). RESULTS: Fifteen consecutive patients were included in this analysis. The diagnoses were as follows: recurrent rectal cancer, n = 11 (73%); primary rectal cancer, n = 3 (20%); and recurrent ovarian cancer, n = 1 (7%). Seven patients (47%) underwent pelvic exenteration with sacrectomy, six patients (40%) underwent abdominoperineal resection (APR) with sacrectomy, and two patients (13%) underwent tumor resection with sacrectomy. The median intraoperative blood loss was 235 ml (range 45-1320 ml). The postoperative complications (Clavien-Dindo grade ≥ 3a) were graded as follows: 3a, n = 6 (40%); 3b, n = 1 (7%); and ≥ 4, n = 0 (0%). Pathological examinations demonstrated that R0 was achieved in 13 patients (87%). During the follow-up period, two patients (13%) developed local re-recurrence due to recurrent cancer. The remaining 13 patients (87%) had no local disease. Fourteen patients (93%) survived. CONCLUSIONS: Although the patient cohort in this study is heterogeneous, MIS with tpMIS was associated with a very small amount of blood loss, a low incidence of severe postoperative complications, and an acceptable R0 resection rate. Further studies are needed to clarify the long-term oncological feasibility.

Feasibility of transanal minimally invasive surgery for total pelvic exenteration for advanced primary and recurrent pelvic malignancies.

BACKGROUND: The purpose of this study was to clarify the efficacy and safety of transanal minimally invasive surgery (TAMIS) for total pelvic exenteration (TPE) in advanced primary and recurrent pelvic malignancies. METHODS: Using a prospectively collected database, we retrospectively analyzed the clinical, surgical, and pathological outcomes of TAMIS for TPE. Surgery was performed between September 2019 and April 2023. The median follow-up period was 22 months (2-45 months). RESULTS: Fifteen consecutive patients were included in this analysis M:F = 14:1 and median (range) age was 63 (36-74). Their diagnoses were as follows: primary rectal cancer (n = 5; 33%), recurrent rectal cancer (n = 4; 27%), primary anorectal cancer (n = 5; 33%), and gastrointestinal stromal tumor (n = 1; 7%). Bladder-sparing TPE was selected for two patients (13%). In nine of 15 patients (60%) the anal sphincter could be successfully preserved, five patients (33%) required combined resection of the internal iliac vessels, and two (13%) required rectus muscle flap reconstruction. The median operative time was 723 min (561-1082), and the median intraoperative blood loss was 195 ml (30-1520). The Clavien-Dindo classifications of the postoperative complications were as follows: grade 0-2 (n = 11; 73%); 3a (n = 3; 20%); 3b (n = 1; 7%); and ≥ 4 (n = 0; 0%). No cases of conversion to laparotomy or mortality were observed. The pathological results demonstrated that R0 was achieved in 14 patients (93%). CONCLUSIONS: The short-term outcomes of this initial experience proved that this novel approach is feasible for TPE, with low blood loss, acceptable postoperative complications, and a satisfactory R0 resection rate.

Colorectal cancer treated by resection and extended lymphadenectomy: patterns of spread in left- and right-sided tumours.

BACKGROUND: Whether tumour side affects the anatomical extent and distribution of lymph node metastasis in colon cancer is unknown. The impact of tumour side on the anatomical pattern of lymphatic spread in colon cancer was assessed. METHODS: Patients with stage III colon cancer from a Japanese multi-institutional database who underwent extensive (D3) lymphadenectomy, which is similar in concept to complete mesocolic excision with central venous ligation, were divided into groups with right- and left-sided tumours. Based on location, mesenteric lymph nodes were categorized as paracolic (L1), intermediate (L2) or central (L3). The Kaplan-Meier method was used to evaluate disease-free survival (DFS) and overall survival (OS), and multivariable Cox models were used to evaluate the association between anatomical lymph node level, metastatic pattern and outcome. RESULTS: A total of 4034 patients with stage III colon cancer (right 1618, left 2416) were included. Unadjusted OS was worse in patients with right colon cancer (hazard ratio 1·23, 95 per cent c.i. 1·08 to 1·40; P = 0·002), but DFS was similar. Right-sided tumours more frequently invaded L3 nodes than left-sided lesions (8·5 versus 3·7 per cent; P < 0·001). The proportion of patients with a skipped pattern of lymphatic spread was higher in right than in left colon cancer (13·7 versus 9·0 per cent; P < 0·001). In multivariable analysis, invasion of L3 nodes was associated with worse OS in left but not in right colon cancer. The presence of skipped metastasis was associated with worse DFS in left, but not right, colon cancer. CONCLUSION: There are significant differences in the pattern of lymph node invasion between right- and left-sided stage III colon cancer, and in their prognostic significance, suggesting that tumour side may dictate the operative approach.

ANTECEDENTES: Se desconoce si la lateralidad del tumor influye en la extensión anatómica y en la distribución de las metástasis en los ganglios linfáticos (lymph node metastasis, LN) en el cáncer de colon. Se evaluó el impacto de la lateralidad del tumor en el patrón anatómico de diseminación linfática en el cáncer de colon. MÉTODOS: Los pacientes con cáncer de colon en estadio III recogidos en una base de datos japonesa multicéntrica, que se sometieron a una linfadenectomía ampliada (D3), conceptualmente similar a la escisión completa del mesocolon con ligadura venosa central, se dividieron en cáncer de colon del lado derecho y cáncer de colon del lado izquierdo. Según la ubicación, las LN mesentéricas se clasificaron como paracólicas (L1), intermedias (L2) o centrales (L3). Se utilizó el método de Kaplan-Meier para evaluar la supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall-survival, OS), y se utilizaron modelos de Cox multivariados para evaluar la asociación entre el nivel L y el patrón metastásico con el resultado. RESULTADOS: Se incluyeron 4.034 pacientes con cáncer de colon en estadio III (cáncer de colon derecho: n = 1.618, cáncer de colon izquierdo: n = 2.416). La OS no ajustada fue peor en el cáncer de colon derecho (cociente de riesgos instantáneos, hazard ratio, HR 1,23, i.c. del 95%: 1,08-1,4; P = 0,002), pero la DFS fue similar. La afectación de los ganglios L3 fue más frecuente en pacientes con cáncer de colon derecho que izquierdo (8,5% versus 3,7%, P < 0,001). En el cáncer de colon derecho, la proporción de pacientes con patrón de diseminación linfática discontinuo, con salto entre niveles, fue mayor en comparación con el cáncer de colon izquierdo (13,7% versus 9%; P < 0,001). En el análisis multivariante, la invasión de los ganglios L3 se asoció con una peor OS en el cáncer de colon izquierdo, pero no en el cáncer de colon derecho. La presencia de metástasis discontinuas se asoció con una peor DFS en el cáncer de colon izquierdo, pero no en el cáncer de colon derecho. CONCLUSIÓN: Existen diferencias significativas en el patrón de invasión de los LN entre el cáncer de colon derecho e izquierdo en estadio III, así como en su importancia pronóstica, lo que sugiere que la lateralidad del tumor puede determinar el abordaje quirúrgico.

Protease IV, a cytoplasmic membrane protein of Escherichia coli, has signal peptide peptidase activity.

During export of the outer membrane lipoprotein across the cytoplasmic membrane, the signal peptide of the lipoprotein undergoes two successive proteolytic attacks, cleavage of the signal peptide by signal peptidase and digestion of the cleaved signal peptide by an enzyme called signal peptide peptidase(s) (Hussain, M., Ichihara, S., and Mizushima, S. (1982) J. Biol. Chem. 257, 5177-5182; Hussain, M., Ozawa, Y., Ichihara, S., and Mizushima, S. (1982) Eur. J. Biochem. 129, 233-239). Here we report that protease IV, a cytoplasmic membrane protease, exhibits the signal peptide peptidase activity. The signal peptide peptidase activity was cofractionated with protease IV throughout the entire process of purification of the latter enzyme. Only the signal peptide was digested by the peptidase among membrane proteins. Both the signal peptide peptidase activity and the protease IV activity were inhibited to similar degrees by antipain, leupeptin, chymostatin, and elastatinal that are known to inhibit the signal peptide peptidase activity in the cell envelope. From these results we conclude that protease IV is the signal peptide peptidase that is responsible for signal peptide digestion in the cytoplasmic membrane. The peptidase attacked the signal peptide only after its release from the precursor protein.